title: Chronotherapy Improves Blood Pressure Control and Reverts the Nondipper Pattern in Patients With Resistant Hypertension Role of Time-of-Day of Hypertension Treatment on the J-Shaped Relationship Between Blood Pressure and Cardiovascular Risk Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. Outcome Results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in Patients With Hypertension and NIDDM Comparative Effects of Ramipril on Ambulatory and Office Blood Pressures: A HOPE Substudy Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. First dose response and 24-hour antihypertensive efficacy of the new once-daily angiotensin converting enzyme inhibitor, ramipril. INFLUENCE OF CIRCADIAN TIME OF HYPERTENSION TREATMENT ON CARDIOVASCULAR RISK: RESULTS OF THE MAPEC STUDY Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. 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). 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8).
abstract: Therapeutic strategies in resistant hypertension include adding another drug or changing drugs in search for a better synergic combination . Most patients , however , receive all of their drugs in a single morning dose . We have evaluated the impact on the circadian pattern of blood pressure on modifying the time of treatment without increasing the number of prescribed drugs . We studied 250 hypertensive patients who were receiving 3 antihypertensive drugs in a single morning dose .  Patients were r and omly assigned to 1 of 2 groups according to the modification in their treatment strategy : changing 1 of the drugs but keeping all 3 in the morning or the same approach but administering the new drug at bedtime .  Blood pressure was measured for 48 hours before and after 12 weeks of treatment . There was no effect on ambulatory blood pressure when all of the drugs were taken on awakening . The baseline prevalence of nondipping ( 79 % ) was slightly increased after treatment ( 86 % ; P=0.131 ) . The ambulatory blood pressure reduction was statistically significant ( 9.4/6.0 mm Hg for systolic/diastolic blood pressure ; P<0.001 ) with 1 drug at bedtime . This reduction was larger in the nocturnal than in the diurnal mean of blood pressure . Thus , whereas only 16 % of the patients in this group were dippers at baseline , 57 % were dippers after therapy ( P<0.001 ) . Results indicate that , in resistant hypertension , time of treatment may be more important for blood pressure control and for the proper modeling of the circadian blood pressure pattern than just changing the drug combination Several previous studies found that too great a reduction of clinic blood pressure ( BP ) by treatment increased cardiovascular disease ( CVD ) risk , whereas moderate reduction decreased it . Thus , it has been suggested that the relationship between BP and CVD events is J-shaped , with CVD risk decreasing as BP is lowered , and then rising as BP is further decreased . Correlation between BP level and CVD risk , however , is stronger for ambulatory BP monitoring ( ABPM ) than clinical BP measurements . We previously established that the hypertension treatment-time regimen , upon awakening versus at bedtime , exerts differential effect on BP control during the day and nighttime , which translates into a differential degree of CVD risk prevention . We , therefore , investigated the role of hypertension treatment-time scheme on the nature of the relationship between achieved clinic and ambulatory BP and CVD risk in the MAPEC ( Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares , i.e. , Ambulatory Blood Pressure Monitoring for Prediction of Cardiovascular Events ) study , a prospect i ve , open-label , blinded-endpoint trial on 2156 hypertensive patients ( 1044 men/1112 women ) , 55.6 ± 13.6 ( mean ± SD ) yrs of age , r and omized to ingest all prescribed once-a-day hypertension medications upon awakening or the entire daily dose of ≥1 of them at bedtime  . Ambulatory BP was measured for 48-h at baseline and annually thereafter , and more frequently ( quarterly ) when adjustment of treatment was necessary . After a median follow-up of 5.6 yrs , a J-shaped relationship was detected between total CVD events and clinic as well as awake BP mean , but only for the group of patients ingesting all medications upon awakening . The relationship was different in the group of patients who ingested ≥1 medications at bedtime ; the risk of CVD events progressively diminished in a linear , rather than J-shaped , manner with treatment-induced decrease in awake BP mean . The adjusted hazard ratio of CVD events was significantly lower with the progressive reduction in the asleep BP mean , independent of the hypertension treatment-time regimen . There was no single major event , i.e. , CVD death , myocardial infa rct ion , or stroke , in patients who achieved an asleep systolic BP mean < 103 mm Hg . Our findings indicate that bedtime hypertension treatment is not associated with a J-shaped relationship between achieved BP and CVD risk . The decreased CVD risk associated with the progressive reduction in asleep BP , more feasible by bedtime than morning hypertension treatment , has clinical implication s , in particular , the need to consider the proper timing of hypertension medications , in conjunction with ABPM for proper assessment of BP control , as an improved and potentially safer means of reducing CVD risk of hypertensive patients . ( Author correspondence : rhermida@uvigo.es CONTEXT Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk , but the benefit compared with other drug classes is controversial . OBJECTIVE To determine whether initial therapy with controlled-onset extended-release ( COER ) verapamil is equivalent to a physician 's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized clinical trial conducted at 661 centers in 15 countries . A total of 16 602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31 , 2000 . After a mean of 3 years of follow-up , the sponsor closed the study before unblinding the results . INTERVENTION Initially , 8241 participants received 180 mg of COER verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide . Other drugs ( eg , diuretic , beta-blocker , or an angiotensin-converting enzyme inhibitor ) could be added in specified sequence if needed . MAIN OUTCOME MEASURES First occurrence of stroke , myocardial infa rct ion , or cardiovascular disease-related death . RESULTS Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the atenolol or hydrochlorothiazide group . There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group ( hazard ratio [ HR ] , 1.02 ; 95 % confidence interval [ CI ] , 0.88 - 1.18 ; P = .77 ) . For fatal or nonfatal stroke , the HR was 1.15 ( 95 % CI , 0.90 - 1.48 ) ; for fatal or nonfatal myocardial infa rct ion , 0.82 ( 95 % CI , 0.65 - 1.03 ) ; and for cardiovascular disease-related death , 1.09 ( 95 % CI , 0.87 - 1.37 ) . The HR was 1.05 ( 95 % CI , 0.95 - 1.16 ) for any prespecified cardiovascular disease-related event and 1.08 ( 95 % CI , 0.93 - 1.26 ) for all-cause mortality . Nonstroke hemorrhage was more common with participants in the COER-verapamil group ( n = 118 ) compared with the atenolol or hydrochlorothiazide group ( n = 79 ) ( HR , 1.54 [ 95 % CI , 1.16 - 2.04 ] ; P = .003 ) . More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil ( 99/277 ) and atenolol or hydrochlorothiazide ( 88/274 ) groups ; HR , 1.15 ( 95 % CI , 0.86 - 1.53 ) . CONCLUSIONS The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or beta-blocker . When considered in the context of other trials of calcium antagonists , these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or beta-blocker treatment OBJECTIVE ACE inhibitors and calcium antagonists may favorably affect serum lipids and glucose metabolism . The primary aim of the Fosinopril Versus Amlodipine Cardiovascular Events R and omized Trial ( FACET ) was to compare the effects of fosinopril and amlodipine on serum lipids and diabetes control in NIDDM patients with hypertension . Prospect ively defined cardiovascular events were assessed as secondary outcomes . RESEARCH DESIGN AND METHODS Inclusion criteria included a diagnosis of NIDDM and hypertension ( systolic blood pressure of > 140 mmHg or diastolic blood pressure of > 90 mmHg ) . Exclusion criteria included a history of coronary heart disease or stroke , serum creatinine > 1.5 mg/dl , albuminuria > 40 μg/min , and use of lipid-lowering drugs , aspirin , or antihypertensive agents other than beta-blockers or diuretics . A total of 380 hypertensive diabetics were r and omly assigned to open-label fosinopril ( 20 mg/day ) or amlodipine ( 10 mg/day ) and followed for up to 3.5 years . If blood pressure was not controlled , the other study drug was added . RESULTS Both treatments were effective in lowering blood pressure . At the end of followup , between the two groups there was no significant difference in total serum cholesterol , HDL cholesterol , HbA1c , fasting serum glucose , or plasma insulin . The patients receiving fosinopril had a significantly lower risk of the combined outcome of acute myocardial infa rct ion , stroke , or hospitalized angina than those receiving amlodipine ( 14/189 vs. 27/191 ; hazards ratio = 0.49 , 95 % CI = 0.26–0.95 ) . CONCLUSIONS Fosinopril and amlodipine had similar effects on biochemical measures , but the patients r and omized to fosinopril had a significantly lower risk of major vascular events , compared with the patients r and omized to amlodipine In the HOPE-trial , the ACE inhibitor ramipril significantly reduced cardiovascular morbidity and mortality in patients at high risk for cardiovascular events . The benefit could only partly be attributed to the modest mean reduction of office blood pressure ( OBP ) during the study period ( 3/2 mm Hg ) . However , because according to the HOPE protocol ramipril was given once daily at bedtime and blood pressure was measured during the day , the 24-hour reduction of blood pressure may be underestimated based on OBP . Thirty-eight patients with peripheral arterial disease enrolled in the HOPE study underwent  24-hour ambulatory blood pressure ( ABP ) measurement  before r and omization and after 1 year . OBP was measured in the sitting position immediately before fitting the ABP measuring equipment to the patients . Ramipril did not significantly reduce OBP ( 8/2 mm Hg , P = NS ) or day ABP ( 6/2 mm Hg , P = NS ) after 1 year . Twenty-four – hour ABP was significantly reduced ( 10/4 mm Hg , P = 0.03 ) , mainly because of a more pronounced blood pressure lowering effect during nighttime ( 17/8 mm Hg , P < 0.001 ) . The night/day ratio was also significantly lowered in the ramipril  group . ABP shows greater falls , especially at night , than OBP during treatment with ramipril given once daily at bedtime . Although , OBP is the correct comparator when comparing with previous large intervention trials and epidemiological studies , the effects on cardiovascular morbidity and mortality seen with ramipril in the HOPE study may , to a larger extent than previously ascribed , relate to effects on blood pressure patterns over the 24-hour period BACKGROUND Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction , whether or not they have heart failure . We assessed the role of an angiotensin-converting-enzyme inhibitor , ramipril , in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure . METHODS A total of 9297 high-risk patients ( 55 years of age or older ) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were r and omly assigned to receive ramipril ( 10 mg once per day orally ) or matching placebo for a mean of five years . The primary outcome was a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes . The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper . RESULTS A total of 651 patients who were assigned to receive  ramipril ( 14.0 percent ) reached the primary end point , as compared with 826 patients who were assigned to receive placebo ( 17.8 percent ) ( relative risk , 0.78 ; 95 percent confidence interval , 0.70 to 0.86 ; P<0.001 ) . Treatment with ramipril reduced the rates of death from cardiovascular causes ( 6.1 percent , as compared with 8.1 percent in the placebo group ; relative risk , 0.74 ; P<0.001 ) , myocardial infa rct ion ( 9.9 percent vs. 12.3 percent ; relative risk , 0.80 ; P<0.001 ) , stroke ( 3.4 percent vs. 4.9 percent ; relative risk , 0.68 ; P<0.001 ) , death from any cause ( 10.4 percent vs. 12.2 percent ; relative risk , 0.84 ; P=0.005 ) , revascularization procedures ( 16.3 percent vs. 18.8 percent ; relative risk , 0.85 ; P<0.001 ) , cardiac arrest ( 0.8 percent vs. 1.3 percent ; relative risk , 0.62 ; P=0.02 ) , [ corrected ] heart failure ( 9.1 percent vs. 11.6 percent ; relative risk , 0.77 ; P<0.001 ) , and complications related to diabetes ( 6.4 percent vs. 7.6 percent ; relative risk , 0.84 ; P=0.03 ) . CONCLUSIONS Ramipril significantly reduces the rates of death , myocardial infa rct ion , and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure The reduction in blood pressure ( BP ) after the first dose and after 8 weeks of treatment with a new once-daily angiotensin converting enzyme ( ACE ) inhibitor , ramipril , was examined in 12 untreated hypertensive patients , using ambulatory intraarterial BP monitoring . The first period of monitoring began 24 hours before the first dose was given , and continued for 24 hours afterwards . A second 24-hour period of monitoring was carried out after 8 weeks of treatment , commencing immediately after the morning dose .  Angiotensin II levels and serum drug levels were measured at 0 , 2 , 6 and 24 hours after the acute dose .  BP decreased progressively from the first hour after the first dose , reached a maximum in the fifth hour ( p less than 0.001 ) and then the effect diminished . The maximum reduction of systolic BP in any patient was 64 mm Hg , the minimum 4 mm Hg . Blood pressure was significantly ( p less than 0.05 ) reduced throughout the 24 hours after dosing , with a mean daytime reduction of 13/12 mm Hg , and a mean nighttime reduction of 15/7 mm Hg . Angiotensin II levels were significantly ( p less than 0.02 ) and maximally reduced by 2 hours after administration , but the reduction was no longer significant after 24 hours . Serum drug levels were also maximal 2 hours after administration . The trial population could be clearly divided into groups of good and poor responders on the basis of BP reduction . The angiotensin II levels were higher before treatment , and decreased further , in all patients with a good response than in those with a poor response . ( ABSTRACT TRUNCATED AT 250 WORDS Clinical studies have documented morning-evening , administration-time differences of several different classes of hypertension medications in blood pressure (BP)-lowering efficacy , duration of action , safety profile , and /or effects on the circadian BP pattern . In spite of these published findings , most hypertensive subjects , including those under combination therapy  , are instructed by their physicians and pharmacists to ingest all of their BP-lowering medications in the morning . The potential differential reduction of cardiovascular ( CVD ) morbidity and mortality risk by a bedtime versus upon-awakening treatment schedule has never been evaluated prospect ively . The prospect i ve MAPEC study was specifically design ed to test the hypothesis that bedtime chronotherapy with ≥1 hypertension medications exerts better BP control and CVD risk reduction than conventional therapy , i.e. , all medications ingested in the morning . A total of 2156 hypertensive subjects , 1044 men/1112 women , 55.6 ± 13.6 ( mean ± SD ) yrs of age , were r and omized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime . At baseline , BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h. Physical activity was simultaneously monitored every min by wrist actigraphy to accurately determine the beginning and end of daytime activity and nocturnal sleep . Identical assessment was scheduled annually and more frequently ( quarterly ) if treatment adjustment was required . Despite lack of differences in ambulatory BP between groups at baseline , subjects ingesting medication at bedtime showed at their last available evaluation significantly lower mean sleep-time BP , higher sleep-time relative BP decline , reduced prevalence of non-dipping ( 34 % versus 62 % ; p < .001 ) , and higher prevalence of controlled ambulatory BP ( 62 % versus 53 % ; p < .001 ) . After a median follow-up of 5.6 yrs , subjects ingesting ≥1 BP-lowering medications at bedtime exhibited a significantly lower relative risk of total CVD events than those ingesting all medications upon awakening ( 0.39 [ 0.29–0.51 ] ; number of events 187 versus 68 ; p < .001 ) . The difference between the treatment-time groups in the relative risk of major events ( including CVD death , myocardial infa rct ion , ischemic stroke , and hemorrhagic stroke ) was also highly statistically significant ( 0.33 [ 0.19–0.55 ] ; number of events : 55 versus 18 ; p < .001 ) . The progressive decrease in asleep BP and increase in sleep-time relative BP decline towards a more normal dipping pattern , two novel therapeutic targets requiring proper patient evaluation by ambulatory BP , were best achieved with bedtime therapy , and they were the most significant predictors of event-free survival . Bedtime chronotherapy with ≥1 BP-lowering medications , compared to conventional upon-waking treatment with all medications , more effectively improved BP control , better decreased the prevalence of non-dipping , and , most importantly , significantly reduced CVD morbidity and mortality . ( Author correspondence : rhermida@uvigo.es Background Isolated systolic hyprtension occurs in around 8 % of Chinese people aged 60 years or older . In 1988 , the Systolic Hypertension in China ( Syst-China ) Collaborative Group started to investigate whether active treatment could reduce the incidence of stroke and other cardiovascular complications in older patients with isolated systolic hypertension . Methods All patients were initially started on masked placebo . After stratification for centre , sex and previous cardiovascular complications , alternate patients ( n = 1253 ) were assigned nitrendipine at 10–40 mg daily , with the addition of captopril at 12.5–50.0 mg daily or hydrochlorothiazide at 12.5–50.0 mg daily , or both , if a sufficient blood pressure fall was not obtained . In the remaining 1141 control patients , matching placebos were administered similarly . Results At entry , sitting blood pressure averaged 170.5 mmHg systolic and 86.0 mmHg diastolic , age averaged 66.5 years and total serum cholesterol was 5.1 mmol/l . After 2 years of follow-up , sitting systolic and diastolic blood pressures had fallen by 10.9 mmHg and 1.9 mmHg in the placebo group and by 20.0 mmHg and 5.0 mmHg in the active treatment group . The intergroup differences were 9.1 mmHg systolic ( 95 % confidence interval 7.6–10.7 mmHg ) and 3.2 mmHg diastolic ( 95 % confidence interval 2.4–4.0 ) . Active treatment reduced total strokes by 38 % ( from 20.8 to 13.0 endpoints per 1000 patient-years , P = 0.01 ) , all-cause mortality by 39 % ( from 28.4 to 17.4 endpoints per 1000 patient-years , P = 0.003 ) , cardiovascular mortality by 39 % ( from 15.2 to 9.4 endpoints per 1000 patient-years , P = 0.03 ) , stroke mortality by 58 % ( from 6.9 to 2.9 endpoints per 1000 patient-years , P = 0.02 ) , and all fatal and nonfatal cardiovascular endpoints by 37 % ( from 33.3 to 21.4 endpoints per 1000 patient-years , P = 0.004 ) . Conclusions Antihypertensive treatment prevents stroke and other cardiovascular complications in older Chinese patients with isolated systolic hypertension . Treatment of 1000 Chinese patients for 5 years could prevent 55 deaths , 39 strokes or 59 major cardiovascular endpoints BACKGROUND Isolated systolic hypertension occurs in about 15 % of people aged 60 years or older . In 1989 , the European Working Party on High Blood Pressure in the Elderly investigated whether active treatment could reduce cardiovascular complications of isolated systolic hypertension . Fatal and non-fatal stroke combined was the primary endpoint . METHODS All patients ( > 60 years ) were initially started on masked placebo .  At three run-in visits 1 month apart , their average sitting systolic blood pressure was 160 - 219 mm Hg with a diastolic blood pressure lower than 95 mm Hg . After stratification for centre , sex , and previous cardiovascular complications , 4695 patients were r and omly assigned to nitrendipine 10 - 40 mg daily , with the possible addition of enalapril 5 - 20 mg daily and hydrochlorothiazide 12.5 - 25.0 mg daily , or matching placebos . Patients withdrawing from double-blind treatment were still followed up . We compared occurrence of major endpoints by intention to treat . FINDINGS At a median of 2 years ' follow-up , sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group ( n = 2297 ) and by 23 mm Hg and 7 mm Hg in the active treatment group ( n = 2398 ) . The between-group differences were systolic 10.1 mm Hg ( 95 % CI 8.8 - 11.4 ) and diastolic , 4.5 mm Hg ( 3.9 - 5.1 ) . Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years ( 42 % reduction ; p = 0.003 ) . Non-fatal stroke decreased by 44 % ( p = 0.007 ) . In the active treatment group , all fatal and non-fatal cardiac endpoints , including sudden death , declined by 26 % ( p = 0.03 ) . Non-fatal cardiac endpoints decreased by 33 % ( p = 0.03 ) and all fatal and non-fatal cardiovascular endpoints by 31 % ( p < 0.001 ) . Cardiovascular mortality was slightly lower on active treatment ( -27 % , p = 0.07 ) , but all-cause mortality was not influenced ( -14 % ; p = 0.22 ) . INTERPRETATION Among elderly patients with isolated systolic hypertension , antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications . Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints 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 Hypertension is the most common condition seen in primary care and leads to myocardial infa rct ion , stroke , renal failure , and death if not detected early and treated appropriately . Patients want to be assured that blood pressure ( BP ) treatment will reduce their disease burden , while clinicians want guidance on hypertension management using the best scientific evidence . This report takes a rigorous , evidence -based approach to recommend treatment thresholds , goals , and medications in the management of hypertension in adults . Evidence was drawn from r and omized controlled trials , which represent the gold st and ard for determining efficacy and effectiveness . Evidence quality and recommendations were grade d based on their effect on important outcomes . There is strong evidence to support treating hypertensive persons aged 60 years or older to a  BP goal  of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg ; however , there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal , or in those younger than 30 years for a diastolic goal , so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion . The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease ( CKD ) as for the general hypertensive population younger than 60 years . There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor , angiotensin receptor blocker , calcium channel blocker , or thiazide-type diuretic in the nonblack hypertensive population , including those with diabetes . In the black hypertensive population , including those with diabetes , a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy . There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes . Although this guideline provides evidence -based recommendations for the management of high BP and should meet the clinical needs of most patients , these recommendations are not a substitute for clinical judgment , and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient
target: Nighttime blood pressure strongly predicts cardiovascular events ( CVEs ) .
  Further , a preliminary trial has shown decreased CVEs from evening vs morning dosing of antihypertensive therapy .
  Unlike other EDTs , the Heart Outcomes Prevention Evaluation ( HOPE ) study administered its entire antihypertensive dose prior to sleep and gave the greatest risk reduction .
  This study provides a third type of evidence suggesting a beneficial effect from evening dosing of antihypertensive therapy .
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