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Pulse pressure has been related to higher risk of cardiovascular events in older persons . Isolated systolic hypertension is common among the elderly and is accompanied by elevated pulse pressure . Treatment of isolated systolic hypertension may further increase pulse pressure if diastolic pressure is lowered to a greater extent than systolic pressure . Little is known regarding pulse pressure as a predictor of cardiovascular outcomes in elderly persons with isolated systolic hypertension , and the influence of treatment on the pulse pressure effect . We assessed the relation between pulse pressure , measured throughout the follow-up period , and the incidence of coronary heart disease ( CHD ) , heart failure ( HF ) , and stroke in 4,632 participants in the Systolic Hypertension in the Elderly Program , a 5-year r and omized , placebo-controlled clinical trial of treatment of isolated systolic hypertension in older adults . In the treatment group , a 10-mm Hg increase in pulse pressure was associated with a statistically significant 32 % increase in risk of HF and a 24 % increase in risk of stroke after controlling for systolic blood pressure and other known risk factors , as well as with a 23 % increase in risk of HF and a 19 % increase in risk of stroke after controlling for diastolic blood pressure and other risk factors . Pulse pressure was not significantly associated with HF or stroke in the placebo group , nor with incidence of CHD in either the placebo or treatment group . These results suggest that pulse pressure is a useful marker of risk for HF and stroke among older adults being treated for isolated systolic hypertension Background There is a marked lack of evidence on the optimal prevention of ischaemic stroke and other thromboembolic events in patients with non-valvular atrial fibrillation and a recent intracerebral haemorrhage during treatment with oral anticoagulation .  These patients are currently treated with oral anticoagulants , antiplatelet drugs , or no antithrombotic treatment , depending on personal and institutional preferences . Compared with warfarin , the direct oral anticoagulant apixaban reduces the risk of stroke or systemic embolism , intracranial haemorrhage , and case fatality in patients with atrial fibrillation . Compared with aspirin , apixaban reduces the risk of stroke or systemic embolism in patients with atrial fibrillation , and has a similar risk of intracerebral haemorrhage . Novel oral anticoagulants have not been evaluated in patients with atrial fibrillation and a recent intracerebral haemorrhage . To inform a phase III trial , the phase II Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation ( APACHE-AF ) trial aims to obtain estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage treated with apixaban and in those in whom oral anticoagulation is avoided . Methods / Design APACHE-AF is a phase II , multicentre , open-label , parallel-group , r and omised clinical trial with masked outcome assessment . One hundred adults with a history of atrial fibrillation and a recent intracerebral haemorrhage during treatment with anticoagulation in whom clinical equipoise exists on the optimal stroke prevention strategy will be enrolled in 14 hospitals in The Netherl and s . These patients will be r and omly assigned in a 1:1 ratio to either apixaban or to avoiding oral anticoagulation . Patients in the control group may be treated with antiplatelet drugs at the discretion of the treating physician . The primary outcome is the composite of vascular death or non-fatal stroke during follow-up . We aim to include 100 patients in 2.5 years . All patients will be followed-up for the duration of the study , but at least for 1 year . Recruitment commenced in September 2014 and is ongoing . This trial is funded by the Dutch Heart Foundation ( 2012 T077 ) and ZonMW (015008048).Trial registration NTR4526 ( 16 April 2014 ) The current guidelines for the detection and management of  high blood pressure  depend exclusively on the measurement of  systolic and diastolic blood pressure  , although these are only two specific points on the arterial pressure wave form [ 1,2 ] . However , it may be more appropriate to describe the cardiac cycle as consisting of a pulsatile ( pulse pressure ) and a steady ( mean pressure ) component . Pulse pressure is defined as the difference between systolic and diastolic pressures and primarily reflects the stiffness of large arteries , especially the aorta . Elevated pulse pressure increases the stretch of arteries , induces fatigue and fracture of elastic elements , and accelerates the development of aneurysms , and ultimately their rupture . Similarly , an increased pulse pressure is more likely to contribute to intimal damage , the prelude to atherosclerosis and arterial thrombotic events . Increased pulse pressure has also been associated with thickening of the carotid intima and media [ 3,4 ] . Systolic blood pressure increases across all age groups , whereas diastolic blood pressure increases until the sixth decade of life and then declines thereafter . As a result , pulse pressure increases as age rises , especially in older people as systolic and diastolic blood pressure move in opposite directions . Hence , pulse pressure may become the key blood pressure measure in older individuals and increase in importance as a risk factor for cerebrovascular diseases and death [ 5,6 ] . Several observational studies have found that pulse pressure is an independent predictor of cardiovascular risk in middle aged and older people , in subjects with high blood pressure , in survivors of myocardial infa rct ion and in patients with left ventricular dysfunction [ 7–11 ] . A meta analysis based on individual patient data from three large trials ( Syst-Eur , SystChina and EWPHE [ 12–14 ] ) showed that isolated systolic hypertension and pulse pressure were the major determinants of cardiovascular risk in elderly hypertensives [ 7 ] . A further meta- analysis of individual patient data in control groups of seven r and omized clinical trials ( SHEP , Syst-Eur , MRC 1 , HEP , MRC 2 , EWPHE and STOP ) in the INDANA project [ 8 ] also reported that pulse pressure , rather than mean pressure , was the major risk factor for adverse cardiovascular events . A 10-mmHg increase in pulse pressure at baseline was associated independently with a 6 % rise in total mortality , a 7 % rise in cardiovascular mortality and a 7 % rise in fatal coronary events . A similar rise in fatal stroke was present , although this was statistically nonsignificant due to the limited number of events . However , the relationship between pulse pressure and fatal stroke became significant ( p = 0.04 ) at higher age [ 8 ] . Importantly , pulse pressure calculated from 24 h ambulatory blood pressure recordings is a better predictor of adverse events than if derived from officemeasured blood pressure in older patients with isolated systolic hypertension [ 15 ] BACKGROUND Oral anticoagulation ( OAC ) is the recommended therapy for patients with atrial fibrillation ( AF ) because it reduces the risk of stroke and other thromboembolic events . Dual antiplatelet therapy ( DAPT ) is required after percutaneous coronary intervention and stenting ( PCI-S ) . In patients with AF requiring PCI-S  , the association of DAPT and OAC carries an increased risk of bleeding , whereas OAC therapy or DAPT alone may not protect against the risk of developing new ischemic or thromboembolic events . OBJECTIVE The MUSICA-2 study will test the hypothesis that DAPT compared with triple therapy ( TT ) in patients with nonvalvular AF at low-to-moderate risk of stroke ( CHADS2 score ≤2 ) after PCI-S reduces the risk of bleeding and is not inferior to TT for preventing thromboembolic complications . DESIGN The MUSICA-2 is a multicenter , open-label r and omized trial that will compare TT with DAPT in patients with AF and CHADS2 score ≤2 undergoing PCI-S.  The primary end point is the incidence of stroke or any systemic embolism or major adverse cardiac events : death , myocardial infa rct ion , stent thrombosis , or target vessel revascularization at 1 year of PCI-S. The secondary end point is the combination of any cardiovascular event with major or minor bleeding at 1 year of PCI-S. The calculated sample size is 304 patients . CONCLUSIONS The MUSICA-2 will attempt to determine the most effective and safe treatment in patients with nonvalvular AF and CHADS2 score ≤2 after PCI-S. Restricting TT for AF patients at high risk for stroke may reduce the incidence of bleeding without increasing the risk of thromboembolic complications Objective To investigate the associations of diastolic blood pressure ( DBP ) and systolic blood pressure ( SBP ) with the risk of coronary heart disease , sudden cardiac and all-cause death in elderly men . Design A cohort study . Setting The Dutch town of Zutphen . Subjects Eight hundred and eighty-five r and omly selected men , aged 64 - 84 years . Main outcome measures Relative risks adjusted for age , body mass index , total and high-density lipoprotein cholesterol , cigarette smoking , alcohol consumption , use of blood pressure-lowering medications without a specific indication for hypertension , and the physician who measured the blood pressure . Results Neither DBP nor SBP was associated significantly with the incidence of a first coronary heart disease event and no clear associations were observed with mortality from coronary heart disease . However , positive associations with sudden cardiac death were observed . The adjusted relative risk for men with definite isolated systolic hypertension was 9.20 . The risk of dying from coronary heart disease not recorded additionally as sudden death was highest in men at the lower end of the DBP and SBP distributions and in men using antihypertensives . DBP and SBP were positively associated with all-cause mortality when possible comorbidity at the time of the blood pressure measurement was accounted for . Overall , the highest risk for all endpoints was observed in men on antihypertensive medication , who formed a distinct group with a clustering of cardiovascular risk factors . Conclusion Elevated DBP and SBP , and especially isolated systolic hypertension , are important predictors of sudden cardiac death in elderly men . The highest risk of nonsudden coronary heart disease mortality was found at the lower end of the blood pressure distributions and among men on antihypertensive medication We performed a subgroup analysis of the first European Stroke Prevention Study including 1,306 patients recruited in a single center , Kuopio , Finl and , to investigate whether or not antiplatelet therapy is effective in the secondary prevention of stroke in hypertensive patients with transient ischemic attack ( TIA ) or stroke . The patients were treated with aspirin , 990 mg/day , plus dipyridamole , 225 mg/day , or placebo for 2 years . The patients with high systolic blood pressure ( > or = 140 mm Hg ; n = 1.105 ) or high diastolic blood pressure ( > or = 85 mm Hg ; n = 1,120 ) at entry , were classified into subgroups by blood pressure level . The effect of treatment was statistically significant in all subgroups with high systolic ( end-point reduction , 55.2 - 68.2 % ) and diastolic blood pressure ( end-point reduction , 47.3 - 82.1 % ) . Risk reduction was , however , greatest in patients with the highest diastolic blood pressure . One possible explanation is that platelets are more activated in these patients , and this can be effectively prevented by antiplatelet therapy . Further studies are needed to confirm this hypothesis 99mTc : technetium-99 m 201TI : thallium 201 ABCB1 : ATP-binding cassette sub-family B member 1 ABI : ankle-brachial index ACC : American College of Cardiology ACCF : American College of Cardiology Foundation ACCOMPLISH : Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension ACE : angiotensin converting enzyme ACIP : Asymptomatic Cardiac Ischaemia Pilot ACS : acute coronary syndrome ADA : American Diabetes Association ADP : adenosine diphosphate AHA : American Heart Association ARB : angiotensin II receptor antagonist ART : Arterial Revascularization Trial ASCOT : Anglo-Sc and inavian Cardiac Outcomes Trial ASSERT : Asymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the atrial fibrillation Reduction atrial pacing Trial AV : atrioventricular BARI 2D : Bypass Angioplasty Revascularization Investigation 2 Diabetes BEAUTIFUL : Morbidity-Mortality Evaluation of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease and Left Ventricular Dysfunction BIMA : bilateral internal mammary artery BMI : body mass index BMS : bare metal stent BNP : B-type natriuretic peptide BP : blood pressure b.p.m . : beats per minute CABG : coronary artery bypass graft CAD : coronary artery disease CAPRIE : Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events CASS : Coronary Artery Surgery Study CCB : calcium channel blocker CCS : Canadian Cardiovascular Society CFR : coronary flow reserve CHARISMA : Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilization , Management and Avoidance CI : confidence interval CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease Epidemiology Collaboration CMR : cardiac magnetic resonance CORONARY : The CABG Off or On Pump Revascularization Study COURAGE : Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation COX-1 : cyclooxygenase-1 COX-2 : cyclooxygenase-2 CPG : Committee for Practice Guidelines CT : computed tomography CTA : computed tomography angiography CV : cardiovascular CVD : cardiovascular disease CXR : chest X-ray CYP2C19 * 2 : cytochrome P450 2C19 CYP3A : cytochrome P3A CYP3A4 : cytochrome P450 3A4 CYP450 : cytochrome P450 DANAMI : Danish trial in Acute Myocardial Infa rct ion DAPT : dual antiplatelet therapy DBP : diastolic blood pressure DECOPI : Desobstruction Coronaire en Post-Infa rct us DES : drug-eluting stents DHP : dihydropyridine DSE : dobutamine stress echocardiography EACTS : European Association for Cardiothoracic Surgery EECP : enhanced external counterpulsation EMA : European Medicines Agency EASD : European Association for the Study of Diabetes ECG : electrocardiogram Echo : echocardiogram ED : erectile dysfunction EF : ejection fraction ESC : European Society of Cardiology EXCEL : Evaluation of XIENCE PRIME or XIENCE V vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization FAME : Fractional Flow Reserve vs. Angiography for Multivessel Evaluation FDA : Food & Drug Administration ( USA ) FFR : fractional flow reserve FREEDOM : Design of the Future Revascularization Evaluation in patients with Diabetes mellitus : Optimal management of Multivessel disease GFR : glomerular filtration rate HbA1c : glycated haemoglobin HDL : high density lipoprotein HDL-C : high density lipoprotein cholesterol HR : hazard ratio HRT : hormone replacement therapy hs-CRP : high-sensitivity C-reactive protein HU : Hounsfield units ICA : invasive coronary angiography IMA : internal mammary artery IONA : Impact Of Nicor and il in Angina ISCHEMIA : International Study of Comparative Health Effectiveness with Medical and Invasive Approaches IVUS : intravascular ultrasound JSAP : Japanese Stable Angina Pectoris KATP : ATP-sensitive potassium channels LAD : left anterior descending LBBB : left bundle branch block LIMA : Left internal mammary artery LDL : low density lipoprotein LDL-C : low density lipoprotein cholesterol LM : left main LMS : left main stem LV : left ventricular LVEF : left ventricular ejection fraction LVH : left ventricular hypertrophy MACE : major adverse cardiac events MASS : Medical , Angioplasty , or Surgery Study MDRD : Modification of Diet in Renal Disease MERLIN : Metabolic Efficiency with Ranolazine for Less Ischaemia in Non-ST-Elevation Acute Coronary Syndromes MERLIN-TIMI 36 : Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes : Thrombolysis In Myocardial Infa rct ion MET : metabolic equivalents MI : myocardial infa rct ion MICRO-HOPE : Microalbuminuria , cardiovascular and renal sub- study of the Heart Outcomes Prevention Evaluation study MPI : myocardial perfusion imaging MRI : magnetic resonance imaging NO : nitric oxide NSAIDs : non-steroidal anti-inflammatory drugs NSTE-ACS : non-ST-elevation acute coronary syndrome NYHA : New York Heart Association OAT : Occluded Artery Trial OCT : optical coherence tomography OMT : optimal medical therapy PAR-1 : protease activated receptor type 1 PCI : percutaneous coronary intervention PDE5 : phosphodiesterase type 5 PES : paclitaxel-eluting stents PET : positron emission tomography PRECOMBAT : Premier of R and omized Comparison of Bypass Surgery vs. Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease PTP : pre-test probability PUFA : polyunsaturated fatty acid PVD : peripheral vascular disease QoL : quality of life RBBB : right bundle branch block REACH : Reduction of Atherothrombosis for Continued Health RITA-2 : Second R and omized Intervention Treatment of Angina ROOBY : Veterans Affairs R and omized On/Off Bypass SAPT : single antiplatelet therapy  SBP : systolic blood pressure SCAD : stable coronary artery disease SCORE : Systematic Coronary Risk Evaluation  SCS : spinal cord stimulation SES : sirolimus-eluting stents SIMA : single internal mammary artery SPECT : single photon emission computed tomography STICH : Surgical Treatment for Ischaemic Heart Failure SWISSI II : Swiss Interventional Study on Silent Ischaemia Type II SYNTAX : SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery TC : total cholesterol TENS : transcutaneous electrical neural stimulation TERISA : Type 2 Diabetes Evaluation of Ranolazine  in Subjects With Chronic Stable Angina TIME : Trial of Invasive vs. Medical therapy TIMI : Thrombolysis In Myocardial Infa rct ion TMR : transmyocardial laser revascularization TOAT : The Open Artery Trial WOEST : What is the Optimal antiplatElet and anticoagulant therapy  in patients with oral anticoagulation and coronary StenTing Guidelines summarize and evaluate all evidence available , at the time of the writing process , on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient with a given condition , taking into account the impact on outcome , as well Abstract Objective : To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice . Design : R and omised controlled trial . Participants : 729 patients aged ≥60 years with atrial fibrillation , recruited in general practice , who had no established indication for coumarin . Mean age was 75 years and mean follow up 2.7 years . Setting : Primary care in the Netherl and s. Interventions : Patients eligible for st and ard intensity coumarin ( international normalised ratio 2.5 - 3.5 ) were r and omly assigned to st and ard anticoagulation , very low intensity coumarin ( international normalised ratio 1.1 - 1.6 ) , or aspirin ( 150 mg/day ) ( stratum 1 ) . Patients ineligible for st and ard anticoagulation were r and omly assigned to low anticoagulation or aspirin ( stratum 2 ) . Main outcome measures : Stroke , systemic embolism , major haemorrhage , and vascular death . Results : 108 primary events occurred ( annual event rate 5.5 % ) , including 13 major haemorrhages ( 0.7 % a year ) . The hazard ratio was 0.91 ( 0.61 to 1.36 ) for low anticoagulation versus aspirin and 0.78 ( 0.34 to 1.81 ) for st and ard anticoagulation versus aspirin . Non-vascular death was less common in the low anticoagulation group than in the aspirin group ( 0.41 , 0.20 to 0.82 ) . There was no significant difference between the treatment groups in bleeding incidence . High systolic and low diastolic blood pressure and age were independent prognostic factors . Conclusion : In a general practice population ( without established indications for coumarin ) neither low nor st and ard intensity anticoagulation is better than aspirin in preventing primary outcome events . Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice . Key messages Studies have shown that patients with non-rheumatic atrial fibrillation may benefit from anticoagulation This study in a general practice population found no benefit of st and ard or low dose anticoagulation on risk of stroke , systemic embolism , major haemorrhage , or vascular death when compared with aspirin Hypertension and age were prognostic factors for event occurrence Aspirin is the treatment of choice for preventing thromboembolism in primary care patients at low ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle – brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute C and esartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease : Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A R and omized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Sc and inavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Sc and inavian Cardiac Outcomes Trial — Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : C And esartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease — EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy C and esartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease  EXPLOR : Amlodipine – Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine – Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infa rct ion in 52 Countries INVEST : INternational VErapamil SR/T Tr and olapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention : an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : r and omized controlled trials RF : risk factor ROADMAP : R and omized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker C and esartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly : Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan R and omised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospect i ve Diabetes Study VADT : Veterans ' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization # # # 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension ( ESH ) and the European Society of Cardiology Objective : Cardiovascular recovery of prestress baseline blood pressure has been implicated as a possible additional determinant of sustained blood pressure elevation . We hypothesize that angry ruminations may slow the recovery process . Method : A within-subjects design was used in which resting baseline blood pressure and heart rate measurements were assessed on 60 subjects , who then took part in two anger-recall tasks .  After each task , subjects sat quietly and alone during a 12-minute recovery period r and omized to with or without distractions . During baseline , task , and recovery , blood pressure was continuously monitored ; during recovery , subjects reported their thoughts at five fixed intervals . Results : Fewer angry thoughts were reported in the distraction condition ( 17 % ) compared with no distraction ( 31 % ; p = .002 ) ; an interaction showed that this effect was largely the result of the two intervals immediately after the anger-recall task . Trait rumination interacted with distraction condition such that high ruminators in the no-distraction condition evidence d the poorest blood pressure recovery , assessed as area under the curve ( p = .044 [ systolic blood pressure ] and p = .046 [ diastolic pressure ] ) . Conclusions : People who have a tendency to ruminate about past anger-provoking events may be at greater risk for target organ damage as a result of sustained blood pressure elevations ; the effect is exacerbated when distractions are not available to interrupt the ruminative process . ANOVA = analysis of variance ; AUC = area under the curve ; BP = blood pressure ; HTN = hypertension ; CHD = coronary heart disease ; CVR = cardiovascular reactivity ; CVD = cardiovascular disease ; HR = heart rate ; DAB-VR = Destructive Anger Behavior-Verbal Rumination ; DBP = diastolic BP ; HPA = hypothalamic-pituitary-adrenal ; SBP = systolic BP Background : Several studies have shown that an elevated heart rate is associated with an increased risk of ischaemic heart disease . The aim of this study was to examine the relationship between heart rate , blood pressure , blood lipids and other cardiovascular risk factors in middle-aged men . Methods : A total of 7735 men , aged 40–59 years at screening , were selected at r and om from one of the general practice s in each of the 24 towns participating in the cross-sectional ( screening ) phase of the British Regional Heart Study .  Blood pressure and levels of blood lipids ( serum total cholesterol , high-density-lipoprotein ( HDL ) cholesterol and triglycerides ) and blood glucose  were measured . Results : All men with pre-existing evidence of ischaemic heart disease and those on regular antihypertensive treatment were excluded from the analysis . In the remaining 5597 men , heart rate showed a strong positive correlation with cigarette smoking and body-mass index and decreased significantly at higher levels of physical activity and FEV1 ( forced expiratory volume in 1 s ) . These associations remained significant after adjustment for each other . Age , alcohol intake and social class were not independently associated with heart rate . There was a significant positive association between heart rate and systolic and diastolic blood pressures , levels of blood cholesterol , triglycerides and blood glucose and a significant inverse association between heart rate and HDL-cholesterol levels , even after adjusting for the above confounding factors . After further adjustment for each of the other physiological variables , heart rate remained independently associated with diastolic and systolic blood pressures and levels of triglycerides and blood glucose . The relationship between heart rate and levels of total cholesterol and HDL cholesterol appeared to be secondary to its association with triglyceride levels . The association between body-mass index and heart rate diminished after further adjustments for systolic blood pressure , suggesting that the primary effect of body weight is on blood pressure rather than on heart rate . Conclusion : Our findings indicate that elevated heart rate is associated with hypertension and with an atherogenic lipoprotein profile and support the suggestion that disturbance of the autonomic nervous system may underlie these associations Abstract Objective : To determine the effect of the angiotensin converting enzyme inhibitor ramipril on the secondary prevention of stroke . Design : R and omised controlled trial with 2 × 2 factorial design . Setting : 267 hospitals in 19 countries . Participants : 9297 patients with vascular disease or diabetes plus an additional risk factor , followed for 4.5 years as part of the HOPE study . Outcome measures : Stroke ( confirmed by computed tomography or magnetic resonance imaging when available ) , transient ischaemic attack , and cognitive function . Blood pressure was recorded at entry to the study , after 2 years , and at the end of the study . Results : Reduction in blood pressure was modest ( 3.8 mm Hg systolic and 2.8 mm Hg diastolic ) . The relative risk of any stroke was reduced by 32 % ( 156 v 226 ) in the ramipril group compared with the placebo group , and the relative risk of fatal stroke was reduced by 61 % ( 17 v 44 ) . Benefits were consistent across baseline blood pressures , drugs used , and subgroups defined by the presence or absence of previous stroke , coronary artery disease , peripheral arterial disease , diabetes , or hypertension . Significantly fewer patients on ramipril  had cognitive or functional impairment . Conclusion : Ramipril  reduces the incidence of stroke in patients at high risk , despite a modest reduction in blood pressure . What is already known on this topic Treatment with aspirin and lowering blood pressure reduce the incidence of stroke What this study adds Ramipril , an angiotensin converting enzyme inhibitor , reduces strokes in patients at high risk whose blood pressure is not elevated , despite only a modest lowering of blood pressure The benefits are observed even when patients receive aspirin and other blood pressure lowering Context Hypertension is a recognized risk factor for the development of congestive heart failure ( CHF ) . By measuring blood pressure , however , we have not yet been able to underst and the significance of pulse pressure as a contributor to CHF in middle-aged men and women . Contribution Using data from the Framingham Heart Study , the authors found that although elevations of systolic , diastolic , and pulse pressure were all related to the risk for CHF , the relation was strongest for systolic and pulse pressure . Caution s Underst and ing the relationships between systolic , diastolic , and pulse pressure and risk for CHF is helpful ; however , they do not help determine the increased risk faced by a person with systolic hypertension who also has increased pulse pressure . The Editors Hypertension is the most common risk factor for congestive heart failure ( CHF ) . It confers a twofold risk for the occurrence of CHF and also carries the highest population attributable risk among all risk factors for CHF ( 1 , 2 ) . Placebo-controlled clinical trials in patients with hypertension have demonstrated a consistent reduction in risk for CHF attributable to the lowering of elevated blood pressure ( 3 - 6 ) . The causal role of hypertension in the pathogenesis of CHF underscores the need to identify high-risk patients because early treatment may prevent or delay the occurrence of CHF ( 2 , 7 ) . The prognostic significance of systolic and diastolic blood pressure in CHF has been reported . However , blood pressure may also be divided into two other components : steady ( mean arterial pressure ) and pulsatile ( pulse arterial pressure ) ( 8 - 10 ) . Pulse pressure , a simple correlate of conduit vessel stiffness , is associated with left ventricular hypertrophy ( 11 ) . Increased pulse pressure has also been implicated in the development and progression of large-vessel atherosclerosis and small-vessel disease ( 12 - 14 ) . Accumulating evidence indicates that pulse pressure ( defined as the difference between systolic and diastolic blood pressure ) may be an important predictor of cardiovascular events ( 15 - 18 ) . Pulse pressure predicts the risk for CHF in elderly persons ( 19 , 20 ) ; however , the association of pulse pressure with CHF in middle-aged men and women has not been examined . The Framingham Heart Study provides an opportunity to examine the long-term associations of systolic , diastolic , and pulse pressure with the new onset of  CHF in middle-aged and elderly men and women .  Blood pressure and traditional risk factors have been measured repeatedly at serial examinations in this community-based cohort with long-term follow-up . We examined systolic blood pressure , diastolic blood pressure , and pulse pressure as predictors of risk for CHF in the Framingham Heart Study . Methods The Framingham Heart Study , which began in 1948 , has followed 5209 participants ( 28 to 62 years of age at entry to the study ) as part of a prospect i ve epidemiologic study of cardiovascular disease . Enrollment criteria and study design have been published previously ( 21 ) . Biennial follow-up visits included a medical history , physical examination , blood pressure measurements , 12-lead electrocardiography , and laboratory tests . Eligibility requirements for inclusion in our study were as follows : Participants had to be free of coronary heart disease and CHF and not be receiving antihypertensive therapy at Framingham Heart Study clinic baseline examinations 10 , 11 , or 12 ( 1968 to 1973 ) . Participants were followed for onset of CHF through mid-1994 . We obtained data for selected risk factors from the baseline examination . Methods for assessing risk factors have been published previously ( 21 , 22 ) . Risk factors , including age , sex , cigarette smoking , heart rate , antihypertensive medication use , and total and high-density lipoprotein cholesterol levels , were assessed .  Sitting systolic and diastolic blood pressure were measured twice by the examining physician ( using a mercury column sphygmomanometer ) and averaged . We used body mass index ( kg/m2 ) as a measure of obesity . Participants were categorized as smokers if they smoked cigarettes regularly within the 1-year period before the baseline examination . Electrocardiography revealed left ventricular hypertrophy when increased voltage was associated with major ST-T repolarization changes ( strain pattern ) ( 22 ) . Diabetes mellitus was defined on the basis of a fasting blood glucose level greater than 7.77 mmol/L ( > 140 mg/dL ) , two r and om nonfasting blood glucose levels greater than 11.10 mmol/L ( > 200 mg/dL ) , or the use of insulin or an oral hypoglycemic agent . Diagnostic criteria for CHF have been described previously ( 21 , 22 ) . At each clinic examination , a history of interim hospitalizations and symptoms of CHF were obtained . Outside medical records of participants who did not attend an examination were evaluated for incident CHF . All suspected interim events were review ed by a panel of three physicians who evaluated relevant Framingham Heart Study clinic notes , outside physician reports , and hospitalization records . Congestive heart failure was diagnosed when at least two major or one major and two minor criteria were present . Minor criteria were considered only if their presence could not be attributed to another disease process . Major criteria were paroxysmal nocturnal dyspnea , pulmonary rales , distended jugular veins , enlarging heart size on chest radiography , acute pulmonary edema , hepatojugular reflux , third heart sound , jugular venous pressure of 16 cm or greater , and weight loss of 4.5 kg or greater in response to diuresis . Major criteria also included pulmonary edema , visceral congestion , or cardiomegaly on autopsy . Minor criteria were bilateral ankle edema , nocturnal cough , shortness of breath on ordinary exertion , hepatomegaly , pleural effusion , decrease in vital capacity by one third from the previous maximum recorded value , and heart rate of 120 beats/min or more . Statistical Analysis We used multivariable Cox proportional-hazards regression models to examine the relations of systolic , diastolic , and pulse pressure with CHF . After accounting for age and sex and using a P value less than 0.15 as the selection criterion , we determined covariates by stepwise selection from the following list : body mass index , diabetes , smoking status , total cholesterol level , high-density lipoprotein ( HDL ) cholesterol level , totalHDL cholesterol ratio , left ventricular hypertrophy , and heart rate . Only total cholesterol level and totalHDL cholesterol ratio did not enter the model . After accounting for relevant covariates , we used Cox proportional-hazards models to obtain hazard ratio estimates with 95 % CIs for st and ardized values of systolic , diastolic , and pulse pressure . These estimates were obtained individually and pairwise by using SAS software ( SAS Institute , Inc. , Cary , North Carolina ) ( 23 ) . We repeated analyses for participants stratified according to hypertension status and sex . Because blood pressure and age are correlated , we conducted separate analyses for participants younger than 60 years of age and 60 years of age and older . To examine constancy of effects over time , follow-up was divided into early and late periods ( < 10 years , 10 years ) , and hazard ratios were calculated separately for early and late follow-up . In addition , we analyzed blood pressure as a time-varying covariate and assessed the effect of antihypertensive treatment after the baseline blood pressure measurements . We used the KaplanMeier method to plot age- and sex-st and ardized cumulative incidence rates for CHF as a function of pulse pressure tertile at baseline . Descriptive data are presented as percentages or means ( SD ) . A P value less than 0.05 was considered statistically significant . Role of the Funding Sources The funding sources had no role in the design , conduct , analyses , and reporting of the study or in the decision to su bmi t the manuscript for publication . Results A total of 894 men and 1146 women , age 50 to 79 years , fulfilled criteria for inclusion in our study . Table 1 presents baseline clinical characteristics for these persons . During 35 497 person-years of follow-up ( mean , 17.4 years [ range , 0.06 to 24 years ] ) , CHF developed in 234 ( 11.8 % ) persons . Myocardial infa rct ion preceded CHF in 59 ( 25 % ) persons . Table 1 . Baseline Clinical Characteristics of the Study Participants Increments of 1 SD in systolic pressure , pulse pressure , and diastolic pressure were associated with hazard ratios for congestive failure of 1.56 , 1.55 , and 1.24 , respectively , after adjustment for age , sex , smoking , left ventricular hypertrophy , body mass index , diabetes mellitus , HDL cholesterol level , and heart rate ( Table 2 ) . When blood pressure tertiles were used , similar associations were observed among various components of blood pressure and CHF . No threshold effect or J-shaped association was documented ( Table 2 ) . The cumulative incidence of CHF according to tertiles of baseline pulse pressure is plotted in the Figure . Table 2 . Risk FactorAdjusted Association of Blood Pressure with Congestive Heart Failure Figure . Cumulative incidence of congestive heart failure according to pulse pressure tertiles at the baseline examination . The joint influences of different blood pressure components were also examined , with adjustment for the covariates mentioned previously . Of note , correlations among the blood pressure variables ranged from modest to very high ( r = 0.20 for diastolic and pulse pressure , r = 0.65 for diastolic and systolic pressure , and r = 0.88 for systolic and pulse pressure ) . Diastolic pressure was not significant ( hazard ratio , 1.12 [ CI , 0.98 to 1.29 ] ) in conjunction with pulse pressure ( hazard ratio , 1.51 [ CI , 1.33 to 1.72 ] ) . Likewise , diastolic pressure was not significant ( hazard ratio , 0.86 [ CI , 0.72 to 1.03 ] ) in conjunction with systolic pressure ( hazard ratio , 1.71 [ CI , 1.45 to 2.01 ] ) , but joint estimates were less stable than those obtained for individual pressure variables . Finally Background : High blood pressure is an important public health concern because it is highly prevalent and a risk factor for adverse health outcomes , including coronary heart disease , stroke , decompensated heart failure , chronic kidney disease , and decline in cognitive function . Observational studies show a progressive increase in risk associated with blood pressure above 115/75 mm Hg . Prior research has shown that reducing elevated systolic blood pressure lowers the risk of subsequent clinical complications from cardiovascular disease . However , the optimal systolic blood pressure to reduce blood pressure – related adverse outcomes is unclear , and the benefit of treating to a level of systolic blood pressure well below 140 mm Hg has not been proven in a large , definitive clinical trial . Purpose : To describe the design considerations of the Systolic Blood Pressure Intervention Trial ( SPRINT ) and the baseline characteristics of trial participants . Methods : The Systolic Blood Pressure Intervention Trial is a multicenter , r and omized , controlled trial that compares two strategies for treating systolic blood pressure : one targets the st and ard target of < 140 mm Hg , and the other targets a more intensive target of < 120 mm Hg . Enrollment focused on volunteers of age ≥50 years ( no upper limit ) with an average baseline systolic blood pressure ≥130 mm Hg and evidence of cardiovascular disease , chronic kidney disease , 10-year Framingham cardiovascular disease risk score ≥15 % , or age ≥75 years . The Systolic Blood Pressure Intervention Trial recruitment also targeted three pre-specified subgroups : participants with chronic kidney disease ( estimated glomerular filtration rate < 60 mL/min/1.73 m2 ) , participants with a history of cardiovascular disease , and participants 75 years of age or older . The primary outcome is first the occurrence of a myocardial infa rct ion ( MI ) , acute coronary syndrome , stroke , heart failure , or cardiovascular disease death . Secondary outcomes include all-cause mortality , decline in kidney function or development of end-stage renal disease , incident dementia , decline in cognitive function , and small-vessel cerebral ischemic disease . Results : Between 8 November 2010 and 15 March 2013 , Systolic Blood Pressure Intervention Trial recruited and r and omized 9361 people at 102 clinics , including 3331 women , 2648 with chronic kidney disease , 1877 with a history of cardiovascular disease , 3962 minorities , and 2636 ≥75 years of age . Limitations : Although the overall recruitment target was met , the numbers recruited in the high-risk subgroups were lower than planned . Conclusions : The Systolic Blood Pressure Intervention Trial will provide important information on the risks and benefits of intensive blood pressure treatment targets in a diverse sample of high-risk participants , including those with prior cardiovascular disease , chronic kidney disease , and those aged ≥75 years BACKGROUND The risk of cardiovascular events among patients with atrial fibrillation is high . We evaluated whether irbesartan , an angiotensin-receptor blocker , would reduce this risk . METHODS We r and omly assigned patients with a history of risk factors for stroke and a systolic blood pressure of at least 110 mm Hg to receive either irbesartan at a target dose of 300 mg once daily or double-blind placebo . These patients were already enrolled in one of two trials ( of clopidogrel plus aspirin versus aspirin alone or versus oral anticoagulants ) . The first co primary outcome was stroke , myocardial infa rct ion , or death from vascular causes ; the second was this composite outcome plus hospitalization for heart failure . RESULTS A total of 9016 patients were enrolled and followed for a mean of 4.1 years . The mean reduction in systolic blood pressure was 2.9 mm Hg greater in the irbesartan group than in the placebo group , and the mean reduction in diastolic blood pressure was 1.9 mm Hg greater . The first co primary outcome occurred at a rate of 5.4 % per 100 person-years in both groups ( hazard ratio with irbesartan , 0.99 ; 95 % confidence interval [ CI ] , 0.91 to 1.08 ; P=0.85 ) . The second co primary outcome occurred at a rate of 7.3 % per 100 person-years among patients receiving irbesartan and 7.7 % per 100 person-years among patients receiving placebo ( hazard ratio , 0.94 ; 95 % CI , 0.87 to 1.02 ; P=0.12 ) . The rates of first hospitalization for heart failure ( a prespecified secondary outcome ) were 2.7 % per 100 person-years among patients receiving irbesartan and 3.2 % per 100 person-years among patients receiving placebo ( hazard ratio , 0.86 ; 95 % CI , 0.76 to 0.98 ) . Among patients who were in sinus rhythm at baseline , there was no benefit of irbesartan in preventing hospitalization for atrial fibrillation or atrial fibrillation recorded on 12-lead electrocardiography , nor was there a benefit in a subgroup that underwent transtelephonic monitoring . More patients in the irbesartan group than in the placebo group had symptomatic hypotension ( 127 vs. 64 ) and renal dysfunction ( 43 vs. 24 ) . CONCLUSIONS Irbesartan did not reduce cardiovascular events in patients with atrial fibrillation . ( Funded by Bristol-Myers Squibb and Sanofi-Aventis ; Clinical Trials.gov number , NCT00249795 . ) BACKGROUND A combination of low-dose aspirin ( A ) and anticoagulation ( AC ) may provide better protection against thromboembolic events compared with AC alone in high-risk patients with atrial fibrillation ( AF ) . METHODS We performed a multicentric placebo-controlled double blind-trial to test the preventive efficacy against thromboembolic events of the addition of aspirin ( A ) ( 100 mg ) or placebo ( P ) to anticoagulant treatment in patients with high-risk atrial fibrillation . A total of 157 patients were included , with atrial fibrillation and previous thromboembolic event or older than 65 years with either a history of hypertension , a recent episode of heart failure or a left ventricular dysfunction . All patients received fluindione ( F ) and P or F and A , with an INR target between 2 and 2.6 . The primary endpoint was a combined endpoint of stroke ( ischaemic or haemorrhagic ) , myocardial infa rct ion , systemic arterial emboli or vascular death . RESULTS The study had to be stopped prematurely owing to a too low recruitment rate . During follow-up ( 0.84 years ) 3 non-fatal thromboembolic events were recorded ( 1P , 2A ) and 6 patients died ( 3P , 3A ) , none of them from a thromboembolic complication . However , 3 deaths were secondary to severe haemorrhagic complications ( 1P , 2A ) . Non-fatal haemorrhagic complications occurred more often in group A ( n = 10 , 13.1 pour cent ) compared with group P ( n = 1 , 1.2 pour cent ) , p = 0.003 . CONCLUSION The FFAACS study was not able to show any therapeutic benefit from the addition of aspirin to anticoagulant in patients with high-risk AF . Such a combination increased the incidence rate of bleeding complications , which therefore greatly reduces its potential overall benefit BACKGROUND The optimal systolic blood pressure ( SBP ) treatment goal is in question , with SPRINT ( Systolic Blood Pressure Intervention Trial ) suggesting benefit for 120 mm Hg . However , achieving an SBP this low may reduce diastolic blood pressure ( DBP ) to levels that could compromise myocardial perfusion . OBJECTIVES This study sought to examine the independent association of DBP with myocardial damage ( using high-sensitivity cardiac troponin-T [ hs-cTnT ] ) and with coronary heart disease ( CHD ) , stroke , or death over 21 years . METHODS The authors studied 11,565 adults from the ARIC ( Atherosclerosis Risk In Communities ) cohort , analyzing DBP and hs-cTnT associations as well as prospect i ve associations between DBP and events . RESULTS Mean baseline age was 57 years , 57 % of patients were female , and 25 % were black . Compared with persons who had DBP between 80 to 89 mm Hg at baseline ( ARIC visit 2 ) , the adjusted odds ratio of having hs-cTnT ≥14 ng/l at that visit was 2.2 and 1.5 in those with DBP < 60 mm Hg and 60 to 69 mm Hg , respectively . Low DBP at baseline was also independently associated with progressive myocardial damage on the basis of estimated annual change in hs-cTnT over the 6 years between ARIC visits 2 and 4 . In addition , compared with a DBP of 80 to 89 mm Hg , a DBP < 60 mm Hg was associated with incident CHD and mortality , but not with stroke . The DBP and incident CHD association was strongest with baseline hs-cTnT ≥14 ng/l ( p value for interaction < 0.001 ) . Associations of low DBP with prevalent hs-cTnT and incident CHD were most pronounced among patients with baseline SBP ≥120 mm Hg . CONCLUSIONS Particularly among adults with an SBP ≥120 mm Hg , and thus elevated pulse pressure , low DBP was associated with sub clinical myocardial damage and CHD events . When titrating treatment to SBP < 140 mm Hg , it may be prudent to ensure that DBP levels do not fall below 70 mm Hg , and particularly not below 60 mm Hg This paper review s a prospect i ve study of occupational factors in coronary heart disease risk incorporated in a r and omised controlled trial of a worksite based occupational health nurse counseling program for reducing coronary heart disease risk factors . The aim of the trial was to evaluate the longterm effectiveness of the counseling program in persons with mildly elevated risk factor levels . Of the 2 , 489 Australian government employees with mildly elevated risk factor levels who entered the intervention trial , 1 , 937 ( 78 % ) attended a followup examination three years later . This paper reports on changes in systolic and diastolic blood pressure . Multiple linear regression models were used with three-year blood pressure reduction as the dependent variable , intervention status as the main determinant , and sex , age , initial risk level and initial blood pressure as covariates . Although systolic and diastolic blood pressure fell in both the intervention and control groups , intervention was significantly associated with systolic blood pressure change only Background Our objective was to test the hypothesis that elevated blood pressure ( BP ) is associated with increased risk of stroke , bleeding and death in patients with incident heart failure ( HF ) . Methods We conducted a prospect i ve cohort study among subjects who were participants in the Diet , Cancer and Health study , born in Denmark , aged 50–64 years at recruitment . We assessed stroke ( ischemic stroke or systemic embolic events ) , major bleeding , death and the composite endpoint according to degree of BP control in patients with incident HF .  BP  was assessed prior to HF at cohort entry . Results Of the whole cohort of 55,748 subjects , n = 2159 ( 35 % female ) had incident HF , of which 12 % had treatment for hypertension . Median follow-up after incident HF was 3.5 years . High systolic ( SBP ) , diastolic ( DBP ) and pulse ( PP ) pressures were associated with an increased risk of stroke , major bleeding and the composite endpoint . For death and stroke/death , the relation appeared U-shaped for SBP and DBP . When comparing the highest quartile group ( Q4 ) to first quartile group ( Q1 ) , SBP ( Q4 : SBP > 163 mmHg ) was associated with significantly higher adjusted hazard rate ratio ( HR ) for stroke ( HR 1.46 , 95 % CI 1.00–2.14 ) and major bleeding ( HR 1.68 , 95 % CI 1.12–2.53 ) . For DBP ( Q4 : DBP > 94 mmHg ) , adjusted HR was significantly higher for major bleeding ( HR 1.63 , 95 % CI 1.13–2.38 ) . The highest quartile of pulse pressure ( Q4 : PP > 74 mmHg ) was associated with non-significantly higher risk of stroke ( HR 1.40 , 95 % CI 0.94–2.06 ) . Conclusion We have shown for the first time that amongst a population with incident HF , higher baseline systolic , diastolic and pulse pressure levels were associated with a higher rate of adverse events . Our data support the importance for optimised BP control , as part of the holistic management of HF patients Context Experts debate the consequences of excessive lowering of diastolic pressure in patients with hypertension and coronary artery disease . Contribution This report is a secondary analysis of data from a large trial of 2 antihypertensive drug regimens in patients with known coronary artery disease . The authors found a J-shaped relationship between diastolic blood pressure and all-cause death and myocardial infa rct ion , with the increased risk occurring at diastolic blood pressures below 70 to 80 mm Hg , that is , the lower the diastolic pressure , the higher the risk . Caution s The study examined associations between blood pressure and outcomes ; it could not prove that the antihypertensive therapy that lowered diastolic pressure too much caused the adverse outcomes . The Editors For 2 decades , the hypertension literature has been haunted by the phenomenon of a paradoxical increase in morbidity and mortality with an excessive decrease in blood pressure ( J-curve ) . Indeed , several reports have shown that low diastolic pressure is associated with an increased risk for coronary heart disease and related mortality in older adults and in patients taking antihypertensive medications ( 1 - 13 ) . After doing a review and meta- analysis of pertinent studies , Farnett and colleagues ( 14 ) concluded that although there was no consistent J-shaped relationship between stroke and systolic or diastolic pressure , there was a consistent J-shaped relationship for cardiac events and diastolic pressure . These authors stated that this dichotomy in the relationship between diastolic pressure and target organ disease may leave a clinician with the uncomfortable choice of whether to prevent stroke or renal disease at the expense of coronary heart disease . These findings were at variance with the generally accepted dogma formulated by the sixth report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) ( 15 ) , which stated that the relationship between pressure and risk was strong , continuous , independent , predictive and etiologically significant . Within the past decade , the phenomenon of a J-curve has been studied in several large trials of normotensive and hypertensive patients ( 16 - 30 ) . Not surprisingly , arguments regarding whether a J-curve could be clinical ly significant have become somewhat contentious . That is , some rely on evidence that on-treatment diastolic pressure below 70 mm Hg does not increase risk for cardiovascular disease and thus deny an impairment of vital organ perfusion within the usual values achievable by antihypertensive treatment . Others , however , consider the J-curve a more real possibility , particularly for the heart . In contrast to other organs , the heart is perfused mostly during diastole and thus could be more vulnerable to diastolic pressure reduction . If a J-curve did exist , it should be most evident in patients with limited coronary perfusion , in other words , in those with manifest coronary artery disease ( CAD ) . Optimal blood pressure in patients with hypertension and CAD remains controversial because few r and omized clinical trials have been done in this population ( 31 , 32 ) . The International Verapamil-Tr and olapril Study ( INVEST ) ( 33 ) , a r and omized trial , evaluated more than 22000 patients with CAD and hypertension . This patient profile , together with unprecedented levels of blood pressure control , provided a unique opportunity to critically investigate the hypothesis that the risk for CAD would increase with an excessive decrease in diastolic pressure . Methods Study Design and Intervention The INVEST design , methods , and principal results have been previously published ( 33 ) . The trial used an open design with blinded end point assessment . In brief , clinical ly stable patients with CAD and hypertension were r and omly assigned to a verapamil sustained-releasebased or atenolol-based strategy .  Patients with previous myocardial infa rct ion ( MI ) within 3 months of enrollment or class IV or V congestive heart failure were excluded .  Blood pressure goals were based on JNC VI ( systolic pressure < 140 mm Hg and diastolic pressure < 90 mm Hg or systolic pressure < 130 mm Hg and diastolic pressure < 85 mm Hg in patients with diabetes or renal impairment ) ( 15 ) . The addition of tr and olapril or hydrochlorothiazide was recommended when necessary to achieve blood pressure goals . Tr and olapril was also recommended for patients with heart failure , diabetes , or renal impairment . Documented CAD was defined as any of the following : remote ( 3 months before enrollment ) confirmed MI , coronary angiography showing more than 50 % narrowing of at least 1 major coronary artery , diagnosis of classic angina pectoris , or concordant abnormalities on 2 different signals ( electrocardiography , echocardiography , or radionuclide scans ) from stress test findings concordant for ischemia ( for example , ST-segment depression or perfusion defects on radionuclide scanning or wall-motion abnormalities on echocardiography or radionuclide scanning ) . Patient Monitoring and Follow-up Protocol visits were scheduled every 6 weeks for the first 6 months and then biannually until 2 years after the last patient was enrolled . Patients were assessed for response to treatment , symptoms , treatment adherence , and adverse effects at each visit and at the end of the study as detailed elsewhere ( 33 ) . Patient follow-up was complete when we received a final assessment form through the online data system or a death report . The Internet-based electronic data collection method used in INVEST did not accept the entry until all required fields were complete . Blood pressure  was measured by using a st and ard mercury sphygmomanometer with an appropriately sized cuff applied to the upper nondominant arm at heart level . By auscultation at the brachial artery , systolic pressure was recorded at the first Korotkoff sound and diastolic pressure was recorded at the disappearance of the fifth Korotkoff sound . Blood pressure was measured twice , at least 2 minutes apart , and the measurements were averaged . Study Outcomes The primary outcome was the first occurrence of all-cause death , nonfatal MI , or nonfatal stroke by intention-to-treat analysis . The MI and stroke definitions are detailed elsewhere ( 34 ) . These 3 components individually were the main secondary outcomes . For this analysis , additional outcomes included fatal and nonfatal MI , fatal and nonfatal stroke , and average on-treatment blood pressure before outcome or censoring . Ascertainment and blinded adjudication of outcomes were described previously ( 32 ) . Follow-up data were available for 22008 ( 97.5 % ) patients . Statistical Analysis The main conclusions of INVEST were that the 2 treatment strategies were equivalent with respect to the primary outcome , main secondary outcomes , and on-treatment systolic and diastolic pressures . Thus , data for all enrolled patients were combined and included in these analyses following the intention-to-treat principle . A P value of 0.05 or less was considered statistically significant . Patients without a primary outcome event were censored at their latest follow-up visit . Average follow-up systolic and diastolic pressures were calculated for each patient by using all post-baseline results , up to the date of primary outcome or censoring . The baseline value was substituted for patients with no post-baseline data ( n= 1154 ) . In this exploratory analysis , the proportions of patients were pooled by 10 mm Hg strata of average follow-up systolic pressure , and the distribution of primary outcome event rate was evaluated to determine whether the relationship was linear . A similar presentation was prepared for diastolic pressure . Because the frequency distributions seemed consistent with a quadratic curve , a quadratic Cox proportional hazards model was formed for the time to primary outcome for each blood pressure variable , with factors for blood pressure and blood pressure squared . Similarly , the relationship between each 10 mm Hg stratum of average systolic pressure and diastolic pressure and all-cause death , fatal and nonfatal MI , and fatal and nonfatal stroke was evaluated . For the time to primary outcome , a second model was fitted , adjusting for the following baseline covariates : age ( 10-year increments ) , sex , race and ethnicity ( white , Asian , black , Hispanic , multiracial , or other ) , previous MI , heart failure ( classes I to III ) , body mass index in increments of 5 kg/m2 , U.S. residency , renal impairment , peripheral vascular disease , left ventricular hypertrophy , smoking history , coronary revascularization , dyslipidemia , stroke or transient ischemic attack , angina pectoris , arrhythmia , diabetes , cancer , aspirin use , and average systolic pressure or diastolic pressure and systolic pressure squared or diastolic pressure squared . To identify clinical ly relevant interactions between the J-shaped curve and baseline diastolic pressure , demographic characteristics , and comorbid conditions for the primary outcome , a 2-step procedure was used . First , baseline covariates were tested individually by adding the variable and 2 interaction terms ( variablediastolic pressure and variable[diastolic pressure squared ] ) to the Cox proportional hazards model . Variables included were age older than 70 years , sex , previous MI , heart failure ( classes I to III ) , previous stroke or transient ischemic attack , diabetes , cancer , renal impairment , hypercholesterolemia , peripheral vascular disease , smoking history , U.S. residency , body mass index greater than 29 kg/m2 ( mean baseline body mass index ) , and diastolic pressure greater than 86 mm Hg ( mean baseline diastolic pressure ) . The change in log likelihood was used to assess the significance of simultaneously adding the 2 interaction terms . The second step in identifying clinical ly relevant interactions between the J-shaped curve and baseline covariates was to plot the hazard ratios for the primary outcome versus diastolic pressure in the OBJECTIVE To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal ( total ) stroke in isolated systolic hypertension . DESIGN Multicenter , r and omized , double-blind , placebo-controlled . SETTING Community-based ambulatory population in tertiary care centers . PARTICIPANTS 4736 persons ( 1.06 % ) from 447,921 screenees aged 60 years and above were r and omized ( 2365 to active treatment , 2371 to placebo ) . Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg . Of the participants , 3161 were not receiving antihypertensive medication at initial contact , and 1575 were . The average systolic blood pressure was 170 mm Hg ; average diastolic blood pressure , 77 mm Hg . The mean age was 72 years , 57 % were women , and 14 % were black . INTERVENTIONS -- Participants were stratified by clinical center and by antihypertensive medication status at initial contact . For step 1 of the trial , dose 1 was chlorthalidone , 12.5 mg/d , or matching placebo ; dose 2 was 25 mg/d . For step 2 , dose 1 was atenolol , 25 mg/d , or matching placebo ; dose 2 was 50 mg/d . MAIN OUTCOME MEASURES Primary . Nonfatal and fatal ( total ) stroke . Secondary . Cardiovascular and coronary morbidity and mortality , all-cause mortality , and quality of life measures . RESULTS Average follow-up was 4.5 years . The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group , and the 5-year average diastolic blood pressure was 72 and 68 mm Hg , respectively . The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo . The relative risk by proportional hazards regression analysis was 0.64 ( P = .0003 ) . For the secondary end point of clinical nonfatal myocardial infa rct ion plus coronary death , the relative risk was 0.73 . Major cardiovascular events were reduced ( relative risk , 0.68 ) . For deaths from all causes , the relative risk was 0.87 . CONCLUSION In persons aged 60 years and over with isolated systolic hypertension , antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36 % , with 5-year absolute benefit of 30 events per 1000 participants . Major cardiovascular events were reduced , with 5-year absolute benefit of 55 events per 1000 Objective To investigate whether baseline systolic blood pressure variability was a risk factor for stroke , cardiovascular mortality or cardiac events during the Syst-Eur trial . Design The Syst-Eur study was a r and omized , double-blind , placebo-controlled trial , powered to detect differences in stroke rate between participants on active antihypertensive treatment and placebo .  Systolic blood pressure variability measurements were made on 744 participants at the start of the trial . Systolic blood pressure variability was calculated over three time frames : 24 h , daytime and night-time . The placebo and active treatment subgroups were analysed separately using an intention-to-treat principle , adjusting for confounding factors using a multiple Cox regression model . Participants An elderly hypertensive European population . Main outcome measures Stroke , cardiac events ( fatal and non-fatal heart failure , fatal and non-fatal myocardial infa rct ion and sudden death ) and cardiovascular mortality ( death attributed to stroke , heart failure , myocardial infa rct ion , sudden death , pulmonary embolus , peripheral vascular disease and aortic dissection ) . Results The risk of stroke increased by 80 % ( 95 % confidence interval : 17–176 % ) for every 5 mmHg increase in night-time systolic blood pressure variability in the placebo group . Risk of cardiovascular mortality and cardiac events was not significantly altered . Daytime variability readings did not predict outcome . Antihypertensive treatment did not affect systolic blood pressure variability over the median 4.4-year follow-up . Conclusion In the placebo group , but not the active treatment group , increased night-time systolic blood pressure variability on admission to the Syst-Eur trial was an independent risk factor for stroke during the trial BACKGROUND Isolated systolic hypertension occurs in about 15 % of people aged 60 years or older . In 1989 , the European Working Party on High Blood Pressure in the Elderly investigated whether active treatment could reduce cardiovascular complications of isolated systolic hypertension . Fatal and non-fatal stroke combined was the primary endpoint . METHODS All patients ( > 60 years ) were initially started on masked placebo .  At three run-in visits 1 month apart , their average sitting systolic blood pressure was 160 - 219 mm Hg with a diastolic blood pressure lower than 95 mm Hg . After stratification for centre , sex , and previous cardiovascular complications , 4695 patients were r and omly assigned to nitrendipine 10 - 40 mg daily , with the possible addition of enalapril 5 - 20 mg daily and hydrochlorothiazide 12.5 - 25.0 mg daily , or matching placebos . Patients withdrawing from double-blind treatment were still followed up . We compared occurrence of major endpoints by intention to treat . FINDINGS At a median of 2 years ' follow-up , sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group ( n = 2297 ) and by 23 mm Hg and 7 mm Hg in the active treatment group ( n = 2398 ) . The between-group differences were systolic 10.1 mm Hg ( 95 % CI 8.8 - 11.4 ) and diastolic , 4.5 mm Hg ( 3.9 - 5.1 ) . Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years ( 42 % reduction ; p = 0.003 ) . Non-fatal stroke decreased by 44 % ( p = 0.007 ) . In the active treatment group , all fatal and non-fatal cardiac endpoints , including sudden death , declined by 26 % ( p = 0.03 ) . Non-fatal cardiac endpoints decreased by 33 % ( p = 0.03 ) and all fatal and non-fatal cardiovascular endpoints by 31 % ( p < 0.001 ) . Cardiovascular mortality was slightly lower on active treatment ( -27 % , p = 0.07 ) , but all-cause mortality was not influenced ( -14 % ; p = 0.22 ) . INTERPRETATION Among elderly patients with isolated systolic hypertension , antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications . Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints BACKGROUND The placement of stents in coronary arteries has been shown to reduce restenosis in comparison to balloon angioplasty . However , clinical use of intracoronary stents is impeded by the risk of subacute stent thrombosis and complications associated with the anticoagulant regimen . To reduce these complications , the hypothesis that systemic anticoagulation is not necessary when adequate stent expansion is achieved was prospect ively evaluated on a consecutive series of patients who received intracoronary stents .  METHODS AND RESULTS From March 1993 to January 1994 , 359 patients underwent Palmaz-Schatz coronary stent insertion .  After an initial successful angiographic result with < 20 % stenosis by visual estimation had been achieved , intravascular ultrasound imaging was performed . Further balloon dilatation of the stent was guided by observation of the intravascular ultrasound images . All patients with adequate stent expansion confirmed by ultrasound were treated only with antiplatelet therapy ( either ticlopidine for 1 month with short-term aspirin for 5 days or only aspirin ) after the procedure . Clinical success ( procedure success without early postprocedural events ) at 2 months was achieved in 338 patients ( 94 % ) . With an inflation pressure of 14.9 + /- 3.0 atm and a balloon-to-vessel ratio of 1.17 + /- 0.19 , optimal stent expansion was achieved in 321 of the 334 patients ( 96 % ) who underwent intravascular ultrasound evaluation , with these patients receiving only antiplatelet therapy after the procedure . Despite the absence of anticoagulation , there were only two acute stent thromboses ( 0.6 % ) and one subacute stent thrombosis ( 0.3 % ) at 2-month clinical follow-up . Follow-up angiography at 3 to 6 months documented two additional occlusions ( 0.6 % ) at the stent site . At 6-month clinical follow-up , angiographically documented stent occlusion had occurred in 5 patients ( 1.6 % ) . At 6-month clinical follow-up , there was a 5.7 % incidence of myocardial infa rct ion , a 6.4 % rate of coronary bypass surgery , and a 1.9 % incidence of death . Emergency intervention ( emergency angioplasty or bailout stent ) for a stent thrombosis event was performed in 3 patients ( 0.8 % ) . The overall event rate was relatively high because of intraprocedural complications that occurred in 16 patients ( 4.5 % ) . Intraprocedural complications , however , decreased to 1 % when angiographically appropriately sized balloons were used for final stent dilations . There was one ischemic vascular complication that occurred at the time of the procedure and one ischemic vascular complication that occurred at the time of angiographic follow-up . By 6 months , repeat angioplasty for symptomatic restenosis was performed in 47 patients ( 13.1 % ) . CONCLUSIONS The Palmaz-Schatz stent can be safely inserted in coronary arteries without subsequent anticoagulation provided that stent expansion is adequate and there are no other flow-limiting lesions present . The use of high-pressure final balloon dilatations and confirmation of adequate stent expansion by intravascular ultrasound provide assurance that anticoagulation therapy can be safely omitted . This technique significantly reduces hospital time and vascular complications and has a low stent thrombosis rate The PIONEER AF-PCI trial ( Open-Label , R and omized , Controlled , Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects with AF who Undergo Percutaneous Coronary Intervention ) is an ambitious , open-label comparison of 3 regimens , almost exclusively in Caucasians , all of whom had coexisting atrial fibrillation and atherosclerotic coronary artery disease requiring stenting ( PCI-S ) . These 2 conditions when they coexist pose a clinical challenge , necessitating concurrent usage of dual antiplatelet and anticoagulation therapy , a cocktail which presents major bleeding risks . Because anticoagulation therapy is suboptimal in preventing stent thrombosis and dual anti platelet therapy is inadequate in averting embolic stroke in atrial fibrillation , neither treatment is sufficient and they must be combined . The study has a unique design and consists of 2 treatment arms and a control ( see Figure 1 for trial design ) , each with about 700 patients and a 20 % dropout rate in groups 1 and 2 but a statistically greater rate of 29 % in group 3 . Both treatment arms are modeled upon previous studies , which involved patients with the need for both antiplatelet therapy and anticoagulation ( see Figure 2 for derivation of trial from WOEST and ATLAS-TIMI 51 ) . The control arm , design ated group 3 in the trial , consists of the US st and ard of practice regimen , in this situation , called “ triple therapy , ” consisting of aspirin 100 mg/d , clopidogrel 75 mg/d , and warfarin maintaining the INR between 2 and 3 . About 7 % of patients in groups 1 and 2 received a different P2Y12 inhibitor , either prasugrel or ticagrelor , and about 4 % in group 3 . Prominent among the numerous exclusions were patients with a previous stroke and a creatinine clearance of under 30 mL/min . In arm 1 , patients with a creatinine clearance between 30 and 60 mL/min received a lower dose of 10 mg of rivaroxaban . The first treatment arm , called arm 1 , is a reprisal of the treatment arm of the Belgian 2013 WOEST trial which showed that clopidogrel 75 mg and warfarin , maintaining an INR of 2 to 3 , were associated with less combined TIMI major and minor bleeding as well as no increase in cardiac or neurological thrombotic complications when compared to the same control arm as is in this study . Despite having studied only 573 patients for just a year , WOEST was influential in generating the recommendation ( level B ) from the European Society of Cardiology to use this regimen in some people at high risk for bleeding with stents who also require anticoagulation . Furthermore in PIONEER , arm 1 , rivaroxaban 15 mg has been substituted for warfarin ; otherwise , the other trial drugs are identical to those in WOEST . A compelling question posed by this arm of the study , although not the primary end point of the study , is whether equivalent stent patency or prevention of atherosclerotic or thromboembolic complications can be achieved with only a single antiplatelet drug throughout the entire 12 months of treatment , including the vital first month poststent . Also addressed is whether the WOEST results can be replicated substituting rivaroxaban , a drug that offers several advantages over warfarin . In treatment group 1 , one would intuitively expect confirmation of the bleeding advantage observed in WOEST , since it contains 2 drugs versus the 3 in the control group , and therefore would be expected to be associated with less bleeding in group 1 versus group 3 . The second treatment group is based on the 2012 ATLAS ACS 2-TIMI 51 trial and consists of very-low-dose rivaroxaban 2.5 mg twice a day along with clopidogrel 75 mg/d and aspirin 100 mg/d . An interesting point of arm 2 versus 3 , although again not the primary end point , is if a dosage of rivaroxaban , which is only 25 % of the FDA -approved dose of that needed to treat atrial fibrillation , would be adequate in preventing embolic strokes . One would anticipate in group 2 that the dual antiplatelet therapy would be equally effective in preventing stent occlusion and recurrent coronary events as the IN A PREVIOUS issue of this journa1,l the details of our national cooperative ControIled study of long-term anticoagulant therapy in cerebral ischemia and cerebral infa rct ion were presented along with an interim report covering some eighteen months . At that time , longterm anticoagulation did not appear to reduce the mortality and there was an added risk due to hemorrhagic complications . The study , embracing 7 clinical centers and extending over a period of forty-two months , was brought to an end in August 1961 , and this is a report of our findings and final conclusions . The important aspects of the study , including selection and classification of cases and method of anticoagulation , were fully covered previously and will not be repeated here . A total of 443 patients were enrolled in the study , each patient being assigned to the anticoagulant or nonanticoagulant therapeutic groups on a statistically r and om basis by means of sealed envelopes . All the patients in the study were divided into 5 diagnostic categories : ( 1 ) transient ischemic attacks , ( 2 ) thrombosis-in-evolution , ( 3 ) thrombosis-completed stroke , ( 4 ) thorem ( thrombosis or embolism ) , and ( 5 ) cerebral embolism . Analysis of the control and treated groups showed that they were remarkably comparable in most respects ( table 1 ) . The number of cases involving the internal carotidmiddle cerebral and vertebral-basilar systems varied from category to category ; in the whole series there were 328 in the carotid and 102 in the vertebral-basilar . In regard to blood pressure , 59.6 per cent of the entire group had an elevated blood pressure . To determine the effect of anticoagulant therapy , the cases were analyzed as to the incidence of ( 1 ) deaths , ( 2 ) progression of cerebral infa rct ion due to either extension of the infa rct ed area or a new infa rct ion , ( 3 ) the advent of extracerebral thrombotic episodes ( ECTE ) , including myocardial infa rct ion , pulmonary embolism , thrombophlebitis , and so forth , and ( 4 ) hemorrhagic complications . Patients whose anticoagulants were stopped within two weeks of death when the patient 's condition was deteriorating were reckoned as deaths while on anticoagulants In 1972 - -1973 , 785 symptom-free men , aged 40 to 49 years , without target organ damage , with systolic blood pressures between 150 and 179 mm Hg and diastolic blood pressure below 110 mm Hg , were assigned at r and om to one of two groups : ( 406 to a drug treatment group and 379 to a control group ) for a five-year controlled drug treatment trial to evaluate the effect of therapy on cardiovascular complications . Drug treatment started with hydrochlorothiazide . If systolic blood pressure remained above 140 mm Hg and /or diastolic blood pressure above 90 mm Hg , alphamethyldopa was added . If there were side effects , methyldopa was replaced with propranolol . The control group was not given a placebo . The mean observation time was 66 months ( range 60 to 78 months ) . A difference in blood pressure between groups of about 17 mm Hg systolic and 10 mm Hg diastolic was maintained throughout the study . The study protocol had a rather low " ethical " blood pressure roof , 180 mm Hg systolic and /or 110 mm Hg diastolic . Seventeen percent of the control group had an increase in blood pressure above this level during the trial , and drug treatment was started . There was no effect on major cardiovascular morbidity comparing groups as established by r and omization , with 18 events in the treatment group and 20 events in the control group . There was no difference between the groups in total mortality and mortality from cardiovascular events . However , in the subgroups with diastolic blood pressure greater than or equal to 100 mm Hg before r and omization , there was a probable reduction in total morbidity from cardiovascular events in favor or the group receiving drug therapy , 7.6 and 16.4 percent events in the treated and control groups , respectively . Cerebrovascular events occurred only in the control group , 7 versus 0 . Two cases of fatal aortic aneurysms also occurred in the control group . Other " pressure " complications , such as marked left ventricular hypertrophy in the electrocardiogram and left ventricular failure , occurred only in the control group . However , regarding coronary heart disease , including sudden death , the incidence tended to be higher in the treated group , although it was not statistically significant . Only 13 men ( 1.7 percent ) failed to meet for regular examinations . At the end of the study these men were also followed up with regard to possible cardiovascular events The perioperative bleeding risk associated with therapeutic anticoagulation at cardiac implantable electronic device implantation has previously been demonstrated to vary by the specific anticoagulant used . Although uninterrupted anticoagulation with warfarin appears to be safe , heparin products have been shown to increase the risk of perioperative bleeding . However , the risk associated with cardiac implantable electronic device implantation with anticoagulation using dabigatran , a novel oral direct thrombin inhibitor , is not known . We performed a prospect i ve observational study of patients receiving dabigatran for anticoagulation who underwent cardiac implantable electronic device implantation from June 2011 through May 2012 . The study end points included thromboembolic and bleeding complications within 30 days of surgery . Major bleeding complications were defined as bleeding requiring surgical intervention , prolongation of hospitalization , and discontinuation of the anticoagulant or transfusion of blood products within 30 days of surgery . Minor bleeding complications included the development of a hematoma not requiring additional intervention . The thrombotic end points included stroke , transient ischemic attack , myocardial infa rct ion , pulmonary embolism , and deep vein thrombosis .  A total of 25 patients were identified for inclusion . During the index hospitalization , no thromboembolic or bleeding complications developed . No major bleeding complications occurred within 30 days of surgery . One minor bleeding event ( 4 % ) occurred within 30 days of surgery in 1 patient who was also receiving dual antiplatelet therapy . In conclusion , although no thromboembolic or major bleeding events were observed , additional studies are required to define the optimal antithrombotic management in the perioperative period As previously reported , 1007 patients with chronic atrial fibrillation participated in the Copenhagen AFASAK study . Before inclusion to trial , they all had a physical examination , chest roentgenogram , and echocardiogram with determination of left atrial size . This study evaluated the importance of cardiovascular risk factors for development of thromboembolic complications . To exclude any treatment effects on occurrence of thromboembolic complications , we included only the 336 patients from the placebo group . Using Cox 's regression model , previous myocardial infa rct ion was a significant risk factor for development of thromboembolic complications . Age , gender , heart failure , chest pain , hypertensive heart disease , diabetes , systolic and diastolic blood pressure , smoking , relative heart volume , and left atrial size were all without statistical importance Background A poor outcome after stroke is associated independently with high blood pressure during the acute phase ; however , relationships with other haemodynamic measures [ heart rate ( HR ) , pulse pressure ( PP ) , rate – pressure product ( RPP ) ] remain less clear . Methods The Tinzaparin in Acute Ischaemic Stroke Trial is a r and omised , controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1484 patients with acute ischaemic stroke .  Systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) and HR measurements taken immediately prior to r and omization were averaged , and the mid-blood pressure ( MBP ) , PP , mean arterial pressure ( MAP ) , pulse pressure index , and RPP were calculated . The relationship between these haemodynamic measures and functional outcome ( death or dependency , modified Rankin Scale > 2 ) and early recurrent stroke , were studied with adjustment for baseline prognostic factors and treatment group . Odds ratios ( OR ) and 95 % confidence intervals ( CI ) refer to a change in haemodynamic measure by 10 points . Results A poor functional outcome was associated with SBP ( adjusted OR ; 1.11 ; 95 % CI , 1.03–1.21 ) , HR ( adjusted OR ; 1.15 ; 95 % CI , 1.00–1.31 ) , MBP ( adjusted OR ; 1.15 , 95 % CI , 1.03–1.29 ) , PP ( adjusted OR ; 1.14 ; 95 % CI , 1.02–1.26 ) , MAP ( adjusted OR ; 1.15 ; 95 % CI , 1.02–1.31 ) and RPP ( adjusted OR ; 1.01 ; 95 % CI , 1.00–1.02 ) . Early recurrent stroke was associated with SBP , DBP , MBP and MAP . Conclusions A poor outcome is independently associated with elevations in blood pressure , HR and their derived haemodynamic variables , including PP and the RPP . Agents that modify these measures may improve functional outcome after stroke BACKGROUND Since the introduction of newer , more potent P2Y12 receptor inhibitors ( P2Y12ris ) , practice patterns and associated clinical outcomes in patients with myocardial infa rct ion ( MI ) undergoing percutaneous coronary intervention ( PCI ) and also requiring oral anticoagulation ( OAC )  have not been fully characterized . METHODS The Canadian Observational Antiplatelet Study was a prospect i ve , multicenter , longitudinal , observational study ( 26 hospitals , December 2011 to May 2013 ) describing P2Y12ri treatment patterns and outcomes in patients with ST-elevation and non-ST-elevation MI undergoing PCI . We describe the clinical characteristics , treatment patterns , bleeding , and ischemic outcomes over the 15-month follow-up within and between the subgroups of patients discharged on either dual-antiplatelet therapy ( DAPT ) ( acetyl salicylic acid [ASA]+P2Y12ri ) or triple therapy ( ASA+P2Y12ri+OAC ) . RESULTS Of the 2,034 patients at discharge , 86 % ( n = 1,757 ) were on DAPT , whereas 14 % ( n = 277 ) were on triple therapy ( 50 % warfarin , 50 % non-vitamin K OAC [ NOAC ] ) . The frequency of newer P2Y12ri use ( prasugrel or ticagrelor ) was similar in the DAPT and triple therapy groups ( 28 % vs 26 % , respectively ) . In the triple therapy group , NOAC use was higher in those receiving a new P2Y12ri compared to those receiving clopidogrel ( 75 % vs 41 % , respectively , P < .0001 ) . The unadjusted and adjusted events of major cardiovascular event ( MACE ) and bleeding were higher in the triple therapy group . For patients on triple therapy , the bleeding or MACE events were not significantly different between those on clopidogrel versus those on ticagrelor or prasugrel . CONCLUSION In this observational study of MI patients requiring PCI , 1 in 8 were discharged on triple antithrombotic therapy , of whom 26 % were on newer P2Y12ris . Patients on triple therapy had higher risk at baseline , with higher unadjusted and adjusted MACE and bleeding events compared to those on DAPT alone . Among triple therapy-treated patients , there was no difference in the MACE and bleeding events regardless of the P2Y12ri used OBJECTIVE Blood pressure ranges associated with cardiovascular disease ( CVD ) events in advanced type 2 diabetes are not clear . Our objective was to determine whether baseline and follow-up ( On- Study ) systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and SBP combined with DBP predict CVD events in the Veterans Affairs Diabetes Trial ( VADT ) . RESEARCH DESIGN AND METHODS Participants in the VADT ( n = 1,791 ) with hypertension received stepped treatment to maintain blood pressure below the target of 130/80 mmHg in st and ard and intensive glycemic treatment groups .  Blood pressure levels of all subjects at baseline and On- Study were analyzed to detect associations with CVD risk . The primary outcome was the time from r and omization to the first occurrence of myocardial infa rct ion , stroke , congestive heart failure , surgery for vascular disease , inoperable coronary disease , amputation for ischemic gangrene , or CVD death . RESULTS Separated SBP ≥140 mmHg had significant risk at baseline ( hazards ratio [ HR ] 1.508 , P < 0.001 ) and On- Study ( HR 1.469 , P = 0.002 ) . DBP < 70 mmHg increased CVD events at baseline ( HR 1.482 , P < 0.001 ) and On- Study ( HR 1.491 , P < 0.001 ) . Combined blood pressure categories indicated high risk for CVD events for SBP ≥140 with DBP < 70 mmHg at baseline ( HR 1.785 , P = 0.03 ) and On- Study ( HR 2.042 , P = 0.003 ) and nearly all SBP with DBP < 70 mmHg . CONCLUSIONS Increased risk of CVD events with SBP ≥140 mmHg emphasizes the urgency for treatment of systolic hypertension . Increased risk with DBP < 70 mmHg , even when combined with SBP in guideline -recommended target ranges , supports a new finding in patients with type 2 diabetes . The results emphasize that DBP < 70 mmHg in these patients was associated with elevated CVD risk and may best be avoided Moderate- to high-intensity strength training is recommended for healthy adults . In young subjects , a single session of strength training decreases blood pressure , while heart rate and cardiac work remain elevated afterwards . However , these effects have not been clearly demonstrated in elderly subjects . To investigate this issue , 16 elderly subjects each underwent a  Control and an Exercise ( 3 sets , 8 RM , 9 exercises ) session conducted in r and om order . Haemodynamic variables and heart rate variability were measured before and after the interventions . Systolic blood pressure did not change after the exercise session but did increase after the control session ( + 8.1±1.6 mm Hg , P≤0.05 ) . Diastolic blood pressure , as well as systemic vascular resistance increased similarly after both sessions . Cardiac output and stroke volume decreased , while heart rate , rate-pressure product and the low- to high-frequency ratio of heart rate variability increased only after the exercise session ( - 0.5±0.1 L/min , - 9.3±2.0 ml,+3.8±1.6 bpm , + 579.3±164.1 mmHg.bpm and + 0.71±0.34 , P≤0.05 ) . Ambulatory blood pressure was similar after both sessions , while heart rate and rate pressure product remained higher after the exercise session for up to 4.5 h. After a single session of strength training  , cardiac sympathetic modulation and heart rate remain elevated in elderly subjects , keeping cardiac work elevated for a long period of time Background Many national and international guidelines recommend that the initiation of blood pressure (BP)-lowering drug treatment for the primary prevention of cardiovascular disease ( CVD ) should no longer be based on BP level alone , but on absolute cardiovascular risk . While BP-lowering drug treatment is beneficial in high-risk individuals at any level of elevated BP , clinicians are concerned about legacy effects on patients with low-to-moderate risk and mildly elevated BP who remain “ untreated ” . Objective We aim to investigate the legacy effect of delayed BP-lowering pharmacotherapy in middle-aged individuals ( 45 - 65 years ) with mildly elevated BP ( systolic BP 140 - 159 mmHg and /or diastolic BP 90 - 99 mmHg ) stratified by absolute risk for primary prevention of CVD , but particularly in the low-risk ( < 10 % five-year absolute risk ) group . Methods R and omized trials of BP-lowering therapy versus placebo or pretreated subjects in active comparator studies with posttrial follow-up will be identified using a 2-step process . First , r and omized trials of BP-lowering therapy will be identified by ( 1 ) retrieving the references of trials included in published systematic review s of BP-lowering therapy , ( 2 ) retrieving studies published by the Blood Pressure Lowering Treatment Trialists ’ Collaboration ( BPLTTC ) , and ( 3 ) checking studies referenced in the 1993 World Health Organization/International Society of Hypertension meeting memor and um on BP management . Posttrial follow-up studies will then be identified by forward citation search ing the r and omized trials identified in step 1 through Web of Science . The search will include r and omized controlled trials with at least 1-year in-trial period and a posttrial follow-up phase . Age is the major determinant of absolute cardiovascular risk , so the participants in our review will be restricted to middle-aged adults who are more likely to have a lower cardiovascular risk profile . The primary outcome will be all-cause mortality . Secondary outcomes will include cardiovascular mortality , fatal stroke , fatal myocardial infa rct ion , and death due to heart failure . Results The search es for existing systematic review s and BPLTTC studies were piloted and modified . The study is expected to be completed before June 2018 . Conclusions The findings of this study will contribute to the body of knowledge concerning the beneficial , neutral , or harmful effects of delayed BP-lowering drug treatment on the primary prevention of CVD in patients with mildly elevated BP and low-to-moderate CVD risk . Trial Registration PROSPERO International Prospect i ve Register of Systematic Review s : CRD42017058414 ; https://www.crd.york.ac.uk/ PROSPERO /display_record.asp?ID = CRD42017058414 ( Archived by WebCite ® at http://www.webcitation.org/6t6sa8O2Q BACKGROUND It is expected that the treatment of hypertension in patients with renal disease decreases the risk of cardiovascular events , but the evidence in these patients is lacking . OBJECTIVE To assess the effect of diuretic-based treatment on cardiovascular events in patients with isolated systolic hypertension and renal dysfunction . METHODS A total of 4336 persons aged 60 years and older with systolic blood pressures of 160 mm Hg and higher and diastolic blood pressures of less than 90 mm Hg were r and omly assigned to receive either placebo or chlorthalidone ( 12.5 - 25.0 mg/d ) , with the addition of atenolol ( 25 - 50 mg/d ) or reserpine ( 0.05 - 0.10 mg/d ) if needed , and observed for 5 years . The risk of first-occurring cardiovascular events , including stroke , transient ischemic attack , myocardial infa rct ion , heart failure , coronary artery bypass surgery , angioplasty , aneurysm , endarterectomy , sudden death , or rapid death , was stratified according to baseline serum creatinine levels ( 35.4 - 84.0 , 84.1 - 101.6 , 101.7 - 119.3 , and 119.4 - 212.2 micromol/L [ 0.4 - 0.9 , 1.0 - 1.1 , 1.2 - 1.3 , and 1.4 - 2.4 mg/dL ] ) . RESULTS Systolic blood pressure reduction was not affected by baseline serum creatinine levels . Active treatment did not affect the risk of serum creatinine levels becoming elevated during follow-up . The risk of hypokalemia with active treatment decreased significantly with increasing baseline serum creatinine levels . In the 4 baseline serum creatinine groups , the relative risk ( 95 % confidence interval ) of cardiovascular events developing with active treatment was 0.73 ( 0.54 - 0.97 ) , 0.63 ( 0.49 - 0.82 ) , 0.62 ( 0.44 - 0.87 ) , and 0.59 ( 0.38 - 0.91 ) . The results were similar for the outcomes of stroke or coronary artery events and in analyses stratified by sex or age . CONCLUSION Diuretic-based treatment of patients with isolated systolic hypertension prevents the development of cardiovascular events in older persons with mild renal dysfunction Current recommendations for the antithrombotic management of patients receiving oral anticoagulation ( OAC ) who undergo percutaneous coronary intervention with stent implantation ( PCI-S ) are based on limited and relatively weak data . To broaden and strengthen available evidence , the management and 1-year outcomes of OAC patients who underwent PCI-S and were included in a prospect i ve , multicenter registry from 2003 to 2007 were evaluated . Among the 632 patients receiving OAC , mostly because of atrial fibrillation ( 58 % ) , who underwent PCI-S , mostly because of acute coronary syndromes ( 63 % ) , dual-antiplatelet therapy with aspirin and clopidogrel was the most frequently prescribed at discharge ( 48 % ) , followed by triple therapy with OAC , aspirin , and clopidogrel ( 32 % ) and OAC plus aspirin ( 18 % ) . The choice of antithrombotic therapy largely matched the thromboembolic risk profiles of patients , with the prescription of regimens including OAC predicted by the presence of non-low-risk features . The cumulative 1-year occurrence of major adverse cardiovascular events was as high as 27 % and was not significantly different among the 3 treatment groups . Stroke and stent thrombosis were limited to 2 % and 3 % , respectively , and although no significant differences were found among the 3 groups , stroke was 4 times less frequent when OAC , with either 1 or 2 antiplatelet agents , was administered . Major bleeding was also limited to 3 % , with no significant differences among the 3 groups . In conclusion , these findings suggest overall real-world management of OAC patients who undergo PCI-S  that is in accordance with their clinical risk profiles and give further support to the reported efficacy and safety of triple therapy for the optimal treatment of these patients Background The prognostic benefits of blood pressure lowering treatment in elderly hypertensive patients were established more than a decade ago , but are less clear in those with mildly to moderately elevated blood pressure . Objective To assess whether c and esartan-based antihypertensive treatment in elderly patients with mildly to moderately elevated blood pressure confers a reduction in cardiovascular events , cognitive decline and dementia . Design Prospect i ve , double-blind , r and omized , parallel-group study conducted in 1997–2002 . Setting and participants The study was of 4964 patients aged 70–89 years , with systolic blood pressure 160–179 mmHg , and /or diastolic blood pressure 90–99 mmHg , and a Mini Mental State Examination ( MMSE ) test score ⩾ 24 . A total of 527 centres in 15 countries participated in the study . Intervention Patients were assigned r and omly to receive the angiotensin receptor blocker c and esartan or placebo , with open-label active antihypertensive therapy added as needed . As a consequence , active antihypertensive therapy was extensively used in the control group ( 84 % of patients ) . Mean follow-up was 3.7 years . Main outcome measures The primary outcome measure was major cardiovascular events , a composite of cardiovascular death , non-fatal stroke and non-fatal myocardial infa rct ion . Secondary outcome measures included cardiovascular death , non-fatal and fatal stroke and myocardial infa rct ion , cognitive function measured by the MMSE and dementia . Results Blood pressure fell by 21.7/10.8 mmHg in the c and esartan group and by 18.5/9.2 mmHg in the control group . A first major cardiovascular event occurred in 242 c and esartan patients and in 268 control patients ; risk reduction with c and esartan was 10.9 % [ 95 % confidence interval ( CI ) , −6.0 to 25.1 , P = 0.19 ] . C and esartan-based treatment reduced non-fatal stroke by 27.8 % ( 95 % CI , 1.3 to 47.2 , P = 0.04 ) , and all stroke by 23.6 % ( 95 % CI , −0.7 to 42.1 , P = 0.056 ) . There were no significant differences in myocardial infa rct ion and cardiovascular mortality . Mean MMSE score fell from 28.5 to 28.0 in the c and esartan group and from 28.5 to 27.9 in the control group ( P = 0.20 ) . The proportions of patients who had a significant cognitive decline or developed dementia were not different in the two treatment groups . Conclusions In elderly hypertensive patients , a slightly more effective blood pressure reduction during c and esartan-based therapy , compared with control therapy , was associated with a modest , statistically non-significant , reduction in major cardiovascular events and with a marked reduction in non-fatal stroke . Cognitive function was well maintained in both treatment groups in the presence of substantial blood pressure reductions . Both treatment regimens were generally well tolerated Elevated arterial pressure enhances the risk for cardiovascular ( CV ) events in patients with diabetic nephropathy . The optimal BP and the component of the elevated BP that affect the risk have not been defined . A post hoc analysis was performed to assess the impact of achieved systolic , diastolic , and pulse pressures on CV outcomes in 1590 adults who had overt diabetic nephropathy and were enrolled in the Irbesartan Diabetic Nephropathy Trial ( IDNT ) and had a baseline serum creatinine above the normal range , up to 266 micromol/L ( 3.0 mg/dL ) , 24-h urine protein > 900 mg/d , and at least 6 mo of follow-up . Patients were r and omized to irbesartan , amlodipine , or placebo , with other antihypertensive agents to a BP goal of < or = 135/85 mmHg . Progressively lower achieved systolic BP ( SBP ) to 120 mmHg predicted a decrease in CV mortality and congestive heart failure ( CHF ) but not myocardial infa rct ions ( MI ) . A SBP below this threshold was associated with increased risk for CV deaths and CHF events . Achieved diastolic BP < 85 mmHg was associated with a trend to increase in all-cause mortality , significant increase in MI , but decreased risk for strokes . Increased pulse pressure predicted increased all-cause mortality , CV mortality , MI , and CHF . It is concluded that achieved SBP approaching 120 mmHg and diastolic BP of 85 mmHg are associated with the best protection against CV events in these patients . BP < or = 120/85 may be associated with an increase in CV events Elevated blood pressure ( BP ) is a causal risk factor for cardiovascular disease ( CVD ) . Epidemiological analyses have established the grade d and continuous association between higher BP and CVD . Moreover , r and omized clinical trials among individuals with hypertension have demonstrated , in aggregate , a reduction in CVD events by 20 % , coronary heart disease ( CHD ) by 17 % , stroke by 27 % , and heart failure by 28 % for every 10 mm Hg systolic BP ( SBP ) lowering with medical therapy.1 Therefore , prevention , detection , treatment , and control of elevated BP , and its clinical correlate hypertension , is an important public health priority and a primary target for CVD prevention . Although national health surveys have demonstrated improvements in hypertension awareness and treatment , strategic opportunities to improve the efficiency and efficacy of applying BP-lowering therapy in patients most likely to benefit remain.2 Global CVD risk assessment , using multivariable prediction models that estimate absolute CVD risk from routinely measured clinical variables , has been promulgated in several CVD prevention guidelines for cholesterol management to target the most intensive preventive therapies to those at highest absolute CVD risk.3–5 Hypertension guidelines , however , have instead relied solely on isolated BP thresholds and BP goals to guide treatment initiation and intensity . In this review , we provide a rationale for incorporating global CVD risk assessment in BP treatment decision-making and propose a framework to guide its implementation in future CVD prevention guidelines . Epidemiological analyses have firmly established that CVD is a multifactorial condition and that modest increases of several CVD risk factors can often lead to greater overall risk than a severe elevation of a Abstract Objective : To determine which groups of patients may derive particular benefit or experience harm from the use of low dose aspirin for the primary prevention of coronary heart disease . Design : R and omised controlled trial . Setting : 108 group practice s in the Medical Research Council 's general practice research framework who were taking part in the thrombosis prevention trial . Participants : 5499 men aged between 45 and 69 years at entry who were at increased risk of coronary heart disease . Main outcome measures : Myocardial infa rct ion , coronary death , and stroke . Results : Aspirin reduced coronary events by 20 % . This benefit , mainly for non-fatal events , was significantly greater the lower the systolic blood pressure at entry ( interaction P=0.0015 ) , the relative risk at pressures 130 mm Hg being 0.55 compared with 0.94 at pressures > 145 mm Hg . Aspirin also reduced strokes at low but not high pressures , the relative risks being 0.41 and 1.42 ( P=0.006 ) respectively . The relative risk of all major cardiovascular events — that is , the sum of coronary heart disease and stroke — was 0.59 at pressures < 130 mm Hg compared with 1.08 at pressures > 145 mm Hg ( P=0.0001 ) . Conclusion : Even with the limitations of subgroup analyses the evidence suggests that the benefit of low dose aspirin in primary prevention may occur mainly in those with lower systolic blood pressures , although it is not clear even in these men that the benefit outweighs the potential hazards . Men with higher pressures may be exposed to the risks of bleeding while deriving no benefit through reductions in coronary heart disease and stroke Background High blood pressure is a common complication in acute stroke and is associated with a poor outcome . Aims This study assesses the effects of transdermal glyceryl trinitrate on 24 h ambulatory blood pressure in patients with recent stroke . Methods One hundred and seven patients with acute ischaemic or haemorrhagic stroke were included . The patients had been enrolled in one of two trials of transdermal glyceryl trinitrate ( 5 mg daily ) or placebo/control , and underwent 24 h ambulatory blood pressure monitoring ( 56 glyceryl trinitrate , 51 control )  . Ambulatory blood pressure data were analysed using area under the curve for the entire 24 h , and day and night periods . Nocturnal dipping was defined as a decline in systolic blood pressure > 10 % . Comparisons of blood pressure between groups were performed by analysis of covariance ( ANCOVA ) with adjustments for trial and baseline measure . Results In comparison with control , glyceryl trinitrate significantly lowered 24 h blood pressure ( systolic blood pressure/ diastolic blood pressure 9·4/4·8 mmHg , P < 0·001/0·001 , n = 104 ) , daytime blood pressure ( 8·7/4·2 , P < 0·001/ < 0·001 , n = 103 ) and night-time blood pressure ( 6·9/1·7 , P = 0·008/0·458 , n = 86 ) . Only 86 patients ( glyceryl trinitrate 45 , placebo/control 41 ) had sufficient night blood pressure measurements to assign dipping status ; 28 were dippers ( 12 glyceryl trinitrate , 16 control ) and 58 were nondippers ( 33 glyceryl trinitrate , 25 control ) ; glyceryl trinitrate significantly lowered systolic but not diastolic blood pressure in both dippers and nondippers . Treatment with glyceryl trinitrate  increased the daytime heart rate ( 4·8 beats/min ) but not the night-time heart rate . Patients whose blood pressure did not dip at night had a worse functional outcome at three-months . Conclusions Transdermal glyceryl trinitrate ( 5 mg ) significantly lowered 24 h blood pressure by 9/5 mmHg ( equivalent to a 6 % reduction ) in both dipping and nondipping patients with acute/subacute stroke . This reduction in blood pressure is clinical ly relevant and is unlikely to be excessive OBJECTIVE To assess the role of treated diastolic blood pressure ( DBP ) level in stroke , coronary heart disease ( CHD ) , and cardiovascular disease ( CVD ) in patients with isolated systolic hypertension ( ISH ) . DESIGN An analysis of the 4736 participants in the Systolic Hypertension in the Elderly Program ( SHEP ) was undertaken . The SHEP was a r and omized multicenter double-blind outpatient clinical trial of the impact of treating ISH in men and women aged 60 years and older . MAIN OUTCOME MEASURES Cox proportional hazards regression analysis , with DBP and systolic blood pressure ( SBP ) as time-dependent covariables . RESULTS After adjustment for the baseline risk factors of race ( black vs other ) , sex , use of antihypertensive medication before the study , a composite variable ( diabetes , previous heart attack , or stroke ) , age , and smoking history ( ever vs never ) and adjustment for the SBP as a time-dependent variable , we found , for the active treatment group only , that a decrease of 5 mm Hg in DBP increased the risk for stroke ( relative risk , [ RR ] , 1.14 ; 95 % confidence interval [ CI ] , 1.05 - 1.22 ) , for CHD ( RR , 1.08 ; 95 % CI , 1.00 - 1.16 ) , and for CVD ( RR , 1.11 ; 95 % CI , 1.05 - 1.16 ) . CONCLUSIONS Some patients with ISH may be treated to a level that uncovers sub clinical disease , and some may be overtreated . Further studies need to determine whether excessively low DBP can be prevented by more careful titration of antihypertensive therapy while maintaining SBP control . It is reassuring that patients receiving treatment for ISH never perform worse than patients receiving placebo in terms of CVD events The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity , largely due to a decreased incidence of stroke , whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies . Furthermore , treated hypertensive patients still have a higher cardiovascular complication rate , compared with matched normotensives . This is particularly evident in patients with left ventricular hypertrophy ( LVH ) , a major independent risk indicator for cardiovascular disease . In addition to elevating blood pressure , angiotensin II ( A-II ) exerts an important influence on cardiac structure and function , stimulating cell proliferation and growth . Thus , to further reduce morbidity and mortality when treating hypertensive patients , it may be important to effectively block the effects of A-II . This can be achieved directly at the A-II receptor level by losartan , the first of a new class of antihypertensive agents . It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy , and thus improves prognosis . The Losartan Intervention For Endpoint reduction ( LIFE ) in Hypertension study is a double-blind , prospect i ve , parallel group study design ed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients ( initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg ) with electrocardiographically documented LVH . The study , which will continue for at least 4 years and until 1,040 patients experience one primary endpoint , has been design ed with a statistical power that will detect a difference of at least 15 % between groups in the incidence of combined cardiovascular morbidity and mortality . It is also the first prospect i ve study with adequate power to link reversal of LVH to reduction in major cardiovascular events . The rationale of the study , which will involve more than 800 clinical centers in Sc and inavia , the United Kingdom , and the United States , is discussed , and the major features of its design and general organization are described . On April 30 , 1997 , when inclusion was stopped , 9,218 patients had been r and omized AIMS Atrial fibrillation patients with prior embolism have a high risk of vascular events in spite of anticoagulant therapy and elderly patients carry an additional risk . We analysed and compared vascular events-rate between older and younger than 75 years atrial fibrillation patients r and omized to anticoagulant-alone or combined antiplatelet plus moderate-level anticoagulant therapy . METHODS AND RESULTS A total of 967 patients stratified by age and the history of prior embolism were r and omized to therapeutic doses of anticoagulant-alone or combined antithrombotic therapy . Primary events were fatal and non-fatal ischaemic or haemorrhagic stroke/transient ischaemic attack , systemic embolism and myocardial infa rct ion , sudden death and death from bleeding . The elderly , compared with the younger patients , had higher event-rate [ hazard ratio 2.31 ( 95 % confidence interval 1.37 - 3.90 ) , P < 0.003 ] . The elderly suffered higher severe bleeding event-rate during anticoagulant therapy . The combined , compared with the anticoagulant therapy , reduced the vascular events-rate in the elderly ( P = 0.012 ) and caused less intracranial haemorrhages and less bleeding mortality , although more non-fatal gastric bleeding . CONCLUSION The elderly with AF had a higher event-rate than the younger patients . A higher severe bleeding event-rate was also registered in elderly patients receiving anticoagulant therapy .  Combined , compared with anticoagulant therapy , significantly reduced vascular events and bleeding mortality in elderly patients The purpose of this study was to determine the effects of exercise and weight loss on cardiovascular responses during mental stress in mildly to moderately overweight patients with elevated blood pressure . Ninety-nine men and women with high normal or unmedicated stage 1 to stage 2 hypertension ( systolic blood pressure 130 to 179 mm Hg , diastolic blood pressure 85 to 109 mm Hg ) underwent a battery of mental stress tests , including simulated public speaking , anger recall interview , mirror trace , and cold pressor , before and after a 6-month treatment program . Subjects were r and omly assigned to 1 of 3 treatments : ( 1 ) aerobic exercise , ( 2 ) weight management combining aerobic exercise with a behavioral weight loss program , or ( 3 ) waiting list control group . After 6 months , compared with control subjects , participants in both active treatment groups had lower levels of systolic blood pressure , diastolic blood pressure , total peripheral resistance , and heart rate at rest and during mental stress . Compared with subjects in the control group , subjects in the exercise and weight management groups also had greater resting stroke volume and cardiac output . Diastolic blood pressure was lower for the weight management group than for the exercise-only group during all mental stress tasks . These results demonstrate that exercise , particularly when combined with a weight loss program , can lower both resting and stress-induced blood pressure levels and produce a favorable hemodynamic pattern resembling that targeted for antihypertensive therapy Background The optimal antithrombotic treatment after percutaneous coronary intervention ( PCI ) with stenting in patients with atrial fibrillation ( AF ) is unknown . In the ENGAGE AF‐TIMI 48 trial , edoxaban was noninferior to a vitamin K antagonist ( VKA ) with respect to the prevention of stroke or systemic embolism and was associated with significantly lower rates of bleeding and cardiovascular death in patients with nonvalvular AF . The effects of edoxaban in combination with single‐ or dual‐antiplatelet therapy in the setting of PCI are unexplored . Design The ENTRUST‐AF PCI trial is a multinational , multicenter , r and omized , open‐label phase 3b trial with blinded end point evaluation involving 1,500 patients on oral anticoagulation for AF . Patients are r and omized between 4 hours and 5 days after successful PCI to either an edoxaban‐based strategy ( experimental arm ; 60 mg [ or 30 mg according to dose reduction criteria ] once daily plus a P2Y12 antagonist [ default clopidogrel , 75 mg once daily ] for 12 months ) or a VKA‐based strategy ( control arm ; VKA plus a P2Y12 antagonist [ as above ] plus acetylsalicylic acid [ 100 mg once daily ] for 30 days to 12 months ) . The primary safety end point is the incidence of International Society on Thrombosis and Haemostasis – defined major or clinical ly relevant nonmajor bleeding . The main efficacy end point is the composite of cardiovascular death , stroke , systemic embolic events , spontaneous myocardial infa rct ion , and definite stent thrombosis . Summary The ENTRUST‐AF PCI trial tests the hypothesis that an edoxaban‐based antithrombotic strategy reduces the risk of bleeding complications after PCI compared with VKA plus conventional dual‐antiplatelet therapy in patients with AF in need of oral anticoagulation . The relative risk of ischemic events between groups will be compared The objectives of the study were to clarify the relationship between blood pressure and mortality from stroke , heart disease , cardiovascular diseases and all causes of death among representative population of Japanese and to estimate category-specific excess mortality from stroke due to blood pressure ( BP ) level . The study design comprised a retrospective cohort study using the 1980 National Survey on Cardiovascular Diseases and identification of underlying causes of death using national vital statistics data . In 1994 , a 14-year follow-up cohort study was conducted among participants of the National Survey on Cardiovascular Diseases in 1980 , r and omly selected from the Japanese population . With a collaboration of 300 public health centres , which had conducted the original survey in 1980 , 91.4 % of the participants of the original survey could be followed up . Total observed person-years were 53 948 for men and 70 932 for women . During follow-up , 1327 deaths were observed . BP levels were significantly related to mortality from strokes , cardiovascular diseases and all causes of death for both sexes ( P<0.001 ) . Heart disease mortality was significantly related to BP levels among men ( P<0.05 ) while not among women . Estimated excess mortality was 130 % for men and 42 % for women and chiefly observed among moderate hypertensives ( 48 % for men and 16 % for women ) . In conclusion , high blood pressure was a risk factor for mortality from all causes as well as those from cardiovascular diseases , stroke and heart disease among Japanese . Since the major part of excess mortality was due to mild hypertension , a population strategy to reduce blood pressure should be encouraged OBJECTIVES The aim of this study was to determine whether pulse pressure is a risk factor for coronary artery disease using data from the MRC trial of treatment of mild hypertension , and whether the effect of anti-hypertensive drug therapy on pulse pressure may be a determinant of outcome in treated patients . METHODS Logistic regression and Cox regression analyses were used to compare systolic and diastolic blood pressure , pulse pressure and mean blood pressure as predictors of coronary events and stroke in the MRC Mild Hypertension Trial . The effects of anti-hypertensive drug treatment with bendrofluazide and propranolol on pulse pressure were assessed using 1-year follow-up data . Event rates in the placebo-treated group and responses to anti-hypertensive treatment were measured in quartiles of age-adjusted entry pulse pressure . A ' four-corners ' analysis was performed , with subjects divided into the upper and lower halves of the distributions of systolic and diastolic blood pressure at entry . RESULTS Pulse pressure was a stronger predictor of coronary events than systolic , diastolic or mean blood pressure in males by logistic regression .  Pulse pressure was similar to systolic pressure as a coronary event predictor on Cox regression . Stroke was predicted most strongly by mean blood pressure . Fatal and non-fatal coronary event rates increased progressively in ascending quartiles of age-adjusted pulse pressure , but there was also a strong correlation with systolic blood pressure . The values of partial logistic regression coefficients in models containing both systolic and diastolic blood pressure also supported a role for pulse pressure in predicting coronary events and for mean blood pressure in predicting stroke . Coronary risk , but not stroke , was inversely related to diastolic blood pressure in the four-corners analysis . In a Cox model , regressions of coronary event probability on systolic blood pressure at entry were significantly and inversely related to diastolic blood pressure categorized in quartiles . Bendrofluazide but not propranolol decreased pulse pressure significantly and was associated with a reduction in cardiovascular events overall , but no definite relationship between the effect of drugs on pulse pressure and specific responses to treatment was seen . CONCLUSION Pulse pressure is a strong risk factor for coronary events in untreated hypertensive male subjects in the MRC Mild Hypertension Trial , whereas stroke is best predicted by mean blood pressure .  Bendrofluazide and propranolol have different effects on pulse pressure which may be related to their relative efficacy in the treatment of hypertension , but this possibility requires further study in more suitable population Background : A combination of low-dose aspirin with anticoagulants may provide better protection against thromboembolic events compared to anticoagulants alone in high-risk patients with atrial fibrillation . Objective : Evaluation of the preventive efficacy against nonfatal thromboembolic events and vascular deaths of the combination of the oral anticoagulant fluindione and aspirin ( 100 mg ) in patients with high-risk atrial fibrillation . Methods : A multicenter , placebo-controlled , double-blind , r and omized trial was conducted at 49 investigating centers in France . Atrial fibrillation patients with a previous thromboembolic event or older than 65 years and with either a history of hypertension , a recent episode of heart failure or decreased left ventricular function were included in the study . Patients were treated with fluindione plus placebo ( i.e. anticoagulant alone ) or fluindione plus aspirin ( i.e. combination therapy ) , with an international normalized ratio target of between 2 and 2.6 . The combined primary endpoint was stroke ( ischemic or hemorrhagic ) , myocardial infa rct ion , systemic arterial emboli or vascular death . The secondary endpoint was the incidence of hemorrhagic complications . Results : The 157 participants ( average age 74 years ; 52 % women ; 42 % with paroxysmal atrial fibrillation ) were followed for an average of 0.84 years . Three nonfatal thromboembolic events were observed ( 1 in the anticoagulation group , 2 in the combination group ) and 6 patients died ( 3 in the anticoagulation group , 3 in the combination group ) , none of them from a thromboembolic complication . However , 3 deaths were secondary to severe hemorrhagic complications ( 1 in the anticoagulation group , 2 in the combination group ) . Nonfatal hemorrhagic complications occurred more often in the combination group ( n = 10 , 13.1 % ) compared to the anticoagulation group ( n = 1 , 1.2 % ) ( p = 0.003 ) . Conclusion : The combination of aspirin with anticoagulant is associated with increased bleeding in elderly atrial fibrillation patients . The effect on thromboembolism and the overall balance of benefit to risk could not be accurately assessed in this study due to the limited number of ischemic events Background Isolated systolic hyprtension occurs in around 8 % of Chinese people aged 60 years or older . In 1988 , the Systolic Hypertension in China ( Syst-China ) Collaborative Group started to investigate whether active treatment could reduce the incidence of stroke and other cardiovascular complications in older patients with isolated systolic hypertension . Methods All patients were initially started on masked placebo . After stratification for centre , sex and previous cardiovascular complications , alternate patients ( n = 1253 ) were assigned nitrendipine at 10–40 mg daily , with the addition of captopril at 12.5–50.0 mg daily or hydrochlorothiazide at 12.5–50.0 mg daily , or both , if a sufficient blood pressure fall was not obtained . In the remaining 1141 control patients , matching placebos were administered similarly . Results At entry , sitting blood pressure averaged 170.5 mmHg systolic and 86.0 mmHg diastolic , age averaged 66.5 years and total serum cholesterol was 5.1 mmol/l . After 2 years of follow-up , sitting systolic and diastolic blood pressures had fallen by 10.9 mmHg and 1.9 mmHg in the placebo group and by 20.0 mmHg and 5.0 mmHg in the active treatment group . The intergroup differences were 9.1 mmHg systolic ( 95 % confidence interval 7.6–10.7 mmHg ) and 3.2 mmHg diastolic ( 95 % confidence interval 2.4–4.0 ) . Active treatment reduced total strokes by 38 % ( from 20.8 to 13.0 endpoints per 1000 patient-years , P = 0.01 ) , all-cause mortality by 39 % ( from 28.4 to 17.4 endpoints per 1000 patient-years , P = 0.003 ) , cardiovascular mortality by 39 % ( from 15.2 to 9.4 endpoints per 1000 patient-years , P = 0.03 ) , stroke mortality by 58 % ( from 6.9 to 2.9 endpoints per 1000 patient-years , P = 0.02 ) , and all fatal and nonfatal cardiovascular endpoints by 37 % ( from 33.3 to 21.4 endpoints per 1000 patient-years , P = 0.004 ) . Conclusions Antihypertensive treatment prevents stroke and other cardiovascular complications in older Chinese patients with isolated systolic hypertension . Treatment of 1000 Chinese patients for 5 years could prevent 55 deaths , 39 strokes or 59 major cardiovascular endpoints Context Risk factors for recurrent events among women with known coronary disease and whether these women commonly receive secondary prevention treatments are mostly unknown . Contribution This large cohort study showed that 11 different factors , including several previous infa rct ions , renal dysfunction , diabetes , angina , heart failure , and uncontrolled hypertension , predicted up to a sixfold increased rate of coronary disease events in postmenopausal women with preexisting coronary disblockers , angiotensin-converting enzyme inhibitors , or cholesterol-lowering drugs . Implication s Clinicians can identify women who have high risks for recurrent coronary events and should promote greater use of secondary prevention treatments for them . The Editors Coronary heart disease ( CHD ) is the leading cause of death in women . The major independent risk factors that predict CHD onset in healthy women are similar to those identified by epidemiologic studies of healthy men ( 1 - 7 ) . A recent report described six independent risk factorsage , low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) cholesterol levels , high blood pressure , diabetes mellitus , and smokingthat were strongly associated with risk for a first CHD event in both men and women ( 8) . However , the strength of the association of certain risk factors with CHD events may vary by sex ( 9 ) as well as age . Diabetes may be a stronger risk factor in women than in men ( 7 ) ; among older women , HDL cholesterol level may be a relatively strong risk factor and LDL cholesterol level a relatively weak one ( 6 ) . In the period immediately after myocardial infa rct ion ( MI ) , studies of mostly male sample s have found that persistent ischemia , impaired left ventricular systolic function , and ventricular arrhythmias are the major determinants of subsequent MI and death ( 10 - 13 ) . In the Coronary Drug Project study of men with a history of heart attack , electrocardiographic abnormalities and heart failure  were stronger predictors than the atherosclerosis risk factors identified in primary prevention setting s ( 14 ) . However , the risk factors for coronary events among women with recognized but stable coronary disease are mostly unknown . Better underst and ing of these factors could improve secondary prevention in this large and high-risk group . The Heart and Estrogen/progestin Replacement Study ( HERS ) was a r and omized clinical trial of estrogen plus progestin for prevention of CHD events in women with coronary disease ( 15 ) . Overall , no significant differences were noted between the hormone and placebo groups in CHD events ; trends of more CHD events with therapy in year 1 were offset by fewer such outcomes during years 4 and 5 . The trial collected extensive data on CHD risk factors and medication use and performed exhaustive outcome ascertainment procedures , with complete mortality follow-up . Therefore , HERS offers a unique opportunity to assess the long-term effect of coronary risk factors and use of recommended treatments in women with established coronary disease . Methods Participants Participants in HERS were postmenopausal women who were younger than 80 years of age , had not had a hysterectomy , and had known coronary artery disease ( MI , coronary artery bypass surgery , percutaneous transluminal coronary angioplasty , or angiographic evidence of 50 % narrowing of one or more major coronary arteries ) . Women were excluded if they had had a coronary event within the 6 months before r and omization , had a serum triglyceride level greater than 3.39 mmol/L ( 300 mg/dL ) , had used hormones within 3 months , or had a history of conditions that would contraindicate estrogen therapy ( 16 ) . Participants in HERS were r and omly assigned within clinical centers to 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate in one tablet daily ( n = 1380 ) or a placebo of identical appearance ( n = 1383 ) . The institutional review boards at the coordinating center and each of the 20 HERS clinical centers approved the protocol , and all participants provided written informed consent . Predictors In the baseline interview , information was obtained by self-report on demographic characteristics , behavioral risk factors , and medical history . Among women who reported ever having smoked at least 100 cigarettes , years of smoking , average cigarettes per day , and current smoking were ascertained . Alcohol use in the past 30 days was assessed for frequency and usual numbers of drinks per occasion .  Exercise  was measured as participation in a regular exercise program such as cardiac rehabilitation or aerobics or walking at least occasionally for exercise more than 10 minutes at a time . Use of  aspirin , -blockers , lipid-lowering medications ( statins , niacin , fibrates , bile acidbinding resins , and probucol ) , angiotensin-converting enzyme ( ACE ) inhibitors , calcium antagonists , and folate or vitamin B was assessed by self-report . In the baseline physical examination , blood pressure , waist-to-hip ratio , and body mass index were measured . A physician assessed history and symptoms of heart failure ( jugular venous distention , third heart sound , significant murmurs , pulmonary rales , and peripheral edema ) . High blood pressure was defined as systolic blood pressure greater than or equal to 140 mm Hg or diastolic blood pressure greater than or equal to 90 mm Hg , according to the Sixth Report of the Joint National Committee on Prevention , Detection , Evaluation and Treatment of High Blood Pressure ( 17 ) . Angina was defined as self-report of chest discomfort in the previous 4 weeks during exercise , emotion , or sexual activity . Serum specimens were obtained , and a central ized laboratory measured fasting levels of LDL cholesterol , HDL cholesterol , lipoprotein(a ) , triglycerides , glucose , and creatinine ( 15 , 16 ) . Creatinine clearance was estimated by using the CockcroftGault equation ( 18 , 19 ) . Outcomes The primary HERS outcome was CHD events , defined as nonfatal MI or CHD death . Suspected outcome events were reported within 24 hours to the coordinating center and were systematic ally assessed every 4 months at the follow-up contacts . An independent morbidity and mortality subcommittee that was blinded to treatment assignment adjudicated all deaths and suspected outcome events . Nonfatal MI was diagnosed by using an algorithm based on ischemic symptoms , electrocardiographic abnormalities , and elevated cardiac enzyme levels ( 16 ) . Death from CHD included fatal documented MI , sudden death within 1 hour of symptom onset , unobserved death that occurred out of the hospital in the absence of other known causes , or death due to a coronary revascularization procedure or congestive heart failure . The date of each event was determined from the documentation obtained by the clinical centers . The total number of events reported here is slightly larger than that published in the primary HERS results ( 15 ) because of subsequent adjudications ( 20 ) . Statistical Analyses We used multivariable Cox proportional-hazards models to assess the associations between risk factors and CHD events . These models were stratified by clinical center to account for potential clustering . Waist-to-hip ratio and LDL and HDL cholesterol levels were modeled as continuous variables , but lipoprotein(a ) level was dichotomized at the median and creatinine clearance was dichotomized at 0.66 mL/s ( 40 mL/min ) to reflect the nonlinear responses we have reported elsewhere ( 19 , 21 ) . We used an indicator for any alcohol use , since almost all of the 39 % of HERS women who reported alcohol use were light or moderate drinkers . Exercise was modeled by an indicator for participation in an exercise program or walking for exercise for more than 10 minutes . The multivariable model includes previously identified risk factors that were significant ( P 0.20 ) in unadjusted models and were not judged redundant on substantive grounds . Body mass index was excluded because it was clearly nonsignificant after adjustment ( P > 0.2 ) and was also highly correlated with waist-to-hip ratio , which was the stronger predictor in unadjusted analysis . Similarly , triglyceride levels were excluded because of their strong negative correlation with HDL cholesterol levels , which in our judgment were more likely to be causal . We also controlled for use of aspirin , statins , other lipid-lowering medications , diuretics , -blockers , ACE inhibitors , calcium antagonists , and folate or vitamin B. The effect of assignment to hormone therapy was modeled separately for each year of follow-up , as in the post hoc analysis of HERS ( 15 ) . Interactions between risk factors and relevant treatments were also examined . Specifically , we compared hazard rates among patients with diagnosed diabetes who reported use of insulin or oral hypoglycemic agents  with rates in the combined group of diabetic persons not using these medications and women with fasting glucose levels greater than 6.94 mmol/L ( > 125 mg/dL ) but no history of diabetes diagnosis . Likewise , we compared estimates for LDL and HDL cholesterol levels stratified by use of any lipid-lowering medication or assignment to hormone therapy ; for lipoprotein(a ) level , stratified by assignment to hormone therapy ; for high blood pressure on examination , stratified by use of at least one antihypertensive medication ; for heart failure and creatinine clearance less than or equal to 0.66 mL/s ( 40 mL/min ) , stratified by use of ACE inhibitors ; and for more than one previous MI and angina , stratified by use of any indicated medications . The final model includes interactions that were significant at a P value less than or equal to 0.2 . We used residuals to assess overall model fit , validity of the proportional hazards assumption , and linearity of associations with continuous predictors . The study lacked power to examine interactions between clinical center and potential risk factors . We tested the assumption of noninformative censoring by considering the two extremes of the possible outcomes Background —Heart failure with preserved ejection fraction ( HF-nlEF ) is common in aged individuals with systolic hypertension and is frequently ascribed to diastolic dysfunction . We hypothesized that such patients also display combined ventricular-systolic and arterial stiffening that can exacerbate blood pressure lability and diastolic dysfunction under stress . Methods and Results —Left ventricular pressure-volume relations were measured in patients with HF-nlEF ( n=10 ) and contrasted with asymptomatic age-matched ( n=9 ) and young ( n=14 ) normotensives and age- and blood pressure-matched controls ( n=25 ) . End-systolic elastance ( stiffness ) was higher in patients with HF-nlEF ( 4.7±1.5 mm Hg/mL ) than in controls ( 2.1±0.9 mm Hg/mL for normotensives and 3.3±1.0 mm Hg/mL for hypertensives;P < 0.001 ) . Effective arterial elastance was also higher ( 2.6±0.5 versus 1.9±0.5 mm Hg/mL ) due to reduced total arterial compliance ; the latter inversely correlated with end-systolic elastance ( P = 0.0001 ) . Body size and stroke volumes were similar and could not explain differences in ventricular-arterial stiffening . HF-nlEF patients also displayed diastolic abnormalities , including higher left ventricular end-diastolic pressures ( 24.3±4.6 versus 12.9±5.5 mm Hg ) , caused by an upward-shifted diastolic pressure-volume curve . However , isovolumic relaxation and the early-to-late filling ratio were similar in age- and blood pressure-matched controls . Ventricular-arterial stiffening amplified stress-induced hypertension , which worsened diastolic function , and predicted higher cardiac energy costs to provide reserve output . Conclusion — Patients with HF-lnEF have systolic-ventricular and arterial stiffening beyond that associated with aging and /or hypertension . This may play an important pathophysiological role by exacerbating systemic load interaction with diastolic function , augmenting blood pressure lability , and elevating cardiac metabolic dem and under stress CONTEXT A frequently cited concept is that individual major risk factors for coronary heart disease ( CHD ) are absent in many patients ( perhaps > 50 % ) with CHD . However , prior studies have not systematic ally evaluated the extent to which CHD patients have previous exposure to at least 1 risk factor , including diabetes , cigarette smoking , or clinical ly elevated levels of cholesterol or blood pressure . OBJECTIVE To determine the frequency of exposure to major CHD risk factors . DESIGN , SETTING , AND PARTICIPANTS Three prospect i ve cohort studies were included : the Chicago Heart Association Detection Project in Industry , with a population sample of 35 642 employed men and women aged 18 to 59 years ; screenees for the Multiple Risk Factor Intervention Trial , including 347 978 men aged 35 to 57 years ; and a population -based sample of 3295 men and women aged 34 to 59 years from the Framingham Heart Study ( FHS ) . Follow-up lasted 21 to 30 years across the studies . MAIN OUTCOME MEASURES Fatal CHD in all cohorts and nonfatal myocardial infa rct ion ( MI ) in the FHS , compared by exposure to major CHD risk factors , defined as total cholesterol of at least 240 mg/dL ( > or = 6.22 mmol/L ) , systolic blood pressure of at least 140 mm Hg , diastolic blood pressure of at least 90 mm Hg , cigarette smoking , and diabetes . Participants were stratified by sex and age ( 18 - 39 vs 40 - 59 years ) . RESULTS For fatal CHD ( n = 20 995 ) , exposure to at least 1 clinical ly elevated major risk factor ranged from 87 % to 100 % . Among those aged 40 to 59 years at baseline with fatal CHD ( n = 19 263 ) , exposure to at least 1 major risk factor ranged from 87 % to 94 % . For nonfatal MI , prior exposure was documented in 92 % ( 95 % CI , 87%-96 % ) ( n = 167 ) of men aged 40 to 59 years at baseline and in 87 % ( 95 % CI , 80%-94 % ) ( n = 94 ) of women in this age group . CONCLUSIONS Antecedent major CHD risk factor exposures were very common among those who developed CHD , emphasizing the importance of considering all major risk factors in determining CHD risk estimation and in attempting to prevent clinical CHD . These results challenge cl aims that CHD events commonly occur in persons without exposure to at least 1 major CHD risk factor A survival analysis was applied to 1,453 patients treated between 1972 and 1978 in 33 French dialysis centers and prospect ively followed up in the computerized Diaphane Dialysis Registry . 198  deaths  ( overall mortality = OM ) were registered , of which 87 ( 43 % ) were secondary to cardiovascular complications ( cardiovascular mortality = CVM ) . Risk factors for OM and CVM ( p values less than 0.05 ) were age , male sex , nephroangiosclerosis or diabetic nephropathy as the primary renal disease , elevated systolic and diastolic blood pressure and two weekly dialysis rather then three . In contrast with the results observed for the general population , a high body mass index and elevated cholesterol , triglycerides and uric acid were not found to be associated with significantly increased CVM or OM . On the contrary , low body mass index ( less than 20 kg/m2 ) , low cholesterol ( less than 4.5 mmol/l ) and low mean predialysis blood urea ( less than 4.6 mmol/l ) were associated with increased OM and CVM , and more especially with high stroke mortality . Results for urea but not for cholesterol remain significant after adjustment for age , sex , weekly dialysis schedule and body mass index . They suggest that , in addition to elevated blood pressure , a poor nutritional state and /or low protein intake may be important factors for explaining the high cardiovascular mortality , particularly for strokes , observed in dialyzed patients Background and Purpose — Among patients with acute stroke , high blood pressure is often associated with poor outcome , although the reason is unclear . We analyzed data from the International Stroke Trial ( IST ) to explore the relationship between  systolic blood pressure ( SBP ) , subsequent clinical events over the next 2 weeks , and functional outcome at 6 months in patients with acute stroke . Methods — We included in the analysis 17 398 patients from IST with confirmed ischemic stroke . A single measurement of SBP was made immediately before r and omization . Clinical events within 14 days of r and omization were recorded : recurrent ischemic stroke , symptomatic intracranial hemorrhage , death result ing from presumed cerebral edema , fatal coronary heart disease , and death . Survival and dependency were assessed at 6 months . Outcomes were adjusted for age , sex , clinical stroke syndrome , time to r and omization , consciousness level , atrial fibrillation , and treatment allocation ( aspirin , unfractionated heparin , both , or neither ) . Results — A U-shaped relationship was found between baseline SBP and both early death and late death or dependency : early death increased by 17.9 % for every 10 mm Hg below 150 mm Hg ( P < 0.0001 ) and by 3.8 % for every 10 mm Hg above 150 mm Hg ( P = 0.016 ) . The rate of recurrent ischemic stroke within 14 days increased by 4.2 % for every 10–mm Hg increase in SBP ( P = 0.023 ) ; this association was present in both fatal and nonfatal recurrence . Death result ing from presumed cerebral edema was independently associated with high SBP ( P = 0.004 ) . No relationship between symptomatic intracranial hemorrhage and SBP was seen . Low SBP was associated with a severe clinical stroke ( total anterior circulation syndrome ) and an excess of deaths from coronary heart disease ( P = 0.002 ) . Conclusions — Both high blood pressure and low blood pressure were independent prognostic factors for poor outcome , relationships that appear to be mediated in part by increased rates of early recurrence and death result ing from presumed cerebral edema in patients with high blood pressure and increased coronary heart disease events in those with low blood pressure . The occurrence of symptomatic intracranial hemorrhage within 14 days was independent of SBP Univariate and multivariate analyses have been made of the relationship of systolic and diastolic blood-pressure measured at study entry to subsequent 14-year mortality among 1233 White males originally age 40 - 59 in 1958 from the Chicago Peoples Gas Company prospect i ve study . With age , serum-cholesterol , and cigarettes per day controlled , both elevated systolic and electaed diastolic blood-pressure in 1958 were found to be strongly related to subsequent mortality from cancer in the men of this study . The possibility that this finding was due either to an association between antihypertensive medication in general , and cancer , or to an association was found that could explain the excess cancer mortality among those with elevated blood-pressure in 1958 , either with medication in general , or with reserpine and rauwolfia in particular . These findings thus pose the question , is high blood-pressure associated with an increased risk of death due to cancer Background Small subcortical strokes , also known as lacunar strokes , comprise more than 25 % of brain infa rcts , and the underlying vasculopathy is the most common cause of vascular cognitive impairment . How to optimally prevent stroke recurrence and cognitive decline in S3 patients is unclear . The aim of the Secondary Prevention of Small Subcortical Strokes study ( Trial registration : NCT00059306 ) is to define strategies for reducing stroke recurrence , cognitive decline , and major vascular events . Methods Secondary Prevention of Small Subcortical Strokes is a r and omised , multicentre clinical trial ( n=3000 ) being conducted in seven countries , and sponsored by the US NINDS/NIH . Patients with symptomatic small subcortical strokes in the six-months before and an eligible lesion on magnetic resonance imaging are simultaneously r and omised , in a 2 × 2 factorial design , to antiplatelet therapy – 325 mg aspirin daily plus 75 mg clopidogrel daily , vs. 325 mg aspirin daily plus placebo , double-blind – and to one of two levels of systolic blood pressure targets –‘intensive ’ ( < 130 mmHg ) vs. ‘ usual ’ ( 130–149 mmHg ) . Participants are followed for an average of four-years . Time to recurrent stroke ( ischaemic or haemorrhagic ) is the primary outcome and will be analysed separately for each intervention . The secondary outcomes are the rate of cognitive decline and major vascular events . The primary and most secondary outcomes are adjudicated central ly by those unaware of treatment assignment . Conclusions Secondary Prevention of Small Subcortical Strokes will address several important clinical and scientific questions by testing two interventions in patients with recent magnetic resonance imaging-defined lacunar infa rcts , which are likely due to small vessel disease . The results will inform the management of millions of patients with this common vascular disorder BACKGROUND Blood pressure is an important determinant of the risks of macrovascular and microvascular complications of type 2 diabetes , and guidelines recommend intensive lowering of blood pressure for diabetic patients with hypertension . We assessed the effects of the routine administration of an angiotensin converting enzyme ( ACE ) inhibitor-diuretic combination on serious vascular events in patients with diabetes , irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs . METHODS The trial was done by 215 collaborating centres in 20 countries . After a 6-week active run-in period , 11 140 patients with type 2 diabetes were r and omised to treatment with a fixed combination of perindopril and indapamide or matching placebo , in addition to current therapy . The primary endpoints were composites of major macrovascular and microvascular events , defined as death from cardiovascular disease , non-fatal stroke or non-fatal myocardial infa rct ion , and new or worsening renal or diabetic eye disease , and analysis was by intention-to-treat . The macrovascular and microvascular composites were analysed jointly and separately . This trial is registered with Clinical Trials.gov , number NCT00145925 . FINDINGS After a mean of 4.3 years of follow-up , 73 % of those assigned active treatment and 74 % of those assigned control remained on r and omised treatment . Compared with patients assigned placebo , those assigned active therapy had a mean reduction in systolic blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg . The relative risk of a major macrovascular or microvascular event was reduced by 9 % ( 861 [ 15.5 % ] active vs 938 [ 16.8 % ] placebo ; hazard ratio 0.91 , 95 % CI 0.83 - 1.00 , p=0.04 ) . The separate reductions in macrovascular and microvascular events were similar but were not independently significant ( macrovascular 0.92 ; 0.81 - 1.04 , p=0.16 ; microvascular 0.91 ; 0.80 - 1.04 , p=0.16 ) . The relative risk of death from cardiovascular disease was reduced by 18 % ( 211 [ 3.8 % ] active vs 257 [ 4.6 % ] placebo ; 0.82 , 0.68 - 0.98 , p=0.03 ) and death from any cause was reduced by 14 % ( 408 [ 7.3 % ] active vs 471 [ 8.5 % ] placebo ; 0.86 , 0.75 - 0.98 , p=0.03 ) . There was no evidence that the effects of the study treatment differed by initial blood pressure level or concomitant use of other treatments at baseline . INTERPRETATION Routine administration of a fixed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events , including death . Although the confidence limits were wide , the results suggest that over 5 years , one death due to any cause would be averted among every 79 patients assigned active therapy BACKGROUND AND PURPOSE The risk of major vascular events after an initial episode of cerebral ischemia in patients with nonrheumatic atrial fibrillation ( NRAF ) varies from 2 % to 15 % in the first year and is approximately 5 % yearly thereafter . Few studies have reported on risk factors that can be used to identify high-risk subgroups within this patient population . METHODS We studied the predictive value of several easily obtainable clinical characteristics in a group of 375 placebo-treated patients with NRAF and a recent episode of transient or nondisabling cerebral ischemia who were entered in a multicenter clinical trial . The mean follow-up was 1.6 years . RESULTS By means of multivariate modeling , six independent variables were identified : history of previous thromboembolism , ischemic heart disease , enlarged cardiothoracic ratio on chest roentgenogram , systolic blood pressure greater than 160 mm Hg at study entry , NRAF for more than 1 year , and presence of an ischemic lesion on CT scan . These variables could also be used to stratify patients in low- , medium- , and high-risk subgroups for the other two arms of the trial , those treated with anticoagulation and aspirin .  Patients older than 75 years with three or more risk factors seemingly benefited less from both aspirin and anticoagulant treatment . CONCLUSIONS Easily obtainable patient characteristics are helpful in estimating the potential effect of adequate secondary prevention in patients with NRAF who recently suffered a transient ischemic attack or minor ischemic stroke BACKGROUND The Tucson Children 's Assessment of Sleep Apnea study ( TuCASA ) was design ed to investigate the prevalence and correlates of objective ly measured sleep-related breathing disorder ( SBD ) in preadolescent Hispanic and white children . OBJECTIVE To describe the associations of SBD and elevation in resting blood pressure in the first 239 children enrolled in TuCASA . DESIGN Children between the ages of 6 and 11 years ( 45 % girls and 51 % Hispanic ) from elementary schools of the Tucson Unified School District were enrolled in this prospect i ve cohort study . Resting systolic and diastolic blood pressure , sleep symptoms , and parental smoking status were obtained during evening home visits , followed by overnight unattended home polysomnography . RESULTS The mean ( SD ) systolic and diastolic blood pressures were 98.4 ( 10.6 ) mm Hg and 62.0 ( 8.9 ) mm Hg , respectively . Fifteen children had hypertension . The mean ( SD ) respiratory disturbance index ( 2 % ) , defined as the number of apneas and hypopneas per hour of sleep associated with a 2 % oxygen desaturation , was 2.3 ( 3.8 ) events per hour . Factors independently associated with systolic and diastolic blood pressure elevation were obesity , sleep efficiency , and respiratory disturbance index ( 2 % ) . CONCLUSIONS In preadolescent children , elevated blood pressure is associated with SBD and obesity , as previously noted in adults . The control of obesity in childhood may be important to reduce the daytime consequences of SBD and to reduce the risks of life-long hypertension BACKGROUND Atherosclerotic peripheral arterial disease is associated with an increased risk of myocardial infa rct ion , stroke , and death from cardiovascular causes . Antiplatelet drugs reduce this risk , but the role of oral anticoagulant agents in the prevention of cardiovascular complications in patients with peripheral arterial disease is unclear . METHODS We assigned patients with peripheral arterial disease to combination therapy with an antiplatelet agent and an oral anticoagulant agent ( target international normalized ratio [ INR ] , 2.0 to 3.0 ) or to antiplatelet therapy alone . The first co primary outcome was myocardial infa rct ion , stroke , or death from cardiovascular causes ; the second co primary outcome was myocardial infa rct ion , stroke , severe ischemia of the peripheral or coronary arteries leading to urgent intervention , or death from cardiovascular causes . RESULTS A total of 2161 patients were r and omly assigned to therapy . The mean follow-up time was 35 months . Myocardial infa rct ion , stroke , or death from cardiovascular causes occurred in 132 of 1080 patients receiving combination therapy ( 12.2 % ) and in 144 of 1081 patients receiving antiplatelet therapy alone ( 13.3 % ) ( relative risk , 0.92 ; 95 % confidence interval [ CI ] , 0.73 to 1.16 ; P=0.48 ) . Myocardial infa rct ion , stroke , severe ischemia , or death from cardiovascular causes occurred in 172 patients receiving combination therapy ( 15.9 % ) as compared with 188 patients receiving antiplatelet therapy alone ( 17.4 % ) ( relative risk , 0.91 ; 95 % CI , 0.74 to 1.12 ; P=0.37 ) . Life-threatening bleeding occurred in 43 patients receiving combination therapy ( 4.0 % ) as compared with 13 patients receiving antiplatelet therapy alone ( 1.2 % ) ( relative risk , 3.41 ; 95 % CI , 1.84 to 6.35 ; P<0.001 ) . CONCLUSIONS In patients with peripheral arterial disease , the combination of an oral anticoagulant and antiplatelet therapy was not more effective than antiplatelet therapy alone in preventing major cardiovascular complications and was associated with an increase in life-threatening bleeding . ( Clinical Trials.gov number , NCT00125671 [ Clinical Trials.gov ] . ) Aims The r and omized PROTECT AF trial demonstrated non-inferiority of left atrial appendage ( LAA ) closure to oral anticoagulation with warfarin . Current guidelines give a class IIb recommendation for LAA closure . We evaluated the efficacy and safety of LAA closure in a consecutive series of non-valvular atrial fibrillation patients with contraindications to long-term oral anticoagulation or at high bleeding risk . Methods and results 101 consecutive non-valvular atrial fibrillation patients ( age 74.7 ± 7.5 years ) at high risk for stroke ( CHA2DS2-VASc Score 4.4 ± 1.6 ) and high bleeding risk ( HAS-BLED Score 4.2 ± 1.3 ) received LAA closure with either the Watchman closure device ( n = 38 ) or the Amplatzer cardiac plug ( n = 63 ) . Dual antiplatelet therapy with aspirin and clopidogrel was recommended for 3–6 months after device implantation , followed by long-term antiplatelet therapy with aspirin . No anticoagulation was given after device implantation . Mean follow-up was 400 days . One patient ( 1 % ) experienced a transient ischemic attack , and two patients ( 2 % ) suffered from ischemic stroke . While on recommended antiplatelet therapy , bleeding occurred in 12/101 patients ( 12 % ) . Bleeding was significantly reduced with 3 compared with 6 months dual antiplatelet therapy ( 3.0 vs. 16.2 % , p < 0.05 ) while ischemic or thrombotic events were similar . Conclusion Left atrial appendage closure in patients with non-valvular atrial fibrillation and high risk for stroke and bleeding events effectively prevented stroke and reduced cerebral ischemic events compared to expected stroke rate according to CHA2DS2-VASc Score . Dual antiplatelet therapy for 3 months reduced the rate of bleeding events compared to 6 months therapy with no increase of thrombotic events BACKGROUND Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension . We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events . In this post hoc analysis , we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients . METHODS After stratification according to center , sex , and presence or absence of previous cardiovascular complications , 4695 patients ( age , > or = 60 years ) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were r and omly assigned to receive active treatment or placebo . Active treatment consisted of nitrendipine ( 10 to 40 mg per day ) with the possible addition or substitution of enalapril ( 5 to 20 mg per day ) or hydrochlorothiazide ( 12.5 to 25 mg per day ) or both , titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg . In the control group , matching placebo tablets were administered similarly . RESULTS At r and omization , 492 patients ( 10.5 percent ) had diabetes . After a median follow-up of two years , the systolic and diastolic blood pressures in the placebo and active-treatment groups differed by 8.6 and 3.9 mm Hg , respectively , among the diabetic patients . Among the 4203 patients without diabetes , systolic and diastolic pressures differed by 10.3 and 4.5 mm Hg , respectively , in the two groups . After adjustment for possible confounders , active treatment was found to have reduced overall mortality by 55 percent ( from 45.1 deaths per 1000 patients to 26.4 deaths per 1000 patients ) , mortality from cardiovascular disease by 76 percent , all cardiovascular events combined by 69 percent , fatal and nonfatal strokes by 73 percent , and all cardiac events combined by 63 percent in the group of patients with diabetes . Among the nondiabetic patients , active treatment decreased all cardiovascular events combined by 26 percent and fatal and nonfatal strokes by 38 percent . In the group of patients receiving active treatment , reductions in overall mortality , mortality from cardiovascular disease , and all cardiovascular events were significantly larger among the diabetic patients than among the nondiabetic patients ( P=0.04 , P=0.02 , and P=0.01 , respectively ) . CONCLUSIONS Nitrendipine-based antihypertensive therapy is particularly beneficial in older patients with diabetes and isolated systolic hypertension . Thus , our findings do not support the hypothesis that the use of long-acting calcium-channel blockers may be harmful in diabetic patients BACKGROUND Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications , yet the benefits and risks of treatment beyond 1 year are uncertain . METHODS Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed . After 12 months of treatment with a thienopyridine drug ( clopidogrel or prasugrel ) and aspirin , patients were r and omly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months ; all patients continued receiving aspirin . The co primary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events ( a composite of death , myocardial infa rct ion , or stroke ) during the period from 12 to 30 months . The primary safety end point was moderate or severe bleeding . RESULTS A total of 9961 patients were r and omly assigned to continue thienopyridine treatment or to receive placebo . Continued treatment with thienopyridine , as compared with placebo , reduced the rates of stent thrombosis ( 0.4 % vs. 1.4 % ; hazard ratio , 0.29 [ 95 % confidence interval { CI } , 0.17 to 0.48 ] ; P<0.001 ) and major adverse cardiovascular and cerebrovascular events ( 4.3 % vs. 5.9 % ; hazard ratio , 0.71 [ 95 % CI , 0.59 to 0.85 ] ; P<0.001 ) . The rate of myocardial infa rct ion was lower with thienopyridine treatment than with placebo ( 2.1 % vs. 4.1 % ; hazard ratio , 0.47 ; P<0.001 ) . The rate of death from any cause was 2.0 % in the group that continued thienopyridine therapy and 1.5 % in the placebo group ( hazard ratio , 1.36 [ 95 % CI , 1.00 to 1.85 ] ; P=0.05 ) . The rate of moderate or severe bleeding was increased with continued thienopyridine treatment ( 2.5 % vs. 1.6 % , P=0.001 ) . An elevated risk of stent thrombosis and myocardial infa rct ion was observed in both groups during the 3 months after discontinuation of thienopyridine treatment . CONCLUSIONS Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent , as compared with aspirin therapy alone , significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding . ( Funded by a consortium of eight device and drug manufacturers and others ; DAPT Clinical Trials.gov number , NCT00977938 . ) OBJECTIVES The aim of the present study was to evaluate whether elevated D-dimer levels can predict subsequent thromboembolic and cardiovascular events in patients with atrial fibrillation during oral anticoagulant therapy .  BACKGROUND Atrial fibrillation is associated with hemostatic abnormalities even during oral anticoagulant therapy . D-dimer levels reflect a pro-thrombogenic state and thus might serve as a marker of thromboembolic and cardiovascular events . METHODS This was a single-center , prospect i ve , observational study . Patients with atrial fibrillation ( 269 patients , age 74 + /- 9 years , 160 paroxysmal atrial fibrillation ) treated with warfarin ( target prothrombin time-international normalized ratio : 1.5 to 3.0 ) were included .  D-dimer levels were measured to assess the relationship of this parameter with subsequent thromboembolic and cardiovascular events . End points were thromboembolic events and combined cardiovascular events ( thromboembolic events , cerebral hemorrhage , myocardial infa rct ion , cardiovascular death ) . RESULTS D-dimer levels were elevated ( > or = 0.5 microg/ml ) in 63 ( 23 % ) patients . During an average follow-up period of 756 + /- 221 days , 10 ( 1.8%/year ) thromboembolic events ( 8 ischemic strokes , 1 transient ischemic attack , and 1 peripheral embolism ) and 27 ( 4.8%/year ) combined cardiovascular events ( 10 thromboembolisms , 9 deaths from heart failure , 3 sudden deaths , 2 myocardial infa rct ions , and 3 cerebral hemorrhages ) occurred . Patients with elevated D-dimer levels experienced higher thromboembolic and combined cardiovascular events . Cox proportional hazard model revealed that elevated D-dimer levels were associated with both thromboembolic ( p < 0.01 , hazard ratio : 15.8 ; 95 % confidence interval : 3.33 to 75.5 ) and combined cardiovascular ( p < 0.01 , hazard ratio : 7.64 ; 95 % confidence interval : 3.42 to 17.1 ) events . CONCLUSIONS D-dimer might be a useful marker of both thromboembolic and cardiovascular events in patients with atrial fibrillation during oral anticoagulant therapy AIM To determine the effects of a perindopril-based blood pressure lowering regimen on major cardiac events among hypertensive and non-hypertensive patients with a history of cerebrovascular disease . METHODS AND RESULTS A total of 6105 individuals with a history of stroke or transient ischaemic attack were r and omly assigned active treatment ( n=3051 ) or placebo ( n=3054 ) . Active treatment comprised the angiotensin-converting-enzyme inhibitor perindopril ( 4 mg daily ) , with the addition of the diuretic indapamide at the discretion of treating physicians . Over a mean of 3.9 years of follow-up , active treatment reduced blood pressure by 9/4 mm Hg compared with placebo and reduced the primary outcome , stroke , by 28 % . Major coronary events occurred in 269 participants ( active 3.8 % , placebo 5.0 % ) and heart failure was diagnosed in 264 participants ( active 3.7 % , placebo 4.9 % ) . Active treatment reduced the risk of major coronary events by 26 % ( 95 % CI : 6 - 42 % ; p=0.02 ) and the risk of congestive heart failure by 26 % ( 5 - 42 % ; p=0.02 ) . For each of these outcomes , there was no clear evidence of differences between the treatment effects in participants classified as hypertensive or non-hypertensive , and those with or without a history of coronary heart disease . CONCLUSIONS Among individuals with cerebrovascular disease , blood pressure lowering with a regimen involving perindopril and indapamide not only reduced the risk of stroke , but also substantially reduced the risks of cardiac outcomes RATIONALE Dual antiplatelet therapy with acetylsalicylic acid in combination with a more potent P2Y12- inhibitor ( ticagrelor or prasugrel ) is recommended in patients with acute coronary syndrome without ST-segment elevation ( NSTE-ACS ) to prevent atherothrombotic complications . The evidence on which this recommendation is based shows that ticagrelor and prasugrel reduce atherothrombotic events at the expense of an increase in bleeding events when compared with clopidogrel . However , it remains unclear whether ticagrelor or prasugrel has a better net clinical benefit in elderly patients with NSTE-ACS when compared with clopidogrel . The POPular AGE trial is design ed to address the optimal antiplatelet strategy in elderly NSTE-ACS patients . STUDY DESIGN POPular AGE is a multicenter , open-label , r and omized controlled trial that aims to include 1000 patients ≥70years of age with NSTE-ACS . Patients are r and omly assigned to receive either clopidogrel or a more potent P2Y12 inhibitor ( ticagrelor or prasugrel ) . The first primary end point is any bleeding event requiring medical intervention . The second primary end point is the net clinical benefit , a composite of all-cause mortality , nonfatal myocardial infa rct ion , nonfatal stroke , " PLATelet inhibition and patient Outcomes " major bleeding , or " PLATelet inhibition and patient Outcomes " minor bleeding . Patients will be followed for 1 year after r and omization , and analyses will be performed on the basis of intention to treat . CONCLUSION The POPular AGE is the first r and omized controlled trial that will assess whether the treatment strategy with clopidogrel will result in fewer bleeding events without compromising the net clinical benefit in patients ≥70years of age with NSTE-ACS when compared with a treatment strategy with ticagrelor or prasugrel
Acetylsalicylic acid ( ASA ) did not reduce stroke or ' all cardiovascular events ' compared to placebo in primary prevention patients with elevated blood pressure and no prior cardiovascular disease .
Antiplatelet therapy with ASA for primary prevention in patients with elevated blood pressure provides a benefit , reduction in myocardial infa rct ion , which is negated by a harm of similar magnitude , increase in major haemorrhage .
The benefit of antiplatelet therapy for secondary prevention in patients with elevated blood pressure is many times greater than the harm .
Benefit has not been demonstrated for warfarin therapy alone or in combination with aspirin in patients with elevated blood pressure .
BACKGROUND Elevated systemic blood pressure results in high intravascular pressure but the main complications , coronary heart disease ( CHD ) , ischaemic strokes and peripheral vascular disease ( PVD ) , are related to thrombosis rather than haemorrhage .
Some complications related to elevated blood pressure , heart failure or atrial fibrillation , are themselves associated with stroke and thromboembolism .
Therefore it is important to investigate if antithrombotic therapy may be useful in preventing thrombosis-related complications in patients with elevated blood pressure .
OBJECTIVES To conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with high blood pressure , including those with elevations in both systolic and diastolic blood pressure , isolated elevations of either systolic or diastolic blood pressure , to address the following hypotheses : ( i ) antiplatelet agents reduce total deaths and /or major thrombotic events when compared to placebo or other active treatment ; and ( ii ) oral anticoagulants reduce total deaths and /or major thromboembolic events when compared to placebo or other active treatment .
Ticlopidine , clopidogrel and newer antiplatelet agents such as prasugrel and ticagrelor have not been sufficiently evaluated in patients with high blood pressure .