Pulse pressure and risk of cardiovascular events in the systolic hypertension in the elderly program. Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation (APACHE-AF): study protocol for a randomised controlled trial Pulse pressure as a predictor of stroke Dual antiplatelet therapy versus oral anticoagulation plus dual antiplatelet therapy in patients with atrial fibrillation and low-to-moderate thromboembolic risk undergoing coronary stenting: design of the MUSICA-2 randomized trial. Blood pressure and isolated systolic hypertension and the risk of coronary heart disease and mortality in elderly men (the Zutphen Elderly Study) Efficacy of antiplatelet treatment in hypertensive patients with TIA or stroke. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin 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). The Role of Angry Rumination and Distraction in Blood Pressure Recovery From Emotional Arousal The Association between Heart Rate and Blood Pressure, Blood Lipids and Other Cardiovascular Risk Factors Use of ramipril in preventing stroke: double blind randomised trial Systolic Blood Pressure, Diastolic Blood Pressure, and Pulse Pressure as Predictors of Risk for Congestive Heart Failure in the Framingham Heart Study The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: The Systolic Blood Pressure Intervention Trial (SPRINT) Irbesartan in patients with atrial fibrillation. [Study of combined anticoagulant (fluindione)-aspirin therapy in patients with atrial fibrillation at high risk for thromboembolic complications. A randomized trial (FFAACS)]. Diastolic Blood Pressure, Subclinical Myocardial Damage, and Cardiac Events: Implications for Blood Pressure Control. A Randomised Controlled Trial of Counseling in a Workplace Setting for Coronary Heart Disease Risk Factor Modification: Effects on Blood Pressure Blood pressure and prognosis in patients with incident heart failure: the Diet, Cancer and Health (DCH) cohort study Dogma Disputed: Can Aggressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous? 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. Systolic blood pressure variability as a risk factor for stroke and cardiovascular mortality in the elderly hypertensive population 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.
Pulse pressure has been related to higher risk of cardiovascular events in older persons . Isolated systolic hypertension is common among the elderly and is accompanied by elevated pulse pressure . Treatment of isolated systolic hypertension may further increase pulse pressure if diastolic pressure is lowered to a greater extent than systolic pressure . Little is known regarding pulse pressure as a predictor of cardiovascular outcomes in elderly persons with isolated systolic hypertension , and the influence of treatment on the pulse pressure effect . We assessed the relation between pulse pressure , measured throughout the follow-up period , and the incidence of coronary heart disease ( CHD ) , heart failure ( HF ) , and stroke in 4,632 participants in the Systolic Hypertension in the Elderly Program , a 5-year r and omized , placebo-controlled clinical trial of treatment of isolated systolic hypertension in older adults . In the treatment group , a 10-mm Hg increase in pulse pressure was associated with a statistically significant 32 % increase in risk of HF and a 24 % increase in risk of stroke after controlling for systolic blood pressure and other known risk factors , as well as with a 23 % increase in risk of HF and a 19 % increase in risk of stroke after controlling for diastolic blood pressure and other risk factors . Pulse pressure was not significantly associated with HF or stroke in the placebo group , nor with incidence of CHD in either the placebo or treatment group . These results suggest that pulse pressure is a useful marker of risk for HF and stroke among older adults being treated for isolated systolic hypertension Background There is a marked lack of evidence on the optimal prevention of ischaemic stroke and other thromboembolic events in patients with non-valvular atrial fibrillation and a recent intracerebral haemorrhage during treatment with oral anticoagulation .  These patients are currently treated with oral anticoagulants , antiplatelet drugs , or no antithrombotic treatment , depending on personal and institutional preferences . Compared with warfarin , the direct oral anticoagulant apixaban reduces the risk of stroke or systemic embolism , intracranial haemorrhage , and case fatality in patients with atrial fibrillation . Compared with aspirin , apixaban reduces the risk of stroke or systemic embolism in patients with atrial fibrillation , and has a similar risk of intracerebral haemorrhage . Novel oral anticoagulants have not been evaluated in patients with atrial fibrillation and a recent intracerebral haemorrhage . To inform a phase III trial , the phase II Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation ( APACHE-AF ) trial aims to obtain estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage treated with apixaban and in those in whom oral anticoagulation is avoided . Methods / Design APACHE-AF is a phase II , multicentre , open-label , parallel-group , r and omised clinical trial with masked outcome assessment . One hundred adults with a history of atrial fibrillation and a recent intracerebral haemorrhage during treatment with anticoagulation in whom clinical equipoise exists on the optimal stroke prevention strategy will be enrolled in 14 hospitals in The Netherl and s . These patients will be r and omly assigned in a 1:1 ratio to either apixaban or to avoiding oral anticoagulation . Patients in the control group may be treated with antiplatelet drugs at the discretion of the treating physician . The primary outcome is the composite of vascular death or non-fatal stroke during follow-up . We aim to include 100 patients in 2.5 years . All patients will be followed-up for the duration of the study , but at least for 1 year . Recruitment commenced in September 2014 and is ongoing . This trial is funded by the Dutch Heart Foundation ( 2012 T077 ) and ZonMW (015008048).Trial registration NTR4526 ( 16 April 2014 ) The current guidelines for the detection and management of  high blood pressure  depend exclusively on the measurement of  systolic and diastolic blood pressure  , although these are only two specific points on the arterial pressure wave form [ 1,2 ] . However , it may be more appropriate to describe the cardiac cycle as consisting of a pulsatile ( pulse pressure ) and a steady ( mean pressure ) component . Pulse pressure is defined as the difference between systolic and diastolic pressures and primarily reflects the stiffness of large arteries , especially the aorta . Elevated pulse pressure increases the stretch of arteries , induces fatigue and fracture of elastic elements , and accelerates the development of aneurysms , and ultimately their rupture . Similarly , an increased pulse pressure is more likely to contribute to intimal damage , the prelude to atherosclerosis and arterial thrombotic events . Increased pulse pressure has also been associated with thickening of the carotid intima and media [ 3,4 ] . Systolic blood pressure increases across all age groups , whereas diastolic blood pressure increases until the sixth decade of life and then declines thereafter . As a result , pulse pressure increases as age rises , especially in older people as systolic and diastolic blood pressure move in opposite directions . Hence , pulse pressure may become the key blood pressure measure in older individuals and increase in importance as a risk factor for cerebrovascular diseases and death [ 5,6 ] . Several observational studies have found that pulse pressure is an independent predictor of cardiovascular risk in middle aged and older people , in subjects with high blood pressure , in survivors of myocardial infa rct ion and in patients with left ventricular dysfunction [ 7–11 ] . A meta analysis based on individual patient data from three large trials ( Syst-Eur , SystChina and EWPHE [ 12–14 ] ) showed that isolated systolic hypertension and pulse pressure were the major determinants of cardiovascular risk in elderly hypertensives [ 7 ] . A further meta- analysis of individual patient data in control groups of seven r and omized clinical trials ( SHEP , Syst-Eur , MRC 1 , HEP , MRC 2 , EWPHE and STOP ) in the INDANA project [ 8 ] also reported that pulse pressure , rather than mean pressure , was the major risk factor for adverse cardiovascular events . A 10-mmHg increase in pulse pressure at baseline was associated independently with a 6 % rise in total mortality , a 7 % rise in cardiovascular mortality and a 7 % rise in fatal coronary events . A similar rise in fatal stroke was present , although this was statistically nonsignificant due to the limited number of events . However , the relationship between pulse pressure and fatal stroke became significant ( p = 0.04 ) at higher age [ 8 ] . Importantly , pulse pressure calculated from 24 h ambulatory blood pressure recordings is a better predictor of adverse events than if derived from officemeasured blood pressure in older patients with isolated systolic hypertension [ 15 ] BACKGROUND Oral anticoagulation ( OAC ) is the recommended therapy for patients with atrial fibrillation ( AF ) because it reduces the risk of stroke and other thromboembolic events . Dual antiplatelet therapy ( DAPT ) is required after percutaneous coronary intervention and stenting ( PCI-S ) . In patients with AF requiring PCI-S  , the association of DAPT and OAC carries an increased risk of bleeding , whereas OAC therapy or DAPT alone may not protect against the risk of developing new ischemic or thromboembolic events . OBJECTIVE The MUSICA-2 study will test the hypothesis that DAPT compared with triple therapy ( TT ) in patients with nonvalvular AF at low-to-moderate risk of stroke ( CHADS2 score ≤2 ) after PCI-S reduces the risk of bleeding and is not inferior to TT for preventing thromboembolic complications . DESIGN The MUSICA-2 is a multicenter , open-label r and omized trial that will compare TT with DAPT in patients with AF and CHADS2 score ≤2 undergoing PCI-S.  The primary end point is the incidence of stroke or any systemic embolism or major adverse cardiac events : death , myocardial infa rct ion , stent thrombosis , or target vessel revascularization at 1 year of PCI-S. The secondary end point is the combination of any cardiovascular event with major or minor bleeding at 1 year of PCI-S. The calculated sample size is 304 patients . CONCLUSIONS The MUSICA-2 will attempt to determine the most effective and safe treatment in patients with nonvalvular AF and CHADS2 score ≤2 after PCI-S. Restricting TT for AF patients at high risk for stroke may reduce the incidence of bleeding without increasing the risk of thromboembolic complications Objective To investigate the associations of diastolic blood pressure ( DBP ) and systolic blood pressure ( SBP ) with the risk of coronary heart disease , sudden cardiac and all-cause death in elderly men . Design A cohort study . Setting The Dutch town of Zutphen . Subjects Eight hundred and eighty-five r and omly selected men , aged 64 - 84 years . Main outcome measures Relative risks adjusted for age , body mass index , total and high-density lipoprotein cholesterol , cigarette smoking , alcohol consumption , use of blood pressure-lowering medications without a specific indication for hypertension , and the physician who measured the blood pressure . Results Neither DBP nor SBP was associated significantly with the incidence of a first coronary heart disease event and no clear associations were observed with mortality from coronary heart disease . However , positive associations with sudden cardiac death were observed . The adjusted relative risk for men with definite isolated systolic hypertension was 9.20 . The risk of dying from coronary heart disease not recorded additionally as sudden death was highest in men at the lower end of the DBP and SBP distributions and in men using antihypertensives . DBP and SBP were positively associated with all-cause mortality when possible comorbidity at the time of the blood pressure measurement was accounted for . Overall , the highest risk for all endpoints was observed in men on antihypertensive medication , who formed a distinct group with a clustering of cardiovascular risk factors . Conclusion Elevated DBP and SBP , and especially isolated systolic hypertension , are important predictors of sudden cardiac death in elderly men . The highest risk of nonsudden coronary heart disease mortality was found at the lower end of the blood pressure distributions and among men on antihypertensive medication We performed a subgroup analysis of the first European Stroke Prevention Study including 1,306 patients recruited in a single center , Kuopio , Finl and , to investigate whether or not antiplatelet therapy is effective in the secondary prevention of stroke in hypertensive patients with transient ischemic attack ( TIA ) or stroke . The patients were treated with aspirin , 990 mg/day , plus dipyridamole , 225 mg/day , or placebo for 2 years . The patients with high systolic blood pressure ( > or = 140 mm Hg ; n = 1.105 ) or high diastolic blood pressure ( > or = 85 mm Hg ; n = 1,120 ) at entry , were classified into subgroups by blood pressure level . The effect of treatment was statistically significant in all subgroups with high systolic ( end-point reduction , 55.2 - 68.2 % ) and diastolic blood pressure ( end-point reduction , 47.3 - 82.1 % ) . Risk reduction was , however , greatest in patients with the highest diastolic blood pressure . One possible explanation is that platelets are more activated in these patients , and this can be effectively prevented by antiplatelet therapy . Further studies are needed to confirm this hypothesis 99mTc : technetium-99 m 201TI : thallium 201 ABCB1 : ATP-binding cassette sub-family B member 1 ABI : ankle-brachial index ACC : American College of Cardiology ACCF : American College of Cardiology Foundation ACCOMPLISH : Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension ACE : angiotensin converting enzyme ACIP : Asymptomatic Cardiac Ischaemia Pilot ACS : acute coronary syndrome ADA : American Diabetes Association ADP : adenosine diphosphate AHA : American Heart Association ARB : angiotensin II receptor antagonist ART : Arterial Revascularization Trial ASCOT : Anglo-Sc and inavian Cardiac Outcomes Trial ASSERT : Asymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the atrial fibrillation Reduction atrial pacing Trial AV : atrioventricular BARI 2D : Bypass Angioplasty Revascularization Investigation 2 Diabetes BEAUTIFUL : Morbidity-Mortality Evaluation of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease and Left Ventricular Dysfunction BIMA : bilateral internal mammary artery BMI : body mass index BMS : bare metal stent BNP : B-type natriuretic peptide BP : blood pressure b.p.m . : beats per minute CABG : coronary artery bypass graft CAD : coronary artery disease CAPRIE : Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events CASS : Coronary Artery Surgery Study CCB : calcium channel blocker CCS : Canadian Cardiovascular Society CFR : coronary flow reserve CHARISMA : Clopidogrel for High Atherothrombotic Risk and Ischaemic Stabilization , Management and Avoidance CI : confidence interval CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease Epidemiology Collaboration CMR : cardiac magnetic resonance CORONARY : The CABG Off or On Pump Revascularization Study COURAGE : Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation COX-1 : cyclooxygenase-1 COX-2 : cyclooxygenase-2 CPG : Committee for Practice Guidelines CT : computed tomography CTA : computed tomography angiography CV : cardiovascular CVD : cardiovascular disease CXR : chest X-ray CYP2C19 * 2 : cytochrome P450 2C19 CYP3A : cytochrome P3A CYP3A4 : cytochrome P450 3A4 CYP450 : cytochrome P450 DANAMI : Danish trial in Acute Myocardial Infa rct ion DAPT : dual antiplatelet therapy DBP : diastolic blood pressure DECOPI : Desobstruction Coronaire en Post-Infa rct us DES : drug-eluting stents DHP : dihydropyridine DSE : dobutamine stress echocardiography EACTS : European Association for Cardiothoracic Surgery EECP : enhanced external counterpulsation EMA : European Medicines Agency EASD : European Association for the Study of Diabetes ECG : electrocardiogram Echo : echocardiogram ED : erectile dysfunction EF : ejection fraction ESC : European Society of Cardiology EXCEL : Evaluation of XIENCE PRIME or XIENCE V vs. Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization FAME : Fractional Flow Reserve vs. Angiography for Multivessel Evaluation FDA : Food & Drug Administration ( USA ) FFR : fractional flow reserve FREEDOM : Design of the Future Revascularization Evaluation in patients with Diabetes mellitus : Optimal management of Multivessel disease GFR : glomerular filtration rate HbA1c : glycated haemoglobin HDL : high density lipoprotein HDL-C : high density lipoprotein cholesterol HR : hazard ratio HRT : hormone replacement therapy hs-CRP : high-sensitivity C-reactive protein HU : Hounsfield units ICA : invasive coronary angiography IMA : internal mammary artery IONA : Impact Of Nicor and il in Angina ISCHEMIA : International Study of Comparative Health Effectiveness with Medical and Invasive Approaches IVUS : intravascular ultrasound JSAP : Japanese Stable Angina Pectoris KATP : ATP-sensitive potassium channels LAD : left anterior descending LBBB : left bundle branch block LIMA : Left internal mammary artery LDL : low density lipoprotein LDL-C : low density lipoprotein cholesterol LM : left main LMS : left main stem LV : left ventricular LVEF : left ventricular ejection fraction LVH : left ventricular hypertrophy MACE : major adverse cardiac events MASS : Medical , Angioplasty , or Surgery Study MDRD : Modification of Diet in Renal Disease MERLIN : Metabolic Efficiency with Ranolazine for Less Ischaemia in Non-ST-Elevation Acute Coronary Syndromes MERLIN-TIMI 36 : Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes : Thrombolysis In Myocardial Infa rct ion MET : metabolic equivalents MI : myocardial infa rct ion MICRO-HOPE : Microalbuminuria , cardiovascular and renal sub- study of the Heart Outcomes Prevention Evaluation study MPI : myocardial perfusion imaging MRI : magnetic resonance imaging NO : nitric oxide NSAIDs : non-steroidal anti-inflammatory drugs NSTE-ACS : non-ST-elevation acute coronary syndrome NYHA : New York Heart Association OAT : Occluded Artery Trial OCT : optical coherence tomography OMT : optimal medical therapy PAR-1 : protease activated receptor type 1 PCI : percutaneous coronary intervention PDE5 : phosphodiesterase type 5 PES : paclitaxel-eluting stents PET : positron emission tomography PRECOMBAT : Premier of R and omized Comparison of Bypass Surgery vs. Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease PTP : pre-test probability PUFA : polyunsaturated fatty acid PVD : peripheral vascular disease QoL : quality of life RBBB : right bundle branch block REACH : Reduction of Atherothrombosis for Continued Health RITA-2 : Second R and omized Intervention Treatment of Angina ROOBY : Veterans Affairs R and omized On/Off Bypass SAPT : single antiplatelet therapy  SBP : systolic blood pressure SCAD : stable coronary artery disease SCORE : Systematic Coronary Risk Evaluation  SCS : spinal cord stimulation SES : sirolimus-eluting stents SIMA : single internal mammary artery SPECT : single photon emission computed tomography STICH : Surgical Treatment for Ischaemic Heart Failure SWISSI II : Swiss Interventional Study on Silent Ischaemia Type II SYNTAX : SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery TC : total cholesterol TENS : transcutaneous electrical neural stimulation TERISA : Type 2 Diabetes Evaluation of Ranolazine  in Subjects With Chronic Stable Angina TIME : Trial of Invasive vs. Medical therapy TIMI : Thrombolysis In Myocardial Infa rct ion TMR : transmyocardial laser revascularization TOAT : The Open Artery Trial WOEST : What is the Optimal antiplatElet and anticoagulant therapy  in patients with oral anticoagulation and coronary StenTing Guidelines summarize and evaluate all evidence available , at the time of the writing process , on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient with a given condition , taking into account the impact on outcome , as well Abstract Objective : To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice . Design : R and omised controlled trial . Participants : 729 patients aged ≥60 years with atrial fibrillation , recruited in general practice , who had no established indication for coumarin . Mean age was 75 years and mean follow up 2.7 years . Setting : Primary care in the Netherl and s. Interventions : Patients eligible for st and ard intensity coumarin ( international normalised ratio 2.5 - 3.5 ) were r and omly assigned to st and ard anticoagulation , very low intensity coumarin ( international normalised ratio 1.1 - 1.6 ) , or aspirin ( 150 mg/day ) ( stratum 1 ) . Patients ineligible for st and ard anticoagulation were r and omly assigned to low anticoagulation or aspirin ( stratum 2 ) . Main outcome measures : Stroke , systemic embolism , major haemorrhage , and vascular death . Results : 108 primary events occurred ( annual event rate 5.5 % ) , including 13 major haemorrhages ( 0.7 % a year ) . The hazard ratio was 0.91 ( 0.61 to 1.36 ) for low anticoagulation versus aspirin and 0.78 ( 0.34 to 1.81 ) for st and ard anticoagulation versus aspirin . Non-vascular death was less common in the low anticoagulation group than in the aspirin group ( 0.41 , 0.20 to 0.82 ) . There was no significant difference between the treatment groups in bleeding incidence . High systolic and low diastolic blood pressure and age were independent prognostic factors . Conclusion : In a general practice population ( without established indications for coumarin ) neither low nor st and ard intensity anticoagulation is better than aspirin in preventing primary outcome events . Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice . Key messages Studies have shown that patients with non-rheumatic atrial fibrillation may benefit from anticoagulation This study in a general practice population found no benefit of st and ard or low dose anticoagulation on risk of stroke , systemic embolism , major haemorrhage , or vascular death when compared with aspirin Hypertension and age were prognostic factors for event occurrence Aspirin is the treatment of choice for preventing thromboembolism in primary care patients at low ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle – brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute C and esartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease : Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A R and omized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Sc and inavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Sc and inavian Cardiac Outcomes Trial — Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : C And esartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease — EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy C and esartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease  EXPLOR : Amlodipine – Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine – Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infa rct ion in 52 Countries INVEST : INternational VErapamil SR/T Tr and olapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention : an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : r and omized controlled trials RF : risk factor ROADMAP : R and omized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker C and esartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly : Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan R and omised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospect i ve Diabetes Study VADT : Veterans ' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization # # # 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension ( ESH ) and the European Society of Cardiology Objective : Cardiovascular recovery of prestress baseline blood pressure has been implicated as a possible additional determinant of sustained blood pressure elevation . We hypothesize that angry ruminations may slow the recovery process . Method : A within-subjects design was used in which resting baseline blood pressure and heart rate measurements were assessed on 60 subjects , who then took part in two anger-recall tasks .  After each task , subjects sat quietly and alone during a 12-minute recovery period r and omized to with or without distractions . During baseline , task , and recovery , blood pressure was continuously monitored ; during recovery , subjects reported their thoughts at five fixed intervals . Results : Fewer angry thoughts were reported in the distraction condition ( 17 % ) compared with no distraction ( 31 % ; p = .002 ) ; an interaction showed that this effect was largely the result of the two intervals immediately after the anger-recall task . Trait rumination interacted with distraction condition such that high ruminators in the no-distraction condition evidence d the poorest blood pressure recovery , assessed as area under the curve ( p = .044 [ systolic blood pressure ] and p = .046 [ diastolic pressure ] ) . Conclusions : People who have a tendency to ruminate about past anger-provoking events may be at greater risk for target organ damage as a result of sustained blood pressure elevations ; the effect is exacerbated when distractions are not available to interrupt the ruminative process . ANOVA = analysis of variance ; AUC = area under the curve ; BP = blood pressure ; HTN = hypertension ; CHD = coronary heart disease ; CVR = cardiovascular reactivity ; CVD = cardiovascular disease ; HR = heart rate ; DAB-VR = Destructive Anger Behavior-Verbal Rumination ; DBP = diastolic BP ; HPA = hypothalamic-pituitary-adrenal ; SBP = systolic BP Background : Several studies have shown that an elevated heart rate is associated with an increased risk of ischaemic heart disease . The aim of this study was to examine the relationship between heart rate , blood pressure , blood lipids and other cardiovascular risk factors in middle-aged men . Methods : A total of 7735 men , aged 40–59 years at screening , were selected at r and om from one of the general practice s in each of the 24 towns participating in the cross-sectional ( screening ) phase of the British Regional Heart Study .  Blood pressure and levels of blood lipids ( serum total cholesterol , high-density-lipoprotein ( HDL ) cholesterol and triglycerides ) and blood glucose  were measured . Results : All men with pre-existing evidence of ischaemic heart disease and those on regular antihypertensive treatment were excluded from the analysis . In the remaining 5597 men , heart rate showed a strong positive correlation with cigarette smoking and body-mass index and decreased significantly at higher levels of physical activity and FEV1 ( forced expiratory volume in 1 s ) . These associations remained significant after adjustment for each other . Age , alcohol intake and social class were not independently associated with heart rate . There was a significant positive association between heart rate and systolic and diastolic blood pressures , levels of blood cholesterol , triglycerides and blood glucose and a significant inverse association between heart rate and HDL-cholesterol levels , even after adjusting for the above confounding factors . After further adjustment for each of the other physiological variables , heart rate remained independently associated with diastolic and systolic blood pressures and levels of triglycerides and blood glucose . The relationship between heart rate and levels of total cholesterol and HDL cholesterol appeared to be secondary to its association with triglyceride levels . The association between body-mass index and heart rate diminished after further adjustments for systolic blood pressure , suggesting that the primary effect of body weight is on blood pressure rather than on heart rate . Conclusion : Our findings indicate that elevated heart rate is associated with hypertension and with an atherogenic lipoprotein profile and support the suggestion that disturbance of the autonomic nervous system may underlie these associations Abstract Objective : To determine the effect of the angiotensin converting enzyme inhibitor ramipril on the secondary prevention of stroke . Design : R and omised controlled trial with 2 × 2 factorial design . Setting : 267 hospitals in 19 countries . Participants : 9297 patients with vascular disease or diabetes plus an additional risk factor , followed for 4.5 years as part of the HOPE study . Outcome measures : Stroke ( confirmed by computed tomography or magnetic resonance imaging when available ) , transient ischaemic attack , and cognitive function . Blood pressure was recorded at entry to the study , after 2 years , and at the end of the study . Results : Reduction in blood pressure was modest ( 3.8 mm Hg systolic and 2.8 mm Hg diastolic ) . The relative risk of any stroke was reduced by 32 % ( 156 v 226 ) in the ramipril group compared with the placebo group , and the relative risk of fatal stroke was reduced by 61 % ( 17 v 44 ) . Benefits were consistent across baseline blood pressures , drugs used , and subgroups defined by the presence or absence of previous stroke , coronary artery disease , peripheral arterial disease , diabetes , or hypertension . Significantly fewer patients on ramipril  had cognitive or functional impairment . Conclusion : Ramipril  reduces the incidence of stroke in patients at high risk , despite a modest reduction in blood pressure . What is already known on this topic Treatment with aspirin and lowering blood pressure reduce the incidence of stroke What this study adds Ramipril , an angiotensin converting enzyme inhibitor , reduces strokes in patients at high risk whose blood pressure is not elevated , despite only a modest lowering of blood pressure The benefits are observed even when patients receive aspirin and other blood pressure lowering Context Hypertension is a recognized risk factor for the development of congestive heart failure ( CHF ) . By measuring blood pressure , however , we have not yet been able to underst and the significance of pulse pressure as a contributor to CHF in middle-aged men and women . Contribution Using data from the Framingham Heart Study , the authors found that although elevations of systolic , diastolic , and pulse pressure were all related to the risk for CHF , the relation was strongest for systolic and pulse pressure . Caution s Underst and ing the relationships between systolic , diastolic , and pulse pressure and risk for CHF is helpful ; however , they do not help determine the increased risk faced by a person with systolic hypertension who also has increased pulse pressure . The Editors Hypertension is the most common risk factor for congestive heart failure ( CHF ) . It confers a twofold risk for the occurrence of CHF and also carries the highest population attributable risk among all risk factors for CHF ( 1 , 2 ) . Placebo-controlled clinical trials in patients with hypertension have demonstrated a consistent reduction in risk for CHF attributable to the lowering of elevated blood pressure ( 3 - 6 ) . The causal role of hypertension in the pathogenesis of CHF underscores the need to identify high-risk patients because early treatment may prevent or delay the occurrence of CHF ( 2 , 7 ) . The prognostic significance of systolic and diastolic blood pressure in CHF has been reported . However , blood pressure may also be divided into two other components : steady ( mean arterial pressure ) and pulsatile ( pulse arterial pressure ) ( 8 - 10 ) . Pulse pressure , a simple correlate of conduit vessel stiffness , is associated with left ventricular hypertrophy ( 11 ) . Increased pulse pressure has also been implicated in the development and progression of large-vessel atherosclerosis and small-vessel disease ( 12 - 14 ) . Accumulating evidence indicates that pulse pressure ( defined as the difference between systolic and diastolic blood pressure ) may be an important predictor of cardiovascular events ( 15 - 18 ) . Pulse pressure predicts the risk for CHF in elderly persons ( 19 , 20 ) ; however , the association of pulse pressure with CHF in middle-aged men and women has not been examined . The Framingham Heart Study provides an opportunity to examine the long-term associations of systolic , diastolic , and pulse pressure with the new onset of  CHF in middle-aged and elderly men and women .  Blood pressure and traditional risk factors have been measured repeatedly at serial examinations in this community-based cohort with long-term follow-up . We examined systolic blood pressure , diastolic blood pressure , and pulse pressure as predictors of risk for CHF in the Framingham Heart Study . Methods The Framingham Heart Study , which began in 1948 , has followed 5209 participants ( 28 to 62 years of age at entry to the study ) as part of a prospect i ve epidemiologic study of cardiovascular disease . Enrollment criteria and study design have been published previously ( 21 ) . Biennial follow-up visits included a medical history , physical examination , blood pressure measurements , 12-lead electrocardiography , and laboratory tests . Eligibility requirements for inclusion in our study were as follows : Participants had to be free of coronary heart disease and CHF and not be receiving antihypertensive therapy at Framingham Heart Study clinic baseline examinations 10 , 11 , or 12 ( 1968 to 1973 ) . Participants were followed for onset of CHF through mid-1994 . We obtained data for selected risk factors from the baseline examination . Methods for assessing risk factors have been published previously ( 21 , 22 ) . Risk factors , including age , sex , cigarette smoking , heart rate , antihypertensive medication use , and total and high-density lipoprotein cholesterol levels , were assessed .  Sitting systolic and diastolic blood pressure were measured twice by the examining physician ( using a mercury column sphygmomanometer ) and averaged . We used body mass index ( kg/m2 ) as a measure of obesity . Participants were categorized as smokers if they smoked cigarettes regularly within the 1-year period before the baseline examination . Electrocardiography revealed left ventricular hypertrophy when increased voltage was associated with major ST-T repolarization changes ( strain pattern ) ( 22 ) . Diabetes mellitus was defined on the basis of a fasting blood glucose level greater than 7.77 mmol/L ( > 140 mg/dL ) , two r and om nonfasting blood glucose levels greater than 11.10 mmol/L ( > 200 mg/dL ) , or the use of insulin or an oral hypoglycemic agent . Diagnostic criteria for CHF have been described previously ( 21 , 22 ) . At each clinic examination , a history of interim hospitalizations and symptoms of CHF were obtained . Outside medical records of participants who did not attend an examination were evaluated for incident CHF . All suspected interim events were review ed by a panel of three physicians who evaluated relevant Framingham Heart Study clinic notes , outside physician reports , and hospitalization records . Congestive heart failure was diagnosed when at least two major or one major and two minor criteria were present . Minor criteria were considered only if their presence could not be attributed to another disease process . Major criteria were paroxysmal nocturnal dyspnea , pulmonary rales , distended jugular veins , enlarging heart size on chest radiography , acute pulmonary edema , hepatojugular reflux , third heart sound , jugular venous pressure of 16 cm or greater , and weight loss of 4.5 kg or greater in response to diuresis . Major criteria also included pulmonary edema , visceral congestion , or cardiomegaly on autopsy . Minor criteria were bilateral ankle edema , nocturnal cough , shortness of breath on ordinary exertion , hepatomegaly , pleural effusion , decrease in vital capacity by one third from the previous maximum recorded value , and heart rate of 120 beats/min or more . Statistical Analysis We used multivariable Cox proportional-hazards regression models to examine the relations of systolic , diastolic , and pulse pressure with CHF . After accounting for age and sex and using a P value less than 0.15 as the selection criterion , we determined covariates by stepwise selection from the following list : body mass index , diabetes , smoking status , total cholesterol level , high-density lipoprotein ( HDL ) cholesterol level , totalHDL cholesterol ratio , left ventricular hypertrophy , and heart rate . Only total cholesterol level and totalHDL cholesterol ratio did not enter the model . After accounting for relevant covariates , we used Cox proportional-hazards models to obtain hazard ratio estimates with 95 % CIs for st and ardized values of systolic , diastolic , and pulse pressure . These estimates were obtained individually and pairwise by using SAS software ( SAS Institute , Inc. , Cary , North Carolina ) ( 23 ) . We repeated analyses for participants stratified according to hypertension status and sex . Because blood pressure and age are correlated , we conducted separate analyses for participants younger than 60 years of age and 60 years of age and older . To examine constancy of effects over time , follow-up was divided into early and late periods ( < 10 years , 10 years ) , and hazard ratios were calculated separately for early and late follow-up . In addition , we analyzed blood pressure as a time-varying covariate and assessed the effect of antihypertensive treatment after the baseline blood pressure measurements . We used the KaplanMeier method to plot age- and sex-st and ardized cumulative incidence rates for CHF as a function of pulse pressure tertile at baseline . Descriptive data are presented as percentages or means ( SD ) . A P value less than 0.05 was considered statistically significant . Role of the Funding Sources The funding sources had no role in the design , conduct , analyses , and reporting of the study or in the decision to su bmi t the manuscript for publication . Results A total of 894 men and 1146 women , age 50 to 79 years , fulfilled criteria for inclusion in our study . Table 1 presents baseline clinical characteristics for these persons . During 35 497 person-years of follow-up ( mean , 17.4 years [ range , 0.06 to 24 years ] ) , CHF developed in 234 ( 11.8 % ) persons . Myocardial infa rct ion preceded CHF in 59 ( 25 % ) persons . Table 1 . Baseline Clinical Characteristics of the Study Participants Increments of 1 SD in systolic pressure , pulse pressure , and diastolic pressure were associated with hazard ratios for congestive failure of 1.56 , 1.55 , and 1.24 , respectively , after adjustment for age , sex , smoking , left ventricular hypertrophy , body mass index , diabetes mellitus , HDL cholesterol level , and heart rate ( Table 2 ) . When blood pressure tertiles were used , similar associations were observed among various components of blood pressure and CHF . No threshold effect or J-shaped association was documented ( Table 2 ) . The cumulative incidence of CHF according to tertiles of baseline pulse pressure is plotted in the Figure . Table 2 . Risk FactorAdjusted Association of Blood Pressure with Congestive Heart Failure Figure . Cumulative incidence of congestive heart failure according to pulse pressure tertiles at the baseline examination . The joint influences of different blood pressure components were also examined , with adjustment for the covariates mentioned previously . Of note , correlations among the blood pressure variables ranged from modest to very high ( r = 0.20 for diastolic and pulse pressure , r = 0.65 for diastolic and systolic pressure , and r = 0.88 for systolic and pulse pressure ) . Diastolic pressure was not significant ( hazard ratio , 1.12 [ CI , 0.98 to 1.29 ] ) in conjunction with pulse pressure ( hazard ratio , 1.51 [ CI , 1.33 to 1.72 ] ) . Likewise , diastolic pressure was not significant ( hazard ratio , 0.86 [ CI , 0.72 to 1.03 ] ) in conjunction with systolic pressure ( hazard ratio , 1.71 [ CI , 1.45 to 2.01 ] ) , but joint estimates were less stable than those obtained for individual pressure variables . Finally Background : High blood pressure is an important public health concern because it is highly prevalent and a risk factor for adverse health outcomes , including coronary heart disease , stroke , decompensated heart failure , chronic kidney disease , and decline in cognitive function . Observational studies show a progressive increase in risk associated with blood pressure above 115/75 mm Hg . Prior research has shown that reducing elevated systolic blood pressure lowers the risk of subsequent clinical complications from cardiovascular disease . However , the optimal systolic blood pressure to reduce blood pressure – related adverse outcomes is unclear , and the benefit of treating to a level of systolic blood pressure well below 140 mm Hg has not been proven in a large , definitive clinical trial . Purpose : To describe the design considerations of the Systolic Blood Pressure Intervention Trial ( SPRINT ) and the baseline characteristics of trial participants . Methods : The Systolic Blood Pressure Intervention Trial is a multicenter , r and omized , controlled trial that compares two strategies for treating systolic blood pressure : one targets the st and ard target of < 140 mm Hg , and the other targets a more intensive target of < 120 mm Hg . Enrollment focused on volunteers of age ≥50 years ( no upper limit ) with an average baseline systolic blood pressure ≥130 mm Hg and evidence of cardiovascular disease , chronic kidney disease , 10-year Framingham cardiovascular disease risk score ≥15 % , or age ≥75 years . The Systolic Blood Pressure Intervention Trial recruitment also targeted three pre-specified subgroups : participants with chronic kidney disease ( estimated glomerular filtration rate < 60 mL/min/1.73 m2 ) , participants with a history of cardiovascular disease , and participants 75 years of age or older . The primary outcome is first the occurrence of a myocardial infa rct ion ( MI ) , acute coronary syndrome , stroke , heart failure , or cardiovascular disease death . Secondary outcomes include all-cause mortality , decline in kidney function or development of end-stage renal disease , incident dementia , decline in cognitive function , and small-vessel cerebral ischemic disease . Results : Between 8 November 2010 and 15 March 2013 , Systolic Blood Pressure Intervention Trial recruited and r and omized 9361 people at 102 clinics , including 3331 women , 2648 with chronic kidney disease , 1877 with a history of cardiovascular disease , 3962 minorities , and 2636 ≥75 years of age . Limitations : Although the overall recruitment target was met , the numbers recruited in the high-risk subgroups were lower than planned . Conclusions : The Systolic Blood Pressure Intervention Trial will provide important information on the risks and benefits of intensive blood pressure treatment targets in a diverse sample of high-risk participants , including those with prior cardiovascular disease , chronic kidney disease , and those aged ≥75 years BACKGROUND The risk of cardiovascular events among patients with atrial fibrillation is high . We evaluated whether irbesartan , an angiotensin-receptor blocker , would reduce this risk . METHODS We r and omly assigned patients with a history of risk factors for stroke and a systolic blood pressure of at least 110 mm Hg to receive either irbesartan at a target dose of 300 mg once daily or double-blind placebo . These patients were already enrolled in one of two trials ( of clopidogrel plus aspirin versus aspirin alone or versus oral anticoagulants ) . The first co primary outcome was stroke , myocardial infa rct ion , or death from vascular causes ; the second was this composite outcome plus hospitalization for heart failure . RESULTS A total of 9016 patients were enrolled and followed for a mean of 4.1 years . The mean reduction in systolic blood pressure was 2.9 mm Hg greater in the irbesartan group than in the placebo group , and the mean reduction in diastolic blood pressure was 1.9 mm Hg greater . The first co primary outcome occurred at a rate of 5.4 % per 100 person-years in both groups ( hazard ratio with irbesartan , 0.99 ; 95 % confidence interval [ CI ] , 0.91 to 1.08 ; P=0.85 ) . The second co primary outcome occurred at a rate of 7.3 % per 100 person-years among patients receiving irbesartan and 7.7 % per 100 person-years among patients receiving placebo ( hazard ratio , 0.94 ; 95 % CI , 0.87 to 1.02 ; P=0.12 ) . The rates of first hospitalization for heart failure ( a prespecified secondary outcome ) were 2.7 % per 100 person-years among patients receiving irbesartan and 3.2 % per 100 person-years among patients receiving placebo ( hazard ratio , 0.86 ; 95 % CI , 0.76 to 0.98 ) . Among patients who were in sinus rhythm at baseline , there was no benefit of irbesartan in preventing hospitalization for atrial fibrillation or atrial fibrillation recorded on 12-lead electrocardiography , nor was there a benefit in a subgroup that underwent transtelephonic monitoring . More patients in the irbesartan group than in the placebo group had symptomatic hypotension ( 127 vs. 64 ) and renal dysfunction ( 43 vs. 24 ) . CONCLUSIONS Irbesartan did not reduce cardiovascular events in patients with atrial fibrillation . ( Funded by Bristol-Myers Squibb and Sanofi-Aventis ; Clinical Trials.gov number , NCT00249795 . ) BACKGROUND A combination of low-dose aspirin ( A ) and anticoagulation ( AC ) may provide better protection against thromboembolic events compared with AC alone in high-risk patients with atrial fibrillation ( AF ) . METHODS We performed a multicentric placebo-controlled double blind-trial to test the preventive efficacy against thromboembolic events of the addition of aspirin ( A ) ( 100 mg ) or placebo ( P ) to anticoagulant treatment in patients with high-risk atrial fibrillation . A total of 157 patients were included , with atrial fibrillation and previous thromboembolic event or older than 65 years with either a history of hypertension , a recent episode of heart failure or a left ventricular dysfunction . All patients received fluindione ( F ) and P or F and A , with an INR target between 2 and 2.6 . The primary endpoint was a combined endpoint of stroke ( ischaemic or haemorrhagic ) , myocardial infa rct ion , systemic arterial emboli or vascular death . RESULTS The study had to be stopped prematurely owing to a too low recruitment rate . During follow-up ( 0.84 years ) 3 non-fatal thromboembolic events were recorded ( 1P , 2A ) and 6 patients died ( 3P , 3A ) , none of them from a thromboembolic complication . However , 3 deaths were secondary to severe haemorrhagic complications ( 1P , 2A ) . Non-fatal haemorrhagic complications occurred more often in group A ( n = 10 , 13.1 pour cent ) compared with group P ( n = 1 , 1.2 pour cent ) , p = 0.003 . CONCLUSION The FFAACS study was not able to show any therapeutic benefit from the addition of aspirin to anticoagulant in patients with high-risk AF . Such a combination increased the incidence rate of bleeding complications , which therefore greatly reduces its potential overall benefit BACKGROUND The optimal systolic blood pressure ( SBP ) treatment goal is in question , with SPRINT ( Systolic Blood Pressure Intervention Trial ) suggesting benefit for 120 mm Hg . However , achieving an SBP this low may reduce diastolic blood pressure ( DBP ) to levels that could compromise myocardial perfusion . OBJECTIVES This study sought to examine the independent association of DBP with myocardial damage ( using high-sensitivity cardiac troponin-T [ hs-cTnT ] ) and with coronary heart disease ( CHD ) , stroke , or death over 21 years . METHODS The authors studied 11,565 adults from the ARIC ( Atherosclerosis Risk In Communities ) cohort , analyzing DBP and hs-cTnT associations as well as prospect i ve associations between DBP and events . RESULTS Mean baseline age was 57 years , 57 % of patients were female , and 25 % were black . Compared with persons who had DBP between 80 to 89 mm Hg at baseline ( ARIC visit 2 ) , the adjusted odds ratio of having hs-cTnT ≥14 ng/l at that visit was 2.2 and 1.5 in those with DBP < 60 mm Hg and 60 to 69 mm Hg , respectively . Low DBP at baseline was also independently associated with progressive myocardial damage on the basis of estimated annual change in hs-cTnT over the 6 years between ARIC visits 2 and 4 . In addition , compared with a DBP of 80 to 89 mm Hg , a DBP < 60 mm Hg was associated with incident CHD and mortality , but not with stroke . The DBP and incident CHD association was strongest with baseline hs-cTnT ≥14 ng/l ( p value for interaction < 0.001 ) . Associations of low DBP with prevalent hs-cTnT and incident CHD were most pronounced among patients with baseline SBP ≥120 mm Hg . CONCLUSIONS Particularly among adults with an SBP ≥120 mm Hg , and thus elevated pulse pressure , low DBP was associated with sub clinical myocardial damage and CHD events . When titrating treatment to SBP < 140 mm Hg , it may be prudent to ensure that DBP levels do not fall below 70 mm Hg , and particularly not below 60 mm Hg This paper review s a prospect i ve study of occupational factors in coronary heart disease risk incorporated in a r and omised controlled trial of a worksite based occupational health nurse counseling program for reducing coronary heart disease risk factors . The aim of the trial was to evaluate the longterm effectiveness of the counseling program in persons with mildly elevated risk factor levels . Of the 2 , 489 Australian government employees with mildly elevated risk factor levels who entered the intervention trial , 1 , 937 ( 78 % ) attended a followup examination three years later . This paper reports on changes in systolic and diastolic blood pressure . Multiple linear regression models were used with three-year blood pressure reduction as the dependent variable , intervention status as the main determinant , and sex , age , initial risk level and initial blood pressure as covariates . Although systolic and diastolic blood pressure fell in both the intervention and control groups , intervention was significantly associated with systolic blood pressure change only Background Our objective was to test the hypothesis that elevated blood pressure ( BP ) is associated with increased risk of stroke , bleeding and death in patients with incident heart failure ( HF ) . Methods We conducted a prospect i ve cohort study among subjects who were participants in the Diet , Cancer and Health study , born in Denmark , aged 50–64 years at recruitment . We assessed stroke ( ischemic stroke or systemic embolic events ) , major bleeding , death and the composite endpoint according to degree of BP control in patients with incident HF .  BP  was assessed prior to HF at cohort entry . Results Of the whole cohort of 55,748 subjects , n = 2159 ( 35 % female ) had incident HF , of which 12 % had treatment for hypertension . Median follow-up after incident HF was 3.5 years . High systolic ( SBP ) , diastolic ( DBP ) and pulse ( PP ) pressures were associated with an increased risk of stroke , major bleeding and the composite endpoint . For death and stroke/death , the relation appeared U-shaped for SBP and DBP . When comparing the highest quartile group ( Q4 ) to first quartile group ( Q1 ) , SBP ( Q4 : SBP > 163 mmHg ) was associated with significantly higher adjusted hazard rate ratio ( HR ) for stroke ( HR 1.46 , 95 % CI 1.00–2.14 ) and major bleeding ( HR 1.68 , 95 % CI 1.12–2.53 ) . For DBP ( Q4 : DBP > 94 mmHg ) , adjusted HR was significantly higher for major bleeding ( HR 1.63 , 95 % CI 1.13–2.38 ) . The highest quartile of pulse pressure ( Q4 : PP > 74 mmHg ) was associated with non-significantly higher risk of stroke ( HR 1.40 , 95 % CI 0.94–2.06 ) . Conclusion We have shown for the first time that amongst a population with incident HF , higher baseline systolic , diastolic and pulse pressure levels were associated with a higher rate of adverse events . Our data support the importance for optimised BP control , as part of the holistic management of HF patients Context Experts debate the consequences of excessive lowering of diastolic pressure in patients with hypertension and coronary artery disease . Contribution This report is a secondary analysis of data from a large trial of 2 antihypertensive drug regimens in patients with known coronary artery disease . The authors found a J-shaped relationship between diastolic blood pressure and all-cause death and myocardial infa rct ion , with the increased risk occurring at diastolic blood pressures below 70 to 80 mm Hg , that is , the lower the diastolic pressure , the higher the risk . Caution s The study examined associations between blood pressure and outcomes ; it could not prove that the antihypertensive therapy that lowered diastolic pressure too much caused the adverse outcomes . The Editors For 2 decades , the hypertension literature has been haunted by the phenomenon of a paradoxical increase in morbidity and mortality with an excessive decrease in blood pressure ( J-curve ) . Indeed , several reports have shown that low diastolic pressure is associated with an increased risk for coronary heart disease and related mortality in older adults and in patients taking antihypertensive medications ( 1 - 13 ) . After doing a review and meta- analysis of pertinent studies , Farnett and colleagues ( 14 ) concluded that although there was no consistent J-shaped relationship between stroke and systolic or diastolic pressure , there was a consistent J-shaped relationship for cardiac events and diastolic pressure . These authors stated that this dichotomy in the relationship between diastolic pressure and target organ disease may leave a clinician with the uncomfortable choice of whether to prevent stroke or renal disease at the expense of coronary heart disease . These findings were at variance with the generally accepted dogma formulated by the sixth report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) ( 15 ) , which stated that the relationship between pressure and risk was strong , continuous , independent , predictive and etiologically significant . Within the past decade , the phenomenon of a J-curve has been studied in several large trials of normotensive and hypertensive patients ( 16 - 30 ) . Not surprisingly , arguments regarding whether a J-curve could be clinical ly significant have become somewhat contentious . That is , some rely on evidence that on-treatment diastolic pressure below 70 mm Hg does not increase risk for cardiovascular disease and thus deny an impairment of vital organ perfusion within the usual values achievable by antihypertensive treatment . Others , however , consider the J-curve a more real possibility , particularly for the heart . In contrast to other organs , the heart is perfused mostly during diastole and thus could be more vulnerable to diastolic pressure reduction . If a J-curve did exist , it should be most evident in patients with limited coronary perfusion , in other words , in those with manifest coronary artery disease ( CAD ) . Optimal blood pressure in patients with hypertension and CAD remains controversial because few r and omized clinical trials have been done in this population ( 31 , 32 ) . The International Verapamil-Tr and olapril Study ( INVEST ) ( 33 ) , a r and omized trial , evaluated more than 22000 patients with CAD and hypertension . This patient profile , together with unprecedented levels of blood pressure control , provided a unique opportunity to critically investigate the hypothesis that the risk for CAD would increase with an excessive decrease in diastolic pressure . Methods Study Design and Intervention The INVEST design , methods , and principal results have been previously published ( 33 ) . The trial used an open design with blinded end point assessment . In brief , clinical ly stable patients with CAD and hypertension were r and omly assigned to a verapamil sustained-releasebased or atenolol-based strategy .  Patients with previous myocardial infa rct ion ( MI ) within 3 months of enrollment or class IV or V congestive heart failure were excluded .  Blood pressure goals were based on JNC VI ( systolic pressure < 140 mm Hg and diastolic pressure < 90 mm Hg or systolic pressure < 130 mm Hg and diastolic pressure < 85 mm Hg in patients with diabetes or renal impairment ) ( 15 ) . The addition of tr and olapril or hydrochlorothiazide was recommended when necessary to achieve blood pressure goals . Tr and olapril was also recommended for patients with heart failure , diabetes , or renal impairment . Documented CAD was defined as any of the following : remote ( 3 months before enrollment ) confirmed MI , coronary angiography showing more than 50 % narrowing of at least 1 major coronary artery , diagnosis of classic angina pectoris , or concordant abnormalities on 2 different signals ( electrocardiography , echocardiography , or radionuclide scans ) from stress test findings concordant for ischemia ( for example , ST-segment depression or perfusion defects on radionuclide scanning or wall-motion abnormalities on echocardiography or radionuclide scanning ) . Patient Monitoring and Follow-up Protocol visits were scheduled every 6 weeks for the first 6 months and then biannually until 2 years after the last patient was enrolled . Patients were assessed for response to treatment , symptoms , treatment adherence , and adverse effects at each visit and at the end of the study as detailed elsewhere ( 33 ) . Patient follow-up was complete when we received a final assessment form through the online data system or a death report . The Internet-based electronic data collection method used in INVEST did not accept the entry until all required fields were complete . Blood pressure  was measured by using a st and ard mercury sphygmomanometer with an appropriately sized cuff applied to the upper nondominant arm at heart level . By auscultation at the brachial artery , systolic pressure was recorded at the first Korotkoff sound and diastolic pressure was recorded at the disappearance of the fifth Korotkoff sound . Blood pressure was measured twice , at least 2 minutes apart , and the measurements were averaged . Study Outcomes The primary outcome was the first occurrence of all-cause death , nonfatal MI , or nonfatal stroke by intention-to-treat analysis . The MI and stroke definitions are detailed elsewhere ( 34 ) . These 3 components individually were the main secondary outcomes . For this analysis , additional outcomes included fatal and nonfatal MI , fatal and nonfatal stroke , and average on-treatment blood pressure before outcome or censoring . Ascertainment and blinded adjudication of outcomes were described previously ( 32 ) . Follow-up data were available for 22008 ( 97.5 % ) patients . Statistical Analysis The main conclusions of INVEST were that the 2 treatment strategies were equivalent with respect to the primary outcome , main secondary outcomes , and on-treatment systolic and diastolic pressures . Thus , data for all enrolled patients were combined and included in these analyses following the intention-to-treat principle . A P value of 0.05 or less was considered statistically significant . Patients without a primary outcome event were censored at their latest follow-up visit . Average follow-up systolic and diastolic pressures were calculated for each patient by using all post-baseline results , up to the date of primary outcome or censoring . The baseline value was substituted for patients with no post-baseline data ( n= 1154 ) . In this exploratory analysis , the proportions of patients were pooled by 10 mm Hg strata of average follow-up systolic pressure , and the distribution of primary outcome event rate was evaluated to determine whether the relationship was linear . A similar presentation was prepared for diastolic pressure . Because the frequency distributions seemed consistent with a quadratic curve , a quadratic Cox proportional hazards model was formed for the time to primary outcome for each blood pressure variable , with factors for blood pressure and blood pressure squared . Similarly , the relationship between each 10 mm Hg stratum of average systolic pressure and diastolic pressure and all-cause death , fatal and nonfatal MI , and fatal and nonfatal stroke was evaluated . For the time to primary outcome , a second model was fitted , adjusting for the following baseline covariates : age ( 10-year increments ) , sex , race and ethnicity ( white , Asian , black , Hispanic , multiracial , or other ) , previous MI , heart failure ( classes I to III ) , body mass index in increments of 5 kg/m2 , U.S. residency , renal impairment , peripheral vascular disease , left ventricular hypertrophy , smoking history , coronary revascularization , dyslipidemia , stroke or transient ischemic attack , angina pectoris , arrhythmia , diabetes , cancer , aspirin use , and average systolic pressure or diastolic pressure and systolic pressure squared or diastolic pressure squared . To identify clinical ly relevant interactions between the J-shaped curve and baseline diastolic pressure , demographic characteristics , and comorbid conditions for the primary outcome , a 2-step procedure was used . First , baseline covariates were tested individually by adding the variable and 2 interaction terms ( variablediastolic pressure and variable[diastolic pressure squared ] ) to the Cox proportional hazards model . Variables included were age older than 70 years , sex , previous MI , heart failure ( classes I to III ) , previous stroke or transient ischemic attack , diabetes , cancer , renal impairment , hypercholesterolemia , peripheral vascular disease , smoking history , U.S. residency , body mass index greater than 29 kg/m2 ( mean baseline body mass index ) , and diastolic pressure greater than 86 mm Hg ( mean baseline diastolic pressure ) . The change in log likelihood was used to assess the significance of simultaneously adding the 2 interaction terms . The second step in identifying clinical ly relevant interactions between the J-shaped curve and baseline covariates was to plot the hazard ratios for the primary outcome versus diastolic pressure in the OBJECTIVE To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal ( total ) stroke in isolated systolic hypertension . DESIGN Multicenter , r and omized , double-blind , placebo-controlled . SETTING Community-based ambulatory population in tertiary care centers . PARTICIPANTS 4736 persons ( 1.06 % ) from 447,921 screenees aged 60 years and above were r and omized ( 2365 to active treatment , 2371 to placebo ) . Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg . Of the participants , 3161 were not receiving antihypertensive medication at initial contact , and 1575 were . The average systolic blood pressure was 170 mm Hg ; average diastolic blood pressure , 77 mm Hg . The mean age was 72 years , 57 % were women , and 14 % were black . INTERVENTIONS -- Participants were stratified by clinical center and by antihypertensive medication status at initial contact . For step 1 of the trial , dose 1 was chlorthalidone , 12.5 mg/d , or matching placebo ; dose 2 was 25 mg/d . For step 2 , dose 1 was atenolol , 25 mg/d , or matching placebo ; dose 2 was 50 mg/d . MAIN OUTCOME MEASURES Primary . Nonfatal and fatal ( total ) stroke . Secondary . Cardiovascular and coronary morbidity and mortality , all-cause mortality , and quality of life measures . RESULTS Average follow-up was 4.5 years . The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group , and the 5-year average diastolic blood pressure was 72 and 68 mm Hg , respectively . The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo . The relative risk by proportional hazards regression analysis was 0.64 ( P = .0003 ) . For the secondary end point of clinical nonfatal myocardial infa rct ion plus coronary death , the relative risk was 0.73 . Major cardiovascular events were reduced ( relative risk , 0.68 ) . For deaths from all causes , the relative risk was 0.87 . CONCLUSION In persons aged 60 years and over with isolated systolic hypertension , antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36 % , with 5-year absolute benefit of 30 events per 1000 participants . Major cardiovascular events were reduced , with 5-year absolute benefit of 55 events per 1000 Objective To investigate whether baseline systolic blood pressure variability was a risk factor for stroke , cardiovascular mortality or cardiac events during the Syst-Eur trial . Design The Syst-Eur study was a r and omized , double-blind , placebo-controlled trial , powered to detect differences in stroke rate between participants on active antihypertensive treatment and placebo .  Systolic blood pressure variability measurements were made on 744 participants at the start of the trial . Systolic blood pressure variability was calculated over three time frames : 24 h , daytime and night-time . The placebo and active treatment subgroups were analysed separately using an intention-to-treat principle , adjusting for confounding factors using a multiple Cox regression model . Participants An elderly hypertensive European population . Main outcome measures Stroke , cardiac events ( fatal and non-fatal heart failure , fatal and non-fatal myocardial infa rct ion and sudden death ) and cardiovascular mortality ( death attributed to stroke , heart failure , myocardial infa rct ion , sudden death , pulmonary embolus , peripheral vascular disease and aortic dissection ) . Results The risk of stroke increased by 80 % ( 95 % confidence interval : 17–176 % ) for every 5 mmHg increase in night-time systolic blood pressure variability in the placebo group . Risk of cardiovascular mortality and cardiac events was not significantly altered . Daytime variability readings did not predict outcome . Antihypertensive treatment did not affect systolic blood pressure variability over the median 4.4-year follow-up . Conclusion In the placebo group , but not the active treatment group , increased night-time systolic blood pressure variability on admission to the Syst-Eur trial was an independent risk factor for stroke during the trial BACKGROUND Isolated systolic hypertension occurs in about 15 % of people aged 60 years or older . In 1989 , the European Working Party on High Blood Pressure in the Elderly investigated whether active treatment could reduce cardiovascular complications of isolated systolic hypertension . Fatal and non-fatal stroke combined was the primary endpoint . METHODS All patients ( > 60 years ) were initially started on masked placebo .  At three run-in visits 1 month apart , their average sitting systolic blood pressure was 160 - 219 mm Hg with a diastolic blood pressure lower than 95 mm Hg . After stratification for centre , sex , and previous cardiovascular complications , 4695 patients were r and omly assigned to nitrendipine 10 - 40 mg daily , with the possible addition of enalapril 5 - 20 mg daily and hydrochlorothiazide 12.5 - 25.0 mg daily , or matching placebos . Patients withdrawing from double-blind treatment were still followed up . We compared occurrence of major endpoints by intention to treat . FINDINGS At a median of 2 years ' follow-up , sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group ( n = 2297 ) and by 23 mm Hg and 7 mm Hg in the active treatment group ( n = 2398 ) . The between-group differences were systolic 10.1 mm Hg ( 95 % CI 8.8 - 11.4 ) and diastolic , 4.5 mm Hg ( 3.9 - 5.1 ) . Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years ( 42 % reduction ; p = 0.003 ) . Non-fatal stroke decreased by 44 % ( p = 0.007 ) . In the active treatment group , all fatal and non-fatal cardiac endpoints , including sudden death , declined by 26 % ( p = 0.03 ) . Non-fatal cardiac endpoints decreased by 33 % ( p = 0.03 ) and all fatal and non-fatal cardiovascular endpoints by 31 % ( p < 0.001 ) . Cardiovascular mortality was slightly lower on active treatment ( -27 % , p = 0.07 ) , but all-cause mortality was not influenced ( -14 % ; p = 0.22 ) . INTERPRETATION Among elderly patients with isolated systolic hypertension , antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications . Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints
Acetylsalicylic acid ( ASA ) did not reduce stroke or ' all cardiovascular events ' compared to placebo in primary prevention patients with elevated blood pressure and no prior cardiovascular disease .
Antiplatelet therapy with ASA for primary prevention in patients with elevated blood pressure provides a benefit , reduction in myocardial infa rct ion , which is negated by a harm of similar magnitude , increase in major haemorrhage .
The benefit of antiplatelet therapy for secondary prevention in patients with elevated blood pressure is many times greater than the harm .
Benefit has not been demonstrated for warfarin therapy alone or in combination with aspirin in patients with elevated blood pressure .
BACKGROUND Elevated systemic blood pressure results in high intravascular pressure but the main complications , coronary heart disease ( CHD ) , ischaemic strokes and peripheral vascular disease ( PVD ) , are related to thrombosis rather than haemorrhage .
Some complications related to elevated blood pressure , heart failure or atrial fibrillation , are themselves associated with stroke and thromboembolism .
Therefore it is important to investigate if antithrombotic therapy may be useful in preventing thrombosis-related complications in patients with elevated blood pressure .
OBJECTIVES To conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with high blood pressure , including those with elevations in both systolic and diastolic blood pressure , isolated elevations of either systolic or diastolic blood pressure , to address the following hypotheses : ( i ) antiplatelet agents reduce total deaths and /or major thrombotic events when compared to placebo or other active treatment ; and ( ii ) oral anticoagulants reduce total deaths and /or major thromboembolic events when compared to placebo or other active treatment .
Ticlopidine , clopidogrel and newer antiplatelet agents such as prasugrel and ticagrelor have not been sufficiently evaluated in patients with high blood pressure .