South African hypertension guideline 2011. The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy. The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. Beta-blocker/thiazide combination for treatment of hypertensive children: a randomized double-blind, placebo-controlled trial. Medical treatment of hypertension in Switzerland. The 2009 Swiss Hypertension Survey (SWISSHYPE). Combined low-dose medication and primary intervention over a 30-month period for sustained high blood pressure in childhood. The Dutch Renal Artery Stenosis Intervention Cooperative (DRASTIC) Study: rationale, design and inclusion data. Hypertension and Its Treatment in Postmenopausal Women: Baseline Data from the Women’s Health Initiative Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension Dogma Disputed: Can Aggressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous? Antihypertensive and renoprotective efficacy and safety of losartan. A long-term study in children with renal disorders. Central blood pressure measurements and antihypertensive therapy: a consensus document. Rationale and design of the Eplerenone combination Versus conventional Agents to Lower blood pressure on Urinary Antialbuminuric Treatment Effect (EVALUATE) trial: a double-blinded randomized placebo-controlled trial to evaluate the antialbuminuric effects of an aldosterone blocker in hypertensive p Effects of Losartan or Atenolol in Hypertensive Patients without Clinically Evident Vascular Disease: A Substudy of the LIFE Randomized Trial Effect of ramipril on ambulatory blood pressure and albuminuria in renal hypertension Pulse pressure as a predictor of stroke A Risk Score for Predicting Near-Term Incidence of Hypertension: The Framingham Heart Study Relationship of Antihypertensive Treatment Regimens and Change in Blood Pressure to Risk for Heart Failure in Hypertensive Patients Randomly Assigned to Doxazosin or Chlorthalidone: Further Analyses from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study: rationale, design, and methods. The LIFE Study Group. Antihypertensive and antiproteinuric efficacy of ramipril in children with chronic renal failure. A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of enalapril for children with hypertension. 2015 guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the management of hypertension. Long-term safety and efficacy of the selective aldosterone blocker eplerenone in patients with essential hypertension. The effect of treatment on mortality in "mild" hypertension: results of the hypertension detection and follow-up program. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. Low-dose erythropoietin is effective and safe in children on continuous ambulatory peritoneal dialysis Prognostic value of ambulatory blood pressure monitoring in refractory hypertension: a prospective study. The pharmacokinetics of irbesartan in hypertensive children and adolescents. Regression of left-ventricular hypertrophy in children and adolescents with hypertension during ramipril monotherapy. Ramipril in the treatment of hypertension and proteinuria in children with chronic kidney diseases. Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). [Detection of the optimal dose of spironolactone for the treatment of benign essential hypertension]. Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial Effects of monotherapy and combination therapy on blood pressure control and target organ damage: a randomized prospective intervention study in a large population of hypertensive patients. A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of lisinopril for children with hypertension.
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 OBJECTIVE To provide up date d , evidence -based recommendations for the therapy of hypertension in adults . OPTIONS For patients with hypertension , a number of antihypertensive agents may control blood pressure . R and omized trials evaluating first-line therapy with thiazides , beta-adrenergic antagonists , angiotensin-converting enzyme inhibitors , calcium channel blockers , alpha-blockers , central ly acting agents or angiotensin II receptor antagonists were review ed . OUTCOMES The health outcomes that were considered were changes in blood pressure , cardiovascular morbidity , and cardiovascular and /or all-cause mortality rates . Economic outcomes were not considered due to insufficient evidence . EVIDENCE MEDLINE was search ed for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension . Reference lists were scanned , experts were polled , and the personal files of the subgroup members and authors were used to identify other published studies . All relevant articles were review ed and appraised , using prespecified levels of evidence , by content experts and method ological experts . VALUES A high value was placed on the avoidance of cardiovascular morbidity and mortality . BENEFITS , HARMS AND COSTS Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension . In certain setting s , and for specific classes of drugs , blood-pressure lowering has been associated with reduced cardiovascular morbidity and /or mortality . RECOMMENDATIONS The present document contains detailed recommendations pertaining to treatment thresholds , target blood pressures , and choice of agents in various setting s in patients with hypertension . The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus , the amalgamation of the previous sections on treatment of hypertension in the young and old into one section , increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke . Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk , the presence and /or absence of target organ damage , and comorbidities . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group . Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation . Only those recommendations achieving high levels of consensus are reported here . These guidelines will continue to be up date d annually OBJECTIVE To provide up date d , evidence -based recommendations for the prevention and management of hypertension in adults . OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions , evidence was review ed from r and omized controlled trials and systematic review s of trials . Changes in cardiovascular morbidity and mortality were the primary outcomes of interest . However , for lifestyle interventions , blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field . For treatment of patients with kidney disease , the progression of kidney dysfunction was also accepted as a clinical ly relevant primary outcome . EVIDENCE A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to up date the 2006 Canadian Hypertension Education Program recommendations . In addition , reference lists were scanned and experts were contacted to identify additional published studies . All relevant articles were review ed and appraised independently by both content and method ological experts using prespecified levels of evidence . RECOMMENDATIONS Dietary lifestyle modifications for prevention of hypertension , in addition to a well-balanced diet , include a dietary sodium intake of less than 100 mmol/day . In hypertensive patients , the dietary sodium intake should be limited to 65 mmol/day to 100 mmol/day . Other lifestyle modifications for both normotensive and hypertensive patients include : performing 30 min to 60 min of aerobic exercise four to seven days per week ; maintaining a healthy body weight ( body mass index of 18.5 kg/m2 to 24.9 kg/m2 ) and waist circumference ( less than 102 cm in men and less than 88 cm in women ) ; limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women ; following a diet reduced in saturated fat and cholesterol , and one that emphasizes fruits , vegetables and low-fat dairy products , dietary and soluble fibre , whole grains and protein from plant sources ; and considering stress management in selected individuals with hypertension . For the pharmacological management of hypertension , treatment thresholds and targets should take into account each individual 's global atherosclerotic risk , target organ damage and any comorbid conditions : blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease . Most patients require more than one agent to achieve these blood pressure targets . In adults without compelling indications for other agents , initial therapy should include thiazide diuretics ; other agents appropriate for first-line therapy for diastolic and /or systolic hypertension include angiotensin-converting enzyme ( ACE ) inhibitors ( except in black patients ) , long-acting calcium channel blockers ( CCBs ) , angiotensin receptor blockers ( ARBs ) or beta-blockers ( in those younger than 60 years of age ) . First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs . Certain comorbid conditions provide compelling indications for first-line use of other agents : in patients with angina , recent myocardial infa rct ion , or heart failure , beta-blockers and ACE inhibitors are recommended as first-line therapy ; in patients with cerebrovascular disease , an ACE inhibitor plus diuretic combination is preferred ; in patients with nondiabetic chronic kidney disease , ACE inhibitors are recommended ; and in patients with diabetes mellitus , ACE inhibitors or ARBs ( or , in patients without albuminuria , thiazides or dihydropyridine CCBs ) are appropriate first-line therapies . All hypertensive patients with dyslipidemia should be treated using the thresholds , targets and agents outlined in the Canadian Cardiovascular Society position statement ( recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease ) . Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy . Once blood pressure is controlled , acetylsalicylic acid therapy should be considered . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence -Based Recommendations Task Force . All recommendations reported here achieved at least 95 % consensus . These guidelines will continue to be up date d annually Antihypertensive medications are used extensively in children despite a paucity of r and omized , placebo-controlled trials . This study was among the first r and omized , controlled pediatric antihypertensive medication trials , in which the combination drug bisoprolol fumarate/hydrochlorothiazide ( B/HT ) was compared with placebo . The study comprised a 2-week single-blind placebo screening period , a 6-week double-blind dose titration period , a 4-week double-blind dose maintenance period , and a 2-week double-blind dose-tapering period . One hundred and forty subjects were enrolled to achieve 94 r and omized subjects treated either with B/HT ( n=62 ) or placebo ( n=32 ) . B/HT induced significant reductions compared with placebo for average sitting systolic blood pressure ( SiSBP ) ( 9.3 vs. 4.9 mmHg , P<0.05 ) and sitting diastolic blood pressure ( SiDBP ) ( 7.2 vs. 2.7 mmHg , P<0.05 ) . The placebo-subtracted BP reductions were greater in younger children and those with more-severe baseline hypertension . The percentage of subjects with BP less than the 90th percentile at study completion was 45 % for B/HT and 34 % for placebo ( P = NS ) . Although the study demonstrated that B/HT  reduced BP safely compared with placebo , the large placebo effect and failure of most subjects to achieve target BP control make it uncertain whether B/HT is appropriate first-line therapy for pediatric hypertension , particularly in adolescents with mild-to-moderate BP elevation OBJECTIVES Despite a broad and efficient pharmacological antihypertensive armamentarium , blood pressure ( BP ) control is suboptimal and heterogeneous throughout Europe . Recent representative data from Switzerl and are limited . The goal of the present survey was therefore to assess the actual control rate of high BP in Switzerl and in accordance with current guidelines . The influence of risk factors , target organ damage and medication on BP levels and control was also evaluated . METHODS A cross-sectional visit-based survey of ambulatory hypertensive patients was performed in 2009 in Switzerl and . 281 r and omly selected physicians provided data on 5 consecutive hypertensive patients attending their practice s for BP follow-up . Data were anonymously collected on demographics , comorbidities and current medication , and BP was recorded . Subsequent modification of pharmacological antihypertensive therapy was assessed . RESULTS Data from 1376 patients were available . Mean age was 65 ± 12 years , 53.9 % were male subjects . 26.4 % had complicated hypertension . Overall , BP control ( < 140/90 mm Hg for uncomplicated and < 130/80 mm Hg for complicated hypertension ) was achieved in 48.9 % . Compared to patients with complicated hypertension , BP control was better in patients with uncomplicated hypertension ( 59.4 % vs. 19.2 % , p < 0.001 ) . As a monotherapy the most prescribed drug class were angiotensin receptor blockers ( ARB , 41 % ) , followed by angiotensin converting enzyme ( ACE ) inhibitors ( 21.5 % ) , betablockers ( 20.8 % ) and calcium channel blockers ( CCB , 10.8 % ) . The most prescribed drug combinations were ARB + diuretic ( 30.1 % ) and ACE inhibitors + diuretic ( 15.3 % ) . 46 % were receiving a fixed drug combination . In only 32.7 % of patients with uncontrolled hypertension was a change in drug therapy made . CONCLUSION This representative survey on treated adult hypertensive patients shows that , compared to earlier reports , the control rate of hypertension has improved in Switzerl and for uncomplicated but not for complicated , particularly diabetes-associated hypertension . ARBs and ACE inhibitors are the most prescribed antihypertensive drugs for monotherapy , whereas diuretics and ARBs were the most used for combination therapy Studies of the pathobiologic consequences of high blood pressure in childhood , as well as those following blood pressure levels into young adulthood , indicate that early intervention in the natural history of essential hypertension is warranted . In an exploratory study of the concept , 95 children out of 1604 ( aged 8 to 18 years ) , who persistently scored higher than the 90th percentile for blood pressure over a 4-month period , considering the race , sex , and height of the children , were studied . Five series of replicate measurements with 30 total observations were obtained . Children with evidence of secondary hypertension were excluded . The study children were r and omly divided into treatment ( n = 48 ) and high-comparison ( n = 47 ) groups . Treatment consisted of low-dose combined drug therapy ( propranolol and chlorthalidone ) with an educational program directed towards hypertension and dietary and exercise modification . Monthly follow-up was continued for 30 months . Significant systolic ( -3.59 mm Hg ) and diastolic ( -1.73 mm Hg ) changes were noted up to 30 months ( p less than 0.05 ) with minimal side effects . Furthermore , analyses suggested that the blood pressure change , at least in the first month , was mostly attributable to drug therapy . Moreover , the mechanism of blood pressure change appeared to be race-specific , with whites having pulse rate changes and blacks having significant weight changes , which were associated with blood pressure change . This trial shows further research is warranted to determine optimum approaches for early treatment of essential hypertension to prevent future hypertensive disease RATIONALE Renal artery stenosis may lead to renovascular hypertension , risking multiple organ damage including damage to the contralateral kidney . Progression of stenosis may impair the function of the affected kidney . It is important to identify individuals with this disease among hypertensive patients . The first aim of the Dutch Renal Artery Stenosis Intervention Cooperative ( DRASTIC ) study is to assess the prevalence of renal artery stenosis in patients with well-defined forms of drug-resistant hypertension , and to determine the predictive value of clinical characteristics and diagnostic tests in these pre-selected patients . With regard to treatment , the effect of renal angioplasty on hypertension is disappointing in atherosclerotic stenosis and technical failure frequently occurs . Therefore , the second aim is to compare the effects of balloon angioplasty and antihypertensive medication on blood pressure in patients with atherosclerotic renal artery stenosis . DESIGN HYPERTENSIVE patients receiving st and ard antihypertensive medication in whom diastolic blood pressure remained > or = 95 mmHg during three consecutive visits to the outpatient clinic underwent full diagnostic work-up , including renal arteriography . The prevalence of renal artery stenosis in this well-defined patient group was then established , and the predictive value of the various diagnostic tests was assessed . Patients with an atherosclerotic renal artery stenosis of > or = 50 % were then r and omly assigned to balloon angioplasty or to treatment with antihypertensive drugs . After 1 year of intensive follow-up of blood pressure and renal function , re-arteriography was performed . CONCLUSION In total , 1205 patients have been included in the study , about 500 have received diagnostic work-up , and it is expected that 100 patients will be r and omly assigned for renal angioplasty or medical treatment Little is known about the patterns of treatment and adequacy of blood pressure control in older women . The Women ’s Health Initiative , a 40-center national study of risk factors and prevention of heart disease , breast and colorectal cancer , and osteoporosis in postmenopausal women , provides a unique opportunity to examine these issues in the largest , multiethnic , best-characterized such cohort . Baseline data from the initial 98 705 women , aged 50 to 79 years , enrolled were analyzed to relate prevalence , treatment , and control of hypertension to demographic , clinical , and risk-factor covariates , and logistic regression analyses were performed to estimate odds ratios after adjusting for multiple potential confounders . Overall , 37.8 % of the women had hypertension , which is defined as systolic blood pressure ≥140 mm Hg and /or diastolic blood pressure ≥90 mm Hg or being on medication for high blood pressure ; 64.3 % were treated with drugs , and blood pressure was controlled in only 36.1 % of the hypertensive women , with lower rates of control in the oldest group . After adjustment for multiple covariates , current hormone users had higher prevalence than did nonusers ( odds ratio 1.25 ) . Hypertensive women had more comorbid conditions than did nonhypertensive women , and women with comorbidities were more likely to be treated pharmacologically . Diuretics were used by 44.3 % of hypertensives either as monotherapy or in combination with other drug classes . As monotherapy ,  calcium channel blockers were used in 16 % , angiotensin-converting enzyme inhibitors in 14 % , & bgr;-blockers in 9 % , and diuretics in 14 % of the hypertensive women . Diuretics as monotherapy were associated with better blood pressure control than any of the other drug classes as monotherapy . In conclusion , hypertension in older women is not being treated aggressively enough because a large proportion , especially those most at risk for stroke and heart disease by virtue of age , does not have sufficient blood pressure control Isolated systolic hypertension is an important risk factor for cardiovascular disease and results primarily from elastic artery stiffening . Although various drug therapies are used to lower peripheral blood pressure ( BP ) in patients with isolated systolic hypertension , the effects of the 4 major classes of antihypertensive agents on central BP , pulse pressure ( PP ) amplification , and arterial stiffness in this condition are not clear . Fifty-nine patients over the age of 60 years with untreated isolated systolic hypertension ( systolic BP ≥140 mm Hg and diastolic BP ≤90 mm Hg ) were r and omly assigned to receive 1 of the following 4 antihypertensive agents : perindopril , atenolol , lercanidipine , or bendrofluazide  . BP was measured using a mercury sphygmomanometer , and augmentation index and carotid-femoral ( aortic ) pulse wave velocity were measured at baseline , after 2 weeks of placebo therapy , and at the end of 10 weeks of active therapy . Peripheral systolic BP and peripheral PP were reduced similarly after treatment with all 4 classes of drug . However , central PP was only reduced significantly by perindopril , lercanidipine , and bendrofluazide , whereas atenolol had no effect . Lercanidipine reduced the augmentation index , whereas atenolol increased it . Aortic pulse wave velocity was not changed by any of the drugs . In summary , despite similar reductions in peripheral systolic and PPs with the 4 classes of drug , changes in central pressure and augmentation index varied . Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension , the choice of therapy may be influenced by these findings in the future 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 BACKGROUND Hypertension is a major risk factor for progressive renal failure . We assessed the long term efficacy and safety of losartan in lowering blood pressure ( BP ) and in preserving renal function in hypertensive children with chronic renal disorders . METHODS Losartan was used in 45 consecutive hypertensive children with chronic renal parenchymal disorders and mean glomerular filtration rate ( GFR ) 99.4 mL/min/1.73 m(2 ) . Of the children , 21 had hypertension alone ( H ) and 24 had both hypertension and proteinuria ( H+P ) . Assessment was done at baseline and at preselected time points : visit I , < 0.25 years ; visit II , > /=0.25 and < 0.5 year;visit III , 0.5 to 1.0 year ; and visit IV > 1 year . Both BP control and GFR were the principal outcome measures , and proteinuria was a secondary outcome measure . RESULTS The mean age was 12.85 years and follow-up was 2.42 years ( visit IV ) . Compared with baseline the systolic , diastolic , and mean arterial BP ( MABP ) fell by 9 to 12 mm Hg ( all P < .01 ) in visit I. Diastolic BP and MABP remained significantly lower in all visits ( P < .05 to .001 ) , whereas systolic BP was not statistically lower in visit II . In visit IV the proportion of normotensive children increased significantly compared with baseline ( P < .03 for systolic BP , P < .0004 for diastolic BP ) . In the H+P subgroup , optimal reduction in proteinuria ranging from 66 % to 71 % occurred in visits II to IV ( all P < .01 ) . Mean GFR declined at a rate of 9.3 mL/min/1.73 m(2 ) /year before starting losartan , and 1.4 mL/min/1.73 m(2 ) /year subsequently ( P = NS ) . On long term follow-up , GFR fell by 15.9 mL/min/1.73 m(2 ) in the H subgroup and by 5.5 mL/min/1.73 m(2 ) in the H+P subgroup ( P = NS ) . There was no correlation between BP measures and GFR or between the magnitude of BP lowering and proteinuria . Adverse effects ( one serious ) led to discontinuation of losartan in five children ( 11 % ) . CONCLUSIONS Losartan therapy was associated with prolonged and sustained antihypertensive and renoprotective benefits in children with a variety of chronic renal parenchymal disorders . Such benefit may be more pronounced in children with combined hypertension and proteinuria . The agent was well tolerated in the majority of the children The 2003 European Society of Hypertension/European Society of Cardiology guidelines for the management of arterial hypertension1 included 2 important novel recommendations : assessment of the total cardiovascular risk should be taken into account in the management of the hypertensive patient , and quantification of risk should include sub clinical target organ damage . These guidelines acknowledged that central ( aortic ) blood pressure ( BP ) , which is the pressure exerted on the heart and brain , may be different from the pressure that is measured at the arm . They also recognized that central pressure may be predictive of outcome in specific population s2 and differently affected by antihypertensive drugs . However , although these guidelines accepted that central augmentation index and pulse wave velocity may be important as measures of sub clinical organ damage , they also stressed the need for prospect i ve trials to establish their predictive values given that such studies were lacking at that time ( 2003 ) . After publication of these guidelines , additional data have strengthened the pathophysiological importance of central BP . Clinical studies have indicated that central BP may have predictive value independent of the corresponding peripheral ( brachial ) BP . More importantly , recent large-scale trials have shown that central hemodynamics may provide a worthwhile treatment target . In addition , central hemodynamics can now be reliably assessed noninvasively with a number of devices . Accordingly , because arterial stiffening and central hemodynamics are markers and manifestations of organ damage , the pertinent key question is whether the balance of evidence on their importance and issues related to clinical practice allows for implementation in patient management . Central ( aortic and carotid ) pressures are pathophysiologically more relevant than peripheral pressures for the pathogenesis of cardiovascular disease.3,4 It is aortic systolic pressure that the left ventricle encounters during systole ( afterload ) , and the aortic pressure during diastole is a determinant of coronary perfusion . Furthermore , the distending pressure in the Although inhibitors of the renin – angiotensin system are effective as first-line antihypertensive drugs in hypertensive patients with chronic kidney disease , they can not completely prevent the progression of renal injury . Many animal studies , including our own , and a few human studies suggest that mineralocorticoid receptor blockade could inhibit the ongoing renal damage in chronic kidney disease . Thus , we design ed this double-blinded , r and omized , placebo-controlled trial to evaluate the antialbuminuric effect of a low dose ( 50 mg day−1 ) of the mineralocorticoid receptor antagonist eplerenone . The study subjects will include 340 hypertensive patients ( blood pressure : 130–180/80–100 mm Hg ) with albuminuria ( urinary albumin/creatinine ratio : 30–600 mg g−1 in the first morning void urine ) , who are treated with an inhibitor of the renin – angiotensin system . Other classes of antihypertensive drugs may be added as needed to achieve the target blood pressure ( < 130/80 mm Hg ) . The primary study end point is the change in the urinary albumin/creatinine ratio after a 1-year study period . This trial is expected to show whether a low dose of mineralocorticoid receptor antagonists can exert an antialbuminuric effect in patients with chronic kidney disease Context The Losartan Intervention for Endpoint reduction in hypertension ( LIFE ) trial showed that losartan-based treatment improved cardiovascular outcomes more than atenolol-based treatment in patients with hypertension and left ventricular hypertrophy . Because the study sample was heterogeneous , clinicians wondered about effects in the lower-risk participants . Contribution This analysis of lower-risk participants without known vascular disease showed that both losartan and atenolol reduced blood pressure similarly . Cardiovascular events , particularly strokes , and new-onset diabetes occurred less frequently with losartan than with atenolol . Implication s Patients with hypertension and left ventricular hypertrophy but no known vascular disease benefit more from losartan than atenolol . The Editors Benefits of lowering blood pressure by using antihypertensive treatment are well established , especially in high-risk individuals ( 1 ) . However , treated hypertensive patients still have more cardiovascular events than matched normotensive adults . Possible reasons are failure to normalize blood pressure ; adverse effects of reninangiotensin system overactivity ; and residual target organ damage , such as left ventricular hypertrophy ( LVH ) . Recent evidence has supported the hypothesis that reversal of LVH has prognostic benefit independent of blood pressure lowering ( 2 , 3 ) . Reducing cardiovascular event rates by reninangiotensin system inhibition was initially shown by a comparison of the angiotensin-converting enzyme inhibitor ramipril with placebo in patients with clinical ly evident vascular disease in the Heart Outcomes Prevention Evaluation ( HOPE ) trial ( 4 ) . Subsequently , the Losartan Intervention for Endpoint reduction in hypertension ( LIFE ) study ( 5 ) showed that the angiotensin II AT1-receptor antagonist losartan reduced cardiovascular morbidity and mortality compared with active antihypertensive therapy with the -blocker atenolol ( 6 - 8 ) . This study also linked this benefit to hypertrophy regression ( 9 ) . The LIFE trial enrolled hypertensive patients with electrocardiogram-defined LVH and included patients at especially high risk because of clinical ly evident vascular disease ( 5 , 10 ) . Thus , antagonism of potentially toxic angiotensin II effects has been shown to reduce cardiovascular events in trials conducted wholly or partly in patients with preexisting atherosclerotic disease , but whether this is also true in most hypertensive patients without clinical ly evident vascular disease has not been extensively analyzed . Accordingly , we performed a subgroup analysis in the LIFE study to determine whether angiotensin II AT1-receptor antagonism with losartan reduces cardiovascular morbidity and mortality , compared with active therapy with established -blockerbased therapy , in hypertensive participants with electrocardiogram-defined LVH who did not have clinical ly evident coronary , cerebral , or peripheral arterial disease at the time of enrollment . Methods Study Design The LIFE study is an investigator-initiated , multinational , multicenter , double-blind , double-dummy , r and omized , active-controlled , parallel-group study . The primary objective was to evaluate the long-term effects of once-daily losartan-based antihypertensive therapy compared with atenolol-based antihypertensive therapy in patients with hypertension and electrocardiogram-defined LVH on cardiovascular morbidity and mortality . The complete LIFE study protocol , with study design , organization , clinical measures , end point definitions , choice of comparative agent , statistical considerations , recruitment details , patient characteristics , and main outcomes , has been published ( 5 - 9 , 11 ) . Patients gave informed consent under protocol s approved by the concerned ethics committees ; an independent data and safety monitoring board oversaw the trial . Target Population , Treatment , and Measurement of LVH A total of 9193 patients 55 to 80 years of age with previously treated or untreated hypertension and electrocardiogram-defined LVH ( 5 ) were r and omly assigned after 1 to 2 weeks of placebo use to losartan or atenolol if trough sitting blood pressures were 160 to 200/95 to 115 mm Hg . The present analysis included all LIFE participants , with particular focus on the subgroup without previous diagnoses of coronary , cerebral , or peripheral vascular disease by either self-report or report of treating physicians . Patients in the present subgroup analysis were enrolled from 26 June 1995 through 2 May 1997 . A total of 6886 r and omly assigned patients from centers in Denmark ( 1030 ) , Finl and ( 1237 ) , Icel and ( 96 ) , Norway ( 1112 ) , Sweden ( 1634 ) , the United Kingdom660 , and the United States ( 1067 ) did not have clinical ly evident vascular disease . Patients were followed for 4 years or longer with regular visits and upward titration of the medication dose to reach the goal blood pressure of less than 140/90 mm Hg ( 5 , 10 ) . Electrocardiogram Coding and LVH Criteria All screening , baseline , annual , and end point electrocardiograms were evaluated at one core reading center . Patients were accepted into the study if a screening electrocardiogram fulfilled the LVH criteria ( 5 , 10 ) . On the basis of evidence that combined electrocardiogram assessment of QRS voltage and duration enhances sensitivity for LVH detection at acceptable levels of specificity ( 12 , 13 ) , the product of QRS duration multiplied by Cornell voltage ( with sex adjustment of 8 mm in women [ 14 ] and a partition value of > 2440 mm ms ) was chosen to recognize hypertrophy . Because of evidence that the sex adjustment was excessive and that patients with LVH by traditional electrocardiogram criteria were being missed , two changes were made for patients recruited after 30 April 1996 :  Sex adjustment of Cornell voltage was reduced to 6 mm , and SokolowLyon voltage greater than 38 mm was accepted as an alternative criterion ( 10 ) . As previously described , it was estimated ( and later confirmed with electrocardiography in a sub study of 960 patients [ 15 ] ) that more than 70 % of patients who met LIFE electrocardiogram criteria from one screening electrocardiogram had anatomic LVH . Outcome Measures The primary end point of cardiovascular morbidity and death was a composite of the first occurrence of cardiovascular death , stroke , or clinical ly evident myocardial infa rct ion . Other prespecified outcomes were total mortality , angina pectoris or heart failure requiring hospitalization , coronary or peripheral revascularization procedures , resuscitated cardiac arrest , and new-onset diabetes . An end point committee , blinded to therapy , separately review ed clinical records for all events reported by clinical centers to determine whether they met protocol end point criteria . The Electrocardiogram Core Center evaluated regression of hypertrophy on the electrocardiogram . New-onset diabetes , defined according to 1985 World Health Organization criteria ( 16 ) , was reported by investigators on the basis of fasting hyperglycemia on two occasions or a positive result on a glucose tolerance test . Sitting blood pressure was measured at trough ( that is , 24 hours after dose ; range , 22 to 26 hours ) . Adverse experiences , classified as drug-related or nondrug-related , as well as serious or nonserious , according to International Conference on Harmonization guidelines for good clinical practice , were recorded by investigators using open-ended worksheets at every visit . The LIFE study ran its full course , and end point follow-up was stopped at midnight local time , 16 September 2001 , which was the time-point for the last end point to count . After the stopping date , patients had a follow-up clinic visit or at least a check of vital status within 6 weeks . Statistical Analysis Allocation numbers were associated with treatment groups by using a computer-generated allocation schedule ; patients were considered r and omly assigned when they received an allocation number . Blinding was maintained in a double-dummy fashion : All patients received both blinded losartan and blinded atenolol : One tablet consisted of active treatment and one tablet consisted of placebo . All cardiovascular end points were analyzed by using the intention-to-treat approach ; all r and omly assigned patients were included in their assigned treatment group , and all available follow-up information was included from r and omization through the end of the study . Only events confirmed by the end point committee were analyzed . Patients with several end points were counted as having had an event in all relevant end point analyses ; however , only the first event in a specific category counted in individual analyses . Safety analyses included all r and omly assigned patients from r and omization through 16 September 2001 or permanent discontinuation of therapy with blinded study medication , whichever came first . Differences between treatment groups in rates of clinical events were assessed by Cox regression models with degree of LVH ( using Cornell voltage duration product and SokolowLyon voltage as continuous variables ) and the Framingham risk score ( 17 ) defined by baseline characteristics as covariates . This adjusted analysis was chosen a priori as primary to account for differences in key risk predictors at baseline . Secondary unadjusted analyses were performed to vali date the adjusted results . Interaction between treatment and vascular disease status was tested by including indicators for these factors and the product of these indicators in a Cox regression model . Treatment effects were measured by hazard ratios ( relative risks ) , and their 95 % CIs were calculated from Cox regression models . The risk reduction for losartan versus atenolol was calculated as : 100 ( 1 relative risk ) . Event rates over time are presented as KaplanMeier curves . Adjustment for blood pressure was based on Cox regression models with blood pressure values throughout the trial as time-varying covariates . Differences between groups in changes in electrocardiogram Abstract Inhibition of the angiotensin-converting enzyme ( ACE ) exerts a renoprotective effect in adult patients with chronic kidney disease . We evaluated prospect ively changes in blood pressure ( BP ) , protein excretion and renal function after administration of the long-acting ACE inhibitor ramipril as monotherapy during 6 months in 14 moderately hypertensive children aged 5–18 years with various nephropathies . Four patients initially had a decreased glomerular filtration rate ( GFR below 60 ml/min/1.73 m2 ) . BP was evaluated by ambulatory 24-h monitoring . After 2 weeks of treatment by oral ramipril ( 1.5 mg/m2 once daily ) , mean values of systolic and diastolic 24-h ambulatory BP fell by more than 5 mmHg in nine patients . In eight patients the dose was doubled . At the end of the study systolic BP was below the 95th percentile in 9 and diastolic BP in 13 patients . The initially reduced nocturnal dip increased significantly . Of 11 patients with an increased albumin excretion ( median 1.3 g/g creatinine ) , 6 responded to ramipril by a median reduction of 78 % ( range 24–83 % ) , whilst in 5 albuminuria increased ( median + 19 % ) . GFR was well preserved and no other adverse effects from the drug were noted . The study demonstrates that ramipril is an efficacious antihypertensive agent in children with renal hypertension . It is well tolerated , even in mild renal insufficiency . In addition , the drug has a persistent antiproteinuric action in about half of the patients contributing to conserve renal function 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 ] Context Identifying adults with a high probability of developing high blood pressure  could help target nonpharmacologic measures to prevent hypertension . Contribution Using data from the Framingham cohort study , the investigators devised a simple risk score with good performance characteristics that identified adults without diabetes who had low ( < 5 % ) , medium ( 5 % to 10 % ) , or high ( > 10 % ) probability of developing hypertension within 4 years . The risk score included points for age , sex , systolic and diastolic blood pressure , body mass index , parental hypertension , and cigarette smoking . Implication If this risk score is vali date d in additional patient population s , it could help clinicians identify high-risk patients with prehypertension . The Editors In 2003 , the Seventh Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure created a prehypertension category for persons with blood pressures ranging from 120 to 139 mm Hg ( systolic ) or from 80 to 89 mm Hg ( diastolic ) . The committee strongly advocated lifestyle and behavioral modification for individuals with prehypertension ( 1 ) . This new recommendation was based largely on epidemiologic evidence that individuals with nonoptimal blood pressure ( > 120/80 mm Hg ) are at increased risk for progression to overt hypertension ( 1 , 2 ) and that cardiovascular disease risk increases in a grade d fashion beginning at a blood pressure of 115/75 mm Hg , well within the normal range ( 1 , 3 ) . However , this new categorization scheme result ed in 70 million people being considered prehypertensive , a situation that poses a challenge for both physicians and patients . Recent clinical trials have focused on the treatment of persons with prehypertension to determine whether hypertension onset can be delayed . A recent clinical trial demonstrated that individuals with blood pressures of 130 to 139 mm Hg ( systolic ) and 80 to 85 mm Hg ( diastolic ) who were treated for 2 years with c and esartan , an angiotensin II receptor blocker , had a 15 % reduction in the incidence of hypertension over 4 years compared with patients r and omly assigned to placebo ( 4 ) . A clinical trial of lifestyle modification among overweight individuals without hypertension demonstrated that a low-salt diet and regular physical exercise reduced hypertension incidence in the short term and several years after the clinical trial ( 5 , 6 ) . Although these investigations have demonstrated the feasibility and efficacy of preventing hypertension , a strategy that targets all individuals with prehypertension is likely to be associated with substantial medical and economic re sources . Evidence suggests that the risk for progression to hypertension depends on clinical factors , such as baseline blood pressure , age , and body mass index ( 2 ) . An individualized approach of risk stratification and targeted treatment of the nonhypertensive persons who are at greatest risk for progression may be more desirable . We developed a simple risk score that can be used in a physician 's office to estimate the probability that an individual will develop hypertension over 1 to 4 years and to identify the persons who are at the highest risk for hypertension . Such high-risk individuals will probably derive the maximal benefit from nonpharmacologic ( lifestyle-related ) and pharmacologic interventions aim ed at preventing hypertension . Thus , we believe that knowledge of the risk for hypertension will aid patient education and counseling , and it will assist clinical decision making and design of future interventional studies . Supplement . Risk Calculator Methods Sample The Framingham Heart Study is a community-based , prospect i ve cohort study that began in 1948 with the enrollment of 5209 men and women ( whom we refer to as the original cohort ) ( 7 ) . In 1971 , 5124 men and women were enrolled into the Framingham Offspring Study cohort , which included the children of the original cohort and the spouses of the children . Participant examinations for the offspring cohort occurred approximately every 4 years . The design and methods of the Framingham Offspring Study are described elsewhere ( 8) . For our investigation , offspring cohort participants were eligible if they attended 2 consecutive examinations between the second ( 1979 to 1983 ) and seventh examinations ( 1998 to 2001 ) and if both of their parents were in the original cohort ( 8813 person-examinations ) ( Figure 1 ) . Participants were eligible for inclusion at more than 1 heart study examination cycle if they reached the next examination without meeting any exclusion criteria . We excluded participants who had prevalent hypertension ( n= 2542 ) , prevalent cardiovascular disease ( n= 233 ) , or serum creatinine values greater than 177 mol/L ( 2 mg/dL ) ( n= 4 ) ; were younger than age 20 years or older than age 69 years ( n= 77 ) ; had missing covariates ( n= 46 ) ; or had prevalent diabetes mellitus ( n= 97 ) . We excluded persons with diabetes from our analysis because lower cut-points of systolic and diastolic pressure define the target blood pressure goal in these individuals ( 1 ) . After we applied the exclusion criteria , 5814 person-examinations from 1717 unique individuals ( 54 % women ) remained eligible for analysis . All participants provided written informed consent , and the study protocol was approved by the Boston University Medical Center Institutional Review Board . Figure 1 . Number of participants available for evaluation of hypertension incidence at baseline examination and number of participants with incident hypertension at follow-up examination . Assessment of Risk Factors At each Framingham Heart Study examination , participants underwent a medical history and physical examination , anthropometric measurements , and laboratory assessment of vascular risk factors . Blood pressure  was measured on the left arm of seated participants by a physician using a mercury-column sphygmomanometer , a cuff of the appropriate size , and a st and ardized protocol . Participants had rested in a chair for 5 minutes before blood pressure was measured , and the average of 2 readings obtained by a physician was considered the examination blood pressure . Systolic blood pressure of 140 mm Hg or higher , diastolic blood pressure of 90 mm Hg or higher , or use of blood pressurelowering medications defined hypertension . Current smoking was defined as regular cigarette smoking in the year before the examination . Body mass index was calculated as body weight ( in kilograms ) divided by the square of height ( in meters ) . Consumption of more than 7 drinks per week in women and more than 14 drinks per week in men defined moderate alcohol intake ( 1 ) . A fasting blood glucose level of 7.0 mmol/L ( 126 mg/dL ) or more , use of hypoglycemic medications , or both defined diabetes mellitus . Parental hypertension was defined as documented maternal and paternal hypertension at or before the baseline examination at which offspring were eligible for our investigation . Parental hypertension status was ascertained on the basis of blood pressure readings of the original cohort participants by using serial data from examination cycle 3 ( 1952 to 1956 ) through examination 27 ( 2002 to 2004 ) . Prevalent cardiovascular disease was defined as presence of coronary heart disease , stroke , transient ischemic attack , intermittent claudication , or heart failure at any examination . The criteria for diagnosis of these cardiovascular events are described elsewhere ( 9 ) . Statistical Analysis We measured hypertension incidence during the interval between offspring cohort examinations ( median , 3.8 years ) . If a person remained without hypertension at the follow-up examination , he or she remained eligible to contribute to the next 4-year period . A Weibull regression model for interval-censored data ( 10 ) was used because only the interval during which new hypertension developed was available ; the exact date of onset of hypertension between 2 Framingham Heart Study examinations could not be determined . Significant predictors of hypertension incidence were identified by entering c and i date risk factors ( age , sex , body weight , body mass index , physical activity index , diabetes , systolic blood pressure , diastolic blood pressure , moderate alcohol intake , current smoking , and parental occurrence of hypertension [ modeled as 0 , 1 , or 2 parents with hypertension ] ) into a stepwise model . These risk factors have been associated with hypertension in other studies ( 1 ) . Because diastolic blood pressure decreases with age ( 11 ) , we evaluated an interaction term for diastolic blood pressure by age , along with the other c and i date risk factors . We also tested the following additional interaction terms in multivariable models : diastolic blood pressure by sex , systolic blood pressure by sex , body mass index by smoking , parental hypertension by age , parental hypertension by sex , and parental hypertension by body mass index . We developed a risk prediction score from -coefficients for variables associated with hypertension incidence in multivariable Weibull regression models by using methods described elsewhere ( 12 ) . Continuous variables were divided into categories to facilitate risk estimation : Age was divided into 10-year groups ; systolic blood pressure was divided into 5 mm Hg categories beginning with 110 mm Hg and ending with 139 mm Hg ; and diastolic blood pressure was divided into 5 mm Hg categories beginning with 70 mm Hg and ending with 89 mm Hg . Body mass index was classified into 3 levels : less than 25 kg/m2 ( normal ) , 25 to less than 30 kg/m2 ( overweight ) , and 30 kg/m2 or more ( obesity ) . We derived 1- , 2- and 4-year rates of hypertension incidence directly from the Weibull model ( Appendix ) . We chose to assess 4-year risk because examination cycles in the Framingham Offspring Study occurred approximately every 4 years , and we were interested in assessing a short-term risk score for hypertension . We present 1- and 2-year risks for hypertension because we believe that these short-term risk Context Previously published results of this r and omized , double-blind trial showed that hypertensive patients treated with doxazosin rather than chlorthalidone more often developed heart failure . Did differences in blood pressure control or treatment with other drugs explain these findings ? Contribution This analysis shows that the slightly worse blood pressure control achieved with doxazosin did not explain higher risks for heart failure . Risks with doxazosin versus chlorthalidone were highest among patients who received monotherapy ( relative risk , 3.10 ) and lowest among patients who received stepped care with additional drugs ( relative risk , 1.42 ) . Implication s Increased risks for heart failure with doxazosin versus chlorthalidone are attenuated but not eliminated when additional antihypertensive drugs are used . The Editors The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , multicenter clinical trial including 42 418 participants at 623 clinical sites , is design ed to determine whether treatment begun with a calcium-channel blocker ( amlodipine ) , an angiotensin-converting enzyme inhibitor ( lisinopril ) , or an -adrenergic blocker ( doxazosin ) compared to treatment with a diuretic ( chlorthalidone ) reduces the incidence of fatal coronary heart disease or nonfatal myocardial infa rct ion in high-risk patients with hypertension ( 1 ) . Secondary end points are all-cause mortality , stroke , and other cardiovascular events . A lipid-lowering trial in a subset of 10 356 participants is design ed to determine whether decreasing cholesterol levels with a hydroxymethyl glutamyl coenzyme A reductase inhibitor ( pravastatin ) compared with usual care reduces all-cause mortality in older , moderately hypercholesterolemic patients . In January 2000 , the doxazosin arm of the trial was discontinued ( 2 ) because major cardiovascular disease ( relative risk , 1.25 [ 95 % CI , 1.17 to 1.33 ] ; P < 0.001 ) , especially heart failure ( relative risk , 2.04 [ 95 % CI , 1.79 to 2.32 ] ; P < 0.001 ) , was significantly increased compared with the chlorthalidone arm . Equally important , a low probability existed that doxazosin would show benefit over chlorthalidone for the primary end point by the scheduled study end , given the lack of difference ( relative risk , 1.02 [ 95 % CI , 0.90 to 1.17 ] ; P > 0.2 ] at that time . These intention-to-treat analyses compared patients assigned to chlorthalidone with patients assigned to doxazosin . In this article , we analyze how treatment changes may have affected the comparison of doxazosin with chlorthalidone in terms of heart failure . Our major objectives are to ascertain to what extent the relative risk with doxazosin versus chlorthalidone depends on 1 ) whether the assigned drugs were used as monotherapy or in combination with other agents and 2 ) the difference in decreases in systolic and diastolic blood pressure . Methods Study Design The rationale and design of ALLHAT are described in detail elsewhere ( 1 ) . In brief , eligible participants were men and women 55 years of age or older who had systolic or diastolic hypertension ( 140/90 mm Hg or hypertension controlled with medication ) plus at least one additional risk factor for coronary heart disease events . The risk factors included previous ( > 6 months ) myocardial infa rct ion or stroke , left ventricular hypertrophy on electrocardiography or echocardiography , history of type 2 diabetes , current cigarette smoking , and a low high-density lipoprotein cholesterol level . Persons with a history of hospitalized or treated symptomatic heart failure or a known ejection fraction less than 0.35 were excluded . Unless the drug regimen required tapering for safety , participants who had been taking antihypertensive medications continued to do so until the day of r and omization , at which point they stopped taking all previous medications . On the day after r and omization , treatment with the study drug was initiated . Enrollment occurred from February 1994 through January 1998 . The original reported number of 42 448 participants and 625 sites changed because 30 patients with poor documentation of informed consent were excluded ( 2 ) . Participants were assigned by a computer-generated r and omization schedule in a ratio of 1.7:1 to receive chlorthalidone or doxazosin . R and omization was stratified by center and blocked over time to maintain the ratio . All participants gave written informed consent , and all centers obtained institutional review board approval . Ascertainment of Outcomes At each clinic visit , occurrence of study end points was assessed by the clinical investigator . A hospital discharge summary was required for each hospitalized study outcome , and a death certificate was required for each death . ALLHAT defined symptomatic heart failure as clear-cut signs or symptoms of left or right ventricular dysfunction that can not be attributed to other causes . A patient had to have at least one symptom ( paroxysmal nocturnal dyspnea , dyspnea at rest , New York Heart Association class III dyspnea or other symptoms [ on less than ordinary exertion ] , or orthopnea ) and one sign ( rales , ankle edema , tachycardia , cardiomegaly or characteristic pulmonary pattern on chest radiography , S3 gallop , or jugular venous distention ) ( 3 ) . Symptoms and signs were determined by the clinic investigator through patient history , chart review , or consultation with the treating physician , but such data were not collected central ly . A one-time sample of 24 hospitalized or fatal heart failure events was review ed in a blinded manner by the ALLHAT Endpoints Subcommittee ; 20 of 24 ( 83 % ) were deemed to have complete data for a definitive diagnosis . Of the 20 cases , the agreement rate between the subcommittee and the clinic investigators was 90 % ( 18 of 20 ) and similar in both treatment groups . Details on the validity of diagnosis of heart failure will be provided in a future report . Measurement and Treatment of Blood Pressure The ALLHAT protocol specified a stepped-care treatment program for hypertension . Trained observers using st and ardized techniques measured blood pressures during the trial ( 1 , 2 ) . All blood pressures were calculated as the average of two measurements obtained with a 30-second interval between them . The blood pressure goal in all four study arms was less than 140/90 mm Hg . This level was to be achieved with the lowest possible dose of blinded first-line drug , with addition of second- and third-line open-label therapy as needed after reaching the maximal dose of first-line drug . Chlorthalidone and doxazosin were to be taken once daily in the morning . By design , doses were selected to achieve equivalent blood pressure control in the treatment groups . The first , second , and third dosage levels were 12.5 mg/d , 12.5 mg/d ( sham titration ) , and 25 mg/d , respectively , for chlorthalidone and 2 mg/d , 4 mg/d , and 8 mg/d for doxazosin . Double-blinded 1-mg and 12.5-mg doses of doxazosin and chlorthalidone , respectively , were used for the first week to minimize the frequency of postural hypotension associated with doxazosin . The identity of drugs was masked at each dosage level , but dosage level was not . After r and omization , patients were seen for dose titration as needed at 1 and 3 months per the protocol , but they could return more often until target blood pressure was reached . Subsequently , required visits occurred at 3-month intervals during the first year and at 4-month intervals thereafter . Open-label second-step drugs were added as needed and tolerated . These agents were reserpine ( 0.05 to 0.2 mg/d ) , clonidine ( 0.1 to 0.3 mg twice daily ) , and atenolol ( 25 to 100 mg/d ) . The choice of second-step drug was at the discretion of the treating clinician-investigator . The third-step agent was hydralazine ( 25 to 100 mg twice daily ) . Details of these therapies are provided elsewhere ( 1 ) . Investigators could choose to prescribe open-label antihypertensive drugs other than those provided by the study . However , use of the drug classes under study thiazide diuretics , calcium antagonists , angiotensin-converting enzyme inhibitors , and -adrenergic blockerswas strongly discouraged to avoid dilution of treatment comparisons . When clinical conditions other than uncontrolled hypertension ( for example , angina or heart failure ) were present , drugs from any study class could be used . If a step 1 drug was specifically required for blood pressure control while blinded drug treatment was continued , the step 1 drug could be added as open-label therapy but the dose could not exceed one half the maximum recommended by the Fifth Joint National Committee ( 4 ) . In most such cases , unblinding the patient or the investigator to treatment assignment was not necessary . ( Overall , < 1 % of drug identities were provided to either participant or investigator . ) Any of nine possible open-label drug typesdiuretic , calcium-channel blocker , angiotensin-converting enzyme inhibitor , -adrenergic blocker , atenolol , reserpine , clonidine , hydralazine , and other antihypertensive drug ( which could include nonatenolol -blockers , although drug name was not logged)could be recorded at each visit . Because diuretics , angiotensin-converting enzyme inhibitors , and -blockers are beneficial in preventing or treating heart failure , we call these antihypertensive heart failure drugs . Data on  antihypertensive drug use before study enrollment were collected , but not by drug class . Statistical Analysis Data were analyzed for use of additional drugs according to participants ' r and omized treatment assignments and regardless of continuation of blinded study treatment . The outcomes all heart failure ( treated outside hospital , hospitalized , or fatal ) and hospitalized or fatal heart failure were examined by treatment group for the entire cohort . The time to event for the previously published as-r and omized analyses was the interval from r and omization to first diagnosis of heart failure for patients who had an outcome , or from r and omization to 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 BACKGROUND While the antihypertensive and renoprotective potency of angiotensin-converting enzyme ( ACE ) inhibitors is well-established in adults with hypertension and /or chronic renal failure , little experience exists in pediatric chronic kidney disease . METHODS As part of a prospect i ve assessment of the renoprotective efficacy of ACE inhibition and intensified blood pressure ( BP ) control , 397 children ( ages 3 to 18 years ) with chronic renal failure [ CRF ; glomerular filtration rate ( GFR ) 11 to 80 mL/min/1.73 m2 ] and elevated or high-normal BP received ramipril ( 6 mg/m2 ) following a 6-month run-in period including a two-month washout of any previous ACE inhibitors .  Drug efficacy was assessed by two monthly office BP and proteinuria assessment s , and by ambulatory BP monitoring at start and after 6 months of treatment . RESULTS In the 352 patients completing six months of treatment , 24-hour mean arterial pressure ( MAP ) had decreased by a mean of 11.5 mm Hg ( -2.2 SDS ) in initially hypertensive subjects , but only by 4.4 mm Hg ( -0.8 SDS ) in patients with initially normal BP . A linear correlation was found between MAP at baseline and the change of MAP during treatment ( r= 0.51 ; P < 0.0001 ) . The antihypertensive response was independent of changes in concomitant antihypertensive medication or underlying renal disease . BP was reduced with equal efficacy during day- and nighttime . Urinary protein excretion was reduced by 50 % on average , with similar relative efficacy in patients with hypo/dysplastic nephropathies and glomerulopathies . The magnitude of proteinuria reduction depended on baseline proteinuria ( r= 0.32 , P < 0.0001 ) , and was correlated with the antihypertensive efficacy of the drug ( r= 0.22 , P < 0.001 ) . The incidence of rapid rises in serum creatinine and progression to end-stage CRF during treatment did not differ from the pretreatment observation period . Mean serum potassium increased by 0.3 mmol/L. Ramipril was discontinued in three patients due to symptomatic hypotension or hyperkalemia . Hemoglobin levels decreased by 0.6 g/dL in the first two treatment months and remained stable thereafter . CONCLUSION Ramipril appears to be an effective and safe antihypertensive and antiproteinuric agent in children with CRF-associated hypertension . The BP lowering and antiproteinuric effects are greatest in severely hypertensive and proteinuric children Despite widespread use to treat childhood hypertension , enalapril has never been studied systematic ally to determine effectiveness , dose response , and safety in a pediatric population . This study was conducted prospect ively in 110 hypertensive children ages 6 to 16 years in two sequential phases . The primary outcome variable for both phases of the study was trough ( 24-h postdose ) sitting diastolic blood pressure . The primary objective of the first phase of the study was to determine whether enalapril lowered blood pressure in children in a dose-dependent manner . During a 2-week , double-blind , r and omized , dose-response period , patients were stratified by weight ( < 50 kg or > or = 50 kg ) , then assigned to one of three dosing groups : low(0.625 or 1.25 mg ) , middle ( 2.5 or 5 mg ) , or high dose ( 20 or 40 mg ) . Reduction in blood pressure was examined as a function of dose ratio ( 1:4:32 ) and on a weight-adjusted basis . On completion of the dose-response phase of the study , patients entered a 2-week , double-blind , r and omized withdrawal to either enalapril or placebo .  Antihypertensive effectiveness , defined as the difference in sitting diastolic blood pressure between the placebo and enalapril groups , was determined . Adverse events were carefully recorded throughout the study . The dose-response relationship for enalapril had a negative slope and was linear over the chosen dosing range , suggesting that larger doses of enalapril were associated with a greater reduction in blood pressure . R and omized withdrawal to active drug orplacebo confirmed the antihypertensive effectiveness of enalapril in the middle- and high-dose groups . The antihypertensive effect of enalapril was maintained across age , gender , race , and Tanner stage . Enalapril appears to be an effective and generally well-tolerated antihypertensive agent in children ages 6 to 16 years . An initial dose of 2.5 mg in children weighing < 50 kg and 5 mg in children weighing > 50 kg ( mean = 0.08 mg/kg ) administered once daily effectively lowered blood pressure within 2 weeks in most patients . Blood pressure was reduced in a dose-dependent fashion , with larger doses result ing in a greater reduction It has been almost 5 years since the publication of the 2010 hypertension guidelines of the Taiwan Society of Cardiology ( TSOC ) . There is new evidence regarding the management of hypertension , including r and omized controlled trials , non-r and omized trials , post-hoc analyses , subgroup analyses , retrospective studies , cohort studies , and registries . More recently , the European Society of Hypertension ( ESH ) and the European Society of Cardiology ( ESC ) published joint hypertension guidelines in 2013 . The panel members who were appointed to the Eighth Joint National Committee ( JNC ) also published the 2014 JNC report . Blood pressure ( BP ) targets have been changed ; in particular , such targets have been loosened in high risk patients . The Executive Board members of TSOC and the Taiwan Hypertension Society ( THS ) aim ed to review up date d information about the management of hypertension to publish an up date d hypertension guideline in Taiwan . We recognized that hypertension is the most important risk factor for global disease burden . Management of hypertension is especially important in Asia where the prevalence rate grows faster than other parts of the world . In most countries in East Asia , stroke surpassed coronary heart disease ( CHD ) in causing premature death . A diagnostic algorithm was proposed , emphasizing the importance of home BP monitoring  and ambulatory BP monitoring  for better detection of night time hypertension , early morning hypertension , white-coat hypertension , and masked hypertension . We disagreed with the ESH/ESH joint hypertension guidelines suggestion to loosen BP targets to < 140/90 mmHg for all patients . We strongly disagree with the suggestion by the 2014 JNC report to raise the BP target to < 150/90 mmHg for patients between 60 - 80 years of age . For patients with diabetes , CHD , chronic kidney disease who have proteinuria , and those who are receiving antithrombotic therapy for stroke prevention , we propose BP targets of < 130/80 mmHg in our guidelines . BP targets are < 140/90 mmHg for all other patient groups , except for patients ≥80 years of age in whom a BP target of < 150/90 mmHg would be optimal . For the management of hypertension , we proposed a treatment algorithm , starting with life style modification ( LSM ) including S-ABCDE ( Sodium restriction , Alcohol limitation , Body weight reduction , Cigarette smoke cessation , Diet adaptation , and Exercise adoption ) . We emphasized a low-salt strategy instead of a no-salt strategy , and that excessively aggressive sodium restriction to < 2.0 gram/day may be harmful . When drug therapy is considered , a strategy called " PROCEED " was suggested ( Previous experience , Risk factors , Organ damage , Contraindications or unfavorable conditions , Expert 's or doctor 's judgment , Expenses or cost , and Delivery and compliance issue ) . To predict drug effects in lowering BP , we proposed the " Rule of 10 " and " Rule of 5 " . With a st and ard dose of any one of the 5 major classes of anti-hypertensive agents , one can anticipate approximately a 10-mmHg decrease in systolic BP ( SBP ) ( Rule of 10 ) and a 5-mmHg decrease in diastolic BP ( DBP ) ( Rule of 5 ) . When doses of the same drug are doubled , there is only a 2-mmHg incremental decrease in SBP and a 1-mmHg incremental decrease in DBP . Preferably , when 2 drugs with different mechanisms are to be taken together , the decrease in BP is the sum of the decrease of the individual agents ( approximately 20 mmHg in SBP and 10 mmHg in DBP ) . Early combination therapy , especially single-pill combination ( SPC ) , is recommended . When patient 's initial treatment can not get BP to targeted goals , we have proposed an adjustment algorithm , " AT GOALs " ( Adherence , Timing of administration , Greater doses , Other classes of drugs , Alternative combination or SPC , and LSM + Laboratory tests ) . Treatment of hypertension in special conditions , including treatment of resistant hypertension , hypertension in women , and perioperative management of hypertension , were also mentioned . The TSOC/THS hypertension guidelines provide the most up date d information available in the management of hypertension . The guidelines are not m and atory , and members of the task force fully realize that treatment of hypertension should be individualized to address each patient 's circumstances . Ultimately , the decision of the physician decision remains of the utmost importance in hypertension management BACKGROUND Even within the normal range , aldosterone levels are linked to end-organ toxicity and mortality in patients with hypertension . Treatment with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers does not sufficiently reduce plasma aldosterone levels . OBJECTIVE This study was conducted to assess the long-term safety profile and efficacy of the selective aldosterone blocker eplerenone . METHODS This was a multicenter , open-label , uncontrolled trial in patients with mild to moderate essential hypertension . After a 1-week washout of previous antihypertensive medications , eplerenone was initiated at 50 mg once daily ; the dose was titrated to a maximum of 200 mg/d to achieve a diastolic blood pressure < 90 mm Hg and a systolic blood pressure < 140 mm Hg . Thereafter , another antihypertensive agent could be added and titrated once , or another agent could be substituted for eplerenone . Eplerenone treatment was continued for up to 14 months in a subset of patients . RESULTS Five hundred eighty-six patients were enrolled in the study . Their adjusted mean blood pressure ( BP ) at baseline was 150/96 mm Hg . The majority ( 80.4 % ) were white ; 51.5 % were male and 48.5 % were female ; 62.3 % were between the ages of 45 and 64 years and 21.7 % were aged > 64 years . Three hundred eighty-five patients ( 65.7 % ) completed the study ; 98 ( 16.7 % ) were withdrawn due to treatment failure ( only 4.8 % of them after month 4 ) , and 40 ( 6.8 % ) were withdrawn due to treatment-emergent adverse events . Four hundred thirty-three of 582 ( 74.4 % ) patients in the intent-to-treat population achieved BP control during eplerenone treatment : 261 ( 44.8 % ) received eplerenone monotherapy and 172 ( 30.0 % ) received eplerenone plus another antihypertensive agent . CONCLUSIONS Eplerenone therapy was effective in the treatment of mild to moderate hypertension over a 14-month period , either as monotherapy or in combination with another antihypertensive agent . Use of eplerenone was well tolerated in the population studied In the Hypertension Detection and Follow-up Program , 7825 ( 71.5 per cent ) of the 10,940 participants had diastolic blood pressures averaging between 90 and 104 mm Hg on entry into the study and were design ated Stratum 1 . Half were referred to their usual source of care in the community ( the referred-care group ) , and half were treated intensively in special clinics ( the stepped-care group ) . Five-year mortality in the Stratum 1 patients given stepped care was 20.3 per cent lower than in those given referred care ( P less than 0.01 ) . Particularly noteworthy was the beneficial effect of stepped-care treatment on persons with diastolic pressures of 90 to 104 mm Hg who had no evidence of end-organ damage and were not receiving antihypertensive medication when they entered the study . This subgroup had 28.6 per cent fewer deaths at five years among those treated with stepped care than among those treated with referred care ( P less than 0.01 ) . These findings support a recommendation that in patients with mild hypertension , treatment should be considered early , before damage to end organs occurs 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 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 Abstract . Hypertension is one of the most important complications of erythropoietin ( rHuEPO ) therapy in dialysis patients . In this study , the effect of two different dosage regiments of subcutaneous rHuEPO on blood pressure [ BP ] was evaluated in 20 anemic children on continuous ambulatory peritoneal dialysis ( CAPD ) . Patients were r and omized to receive rHuEPO 50 U/kg , either once a week ( group 1 , 50 U/kg per week ) or three times a week ( group 2 , 150 U/kg per week ) . At the beginning of the study , 8 patients in group 1 and 8 patients in group 2 were on antihypertensive therapy . In group 1 , the hematocrit increased gradually and significantly from 18.98%±1.79 % to 30.1%±1.62 % after 6 months , while in group 2 it rapidly increased from 19.53%±1.86 % to 32.4%±1.11 % after 3 months . A significant increase in the mean arterial BP was observed in group 2 . Antihypertensive therapy had to be increased in all of the 8 previously hypertensive patients and had to be initiated in 1 of the 2 originally normotensive patients in the same group . None of the patients in group 1 required a change in antihypertensive medication . We conclude that during treatment with rHuEPO pre-existing hypertension and the dose of rHuEPO are the most important risk factors for the development or worsening of hypertension in children on CAPD , and gradual elevation of hematocrit by low-dose rHuEPO avoids the development of severe hypertension The objective of this study was to establish whether ambulatory blood pressure offers a better estimate of cardiovascular risk than does its clinical blood pressure counterpart in refractory hypertension . This prospect i ve study assessed the incidence of cardiovascular events over time during an average follow-up of 49 months ( range , 6 to 96 ) . Patients were referred to specialized hypertension clinics ( 86 essential hypertension patients who had diastolic blood pressure > 100 mm Hg during antihypertensive treatment that included three or more antihypertensive drugs , one being a diuretic ) . Twenty-four-hour ambulatory blood pressure monitoring ( ABPM ) was performed at the time of entrance . End-organ damage was monitored yearly , and the incidence of cardiovascular events was recorded . Patients were divided into tertiles of average diastolic blood pressure during activity according to the ABPM , with the lowest tertile < 88 mm Hg ( LT , n=29 ) , the middle tertile 88 to 97 mm Hg ( MT , n=29 ) , and the highest tertile > 97 mm Hg ( HT , n=28 ) . While significant differences in systolic and diastolic ambulatory blood pressures were observed among groups , no differences were observed at either the beginning or at the time of the last evaluation for office blood pressure . During the last evaluation , a progression in the end-organ damage score was observed for the HT group but not for the two other groups . Twenty-one of the patients had a new cardiovascular event ; the incidence of events was significantly lower for the LT group ( 2.2 per 100 patient-years ) than it was for the MT group ( 9.5 per 100 patient-years ) or for the HT group ( 13.6 per 100 patient-years ) . The probability of event-free survival was also significantly different when comparing the LT group with the other two groups ( LT versus MT log-rank , P<.04 ; LT versus HT log-rank , P<.006 ) . The HT group was an independent risk factor for the incidence of cardiovascular events ( relative risk , 6.20 ; 95 % confidence interval , 1.38 to 28.1 , P<.02 ) . Higher values of ambulatory blood pressure result in a worse prognosis in patients with refractory hypertension , supporting the recommendation that ABPM is useful in stratifying the cardiovascular risk in patients with refractory hypertension An open-label study was conducted to characterize the pharmacokinetics and antihypertensive response to irbesartan in children ( 1 - 12 years ) and adolescents ( 13 - 16 years ) with hypertension . Patients received single once-daily oral doses of irbesartan 2 mg/kg ( maximum of 150 mg once daily ) for 2 to 4 weeks ( + /- nifedipine or hydrochlorothiazide ) . Plasma irbesartan concentrations were determined by a vali date d high-performance liquid chromatography/fluorescence method from blood sample s taken predose , up to 24 hours after dosing on Day 1 , and up to 48 hours after the final dose . The plasma concentration-time profiles were similar between the 6- to 12-year and the 13- to 16-year age groups and to that previously determined from a study of adult subjects receiving approximately 2 mg/kg ( i.e. , 150 mg ) oral irbesartan once daily . Mean reductions in systolic/diastolic blood pressure were 16/10 mmHg at Day 28 with irbesartan monotherapy ( n = 8) . Irbesartan was well tolerated and may be a treatment option for pediatric hypertensive patients BACKGROUND Left-ventricular hypertrophy ( LVH ) is a risk factor for cardiovascular morbidity . Antihypertensive treatment with angiotensin-converting enzyme inhibitors ( ACEI ) is able to induce the regression of LVH in adults . However , there has been no study of the ability of ACEI to induce the regression of LVH in children . Our aim was to investigate the effect of ramipril on left-ventricular mass and blood pressure ( BP ) in hypertensive children . METHODS Twenty-one children ( median age , 15 years ) with renal ( 76 % ) or primary ( 24 % ) hypertension were prospect ively treated with ramipril monotherapy for 6 months . Blood pressure was evaluated using ambulatory BP monitoring , with hypertension defined as mean BP > or=95th percentile . Left-ventricular hypertrophy was defined either as left-ventricular mass index ( LVMI ) > 38.6 g/m(2.7 ) ( pediatric definition ) or as LVMI > 51.0 g/m(2.7 ) ( adult definition ) . RESULTS Nineteen children completed the study . The median LVMI decreased from 36.8 g/m(2.7 ) ( range , 18.9 to 55.8 g/m(2.7 ) ) to 32.6 g/m(2.7 ) ( range , 19.0 to 52.1 g/m(2.7 ) ; P < .05 ) after 6 months . The prevalence of LVH decreased from 42 % to 11 % using the pediatric definition ( P < .05 ) and did not change using the adult definition ( ie , it remained at 5 % ) . The median ambulatory BP decreased by 11 , 7 , 8 , and 7 mm Hg for daytime systolic , daytime diastolic , nighttime systolic , and nighttime diastolic BP ( P < .05 ) , respectively . A positive correlation was found between LVMI and nighttime systolic BP at the start of the study ( r = 0.46 , P < .05 ) . CONCLUSIONS Ramipril is an effective drug in children with hypertension , for its ability to reduce not only BP but also left-ventricular mass and induce regression of LVH BACKGROUND Angiotensin-converting enzyme inhibitors are the drugs of choice in renal hypertension . The efficacy and safety of ramipril in adults has been proved ; however , data on effectiveness of ramipril in children are few . The aim of the present study was to investigate the effect of ramipril on blood pressure ( BP ) and proteinuria in children with chronic kidney diseases . METHODS A total of 31 children ( median age 11.3 years , range 1.9 - 19.8 years ) with various chronic nephropathies and hypertension or proteinuria were prospect ively treated with ramipril for 6 months . Blood pressure was evaluated using ambulatory BP monitoring and hypertension was defined as mean BP equal to or greater than the 95th percentile for healthy children .  Proteinuria was defined as protein excretion > or = 100 mg/m(2)/24 h. The starting dose of ramipril was 1.5 mg/m(2)/24 h once daily . In 27 children it was given as monotherapy . RESULTS The median decrease in ambulatory BP was 11 mm Hg for daytime systolic , 10 mm Hg for daytime and nighttime diastolic , and 8 mm Hg for nighttime systolic BP . Hypertension normalized in 55 % of the children . Proteinuria decreased in 84 % of the children with pathologic proteinuria ; the median decrease was 51 % . A positive correlation was found between initial proteinuria and change of proteinuria ( r = 0.95 , P < .001 ) . Glomerular filtration rate and serum potassium level did not change significantly . One child developed a cough that was believed to be related to ramipril . CONCLUSIONS Ramipril is an effective and safe drug in children with chronic kidney diseases associated with hypertension , proteinuria , or both CONTEXT Blood pressure control ( < 140/90 mm Hg ) rates for hypertension fall far short of the US national goal of 50 % or more . Achievable control rates in varied practice setting s and geographic regions and factors that predict improved blood pressure control are not well identified . OBJECTIVE To determine the success and predictors of blood pressure control in a large hypertension trial involving a multiethnic population in diverse practice setting s. DESIGN The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial is a r and omized , double-blind , active-controlled clinical trial with a mean follow-up of 4.9 years . Participant enrollment began in February 1994 and follow-up was completed in March 2002 . SETTING A total of 623 centers in the United States , Canada , and the Caribbean . PARTICIPANTS A total of 33,357 participants ( aged > or = 55 years ) with hypertension and at least one other coronary heart disease risk factor . INTERVENTIONS Participants were r and omly assigned to receive ( double-blind ) chlorthalidone , 12.5 - 25 mg/d ( n=15,255 ) , amlodipine 2.5 - 10 mg/d ( n=9048 ) , or lisinopril 10 - 40 mg/d ( n=9054 ) after other medication was discontinued . Doses were increased within these ranges and additional drugs from other classes were added as needed to achieve blood pressure control ( < 140/90 mm Hg ) . MAIN OUTCOME MEASURES The outcome measures for this report are systolic and diastolic blood pressure , the proportion of participants achieving blood pressure control ( < 140/90 mm Hg ) , and the number of drugs required to achieve control in all three groups combined . RESULTS Mean age was 67 years , 47 % were women , 35 % black , 36 % diabetic ; 90 % were on antihypertensive drug treatment at entry . At the first of two pre-r and omization visits , blood pressure was < 140/90 mm Hg in only 27.4 % of participants . After 5 years of follow-up , the percent controlled improved to 66 % . Systolic blood pressure was < 140 mm Hg in 67 % of participants , diastolic blood pressure was < 90 mm Hg in 92 % , the mean number of drugs prescribed was 2.0+/-1.0 , and the percent on > or = 2 drugs was 63 % . Blood pressure control varied by geographic regions , practice setting s , and demographic and clinical characteristics of participants . CONCLUSIONS These data demonstrate that blood pressure may be controlled in two thirds of a multiethnic hypertensive population in diverse practice setting s. Systolic blood pressure is more difficult to control than diastolic blood pressure , and at least two antihypertensive medications are required for most patients to achieve blood pressure control . It is likely that the majority of people with hypertension could achieve a blood pressure < 140/90 mm Hg with the antihypertensive medications available today The blood pressure lowering effects of spironolactone have been studied in 40 subjects with benign essential hypertension in an attempt to determine the optimum starting dose for the drug . The trial was carried out by the double blind method . In almost all patients 100 - 400 mg spironolactone caused a signnificant decrease in diastolic and systolic arterial pressure . Present findings indicate that 100 - 200 mg spironolactone represents the optimum attack dose . The medication caused a significant rise in serum potassium . Other parameters were not affected by the treatment . In conclusion , it would appear that spironolactone -- in association with other antihypertensive regiments -- may improve the treatment of essential hypertension , especially in patients showing a tendency to hypokalemia and uricemia , and may offer an additional possibility or alternative in the therapy of hypertensive diseases Background Blood pressure ( BP ) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension , which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age . Non-drug interventions to prevent hypertension have had low effectiveness . In individuals with previous cardiovascular disease or diabetes , the use of BP-lowering agents reduces the incidence of major cardiovascular events . In the absence of higher baseline risk , the use of BP agents reduces the incidence of hypertension . The PREVER-prevention trial aims to investigate the efficacy , safety and feasibility of a population -based intervention to prevent the incidence of hypertension and the development of target-organ damage . Methods This is a r and omized , double-blind , placebo-controlled clinical trial , with participants aged 30 to 70 years , with pre-hypertension . The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo . The primary outcomes will be the incidence of hypertension , adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG . The secondary outcomes will be fatal or non-fatal cardiovascular events : myocardial infa rct ion , stroke , heart failure , evidence of new sub- clinical atherosclerosis , and sudden death . The study will last 18 months . The sample size was calculated on the basis of an incidence of hypertension of 14 % in the control group , a size effect of 40 % , power of 85 % and P alpha of 5 % , result ing in 625 participants per group . The project was approved by the Ethics committee of each participating institution . Discussion The early use of blood pressure-lowering drugs , particularly diuretics , which act on the main mechanism of blood pressure rising with age , may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension . If this intervention shows to be effective and safe in a population -based perspective , it could be the basis for an innovative public health program to prevent hypertension in Brazil . Trial Registration Clinical Trials NCT00970931 This prospect i ve , r and omized trial evaluated the effect of monotherapy and different combination therapies on cardiovascular target organ damage and metabolic profile in 520 hypertensive patients . Patients were allocated to a single agent : carvedilol 25 mg , amlodipine 10 mg , enalapril 20 mg , or losartan 50 mg ( groups C , A , E , and L , respectively ) . After 2 months ( level 2 ) , nonresponders received a low-dose thiazide diuretic , and after 4 months ( level 3 ) , amlodipine ( groups E , C , and L ) and carvedilol ( group A ) . Twenty-four-hour blood pressure was significantly lowered in all treatment groups . Blood pressure control was more pronounced in patients receiving two or three drugs . At the end of the study , the carotid intima-media thickness decreased in group L ( P<.01 ) , left ventricular mass index in groups E and L ( P<.05 and P<.001 , respectively ) , with a concomitant reduction in cholesterol in group L ( P<.03 ) . Diastolic function improved significantly in group L ( P<.05 ) . This study describes the need to control blood pressure with two or more drugs in most hypertensive patients and illustrates good clinical outcomes , independent of blood pressure lowering , using combination therapy with losartan , low-dose thiazide , and amlodipine BACKGROUND Despite widespread use in hypertensive children , the safety and effectiveness of lisinopril had not been previously tested in a controlled study . METHODS This study explored the dose-response relationship and safety of lisinopril in 115 hypertensive children , aged 6 to 16 years . Patients were r and omized in a double-blind fashion for 2 weeks to one of three doses by body weight at baseline : < 50 kg : low ( 0.625 mg ) , middle ( 2.5 mg ) , high ( 20 mg ) , and > or = 50 kg : low ( 1.25 mg ) , middle ( 5 mg ) , high ( 40 mg ) . The dose-response for lisinopril was evaluated by analyzing the change in slope in sitting diastolic and systolic blood pressure ( BP ) by dose after 2 weeks of therapy compared to baseline . Patients then entered a double-blind withdrawal , where patients were either switched to placebo or continued their current lisinopril treatment for up to 2 weeks . Patients completed period II when their BP returned to baseline . Antihypertensive effectiveness , between placebo and lisinopril was determined for all doses . Adverse events were carefully monitored . RESULTS There was a dose-response relationship between the lowest and each of the higher doses of lisinopril . Blood pressure in the placebo group increased after withdrawal of lisinopril . The dose-response relationship was consistent across all subgroups ( ie , age , Tanner stage , ethnicity , gender ) . CONCLUSIONS Lisinopril , once daily , is an effective and well-tolerated antihypertensive in children aged 6 to 16 years . An initial dose of 0.07 mg/kg , administered once daily , effectively lowered BP within 2 weeks . Blood pressure was reduced in a dose-dependent fashion
The adverse events associated with the antihypertensive agents were mostly minor and included headaches , dizziness and upper respiratory infections .
The most data are available for c and esartan , for which there is low- quality evidence of a modest lowering effect on blood pressure .
We did not find evidence of a consistent dose response relationship for escalating doses of angiotensin receptor blockers , calcium channel blockers or angiotensin-converting enzyme inhibitors .
All agents appear safe , at least in the short term
BACKGROUND Hypertension is a major risk factor for stroke , coronary artery disease and kidney damage in adults .
There is a paucity of data on the long-term sequelae of persistent hypertension in children , but it is known that children with hypertension have evidence of end organ damage and are at risk of hypertension into adulthood .
The prevalence of hypertension in children is rising , most likely due to a concurrent rise in obesity rates .
In children with hypertension , non-pharmacological measures are often recommended as first-line therapy , but a significant proportion of children will eventually require pharmacological treatment to reduce blood pressure , especially those with evidence of end organ damage at presentation or during follow-up .
A systematic review of the effects of antihypertensive agents in children has not previously been conducted .
OBJECTIVES To determine the dose-related effects of different classes of antihypertensive medications , as monotherapy compared to placebo ; as combination therapy compared to placebo or a single medication ; or in comparisons of various doses within the same class , on systolic or diastolic blood pressure ( or both ) in children with hypertension .