Legacy Effect of Delayed Blood Pressure-Lowering Pharmacotherapy in Middle-Aged Individuals Stratified by Absolute Cardiovascular Disease Risk: Protocol for a Systematic Review The Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS): Protocol, Patient Characteristics, and Blood Pressure during the First 12 Months South African hypertension guideline 2011. On-treatment diastolic blood pressure and prognosis in systolic hypertension. Effect of Antihypertensive Treatment on Cardiovascular Events in Elderly Hypertensive Patients: Japan's Benidipine Research on Anti-Hypertensive Effects in the Elderly (J-BRAVE) Antihypertensive effects of sesamin in humans. Protocol for Past BP: a randomised controlled trial of different blood pressure targets for people with a history of stroke of transient ischaemic attack (TIA) in primary care Principal Results of the Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS) Is a systolic blood pressure target <140 mmHg indicated in all hypertensives? Subgroup analyses of findings from the randomized FEVER trial. Treatment of Hypertension in Patients 85 Years of Age or Older: A J-BRAVE Substudy Renal denervation improves exercise blood pressure: insights from a randomized, sham-controlled trial Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly. Effect of Exercise on Blood Pressure in Type 2 Diabetes: A Randomized Controlled Trial Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP‐Hypertension‐2 Effectiveness of blood pressure-lowering drug treatment by levels of absolute risk: post hoc analysis of the Australian National Blood Pressure Study Efficacy of a Very‐low‐dose Combination of Perindopril and Indapamide—Preterax Compared with Cilazapril Monotherapy in Patients with Inadequate Blood Pressure Control—A Randomized, Double‐blind, Add‐on Study Antihypertensive efficacy and safety of olmesartan medoxomil and ramipril in elderly patients with mild to moderate essential hypertension: the ESPORT study Prevalence, awareness and control of hypertension in Chennai--The Chennai Urban Rural Epidemiology Study (CURES-52). Treatment of mild-to-moderate hypertension with calcium channel blockers: a multicentre comparison of once-daily nifedipine GITS with once-daily amlodipine Artichoke Leaf Juice Contains Antihypertensive Effect in Patients With Mild Hypertension Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study Reductions in ambulatory blood pressure in young normotensive men and women after isometric resistance training and its relationship with cardiovascular reactivity A cluster randomised controlled trial of the effect of a treatment algorithm for hypertension in patients with type 2 diabetes. Influence of gender and age on preventing cardiovascular disease by antihypertensive treatment and acetylsalicylic acid. The HOT study. Hypertension Optimal Treatment. Orthostatic hypotension predicts all-cause mortality and coronary events in middle-aged individuals (The Malmö Preventive Project) The Felodipine Event Reduction (FEVER) Study: a randomized long-term placebo-controlled trial in Chinese hypertensive patients Lipid lowering in patients with treatment-resistant hypertension: an analysis from the Treating to New Targets (TNT) trial. Appropriate Blood Pressure Control in NIDDM (ABCD) Trial Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) analyses performed up to 1992. Management of uncontrolled hypertension in a nurse-led clinic compared with conventional care for patients with type 2 diabetes. The Study on COgnition and Prognosis in the Elderly (SCOPE); outcomes in patients not receiving add-on therapy after randomization Rationale and design of the Optimal Macro-Nutrient Intake Heart Trial to Prevent Heart Disease (OMNI-Heart) Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial.
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 The benefits of a systolic blood pressure ( BP ) below 150–160 mmHg are well established ; whether a systolic BP of less than 140 mmHg provides additional benefits remains controversial . This study was design ed to compare the 2-year effect of a strict treatment to maintain systolic BP below 140 mmHg ( group A ) and that of a mild treatment to maintain systolic BP at between 140 and below 160 mmHg ( group B ) . The study design followed the Prospect i ve R and omized Open Blinded End-point ( PROBE ) study . The subjects were elderly patients ( 65–85 years old ) who consistently had a systolic BP of 160 mmHg or higher . The baseline drug was efonidipine hydrochloride ( efonidipine ) , a long-acting dihydropiridine calcium antagonist . The primary endpoints were stroke , cardiac disease , vascular disease , and renal failure . After a run-in period of 2 to 4 weeks , 2,165 patients were assigned to group A and 2,155 patients to group B. There were no significant differences between the groups in sex , age , baseline BP , or other cardiovascular risk factors . The systolic BP was 7.2 mmHg lower ( p<0.0001 ) and the diastolic BP 2.4 mmHg lower ( p<0.0001 ) in group A than in group B after 12 months of treatment . As of this interim analysis , primary endpoints have occurred in 87 patients ( stroke in 58 patients , cardiac disease in 27 patients , occlusive arterial disease in 1 patient , and renal failure in 1 patient ) . Five patients have died of stroke and 2 patients of myocardial infa rct ion . The primary -endpoint-related morbidity rate was 20.9/1,000 patient-years , and the mortality rate was 1.7/1,000 patient-years . Currently available results indicate that this study , one of the largest r and omized trials of antihypertensive therapy in elderly patients in Japan , was conducted safely . The final results are expected to provide important and practical information for the management of hypertension in elderly patients OUTCOMES Extensive data from r and omised controlled trials have shown the benefit of treating hypertension . The target blood pressure ( BP ) for antihypertensive management is systolic < 140 mmHg and diastolic < 90 mmHg with minimal or no drug side-effects ; however , stricter BP control is required for patients with end-organ damage , co-existing risk factors and co-morbidity , e.g. diabetes mellitus . The reduction of BP in the elderly and in those with severe hypertension should be achieved gradually over 1 month . Co-existent risk factors should also be controlled . BENEFITS Benefits of management include reduced risks of stroke , cardiac failure , chronic kidney disease and coronary heart disease . RECOMMENDATIONS The correct BP measurement procedure is described , and evaluation of cardiovascular risk factors and recommendations for antihypertensive therapy are stipulated . The total cardiovascular disease risk profile should be determined for all patients to inform management strategies . Lifestyle modification and patient education are cornerstones in the management of every patient . Major indications , pre caution s and contra-indications to each recommended antihypertensive drug are listed . Combination therapy should be considered ab initio if the BP is ≥ 20/10 mmHg . First-line drug therapy for uncomplicated hypertension includes low-dose thiazide-like diuretics , calcium channel blockers ( CCBs ) or angiotensin-converting enzyme inhibitors ( ACE-Is ) ( or ARBs - angiotensin II receptor blockers ) . If the target BP is not obtained , a second antihypertensive should be added from the aforementioned list . If the target BP is still not met , the third remaining antihypertensive agent should be used . In black patients  either thiazide-like diuretics or CCBs can be used initially , because response rates are better than with ACE-Is or β-blockers . In treating resistant hypertension , a central ly acting drug , vasodilator , α-blocker , spironolactone or β-locker should be added . This guideline includes management of specific situations , i.e. hypertensive emergency and urgency , severe hypertension with target organ damage , hypertension in diabetes mellitus , resistant hypertension , fixed drug combinations , new trials in hypertension , and interactions of antihypertensive agents with other drugs . VALIDITY The guideline was developed by the Southern African Hypertension Society BACKGROUND It has been suggested that low diastolic blood pressure ( BP ) while receiving antihypertensive treatment ( hereinafter called on-treatment BP ) is harmful in older patients with systolic hypertension . We examined the association between on-treatment diastolic BP , mortality , and cardiovascular events in the prospect i ve placebo-controlled Systolic Hypertension in Europe Trial . METHODS Elderly patients with systolic hypertension were r and omized into the double-blind first phase of the trial , after which all patients received active study drugs ( phase 2 ) . We assessed the relationship between outcome and on-treatment diastolic BP by use of multivariate Cox regression analysis during receipt of placebo ( phase 1 ) and during active treatment ( phases 1 and 2 ) . RESULTS Rates of noncardiovascular mortality , cardiovascular mortality , and cardiovascular events were 11.1 , 12.0 , and 29.4 , respectively , per 1000 patient-years with active treatment ( n = 2358 ) and 11.9 , 12.6 , and 39.0 , respectively , with placebo ( n = 2225 ) . Noncardiovascular mortality , but not cardiovascular mortality , increased with low diastolic BP with active treatment ( P < .005 ) and with placebo ( P < .05 ) ; for example , hazard ratios for lower diastolic BP , that is , 65 to 60 mm Hg , were , respectively , 1.15 ( 95 % confidence interval , 1.00 - 1.31 ) and 1.28 ( 95 % confidence interval , 1.03 - 1.59 ) . Low diastolic BP with active treatment was associated with increased risk of cardiovascular events , but only in patients with coronary heart disease at baseline ( P < .02 ; hazard ratio for BP 65 - 60 mm Hg , 1.17 ; 95 % confidence interval , 0.98 - 1.38 ) . CONCLUSIONS These findings support the hypothesis that antihypertensive treatment can be intensified to prevent cardiovascular events when systolic BP is not under control in older patients with systolic hypertension , at least until diastolic BP reaches 55 mm Hg . However , a prudent approach is warranted in patients with concomitant coronary heart disease , in whom diastolic BP should probably not be lowered to less than 70 mm Hg The achievement rate of blood pressure ( BP ) target and the relationship between on-treatment BP and development of cardiovascular events ( i.e. , stroke , myocardial infa rct ion , and heart failure ) were investigated in a total of 8,897 patients in the Japan 's Benidipine Research on Antihypertensive Effects in the Elderly ( J-BRAVE ) study , a prospect i ve , 3-year observational study of a  calcium channel blocker-based treatment in hypertensive patients aged ≥65 years as a post-marketing  surveillance . Blood pressure decreased significantly from 164.8 ± 14.1/88.2 ± 10.3 mmHg to 137.0 ± 13.5/75.6 ± 9.5 mmHg and the percentage of patients who achieved BP < 140/90 mmHg was 57.2 % after 3 years . The incidence of cardiovascular events was 7.54/1,000 patient-years . Subgroups of patients stratified by on-treatment systolic blood pressure ( SBP ) were analyzed . Baseline BP , body mass index ( BMI ) , the dose of benidipine , the mean number of anti-hypertensive drugs , and the incidence of cardiovascular events were higher in patients with on-treatment SBP ≥160 mmHg than in those with an SBP of < 130 mmHg . In patients aged 65 to 74 years ( n = 5,092 ) and patients aged ≥75 years ( n = 3,805 ) , the percentages of patients who achieved the BP target of < 140/90 mmHg were 57.5 % and 56.6 % after 3 years , respectively , and the incidence of cardiovascular events was higher in patients with on-treatment SBP ≥160 mmHg in both age subgroups . The results of the J-BRAVE study show that on-treatment SBP ≥160 mmHg is associated with a higher incidence of cardiovascular events in elderly hypertensive patients Sesamin , one of the lignans contained in sesame , has been considered to have medicinal effects . It has been reported that sesamin suppressed the development of hypertension in rats . In this study , using a double-blind , cross-over , placebo-controlled trial , we investigated the effect of 4-wk administration of sesamin on blood pressure ( BP ) in mildly hypertensive humans . Twenty-five middle-aged subjects with mild hypertension were divided into two groups , matched by age and body mass index . Twelve subjects were allocated to 4-wk intake of capsules with 60 mg sesamin per day and 13 subjects to 4-wk intake of a placebo ( period 1 ) . After a 4-wk washout period , the subjects received the alternative administration for 4 wk ( period 2 ) . BP decreased with statistical significance with the administration of sesamin ( systolic : 137.6+/-2.2 to 134.1+/-1.7 mmHg , p=0.044 , diastolic : 87.7+/-1.3 to 85.8+/-1.0 mmHg , p=0.045 ) , but little changed with the placebo ( systolic : 135.0+/-1.8 to 135.1+/-1.7 mmHg , diastolic : 85.9+/-1.2 to 86.6+/-1.2 mmHg ) . In conclusion , 4-wk administration of 60 mg sesamin significantly decreased BP by an average of 3.5 mmHg systolic BP and 1.9 mmHg diastolic BP . These results suggest that sesamin has an antihypertensive effect in humans . Epidemiological studies suggested that a 2 - 3 mmHg decrease in BP reduces the rate of cardiovascular diseases ; therefore , it is considered that BP reduction achieved by sesamin may be meaningful to prevent cardiovascular diseases Background Blood pressure ( BP ) lowering in people who have had a stroke or transient ischaemic attack ( TIA ) leads to reduced risk of further stroke . However , it is not clear what the target BP should be , since intensification of therapy may lead to additional adverse effects . PAST BP will determine whether more intensive BP targets can be achieved in a primary care setting , and whether more intensive therapy is associated with adverse effects on quality of life . Methods / Design This is a r and omised controlled trial ( RCT ) in patients with a past history of stroke or TIA . Patients will be r and omised to two groups and will either have their blood pressure ( BP ) lowered intensively to a target of 130 mmHg systolic , ( or by 10 mmHg if the baseline systolic pressure is between 125 and 140 mmHg ) compared to a st and ard group where the BP will be reduced to a target of 140 mmHg systolic . Patients will be managed by their practice at 1 - 3 month intervals depending on level of BP and followed-up by the research team at six monthly intervals for 12 months.610 patients will be recruited from approximately 50 general practice s. The following exclusion criteria will be applied : systolic BP < 125 mmHg at baseline , 3 or more anti-hypertensive agents , orthostatic hypotension , diabetes mellitus with microalbuminuria or other condition requiring a lower treatment target or terminal illness . The primary outcome will be change in systolic BP over twelve months . Secondary outcomes include quality of life , adverse events and cardiovascular events . In-depth interviews with 30 patients and 20 health care practitioners will be undertaken to investigate patient and healthcare professionals underst and ing and views of BP management . Discussion The results of this trial will inform whether intensive blood pressure targets can be achieved in people who have had a stroke or TIA in primary care , and help determine whether or not further research is required before recommending such targets for this population .Trial Registration IS RCT The benefits of lowering a systolic blood pressure below 140 mmHg in elderly hypertension remain controversial . This study is a prospect i ve , r and omized , open-label study with blinded assessment of endpoints to compare the 2-year effect of strict treatment to maintain systolic blood pressure below 140 mmHg with that of mild treatment to maintain systolic blood pressure below 160 but at or above 140 mmHg in elderly hypertensive patients . Patients with essential hypertension ( 65–85 years old , with a pretreatment systolic blood pressure of above 160 mmHg ) were r and omly assigned to receive strict treatment ( n=2,212 ) or mild treatment ( n=2,206 ) . The baseline drug was efonidipine hydrochloride , a long-acting calcium antagonist . The primary endpoint was the combined incidence of cardiovascular disease and renal failure , and the secondary endpoints were total deaths and any safety problems . Although final blood pressures ( systolic/diastolic ) were significantly lower in the strict-treatment group compared with the mild-treatment group ( 135.9/74.8 vs. 145.6/78.1 mmHg ; p<0.001 ) , the incidence of the primary endpoint was similar in the two groups ( 86 patients in each group ; p=0.99 ) . Total deaths were 54 in the strict-treatment group vs. 42 in the mild-treatment group ( p=0.22 ) , and treatment was withdrawn because of adverse events in 36 patients in each group ( p=0.99 ) . An interaction between age and treatment for the primary endpoints ( p=0.03 ) was seen . Complex clinical features associated with aging seem to have obscured the difference in effect between the two treatments . Further studies are needed to assess the optimal treatment strategy for hypertension in the elderly AIMS Major guidelines recommend lowering systolic blood pressure ( SBP ) to < 140 mmHg in all hypertensives , but evidence is missing whether this is beneficial in ( i ) uncomplicated hypertensives , ( ii ) grade 1 hypertensives , and ( iii ) elderly hypertensives . Providing this missing evidence is important to justify efforts and costs of aggressive therapy in all hypertensives . METHODS AND RESULTS Felodipine Event Reduction ( FEVER ) was a double-blind , r and omized trial on 9711 Chinese hypertensives , in whom cardiovascular outcomes  were significantly reduced by more intense therapy ( low-dose hydrochlorothiazide and low-dose felodipine ) achieving a mean of 138 mmHg SBP compared with less-intense therapy ( low-dose hydrochlorothiazide and placebo ) achieving a mean of 142 mmHg . FEVER included older and younger patients , and patients with and without diabetes or cardiovascular disease . In the analyses here reported , Cox regression models assessed outcome differences between more and less-intense treatments in groups of patients with different baseline characteristics . Significant reductions in stroke were found in uncomplicated hypertensives ( -39 % , P = 0.002 ) , in hypertensives with r and omization SBP < 153 mmHg ( -29 % , P = 0.03 ) , and in elderly hypertensives ( -44 % , P < 0.001 ) , when their SBP was lowered by more intense treatment . Significant reductions ( between -29 and -47 % , P = 0.02 to < 0.001 ) were also found in all cardiovascular events and all deaths . Achieving mean SBP values < 140 mmHg by adding a small dose of a generic drug prevented 2.1 ( uncomplicated hypertensives ) and 5.2 ( elderly ) cardiovascular events every 100 patients treated for 3.3 years . CONCLUSIONS These analyses provide strong support , missing so far , to guidelines recommending goal SBP < 140 mmHg in uncomplicated hypertensives , individuals with moderately elevated BP and elderly hypertensives Whether the strict control of blood pressure ( BP ) of patients with hypertension who are aged 85 years or older is beneficial is unclear . The Japan ’s Benidipine Research on Antihypertensive Effects in the Elderly study is a prospect i ve , observational 3-year study to evaluate the safety and effectiveness of treatment with a calcium channel blocker benidipine in 8897 hypertensive patients aged 65 years or older as a post-marketing surveillance . We examined the relationship between the achieved BP and cardiovascular events ( i.e. , stroke , myocardial infa rct ion , and heart failure ) in a subgroup of 415 patients aged 85 years or older ( mean age 88 years ) . BP decreased significantly from 165 ± 14/84 ± 10 mmHg to 130 ± 11/71 ± 10 mmHg during treatment in patients with a treated systolic BP ( SBP ) < 140 mmHg ( n = 230 ) and BP decreased significantly from 169 ± 16/86 ± 12 mmHg to 143 ± 13/75 ± 10 mmHg in those with a treated SBP ≥ 140 mmHg ( n = 185 ) . There was a nonsignificant trend toward a lower rate of cardiovascular events and higher rate of total death in patients with a treated SBP < 140 mmHg . On-treatment SBP ≥ 160 mmHg is tended to associate with a higher incidence of cardiovascular events . There was no significant difference in the incidence of adverse reactions between the controlled BP group ( 3.04 % ) and the less well controlled BP group ( 3.24 % ) . In conclusion , although this study was not powered for definitive conclusion , there was a nonsignificant trend toward a lower rate of cardiovascular events and higher total death in patients aged 85 years or older with a treated SBP < 140 mmHg Introduction Despite the ongoing debate on the role of renal sympathetic denervation ( RSD ) in the management of therapy-resistant hypertension , little is known about its possible effects on exercise blood pressure ( BP ) , a known predictor for future cardiovascular events . We sought to evaluate the effect of RSD on exercise BP in a r and omized , sham-controlled trial in patients with mild hypertension . Methods and results Patients with therapy-resistant mild hypertension ( defined by mean daytime systolic BP between 135 and 149 mmHg or mean daytime diastolic BP between 90 and 94 mmHg on 24-h ambulatory BP measurement ) were r and omized to either radiofrequency-based RSD or a sham procedure . Patients underwent cardiopulmonary exercise testing at baseline and after 6 months . Of the 71 patients r and omized , data from cardiopulmonary exercise testing were available for 48 patients ( 22 in the RSD group , 26 in the sham group ) . After 6 months , patients undergoing RSD had a significantly lower systolic BP at maximum exercise workload compared to baseline ( −14.2 ± 26.1 mmHg , p = 0.009 ) . In contrast , no change was observed in the sham group ( 0.6 ± 22.9 mmHg , p = 0.45 , p = 0.04 for between-group comparison ) . When analyzing patients with exaggerated baseline exercise BP only , the effect was even more pronounced ( RSD vs. sham −29.5 ± 23.4 vs. 0.1 ± 25.3 mmHg , p = 0.008 ) . Conclusion Exercise systolic BP values in patients with mild therapy-resistant hypertension are reduced after RSD as compared to a sham-procedure BACKGROUND In 1989 , the European Working Party on High Blood Pressure in the Elderly started the double-blind , placebo-controlled , Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension . This report addresses whether the benefit of antihypertensive treatment varied according to sex , previous cardiovascular complications , age , initial blood pressure ( BP ) , and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per- protocol analysis . METHODS After stratification for center , sex , and cardiovascular complications , 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were r and omized . Active treatment consisted of nitrendipine ( 10 - 40 mg/d ) , with the possible addition of enalapril maleate ( 5 - 20 mg/d ) and /or hydrochlorothiazide ( 12.5 - 25 mg/d ) , titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg , to below 150 mm Hg . In the control group , matching placebo tablets were employed similarly . RESULTS In the intention-to-treat analysis , male sex , previous cardiovascular complications , older age , higher systolic BP , and smoking at r and omization were positively and independently correlated with cardiovascular risk . Furthermore , for total ( P = .009 ) and cardiovascular ( P = .09 ) mortality , the benefit of antihypertensive drug treatment weakened with advancing age ; for total mortality ( P = .05 ) , the benefit increased with higher systolic BP at entry , while for fatal and nonfatal stroke ( P = .01 ) , it was most evident in nonsmokers ( 92.5 % of all patients ) . In the per protocol analysis , active treatment reduced total mortality by 24 % ( P = .05 ) , reduced all fatal and nonfatal cardiovascular end points by 32 % ( P<.001 ) , reduced all strokes by 44 % ( P = .004 ) , reduced nonfatal strokes by 48 % ( P = .005 ) , and reduced all cardiac end points , including sudden death , by 26 % ( P = .05 ) . CONCLUSIONS In elderly patients with isolated systolic hypertension , stepwise antihypertensive drug treatment , starting with the dihydropyridine calcium channel blocker nitrendipine , improves prognosis . The per- protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths , 54 major cardiovascular end points , 29 strokes , or 25 cardiac end points . The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients BACKGROUND Increased blood pressure ( BP ) in type 2 diabetes ( T2DM ) markedly increases cardiovascular disease morbidity and mortality risk compared to having increased BP alone . OBJECTIVE To investigate whether exercise reduces suboptimal levels of untreated suboptimal BP or treated hypertension . DESIGN Prospect i ve , r and omized controlled trial for 6 months . SETTING Single center in Baltimore , MD , USA . PATIENTS 140 participants with T2DM not requiring insulin and untreated SBP of 120–159 or DBP of 85–99 mmHg , or , if being treated for hypertension , any SBP < 159 mmHg or DBP < 99 mmHg ; 114 completed the study . INTERVENTIONS upervised exercise , 3 times per week for 6 months compared with general advice about physical activity .  MEASUREMENTS Resting SBP and DBP ( primary outcome ) ; diabetes status , arterial stiffness assessed as carotid-femoral pulse-wave velocity ( PWV ) , body composition and fitness ( secondary outcomes ) . RESULTS Overall baseline BP was 126.8 ± 13.5 / 71.7 ± 9.0 mmHg , with no group differences . At 6 months , BP was unchanged from baseline in either group , BP 125.8 ± 13.2 / 70.7 ± 8.8 mmHg in controls ; and 126.0 ± 14.2 / 70.3 ± 9.0 mmHg in exercisers , despite attaining a training effects as evidence d by increased aerobic and strength fitness and lean mass and reduced fat mass ( all p < 0.05 ) , Overall baseline PWV was 959.9 ± 333.1 cm/s , with no group difference . At 6-months , PWV did not change and was not different between group ; exercisers , 923.7 ± 319.8 cm/s , 905.5 ± 344.7 , controls . LIMITATIONS A completion rate of 81 % . CONCLUSIONS Though exercisers improve fitness and body composition , there were no reductions in BP . The lack of change in arterial stiffness suggests a resistance to exercise-induced BP reduction in persons with T2DM Objective : To perform a subgroup analysis on those patients in STOP‐Hypertension‐2 who had isolated systolic hypertension . Design and methods : The STOP‐Hypertension‐2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs ( diuretics , beta‐blockers ) with that of newer ones [ angiotensin‐converting enzyme ( ACE ) inhibitors , calcium antagonists ] . In all , 6614 elderly patients with hypertension ( mean age 76.0 years , range 70–84 years at baseline ) were included in STOP‐Hypertension‐2 . In the present subgroup analysis of STOP‐Hypertension‐2 , isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg , in accordance with the Syst‐Eur and Syst‐China study criteria . In total , 2280 patients in STOP‐Hypertension‐2 met these criteria . In the study , patients were r and omized to one of three treatment groups : “ conventional ” antihypertensive therapy with beta‐blockers or diuretics ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or fixed‐ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) ; ACE inhibitors ( enalapril 10 mg or lisinopril 10 mg daily ) ; or calcium antagonists ( felodipine 2.5 mg or isradipine 2.5 mg daily ) . Analysis was by intention to treat . Results : The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens : 35/13 mmHg in the conventional group ( n = 717 ) , 34/12 mmHg in the ACE inhibitor group ( n = 724 ) , and 35/13 mmHg in the calcium antagonist group ( n = 708 ) . Prevention of cardiovascular mortality , the primary endpoint of the study , did not differ between the three treatment groups . All stroke events , i.e. fatal and non‐fatal stroke together , were significantly reduced by 25 % in the newer‐drugs group compared with the conventional group ( 95 % CI 0.58–0.97 ; p = 0.027 ) . This difference was attributable to reduction of non‐fatal stroke while fatal stroke events did not differ between groups . New cases of atrial fibrillation were significantly increased by 43 % ( 95 % CI 1.02–1.99 ; p = 0.037 ) on “ newer ” drugs compared with “ conventional ” therapy , mainly attributable to the calcium antagonists . There were no significant differences between the three treatment groups with respect to the risks of myocardial infa rct ion , sudden death or congestive heart failure . Conclusions : The analysis demonstrated that “ newer ” therapy ( ACE inhibitors/calcium antagonists ) was significantly better ( 25 % ) than “ conventional ” ( diuretics/beta‐blockers ) in preventing all stroke in elderly patients with isolated systolic hypertension Objectives In many current guidelines , blood pressure (BP)-lowering drug treatment for primary prevention of cardiovascular disease ( CVD ) is based on absolute risk . However , in clinical practice , therapeutic decisions are often based on BP levels alone . We sought to investigate which approach was superior by conducting a post hoc analysis of the Australian National Blood Pressure ( ANBP ) cohort , a seminal study establishing the efficacy of BP lowering in ‘ mild hypertensive ’ persons . Design A post hoc subgroup analysis of the ANBP trial results by baseline absolute risk tertile . Setting and participants 3244 participants aged 35–69 years in a community-based r and omised placebo controlled trial of blood pressure-lowering medication . Interventions Chlorothiazide500 mg versus placebo . Primary outcome measures All-cause mortality and non-fatal events ( non-fatal CVD , congestive cardiac failure , renal failure , hypertensive retinopathy or encephalopathy ) . Results Treatment effects were assessed by HR , absolute risk reduction and number needed to treat . Participants had an average 5-year CVD risk in the intermediate range ( 10.5±6.5 ) with moderately elevated BP ( mean 159/103 mmHg ) and were middle aged ( 52±8 years ) . In a subgroup analysis , the relative effects ( HR ) and absolute effects ( absolute risk reduction and number needed to treat ) did not statistically differ across the three risk groups except for the absolute benefit in all-cause mortality ( p for heterogeneity=0.04 ) . With respect to absolute benefit , drug treatment significantly reduced the number of events in the high-risk group regarding any event with a number needed to treat of 18 ( 10 to 64 ) , death from any cause with 45 ( 25 to 196 ) and major CVD events with 23 ( 12 to 193 ) . Conclusion Our analysis confirms that the benefit of treatment was substantial only in the high-risk tertile , reaffirming the rationale of treating elevated blood pressure in the setting of all risk factors rather than in isolation Background : Combined regimen may be superior to monotherapy in blood pressure ( BP ) control . Since BP control is crit‐ically related to cardiovascular mortality and morbidity in hypertensive patients , this study aim ed to evaluate the efficacy and safety of a low‐dose combined regimen of preterax compared with cilazapril monotherapy for better BP control in treated hypertensive patients . Methods : Stable hypertensive patients were evaluated if their systolic BP ( SBP ) was > 130 mmHg and /or diastolic BP ( DBP ) was > 85 mmHg even with up to 2 antihypertensive drugs . Patients were excluded if they were on angiotensin‐converting enzyme inhibitors , angiotensin II receptor blockers or a diuretic . They were then r and omized to receive either preterax ( perindopril 2 mg and indapamide 0.625 mg ) or cilazapril 2.5 mg once daily in a double‐blind fashion for a period of 12 weeks after a 2‐week placebo run‐in phase . Sitting BP was recorded and the safety and efficacy were evaluated at each visit every 4 weeks . Response was defined as positive if SBP was ≤140 mmHg and DBP was ≤90 mmHg at the last visit or there was > 20 mmHg reduction in SBP and /or > 10 mmHg reduction in DBP using either treatment . Plasma biochemical analysis was performed both before and after the treatment . Results : Among the 47 patients initially enrolled , 41 completed the study ( 21 in the preterax group , 20 in the cilazapril group ) . There was no difference in the number of adverse events between the 2 groups . SBP was significantly reduced by preterax ( 13.43 ±12.48 mmHg , p < 0.0001 ) and cilazapril ( 9.00 ±13.75 mmHg , p < 0.05 ) . However , DBP was significantly reduced only by preterax ( 7.67 ±9.40 mmHg , p = 0.0009 ) but not by cilazapril ( 3.60 ±8.37 mmHg , p > 0.05 ) . The response rate was significantly higher to preterax ( 100 % ) than to cilazapril ( 70 % ) ( p = 0.0086 ) . Conclusion : Though similar in safety , combined regimen preterax was more effective than cilazapril to facilitate adequate BP control in already‐treated hypertensives . It can be added on to other antihypertensives for better BP control in clinical hypertension . [ J Chin Med Assoc 2008;71(5):247–253 Objective To compare the efficacy and safety of the angiotensin II antagonist olmesartan medoxomil ( O ) and the ACE inhibitor ramipril ( R ) in elderly patients with essential arterial hypertension . Methods After a 2-week placebo wash-out 1102 treated or untreated elderly hypertensive patients aged 65–89 years ( office sitting diastolic blood pressure , DBP , 90–109 mmHg and /or office sitting systolic blood pressure , SBP , 140–179 mmHg ) were r and omized double-blind to 12-week treatment with O 10 mg or R 2.5 mg once-daily . After the first 2 and 6 weeks doses could be doubled in non-normalized [ blood pressure ( BP ) < 140/90 mmHg for nondiabetic and < 130/80 mmHg for diabetic ) individuals , up to 40 mg for O and 10 mg for R. Office BPs were assessed at r and omization , after 2 , 6 and 12 weeks of treatment , whereas 24-h ambulatory BP was recorded at r and omization and after 12 weeks . Results In the intention-to-treat population ( 542 patients O and 539 R ) after 12 weeks of treatment baseline-adjusted office SBP and DBP reductions were greater ( P < 0.01 ) with O [ 17.8 ( 95 % confidence interval : 16.8/18.9 ) and 9.2 ( 8.6/9.8 ) mmHg ] than with R [ 15.7 ( 14.7/16.8 ) and 7.7 ( 7.1/8.3 ) mmHg ] . BP normalization rate was also greater under O ( 52.6 vs. 46.0 % R , P < 0.05 ) . In the subgroup of patients with valid ambulatory BP recording ( 318 O and 312 R ) the reduction in 24-h average BP was larger ( P < 0.05 ) with O [ SBP : 11.0 ( 12.2/9.9 ) and DBP : 6.5 ( 7.2/5.8 ) mmHg ] than with R [ 9.0 ( 10.2/7.9 ) and 5.4 ( 6.1/4.7 ) mmHg ] . The larger blood pressure reduction obtained with O was particularly evident in the last 6 h from the dosing interval ; a better homogeneity of the 24-h BP control with O was confirmed by higher smoothness indices . The proportion of patients with drug-related adverse events was comparable in the two groups ( 3.6 O vs. 3.6 % R ) , as well as the number of patients discontinuing study drug because of a side effect ( 14 O vs. 19 R ) . Conclusion In elderly patients with essential arterial hypertension O provides an effective , prolonged and well tolerated BP control , representing a useful option among first-line drug treatments of hypertension in this age group OBJECTIVE To study the prevalence , awareness and control of  hypertension in Chennai representing Urban South India . METHODS The Chennai Urban Rural Epidemiology Study ( CURES ) is one of the largest epidemiological studies on diabetes carried out in India , where 26,001 individuals aged > or = 20 years were screened using systematic r and om sampling method .  Every tenth subject recruited in Phase 1 of CURES was requested to participate in Phase 3 of CURES and the response rate was 2,350/26,001 or 90.4 % . An  oral glucose tolerance test  was performed in all individuals except self-reported diabetic subjects . Anthropometric measurements and lipid estimations were done in all subjects . Hypertension was diagnosed in all subjects who were on drug treatment for hypertension or if the blood pressure > or = 140/90 mmHg . RESULTS Hypertension was present in 20 % [ men:23.2 % vs. women:17.1 % , p<0.001 ] of the study population . Isolated systolic hypertension ( Systolic BP > or = 140 and Diastolic BP<90 mmHg ) was present in 6.6 % while isolated diastolic hypertension ( DBP > or = 90 and SBP<140 mmHg ) was present in 4.2 % of the population . Among the elderly population ( aged > or = 60 years ) , 25.2 % had isolated systolic hypertension . Age , body mass index , smoking , serum cholesterol and triglycerides were found to be strongly associated with hypertension . Among the total hypertensive subjects , only 32.8 % were aware of their blood pressure , of these , 70.8 % were under treatment and 45.9 % had their blood pressure under control . CONCLUSION Hypertension was present in one-fifth of this urban south Indian population and isolated systolic hypertension was more common among elderly population . Majority of hypertensive subjects still remain undetected and the control of hypertension is also inadequate . This calls for urgent prevention and control measures for hypertension SUMMARY Background : Hypertension is one of the most important causes of cardiovascular disease , and treatment of hypertension leads to a significant reduction in cardiovascular mortality and morbidity . Although calcium channel blockers are regarded as an important part of the therapeutic armamentarium against cardiovascular diseases , and are among the most frequently prescribed antihypertensive medications , concern has been aroused about these drugs , particularly the short-acting dihydropyridine derivatives . However , the value of nifedipine GITS ( Adalat-Crono * ) , the long-acting dihydropyridine , is in need of being re-established . * Adalat-Crono is a registered tradename of Bayer AG , Leverkusen , Germany Objective : To compare the effectiveness , safety and tolerability of once-daily nifedipine and amlodipine treatment in patients with mild-to-moderate essential hypertension . Design : R and omised multicentre trial with an open comparison of treatments for 12 weeks , with a preceding placebo run-in period of 2 weeks ( patients on beta-blockers at the time of enrolment entered a m and atory 2-week wash-out period before being allowed in the placebo run-in period ; this wash-out period was one week for patients using any antihypertensive medication other than beta-blockers ) . Setting : Nine centres ( all university hospitals ) in Turkey . Patients : 155 patients with essential hypertension ( diastolicblood pressure 95 - 109 mmHg ) . Interventions : Initial treatment ( step 1 ) consisted of 30 mg nifedipine GITS ( n = 76 ; ( Adalat-Crono tablets ) , or 5 mg amlodipine ( n = 79 ; Norvasc * 5-mg tablets ) , either administered once daily , as a morning dose , or if the blood pressure was not below 140/90 mmHg , or the reduction in diastolic blood pressure was lower than 10 mmHg after a treatment period of 6 weeks , the dose was increased ( Step 2 ) to 60 mg once daily in the nifedipine group , or 10 mg once daily in the amlodipine group . Main efficacy parameter : Diastolic blood pressure at trough after 12 weeks of active compound therapy adjusted to baseline . Results : After 12 weeks of treatment , the mean diastolic blood pressure was 83.1 and 81.9 mmHg , in the nifedipine and amlodipine groups , respectively ( p = 0.436 ) . The mean decrease in systolic blood pressure ( 28.5 ± 11.9 and 28.2 ± 11.2 mmHg in the nifedipine and amlodipine groups , respectively ) and the mean decrease in diastolic blood pressure ( 16.4 ± 7.0 and 17.5 ± 6.9 mmHg in the nifedipine and amlodipine groups , respectively ) , as well as the responder rates ( 88.1 % and 92.1 % , in the nifedipine and amlodipine groups , respectively ) were comparable at the end of the study . No significant differences between groups were detected in the efficacy parameters assessed in this study . Both drugs were well tolerated . The overall incidence of adverse events was 7.9 % in the nifedipine group and 10.1 % in the amlodipine group . However , more patients discontinued treatment prematurely in the amlodipine group ( 13 patients ; 19.7 % ) , than in the nifedipine group ( four patients ; 5.6 % ) . Conclusions : The results of this study demonstrated that once-daily nifedipine in GITS formulation and amlodipine are comparably safe and effective treatment options in patients with mild-to-moderate essential hypertensi on ABSTRACT . Lifestyle modifications are effective for the management and prevention of hypertension . We conducted a r and omized , placebo-controlled trial to evaluate the efficacy of an oral concentrated leaf juice of artichoke ( Cynara scolymus L. ; CS ) in patients with mild hypertension ( systolic blood pressure [SBP]/diastolic blood pressure [ DBP ] , 140–159/90−99 mmHg ) . Subjects were r and omized into a placebo and two drug groups that received 50 and 100 mg of artichoke juice concentrate . After 12 weeks , SBP significantly reduced as compared with the baseline data in case groups and DBP was significantly lower from the baseline as compared with the placebo group . It is concluded that the use of artichoke juice concentrate may have a blood pressure-lowering effect in mild hypertension BACKGROUND The efficacy of new antihypertensive drugs has been question ed . We compared the effects of conventional and newer antihypertensive drugs on cardiovascular mortality and morbidity in elderly patients . METHODS We did a prospect i ve , r and omised trial in 6614 patients aged 70 - 84 years with hypertension ( blood pressure > or = 180 mm Hg systolic , > or = 105 mm Hg diastolic , or both ) . Patients were r and omly assigned conventional antihypertensive drugs ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) or newer drugs ( enalapril 10 mg or lisinopril 10 mg , or felodipine 2.5 mg or isradipine 2 - 5 mg daily ) . We assessed fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease . Analysis was by intention to treat . FINDINGS Blood pressure was decreased similarly in all treatment groups . The primary combined endpoint of fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease occurred in 221 of 2213 patients in the conventional drugs group ( 19.8 events per 1000 patient-years ) and in 438 of 4401 in the newer drugs group ( 19.8 per 1000 ; relative risk 0.99 [ 95 % CI 0.84 - 1.16 ] , p=0.89 ) . The combined endpoint of fatal and non-fatal stroke , fatal and non-fatal myocardial infa rct ion , and other cardiovascular mortality occurred in 460 patients taking conventional drugs and in 887 taking newer drugs ( 0.96 [ 0.86 - 1.08 ] , p=0.49 ) . INTERPRETATION Old and new antihypertensive drugs were similar in prevention of cardiovascular mortality or major events . Decrease in blood pressure was of major importance for the prevention of cardiovascular events Background There has been very little published work exploring the comparative effects of isometric resistance training ( IRT ) on  blood pressure ( BP ) in men and women . Most of the previously published work has involved men and used resting BP as the primary outcome variable . Early evidence suggests that IRT is particularly effective in older women and has a positive influence on ambulatory BP , a better predictor of disease risk . Objectives With the WHO now placing global emphasis on the primary prevention of hypertension , the goals of this proof-of-concept study were to ( i ) examine whether sex differences exist in the ambulatory BP-lowering effects of IRT in young , normotensive men and women and ( ii ) determine whether these reductions can be predicted by simple laboratory stress tasks ( a 2-min sustained isometric contraction and a math task involving subtracting a two-digit number from a series of numbers ) . Results There were no differences in the  IRT-induced reductions in 24-h ( men : & Dgr;4 mmHg , women : & Dgr;4 mmHg ) , daytime ( men : & Dgr;3 mmHg , women : & Dgr;4 mmHg ) , or night-time ( men : & Dgr;4 mmHg , women : & Dgr;3 mmHg ) ambulatory BP in men ( n=13 ) and women ( n=11 ) ( P<0.05 ) and these changes were not associated with systolic BP reactivity to either stress task ( all P>0.05 ) . Conclusion Our data suggest that lower ambulatory BP can be achieved , to a similar magnitude in young healthy women as well as men , with IRT ; however , the BP-lowering effectiveness can not be predicted by systolic BP reactivity . Taken together , this work heralds a potentially novel approach to the primary prevention of hypertension in both men and women and warrants further investigation in a larger clinical outcome trial BACKGROUND Good blood pressure ( BP ) control reduces the risk of complications in people with type 2 diabetes , yet many do not achieve this . Guidelines for managing hypertension recommend increasing antihypertensive medications until control is achieved , but the effect of such recommendations in routine primary care is unknown . AIM To evaluate the effectiveness of a BP treatment algorithm in primary care patients with type 2 diabetes . DESIGN OF STUDY A cluster r and omised controlled trial of 1534 patients with type 2 diabetes . SETTING Forty-two practice s in Nottingham , UK . METHOD Practice s were r and omised to continue usual care or to use a treatment algorithm design ed so that practice nurses and GPs would increase antihypertensive treatment in steps until the target of 140/80 mmHg was reached . Participants were assessed by a clinical interview and case note review at recruitment and at 1 year . The primary outcome measure was the proportion of participants achieving target BP at 1 year . RESULTS At 1 year there was no difference between the proportions of participants with well controlled BP in the intervention and control arms ( 36.6 % versus 34.3 % ; P = 0.27 ) . Mean systolic and diastolic blood pressures were identical in the two arms ( 143/78 mmHg ) . There was some evidence that participants in the intervention arm were more likely to be receiving higher doses of their antihypertensive drugs , although there was no significant difference in the number of different antihypertensive drugs prescribed . Participants in the intervention arm had a higher rate of primary care BP-related consultations over 12 months than those receiving usual care ( rate ratio = 1.55 , 95 % confidence interval [ CI ] = 1.26 to 1.88 , P<0.001 ) . CONCLUSION Despite increased monitoring and possibly higher doses of medication there was no improvement in blood pressure control . Improvements achieved by specialist nurse-led clinics in secondary care may not translate to people with type 2 diabetes in primary care setting OBJECTIVE We have assessed the influence of gender and age on the main outcome results of the Hypertension Optimal Treatment ( HOT ) study . DESIGN AND INTERVENTIONS The aims of the HOT study were to study the relationship between three levels of target office diastolic blood pressure ( BP ) ( < or = 90 , < or = 85 or < or = 80 mmHg ) and  cardiovascular ( CV ) events in hypertensive patients , and to examine the effects of 75 mg acetylsalicylic acid ( ASA ) daily versus placebo . SETTING Outpatient clinical trial in 26 countries . PATIENTS A total of 18790 patients ( mean age 61.5 years , range 50 - 80 ) were r and omized and followed for an average of 3.8 years until 71051 patient-years and 683 events had occurred . MAIN OUTCOME MEASURES CV death , myocardial infa rct ion ( MI ) and stroke . RESULTS There were significantly fewer MIs in those in the lower diastolic BP target groups ( 3.0 versus 1.2 and 1.7 MIs/1000 patient-years , P for trend = 0.034 ) in women ( n = 8883 ) , whereas the similar but smaller trend ( 4.1 versus 4.1 and 3.4 MIs/1000 patient-years ) was not statistically significant in men nor in the subgroup analysis of younger and older subjects . The effect of ASA on preventing MI was not influenced by age < 65 years ( P= 0.02 ) or age > or = 65 years ( P = 0.04 ) but was influenced by gender ( P = 0.38 in women and P = 0.001 in men , lowered by 42 % corresponding to a reduction from 5.0 to 2.9 MIs/1000 patient-years ) . CONCLUSIONS The data of this HOT study sub- analysis suggest somewhat differentiated optimal gender- and age-dependent effects of anti-hypertensive and anti-platelet therapies ; lowering of diastolic BP to about 80 mmHg in hypertensive women and , in addition , the administration of 75 mg of ASA to well-treated hypertensive men appear to effectively reduce the most common cardiovascular complication , i.e. myocardial infa rct ion , in patients with essential hypertension Aims Orthostatic hypotension ( OH ) has been linked to increased mortality and incidence of cardiovascular disease in various risk groups , but determinants and consequences of OH in the general population are poorly studied . Methods and results Prospect i ve data of the Swedish ‘ Malmö Preventive Project ’ ( n = 33 346 , 67.3 % men , mean age 45.7 ± 7.4 years , mean follow-up 22.7 ± 6.0 years ) were analysed .  Orthostatic hypotension  was found in 6.2 % of study participants and was associated with age , female gender , hypertension , antihypertensive treatment , increased heart rate , diabetes , low BMI , and current smoking . In Cox regression analysis , individuals with OH had significantly increased all-cause mortality ( in particular those aged less than 42 years ) and coronary event ( CE ) risk . Mortality and CE risk were distinctly higher in those with systolic blood pressure ( BP ) fall ≥30 mmHg [ hazard ratio ( HR ) : 1.6 , 95 % CI 1.3–1.9 , P < 0.0001 and 1.6 , 95 % CI 1.2–2.1 , P = 0.001 ] and diastolic BP fall ≥15 mmHg ( HR : 1.4 , 95 % CI 1.1–1.9 , P = 0.024 and 1.7 , 95 % CI 1.1–2.5 , P = 0.01 ) . In addition , impaired diastolic BP response had relatively greater impact ( per mmHg ) on CE incidence than systolic reaction .  Conclusion Orthostatic hypotension can be detected in ∼6 % of middle-aged individuals and is often associated with such comorbidities as hypertension or diabetes . Presence of OH increases mortality and CE risk , independently of traditional risk factors . Although both impaired systolic and diastolic responses predict adverse events , the diastolic impairment shows stronger association with coronary disease Objective To compare the incidence of stroke and other cardiovascular events in hypertensive patients receiving a low-dose diuretic and low-dose calcium antagonist combination with those receiving low-dose diuretic monotherapy  , and assess the effects of a small blood pressure difference at achieved levels lower than those achieved in previous placebo-controlled trials . Methods The Felodipine Event Reduction ( FEVER ) trial was an investigator- design ed , prospect i ve , multicentre , double-blind , r and omized , placebo-controlled , parallel group trial . It enrolled 9800 Chinese patients , of either sex , aged 50–79 years , with one or two additional cardiovascular risk factors or disease , whose blood pressure , 6 weeks after switching from previous antihypertensive therapy to low-dose ( 12.5 mg a day ) hydrochlorothiazide , was in the range 140–180 mmHg ( systolic ) or 90–100 mmHg ( diastolic ) . These patients were r and omly assigned either to low-dose felodipine extended release or placebo , and followed at 3-month intervals for an average of 40 months . Results The intention-to-treat analysis included 9711 r and omly selected patients with only 30 ( 0.3 % ) lost to follow-up . A total of 31 842 patient-years of follow-up were accumulated , with 85.9 % of patients remaining on blinded r and omized treatment . Add-on therapy was given to 33.9 % of the hydrochlorothiazide – felodipine patients and to 42.3 % of the hydrochlorothiazide – placebo patients . In the felodipine  group , systolic blood pressure (SBP)/diastolic blood pressure ( DBP ) decreased ( from r and omization to study end ) from 154.2/91.0 to 137.3/82.5 mmHg , and in the placebo group from 154.4/91.3 to 142.5/85.0 mmHg , with an average difference throughout the trial of 4.2/2.1 mmHg . In the felodipine group , the primary endpoint ( fatal and non-fatal stroke ) was reduced by 27 % ( P = 0.001 ) . Among secondary endpoints , all cardiovascular events were reduced by 27 % ( P < 0.001 ) , all cardiac events by 35 % ( P = 0.012 ) , death by any cause by 31 % ( P = 0.006 ) , coronary events by 32 % ( P = 0.024 ) , heart failure by 30 % ( P = 0.239 ) , cardiovascular death by 33 % ( P = 0.019 ) , cancer by 36 % ( P = 0.017 ) in the felodipine group . No significant differences were found in new-onset diabetes . Both treatments were very well tolerated . Conclusions In moderately complicated hypertensive patients from China even a difference in SBP/DBP as small as 4/2 mmHg , such as that induced by adding low-dose felodipine to low-dose hydrochlorothiazide , is associated with very substantial reductions in the incidence of most types of cardiovascular events . As the SBP achieved in the felodipine group was below the recommended goal of less than 140 mmHg , and SBP in the placebo group was slightly above that level , FEVER provides the required evidence in support of the guidelines recommended goal , even for a hypertensive population not entirely consisting of patients with diabetes or previous cardiovascular events AIM Patients with resistant hypertension are at high risk for adverse cardiovascular events . Efforts have been focused on lowering the surrogate endpoint of blood pressure ( BP ) with scant focus on reduction of hard cardiovascular endpoints . However , whether or not intensive lipid lowering is beneficial for reducing the risk of cardiovascular events in this high-risk cohort is not known . METHODS AND RESULTS We evaluated 10 001 patients with coronary artery disease and a low-density lipoprotein cholesterol level < 130 mg/dL , r and omized to atorvastatin 80 vs. 10 mg , enrolled in the Treating to New Targets trial . Treatment-resistant hypertension ( TRH ) was defined as BP ≥140 mmHg despite being on three antihypertensive agents or < 140 mmHg on four or more agents . Subjects were followed up for a median duration of 4.9 years . The primary outcome was major cardiovascular events ( composite of non-fatal myocardial infa rct ion ( MI ) , fatal coronary heart disease ( CHD ) , resuscitated cardiac arrest , and stroke ) . Among the 10 001 patients in the trial , 1112 ( 11.1 % ) patients had TRH . Atorvastatin 80 mg , in patients with TRH , was associated with a significant reduction in the risk of the primary outcome ( HR = 0.70 ; 95 % CI 0.52 - 0.93 ; P = 0.01 ) , driven largely by a significant reduction in CHD deaths ( HR = 0.55 ; 95 % CI 0.32 - 0.97 ; P = 0.04 ) . In addition , atorvastatin 80 mg was associated with a reduction in major coronary events ( HR = 0.67 ; 95 % CI 0.49 - 0.93 ; P = 0.02 ) , and any cardiovascular or coronary event and with a trend ( P = 0.05 ) towards reduction in all-cause mortality ( HR = 0.68 ; 95 % CI 0.46 - 1.01 ) when compared with atorvastatin 10 mg . The results were similar when analysed for the two separate components of the TRH cohort . CONCLUSION In subjects with TRH , intensive lipid lowering with atorvastatin 80 mg is associated with a significant reduction in cardiovascular events Summary The ABCD ( Appropriate Blood Pressure Control in Diabetes ) Trial is a large , prospect i ve , r and omized clinical trial of 950 patients with non-insulin-dependent diabetes mellitus ( NIDDM ) design ed to compare the effects of intensive blood pressure control with moderate control on the prevention and progression of diabetic nephropathy , retinopathy , cardiovascular disease , and neuropathy in NIDDM . The secondary objective is to determine equivalency of the effects of a calcium channel blocker ( nisoldipine ) and an angiotensin-converting-enzyme inhibitor ( enalapril ) as a first-line antihypertensive agent in the prevention and /or progression of these diabetic vascular complications . The study consists of two study population s aged 40–74 years , 470 hypertensive patients ( diastolic blood pressure of ≥ 90.0 mmHg at time of r and omization ) and 480 normotensive patients ( diastolic blood pressure of 80.0 mmHg at time of r and omization ) . The study duration is 5 years and is scheduled to end in May of 1998 . Patients are r and omized to receive either intensive antihypertensive drug therapy or moderate antihypertensive drug therapy . Patients are also r and omized to nisoldipine or enalapril , with open-label medications added if further blood pressure control is necessary . The primary outcome measure is glomerular filtration rate as assessed by 24-h creatinine clearance . Secondary outcome measures are urinary albumin excretion , left ventricular hypertrophy , retinopathy , and neuropathy . Cardiovascular morbidity and mortality will also be evaluated . Given the data showing the impact of hypertension on complications in NIDDM , the ABCD Trial is design ed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of diabetic complications in NIDDM . [ Diabetologia ( 1996 ) 39 : 1646–1654 Hypertension is increasingly common with advancing age and a risk factor for all kinds of cardiovascular complications . Moreover , cardiovascular disease is a major cause of morbidity and mortality in the elderly . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was set up by the Swedish Hypertension Society to investigate the value of antihypertensive treatment in the elderly . In this placebo controlled r and omised prospect i ve study 1,627 men and women aged 70 - 84 years with a supine blood pressure > or = 180/105 mmHg ( and /or ) but not isolated systolic hypertension participated . Three beta-blockers and one diuretic were used as blood pressure lowering agents and the average follow-up in the study was 25 months ( 3,390 patient-years ) . Administration of active antihypertensive therapy , reduced supine blood pressure from 195/102 mmHg to 167/87 mmHg at longest follow-up in comparison with placebo . A majority of the patients needed combined treatment to reach the goal blood pressure ( 160/95 mmHg ) . Associated with a fall in blood pressure were significant reductions in all cardiovascular primary endpoints ( -40 % , p = 0.0031 ) , in fatal and non-fatal stroke ( -47 % , p = 0.0081 ) and in total mortality ( -43 % , p = 0.0079 ) . In addition to the substantial effects on primary endpoints active treatment also showed clinical ly relevant effects on secondary endpoints ( e.g. heart failure ) . The impact on cardiovascular morbidity and mortality with antihypertensive treatment in this elderly cohort was greater than previously seen in middle-aged hypertensive patients , with maintained tolerability and a favourable cost-effectiveness ratio . Finally , women benefited from treatment at least as much as men OBJECTIVE To compare the effectiveness of a nurse-led hypertension clinic with conventional community care in general practice in the management of uncontrolled hypertension in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We studied 120 men and women outpatient attendees ( 61 % non-Caucasian ) with type 2 diabetes and a seated blood pressure ( BP ) > or=140/80 mmHg . All patients were being treated for hypertension , and 71 % had increased urinary albumin excretion ( UAE ) . Patients were allocated to either a nurse-led hypertension clinic or conventional primary care . The primary outcome measure was a change in systolic BP . Secondary outcome measures were total cholesterol , HDL cholesterol , total triglycerides , HbA(1c ) , UAE , serum creatinine , and changes in absolute stroke and coronary heart disease ( CHD ) risk scores . RESULTS The mean ( 95 % CI ) difference in the decrement of systolic BP was 12.6 mmHg ( 5.9 - 19.3 ) ( P = 0.000 ) in favor of the nurse-led group , whose patients were three times more likely to a reach target systolic BP < 140 mmHg compared with conventional care ( P = 0.003 ) . A significant fall in 10-year CHD ( P = 0.004 ) and stroke risk ( P = 0.000 ) scores occurred only in the nurse-led group . There were no significant differences in the reduction of diastolic BP or any of the other secondary outcome measures at 6 months . CONCLUSIONS Compared with conventional care , a nurse-led hypertension clinic is a more effective intervention for patients with type 2 diabetes and uncontrolled hypertension . A target systolic BP < 140 mmHg is more readily achieved and may be associated with significant reductions in 10-year cardiovascular disease risk scores Objective To assess clinical outcomes in the Study on COgnition and Prognosis in the Elderly ( SCOPE ) in patients who did not receive add-on antihypertensive therapy after r and omization , i.e. in patients that best reflect the original intention of a placebo-controlled trial . Design Post-hoc analysis of a prospect i ve , r and omized , controlled trial . Setting s and participants Five hundred and twenty-seven centres in 15 countries participated in SCOPE . Patients aged 70–89 years , with systolic blood pressure 160–179 mmHg and /or diastolic blood pressure 90–99 mmHg , and preserved cognitive function were eligible . Out of 4937 patients in SCOPE , 2098 did not receive add-on therapy . Intervention The number of patients who received c and esartan 8–16 mg once daily was 1253 , and 845 received placebo . Mean follow-up was 3.7 and 3.5 years , respectively . Main outcome measures Primary : major cardiovascular events ( cardiovascular mortality , non-fatal stroke or non-fatal myocardial infa rct ion ) . Secondary : total mortality , cardiovascular mortality , fatal and non-fatal myocardial infa rct ion , fatal and non-fatal stroke , cognitive function , and dementia . Results The treatment groups were generally well balanced for baseline characteristics . Blood pressure fell by 21.8/11.0 mmHg in the c and esartan group and by 17.2/8.4 mmHg in the placebo group . There were significant relative risk reductions with c and esartan in major cardiovascular events ( 32 % , P = 0.013 ) , cardiovascular mortality ( 29 % , P = 0.049 ) , and total mortality ( 27 % , P = 0.018 ) . There were no significant differences between the treatment groups in cognitive outcomes . Both treatments were generally well tolerated . Conclusions Treatment of elderly patients with mild hypertension is beneficial and supports current recommendations . C and esartan appears an appropriate therapy in such patients , in view of its favourable tolerability profile and ability to reduce major cardiovascular events Background The DASH ( Dietary Approaches to Stop Hypertension ) diet is a carbohydrate-rich , reduced-fat diet that lowers blood pressure ( BP ) and LDL-cholesterol . Whether partial replacement of some carbohydrate ( C ) with either protein ( P ) or unsaturated fat ( U ) can further improve these and other cardiovascular ( CVD ) risk factors is unknown . Methods OmniHeart is a r and omized , three-period , crossover feeding study design ed to compare the effects on BP and blood lipids of a carbohydrate-rich diet ( CARB , similar to the DASH diet ) with a diet rich in protein ( PROT , predominantly from nonmeat sources ) and a diet rich in unsaturated fat ( UNSAT , predominantly monounsaturated ) . Throughout feeding ( run in and the three intervention periods ) , participants are provided with all of their meals that meet the nutrient profile of their assigned diet . Calorie intake is adjusted to maintain weight . The target sample size is 160 ( 50 % African-American ) . Participants are adults , aged 30 or older , with prehypertension or Stage 1 hypertension ( systolic BP 120–159 or diastolic BP 80–99 mmHg ) . The primary outcome variables are systolic BP and LDL-cholesterol . Secondary outcomes are diastolic BP , HDL-cholesterol , and triglycerides . Other outcome variables are total cholesterol , apolipoproteins VLDL-apoB , VLDL-apoCIII , apolipoprotein B , non-HDL cholesterol , and lipoprotein(a ) , and insulin resistance , as measured by Homeostasis Model Assessment ( HOMA ) . Conclusions OMNI-Heart should advance our fundamental knowledge of the effects of diet on both traditional and emerging risk factors , and , in the process , guide policy makers , health care providers and the general public on the relative benefits of carbohydrate , protein , and unsaturated fat as a means to reduce CVD risk The Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints ( CONVINCE ) Trial is a r and omized , prospect i ve , double-blind , parallel-group , two-arm , actively controlled , multicenter , international 5-year clinical trial involving 15,000 patients . CONVINCE will compare the incidence of fatal or nonfatal myocardial infa rct ion ( MI ) , fatal or nonfatal stroke , or cardiovascular-disease-related death in two antihypertensive treatment regimens . One treatment arm begins with controlled onset-extended release (COER)-verapamil , which has its major antihypertensive effect 6 - 12 hours after administration . The other arm ( st and ard of care ( SOC ) ) begins with either hydrochlorothiazide ( HCTZ ) or atenolol , one of which is preselected by the investigator for an individual patient prior to r and omization . Secondary objectives include comparisons of the regimens for each of the components of the primary endpoint ( separately ) , death or hospitalization related to cardiovascular disease , efficacy in lowering blood pressure to goal , primary events occurring between 6 am and noon , all-cause mortality , withdrawals from blinded therapy , cancer , and hospitalizations due to bleeding .  Patients may be enrolled if they are hypertensive and at least 55 years of age and have an established second risk factor for cardiovascular disease . Initial medications include COER-verapamil ( 180 mg/d ) , HCTZ ( 12.5 mg/d ) , or atenolol ( 50 mg/d ) . Initial doses are doubled if blood pressure ( BP ) does not reach goal ( systolic BP < 140 mm and diastolic BP < 90 mm Hg ) . If BP is not controlled by the higher dose of the initial medication , HCTZ is added to COER-verapamil , or the SOC choice not initially selected is added in the SOC arm . An ACE-inhibitor is recommended ( although nearly any open-label medication is allowed ) as the third step for patients whose BP is not adequately controlled or who have a contraindication to one of the two SOC medications . Patients take two sets of tablets daily , one in the morning and one in the evening . Although most patients switch from an established antihypertensive medication to r and omized treatment , untreated patients with stages I-III hypertension ( SBP between 140 and 190 or DBP between 90 and 110 mm Hg ) are eligible . Outcomes are monitored by an independent Data and Safety Monitoring Board . Enrollment began during the third quarter of 1996 , and follow-up is to be completed in the third quarter of 2002
Antihypertensive drugs used in the treatment of adults ( primary prevention ) with mild hypertension ( systolic BP 140 - 159 mmHg and /or diastolic BP 90 - 99 mmHg ) have not been shown to reduce mortality or morbidity in RCTs .
More RCTs are needed in this prevalent population to know whether the benefits of treatment exceed the harms
BACKGROUND People with no previous cardiovascular events or cardiovascular disease represent a primary prevention population .
The benefits and harms of treating mild hypertension in primary prevention patients are not known at present .
This review examines the existing r and omised controlled trial ( RCT ) evidence .
OBJECTIVES PRIMARY OBJECTIVE To quantify the effects of antihypertensive drug therapy on mortality and morbidity in adults with mild hypertension ( systolic blood pressure ( BP ) 140 - 159 mmHg and /or diastolic BP 90 - 99 mmHg ) and without cardiovascular disease .