Diastolic Blood Pressure, Subclinical Myocardial Damage, and Cardiac Events: Implications for Blood Pressure Control. The role of diastolic blood pressure when treating isolated systolic hypertension. Systolic Blood Pressure Goals to Reduce Cardiovascular Disease Among Older Adults Blood pressure and isolated systolic hypertension and the risk of coronary heart disease and mortality in elderly men (the Zutphen Elderly Study) J-curve revisited: An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial. 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) Blood pressure and outcomes in very old hypertensive coronary artery disease patients: an INVEST substudy. Impact of achieved blood pressure on cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial. Dogma Disputed: Can Aggressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous? Blood Pressure and Cardiovascular Disease Risk in the Veterans Affairs Diabetes Trial Predictors of adverse outcome among patients with hypertension and coronary artery disease. Effect of screening for coronary artery disease using CT angiography on mortality and cardiac events in high-risk patients with diabetes: the FACTOR-64 randomized clinical trial. Blood pressure, stroke, and coronary heart disease: Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. The Systolic Hypertension in the Elderly Program (SHEP): an intervention trial on isolated systolic hypertension. SHEP Cooperative Research Group. An ambulatory blood pressure monitoring study of the comparative antihypertensive efficacy of two angiotensin II receptor antagonists, irbesartan and valsartan Evidence Supporting a Systolic Blood Pressure Goal of Less Than 150 mm Hg in Patients Aged 60 Years or Older: The Minority View
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 OBJECTIVE To assess the role of treated diastolic blood pressure ( DBP ) level in stroke , coronary heart disease ( CHD ) , and cardiovascular disease ( CVD ) in patients with isolated systolic hypertension ( ISH ) . DESIGN An analysis of the 4736 participants in the Systolic Hypertension in the Elderly Program ( SHEP ) was undertaken . The SHEP was a r and omized multicenter double-blind outpatient clinical trial of the impact of treating ISH in men and women aged 60 years and older . MAIN OUTCOME MEASURES Cox proportional hazards regression analysis , with DBP and systolic blood pressure ( SBP ) as time-dependent covariables . RESULTS After adjustment for the baseline risk factors of race ( black vs other ) , sex , use of antihypertensive medication before the study , a composite variable ( diabetes , previous heart attack , or stroke ) , age , and smoking history ( ever vs never ) and adjustment for the SBP as a time-dependent variable , we found , for the active treatment group only , that a decrease of 5 mm Hg in DBP increased the risk for stroke ( relative risk , [ RR ] , 1.14 ; 95 % confidence interval [ CI ] , 1.05 - 1.22 ) , for CHD ( RR , 1.08 ; 95 % CI , 1.00 - 1.16 ) , and for CVD ( RR , 1.11 ; 95 % CI , 1.05 - 1.16 ) . CONCLUSIONS Some patients with ISH may be treated to a level that uncovers sub clinical disease , and some may be overtreated . Further studies need to determine whether excessively low DBP can be prevented by more careful titration of antihypertensive therapy while maintaining SBP control . It is reassuring that patients receiving treatment for ISH never perform worse than patients receiving placebo in terms of CVD events Abstract : The 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) was recently published . This guideline recommended that older adults ( ≥60 years ) without diabetes or chronic kidney disease with systolic blood pressure ( SBP ) ≥150 mm Hg or diastolic blood pressure ( DBP ) ≥90 mm Hg be initiated on antihypertensive medication with a treatment goal SBP/DBP < 150/90 mm Hg . In contrast , the previous 3 JNC guidelines recommended treatment for these individuals be initiated at SBP/DBP ≥140/90 mm Hg with goal SBP/DBP < 140/90 mm Hg . In this article , we review r and omized trials of antihypertensive medication and observational data on SBP and DBP with cardiovascular outcomes among older adults , possible explanations underlying the different findings from these r and omized trials and observational studies , and contemporary antihypertensive treatment patterns among older U.S. adults . In closing , we highlight future research needs related to hypertension and outcomes among older adults 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 AIM In patients with coronary artery disease ( CAD ) , a J-curve relationship has been reported between blood pressure ( BP ) and future cardiovascular events . However , this is controversial . The purpose of the study was to determine the relationship between on-treatment BP and cardiovascular outcomes in patients with CAD . METHODS AND RESULTS We evaluated 10 001 patients with CAD and a low-density lipoprotein ( LDL ) cholesterol level < 130 mg/dL , r and omized to atorvastatin 80 vs. 10 mg , enrolled in the TNT trial . The post-baseline , time-dependent BPs [ systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) ] were categorized into 10 mmHg increments . The primary outcome was a composite of death from coronary disease , non-fatal myocardial infa rct ion ( MI ) , resuscitated cardiac arrest , and fatal or non-fatal stroke . Among the 10 001 patients , 982 ( 9.82 % ) experienced a primary outcome at 4.9 years ( median ) of follow-up . The relationship between SBP or DBP and primary outcome followed a J-curve with increased event rates above and below the reference BP range , both unadjusted and adjusted ( for baseline covariates , treatment effect , and LDL levels ) . A time-dependent , non-linear , multivariate Cox proportional hazard model identified a nadir of 146.3/81.4 mmHg where the event rate was lowest . A similar non-linear relationship with a higher risk of events at lower pressures was found for most of the secondary outcomes of all-cause mortality , cardiovascular mortality , non-fatal MI , or angina . However , for the outcome of stroke , lower was better for SBP . CONCLUSION In patients with CAD , a low BP ( < 110 - 120/<60 - 70 mmHg ) portends an increased risk of future cardiovascular events ( except stroke ) 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 Our underst and ing of the growing population of very old patients ( aged > or=80 years ) with coronary artery disease and hypertension is limited , particularly the relationship between blood pressure and adverse outcomes . METHODS This was a secondary analysis of the INternational VErapamil SR-Tr and olapril STudy ( INVEST ) , which involved 22,576 clinical ly stable hypertensive coronary artery disease patients aged > or=50 years . The patients were grouped by age in 10-year increments ( aged > or=80 , n=2180 ; 70-<80 , n=6126 ; 60-<70 , n=7602 ; < 60 , n=6668 ) . Patients were r and omized to either verapamil SR- or atenolol-based treatment strategies , and primary outcome was first occurrence of all-cause death , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS At baseline , increasing age was associated with higher systolic blood pressure , lower diastolic blood pressure , and wider pulse pressure ( P < .001 ) . Treatment decreased systolic , diastolic , and pulse pressure for each age group . However , the very old retained the widest pulse pressure and the highest proportion ( 23.6 % ) with primary outcome . The adjusted hazard ratio for primary outcomes showed a J-shaped relationship among each age group with on-treatment systolic and diastolic pressures . The systolic pressure at the hazard ratio nadir increased with increasing age , highest for the very old ( 140 mm Hg ) . However , diastolic pressure at the hazard ratio nadir was only somewhat lower for the very old ( 70 mm Hg ) . Results were independent of treatment strategy . CONCLUSION Optimal management of hypertension in very old coronary artery disease patients may involve targeting specific systolic and diastolic blood pressures that are higher and somewhat lower , respectively , compared with other age groups Elevated arterial pressure enhances the risk for cardiovascular ( CV ) events in patients with diabetic nephropathy . The optimal BP and the component of the elevated BP that affect the risk have not been defined . A post hoc analysis was performed to assess the impact of achieved systolic , diastolic , and pulse pressures on CV outcomes in 1590 adults who had overt diabetic nephropathy and were enrolled in the Irbesartan Diabetic Nephropathy Trial ( IDNT ) and had a baseline serum creatinine above the normal range , up to 266 micromol/L ( 3.0 mg/dL ) , 24-h urine protein > 900 mg/d , and at least 6 mo of follow-up . Patients were r and omized to irbesartan , amlodipine , or placebo , with other antihypertensive agents to a BP goal of < or = 135/85 mmHg . Progressively lower achieved systolic BP ( SBP ) to 120 mmHg predicted a decrease in CV mortality and congestive heart failure ( CHF ) but not myocardial infa rct ions ( MI ) . A SBP below this threshold was associated with increased risk for CV deaths and CHF events . Achieved diastolic BP < 85 mmHg was associated with a trend to increase in all-cause mortality , significant increase in MI , but decreased risk for strokes . Increased pulse pressure predicted increased all-cause mortality , CV mortality , MI , and CHF . It is concluded that achieved SBP approaching 120 mmHg and diastolic BP of 85 mmHg are associated with the best protection against CV events in these patients . BP < or = 120/85 may be associated with an increase in CV events 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 Blood pressure ranges associated with cardiovascular disease ( CVD ) events in advanced type 2 diabetes are not clear . Our objective was to determine whether baseline and follow-up ( On- Study ) systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and SBP combined with DBP predict CVD events in the Veterans Affairs Diabetes Trial ( VADT ) . RESEARCH DESIGN AND METHODS Participants in the VADT ( n = 1,791 ) with hypertension received stepped treatment to maintain blood pressure below the target of 130/80 mmHg in st and ard and intensive glycemic treatment groups .  Blood pressure levels of all subjects at baseline and On- Study were analyzed to detect associations with CVD risk . The primary outcome was the time from r and omization to the first occurrence of myocardial infa rct ion , stroke , congestive heart failure , surgery for vascular disease , inoperable coronary disease , amputation for ischemic gangrene , or CVD death . RESULTS Separated SBP ≥140 mmHg had significant risk at baseline ( hazards ratio [ HR ] 1.508 , P < 0.001 ) and On- Study ( HR 1.469 , P = 0.002 ) . DBP < 70 mmHg increased CVD events at baseline ( HR 1.482 , P < 0.001 ) and On- Study ( HR 1.491 , P < 0.001 ) . Combined blood pressure categories indicated high risk for CVD events for SBP ≥140 with DBP < 70 mmHg at baseline ( HR 1.785 , P = 0.03 ) and On- Study ( HR 2.042 , P = 0.003 ) and nearly all SBP with DBP < 70 mmHg . CONCLUSIONS Increased risk of CVD events with SBP ≥140 mmHg emphasizes the urgency for treatment of systolic hypertension . Increased risk with DBP < 70 mmHg , even when combined with SBP in guideline -recommended target ranges , supports a new finding in patients with type 2 diabetes . The results emphasize that DBP < 70 mmHg in these patients was associated with elevated CVD risk and may best be avoided OBJECTIVES We sought to determine predictors for adverse outcomes in hypertensive patients with coronary artery disease ( CAD ) . BACKGROUND Factors leading to adverse outcomes in hypertensive patients with CAD are poorly understood . The INternational VErapamil-tr and olapril STudy ( INVEST ) compared outcomes in hypertensive patients with CAD that were assigned r and omly to either a verapamil sustained-release (SR)- or an atenolol-based strategy for blood pressure ( BP ) control . Tr and olapril and hydrochlorothiazide were used as added agents . During follow-up ( 61,835 patient-years ) , BP control and the primary outcome ( death , nonfatal myocardial infa rct ion , and nonfatal stroke ) were not different between strategies . METHODS We investigated risk for adverse outcome associated with baseline factors , follow-up BP , and drug treatments using Cox modeling . RESULTS Previous heart failure ( adjusted hazard ratio [ HR ] 1.96 ) , as well as diabetes ( HR 1.77 ) , increased age ( HR 1.63 ) , U.S. residency ( HR 1.61 ) , renal impairment ( HR 1.50 ) , stroke/transient ischemic attack ( HR 1.43 ) , smoking ( HR 1.41 ) , myocardial infa rct ion ( HR 1.34 ) , peripheral vascular disease ( HR 1.27 ) , and revascularization ( HR 1.15 ) predicted increased risk . Follow-up systolic BP < 140 mm Hg or diastolic BP < 90 mm Hg ( HRs 0.82 or 0.70 , respectively ) and tr and olapril with verapamil SR ( HRs 0.78 and 0.79 ) were associated with reduced risk . CONCLUSIONS In hypertensive patients with CAD , increased risk for adverse outcomes was associated with conditions related to the severity of CAD and diminished left ventricular function . Lower follow-up BP and addition of tr and olapril to verapamil SR each were associated with reduced risk IMPORTANCE Coronary artery disease ( CAD ) is a major cause of cardiovascular morbidity and mortality in patients with diabetes mellitus , yet CAD often is asymptomatic prior to myocardial infa rct ion ( MI ) and coronary death . OBJECTIVE To assess whether routine screening for CAD by coronary computed tomography angiography ( CCTA ) in patients with type 1 or type 2 diabetes deemed to be at high cardiac risk followed by CCTA-directed therapy  would reduce the risk of death and nonfatal coronary outcomes . DESIGN , SETTING , AND PARTICIPANTS The FACTOR-64 study was a r and omized clinical trial in which 900 patients with type 1 or type 2 diabetes of at least 3 to 5 years ' duration and without symptoms of CAD were recruited from 45 clinics and practice s of a single health system ( Intermountain Healthcare , Utah ) , enrolled at a single-site coordinating center , and r and omly assigned to CAD screening with CCTA ( n = 452 ) or to st and ard national guidelines -based optimal diabetes care ( n = 448 ) ( targets : glycated hemoglobin level < 7.0 % , low-density lipoprotein cholesterol level < 100 mg/dL , systolic blood pressure < 130 mm Hg ) . All CCTA imaging was performed at the coordinating center . St and ard therapy or aggressive therapy ( targets : glycated hemoglobin level < 6.0 % , low-density lipoprotein cholesterol level < 70 mg/dL , high-density lipoprotein cholesterol level > 50 mg/dL [ women ] or > 40 mg/dL [ men ] , triglycerides level < 150 mg/dL , systolic blood pressure < 120 mm Hg ) , or aggressive therapy with invasive coronary angiography , was recommended based on CCTA findings . Enrollment occurred between July 2007 and May 2013 , and follow-up extended to August 2014 . MAIN OUTCOMES AND MEASURES The primary outcome was a composite of all-cause mortality , nonfatal MI , or unstable angina requiring hospitalization ; the secondary outcome was ischemic major adverse cardiovascular events ( composite of CAD death , nonfatal MI , or unstable angina ) . RESULTS At a mean follow-up time of 4.0 ( SD , 1.7 ) years , the primary outcome event rates were not significantly different between the CCTA and the control groups ( 6.2 % [ 28 events ] vs 7.6 % [ 34 events ] ; hazard ratio , 0.80 [ 95 % CI , 0.49 - 1.32 ] ; P = .38 ) . The incidence of the composite secondary end point of ischemic major adverse cardiovascular events also did not differ between groups ( 4.4 % [ 20 events ] vs 3.8 % [ 17 events ] ; hazard ratio , 1.15 [ 95 % CI , 0.60 - 2.19 ] ; P = .68 ) . CONCLUSIONS AND RELEVANCE Among asymptomatic patients with type 1 or type 2 diabetes , use of CCTA to screen for CAD did not reduce the composite rate of all-cause mortality , nonfatal MI , or unstable angina requiring hospitalization at 4 years . These findings do not support CCTA screening in this population . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00488033 The associations of  diastolic blood pressure ( DBP )  with  stroke  and with coronary heart disease ( CHD ) were investigated in nine major prospect i ve observational studies : total 420,000 individuals , 843 strokes , and 4856 CHD events , 6 - 25 ( mean 10 ) years of follow-up . The combined results demonstrate positive , continuous , and apparently independent associations , with no significant heterogeneity of effect among different studies . Within the range of DBP studied ( about 70 - 110 mm Hg ) , there was no evidence of any " threshold " below which lower levels of DBP were not associated with lower risks of stroke and of CHD . Previous analyses have described the uncorrected associations of DBP measured just at " baseline " with subsequent disease rates . But , because of the diluting effects of r and om fluctuations in DBP , these substantially underestimate the true associations of the usual DBP ( ie , an individual 's long-term average DBP ) with disease . After correction for this " regression dilution " bias , prolonged differences in usual DBP of 5 , 7.5 , and 10 mm Hg were respectively associated with at least 34 % , 46 % , and 56 % less stroke and at least 21 % , 29 % , and 37 % less CHD . These associations are about 60 % greater than in previous uncorrected analyses . ( This regression dilution bias is quite general , so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths . ) The DBP results suggest that for the large majority of individuals , whether conventionally " hypertensive " or " normotensive " , a lower blood pressure should eventually confer a lower risk of vascular disease CONTEXT Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients , safety and efficacy of antihypertensive agents for coronary artery disease ( CAD ) have been discerned only from subgroup analyses in large trials . OBJECTIVE To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy ( CAS ) or a non-calcium antagonist strategy ( NCAS ) .  DESIGN , SETTING , AND PARTICIPANTS R and omized , open label , blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older , which was conducted September 1997 to February 2003 at 862 sites in 14 countries . INTERVENTIONS Patients were r and omly assigned to either CAS ( verapamil sustained release ) or NCAS ( atenolol ) . Strategies specified dose and additional drug regimens . Tr and olapril and /or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) of less than 140 mm Hg ( systolic ) and less than 90 mm Hg ( diastolic ) ; and less than 130 mm Hg ( systolic ) and less than 85 mm Hg ( diastolic ) if diabetes or renal impairment was present . Tr and olapril was also recommended for patients with heart failure , diabetes , or renal impairment . MAIN OUTCOME MEASURES Primary : first occurrence of death ( all cause ) , nonfatal myocardial infa rct ion , or nonfatal stroke ; other : cardiovascular death , angina , adverse experiences , hospitalizations , and blood pressure control at 24 months . RESULTS At 24 months , in the CAS group , 6391 patients ( 81.5 % ) were taking verapamil sustained release ; 4934 ( 62.9 % ) were taking tr and olapril ; and 3430 ( 43.7 % ) were taking hydrochlorothiazide . In the NCAS group , 6083 patients ( 77.5 % ) were taking atenolol ; 4733 ( 60.3 % ) were taking hydrochlorothiazide ; and 4113 ( 52.4 % ) were taking tr and olapril . After a follow-up of 61 835 patient-years ( mean , 2.7 years per patient ) , 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies ( 9.93 % in CAS and 10.17 % in NCAS ; relative risk [ RR ] , 0.98 ; 95 % confidence interval [ CI ] , 0.90 - 1.06 ) . Two-year blood pressure control was similar between groups . The JNC VI blood pressure goals were achieved by 65.0 % ( systolic ) and 88.5 % ( diastolic ) of CAS and 64.0 % ( systolic ) and 88.1 % ( diastolic ) of NCAS patients . A total of 71.7 % of CAS and 70.7 % of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg . CONCLUSION The verapamil-tr and olapril-based strategy was as clinical ly effective as the atenolol-hydrochlorothiazide-based strategy in hypertensive CAD patients The Systolic Hypertension in the Elderly Program ( SHEP ) is a r and omized double-blind placebo-controlled trial to determine if antihypertensive treatment of isolated systolic hypertension ( ISH ) [ systolic blood pressure ( SBP ) greater than or equal to 160 mmHg , diastolic blood pressure ( DBP ) less than 90 mmHg ] reduces the 5 year incidence of fatal and nonfatal stroke . Between March 1 , 1985 and January 15 , 1988 , 4736 persons ( target 4800 ) with ISH , age 60 years and over , were enrolled . Potential participants met blood pressure ( BP ) and age criteria . Those on antihypertensive medication prior to enrollment without documented diastolic hypertension had their medication tapered and discontinued , and then met BP criteria ( 33 % of cohort ) . Stepped-care therapy with chlorthalidone and atenolol ( alternative , reserpine ) or matching placebos was initiated as first and second steps . At baseline the trial population was 43.1 % male , 56.9 % female ; 13.9 % black , 86.1 % non-black . Also , the mean age was 71.6 years ; the mean SBP was 170.3 mmHg and the mean DBP was 76.6 mmHg ; 59.8 % had codeable resting electrocardiographic abnormalities .  The trial is now in follow-up phase with scheduled termination in 1991 Background The primary objective of this study was to compare the change from baseline in mean diastolic ambulatory blood pressure ( ABP ) at 24 h post dose ( trough measurement ) after 8 weeks of treatment with irbesartan or valsartan in subjects with mild-to-moderate hypertension . Secondary objectives included comparing the mean changes from baseline in systolic ABP at trough ; 24-h ABP ; morning and night-time ABP ; self-measured systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) ; and office-measured SBP and DBP at trough . Design After a 3-week , single blind , placebo lead-in period , 426 subjects were r and omized to receive either irbesartan 150 mg or valsartan 80 mg for 8 weeks . Methods Ambulatory blood pressure measurements were obtained at baseline and at week 8 . Self-measured morning and evening DBP and SBP readings were obtained at home over a 7-day period at baseline and at week 8 . Office-measured seated DBP and SBP measurements were obtained at trough , at baseline , and at week 8 . Results Irbesartan demonstrated significantly greater reductions than valsartan for mean change from baseline in diastolic ABP at trough ( −6.73 versus −4.84 mmHg , respectively;P = 0.035 ) . Irbesartan produced significantly greater reductions than valsartan for mean systolic ABP at trough ( −11.62 versus −7.5 mmHg , respectively;P < 0.01 ) and for mean 24-h diastolic ABP ( −6.38 versus −4.82 mmHg , respectively;P = 0.023 ) and systolic ABP ( −10.24 versus −7.76 mmHg;P < 0.01 ) . Irbesartan also produced significantly greater reductions than valsartan for office-measured seated DBP ( −10.46 versus 7.28 mmHg , respectively;P < 0.01 ) and SBP ( −16.23 versus −9.96 mmHg , respectively;P < 0.01 ) and for self-measured morning DBP ( −6.28 versus −3.75 mmHg , respectively;P < 0.01 ) and SBP ( −10.21 versus −6.97 mmHg , respectively;P < 0.01 ) . Both drugs were well tolerated . Conclusion Irbesartan was more effective than valsartan in reducing DBP and SBP at trough and in providing greater overall 24-h blood pressure-lowering efficacy The 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) recommends several major changes from the JNC 7 report ( 1 , 2 ) . The 2014 guideline is based on a systematic review of r and omized , controlled trials ( RCTs ) by a multidisciplinary panel using a process informed by Institute of Medicine recommendations for guideline development ( 3 ) . Although there was almost unanimous agreement on nearly all recommendations , a minority of the panel ( the authors of this commentary ) disagreed with the recommendation to increase the target systolic blood pressure ( SBP ) from 140 to 150 mm Hg in persons aged 60 years or older without diabetes mellitus ( DM ) or chronic kidney disease ( CKD ) . This target guides both the initiation of therapy and treatment goals . Although this issue has major clinical and public health implication s , the guideline only briefly summarized the concerns underlying the minority opinion to maintain the target of less than 140 mm Hg . The Institute of Medicine recommendation for guideline development encourages guidelines to provide a description and explanation of any differences of opinion regarding the recommendation ( 3 ) . This summarizes the evidence and rationale underlying the minority opinion to maintain the SBP target of 140 mm Hg or lower in persons aged 60 years or older until there is greater certainty of the risks and benefits of a higher target . First , increasing the target will probably reduce the intensity of antihypertensive treatment in a large population at high risk for cardiovascular disease ( CVD ) ( Table 1 ) . The higher SBP goal would apply to some of the groups at highest cardiovascular risk , such as African Americans , hypertensive patients with multiple CVD risk factors other than DM or CKD , and those with clinical CVD . Second , the evidence supporting increasing the SBP target from 140 to 150 mm Hg in persons aged 60 years or older was insufficient and inconsistent with the evidence supporting the panel 's recommendations for an SBP target of less than 140 mm Hg in persons younger than 60 years and those aged 60 years or older with DM or CKD . Third , the higher SBP goal in individuals aged 60 years or older may reverse the decades-long decline in CVD , especially stroke mortality ( 4 ) . In the absence of definitive evidence defining the optimum SBP target , observational studies and RCT data that the panel did not systematic ally review more strongly support the SBP goal of less than 140 mm Hg , especially in high-risk individuals . Other recent guideline groups review ing similar evidence have recommended a goal of less than 140 mm Hg , particularly in persons aged 80 years or younger ( 59 ) . Table 1 . U.S. Cardiovascular Disease Death Rates for Persons Younger and Older Than 65 y Persons Aged 60 Years or Older With Hypertension and SBP Controlled to 140 mm Hg or Lower More than half of the 72 million persons with hypertension in the United States are aged 60 years or older ( 10 , 11 ) . Among these individuals , the 2014 guideline recommends the SBP goal of 140 mm Hg or lower only for those with DM and those younger than 70 years with CKD ( 2 ) . Although the prevalence of hypertension in this age group ( 65 % to 67 % ) did not change between 1999 and 2010 , the percentage with adequate blood pressure control increased from 27.4 % ( 19992000 ) to 50.5 % ( 20112012 ) , with 82.2 % now receiving antihypertensive medications ( 10 , 12 ) . Data from NHANES ( National Health and Nutrition Examination Survey ) from 2001 to 2008 show that among treated and untreated hypertensive adults aged 60 years or older , median SBPs were 136 mm Hg and 152 mm Hg , respectively ( 13 ) , and SBPs have been decreasing in this age group over the past 5 decades ( Figure ) ( 4 ) . Thus , a target of less than 150 mm Hg would likely increase blood pressures in the treated hypertensive population and would suggest that nearly half of the untreated hypertensive patients in this age range should remain untreated . The large population at high risk for CVD , with most currently at an SBP of 140 mm Hg or lower , creates concern that a higher SBP target will adversely affect public health . Figure . Smoothed weighted frequency distribution , median , and 90th percentile of systolic blood pressure for persons aged 60 to 74 y : United States , 19592010 . Reproduced from Lackl and and colleagues ( 4 ) . NHANES = National Health and Nutrition Examination Survey ; NHES = National Health Examination Survey . High Risk in Persons With the Higher Goal Age substantially increases risk for cardiovascular events ( Table 1 ) , so differences in cardiovascular risk do not justify different targets for patients older and younger than 60 years . The risk range for white and African American men aged 60 years is 9 % to 30 % , depending on risk factor profile . For men of both ethnicities who are aged 70 years or older and have SBP controlled to 140 mm Hg , even without clinical CVD or DM , the 10-year risk exceeds 20 % ( 14 ) . Thus , on the basis of absolute risk , using an age threshold of 60 years to define eligibility for less aggressive treatment lacks consistency . Persons aged 60 to 79 years are at higher risk than those who are younger , even if the younger persons have DM . Insufficient Evidence for Differential Hypertension Treatment Benefit for Patients Older and Younger Than 60 Years The 2014 guideline panel failed to identify evidence of differential benefits or harms of treatment using an SBP goal of 140 mm Hg with an age threshold of 60 years . There is little RCT evidence of risk or benefit in treating persons younger than 60 years to this target , except in those with diastolic hypertension . The guideline indicates that no qualifying evidence was found comparing an SBP less than 140 mm Hg to any other SBP goal for persons younger than 60 years ( 2 ) . However , in persons aged 60 years or older , the SHEP ( Systolic Hypertension in the Elderly Program ) trial showed benefit of treating hypertension to an SBP goal between 140 and 145 mm Hg ( Table 2 ) ( 15 ) . HYVET ( Hypertension in the Very Elderly Trial ) found a benefit of an SBP target of less than 150 mm Hg on health outcomes , including mortality in persons aged 80 years or older ( 16 ) . Patients in the HYVET treatment group achieved an SBP of 144 mm Hg at 2 years compared with 159 mm Hg in the control group , and blood pressures continued to decrease in both groups until the end of the trial . Therefore , HYVET and the SHEP trial provide evidence that reducing SBP to around 140 mm Hg has substantial benefit without major harm in older persons . Thus , the best evidence available for an SBP target around 140 mm Hg , which meets the guideline RCT criteria , is in persons older than 60 years . The lack of benefit seen in 2 Japanese trials in older individuals ( JATOS [ Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients ] [ 17 ] and the VALISH [ Valsartan in Elderly Isolated Systolic Hypertension ] trial [ 18 ] ) was cited by some to rationalize the higher SBP target , but these trials were underpowered ( Table 2 ) . The SHEP trial and HYVET together reported 365 strokes and more than 285 coronary heart disease events , whereas JATOS and the VALISH trial only had a combined total of 125 strokes and 67 coronary heart disease events . In addition , the much larger FEVER ( Felodipine Event Reduction ) trial ( 19 ) did not meet criteria for inclusion in the panel 's deliberation ( Table 2 ) . This trial , which was conducted in a Chinese population ( age range , 50 to 79 years ; mean age , 62 years ) , reported a significant 27 % reduction in its primary outcome , as well as significant reductions in all CVD , total mortality , coronary heart disease , and heart failure in patients treated to an SBP of 137 mm Hg with a thiazide diureticcalcium-channel blocker combination versus 143 mm Hg with a thiazide diuretic plus placebo ( 19 ) . Table 2 . Trials Comparing Different Systolic Blood Pressure Thresholds In addition , generalizability of the Japanese trials to other population s of patients older than 60 years , such as African Americans , is uncertain . African Americans are at highest risk for all complications of hypertension and are historically undertreated . Thus , we believe that recommending less aggressive targets in this or other high-risk population s requires stronger justification than the guideline cites . Three recent guidelines from other countries have concluded that the appropriate cut point for an age-related differential SBP goal is 80 years or older ( 57 ) . We agree that this higher treatment target in frail hypertensive patients aged 80 years or older better reflects existing evidence . Safety and Adverse Event Risk in Hypertensive Patients Aged 60 Years or Older Despite the limited number of end points in JATOS and the VALISH trial , their size and duration provide evidence of safety of the SBP target of less than 140 mm Hg . The VALISH investigators concluded that this target was safe in relatively healthy patients aged 70 years or older with isolated systolic hypertension ( 18 ) . In JATOS , adverse events requiring treatment discontinuation were reported in only 36 patients , with no differences in discontinuation rate between groups ( 17 ) . This evidence and the favorable results at slightly higher blood pressures in the SHEP trial and HYVET provide reassurance of the safety of an SBP goal of less than 140 mm Hg in older , nonfrail persons . Other Trial Evidence of Benefit of Treatment at an SBP of 140 mm Hg or Lower Results of the SPS3 ( Secondary Prevention of Small Subcortical Strokes ) trial indicated that an SBP target of less than 130 mm Hg versus 144 mm Hg in 3020 patients ( mean age , 63 years ) reduced subsequent strokes by 19 % ( P= 0.08 ) and hemorrhagic strokes by nearly 50 % ( P < 0.01 ) ( 20 ) . Of note , the FEVER trial reported a 44 % ( P < 0.001 ) reduction in all strokes in a subgroup analysis of patients older than 65 years ( 17 ) . Finally , 2 meta-analyses
These results suggest that reducing DBP to 80 mmHg or less would significantly reduce coronary revascularization and heart failure but at the expense of causing hypotension in CAD patients .
The target of diastolic blood pressure ( DBP ) remains controversial in patients with coronary artery disease ( CAD ) .