Visit-to-Visit Blood Pressure Variability, Coronary Atheroma Progression, and Clinical Outcomes.
Clark Donald,Nicholls Stephen J,St John Julie,Elshazly Mohamed B,Ahmed Haitham M,Khraishah Haitham,Nissen Steven E,Puri Rishi
JAMA cardiology
Importance:Visit-to-visit blood pressure variability (BPV) is associated with cardiovascular events, but mechanisms and therapeutic implications underlying this association are not well understood. Objective:To examine the association of intraindividual BPV, coronary atheroma progression, and clinical outcomes using serial intravascular ultrasonography. Design, Setting, and Participants:Post hoc patient-level analysis of 7 randomized clinical trials conducted from 2004 to 2016 involving 3912 patients in multicenter, international, clinic-based primary and tertiary care centers. Adult patients with coronary artery disease who underwent serial intravascular ultrasonography in the setting of a range of medical therapies were included. Data were analyzed between November 2017 and March 2019. Exposures:Visit-to-visit BPV measured using intraindividual standard deviation over 3, 6, 12, 18, and 24 months. Main Outcomes and Measures:Percent atheroma volume (PAV) progression and major adverse cardiovascular events (defined as death, myocardial infarction, stroke, urgent revascularization for acute coronary syndrome, and hospitalization for unstable angina). Results:Of 3912 patients, the mean (SD) age was 58 (9) years, 1093 (28%) were women, and 3633 (93%) were white . Continuous change in PAV was significantly associated with systolic BPV (β, .049; 95% CI, 0.021-0.078; P = .001), diastolic BPV (β, .031; 95% CI, 0.002-0.059; P = .03), and pulse pressure variability (β, .036; 95% CI, 0.006-0.067; P = .02), without a signal for differential effect greater than or less than a mean BP of 140/90 mm Hg. The PAV progression as a binary outcome was significantly associated with systolic BPV (odds ratio, 1.09; 95% CI, 1.01-1.17; P = .02) but not diastolic BPV (odds ratio, 1.04; 95% CI, 0.97-1.11; P = .30) or pulse pressure variability (odds ratio, 1.03; 95% CI, 0.96-1.10; P = .47). Survival curves revealed a significant stepwise association between cumulative major adverse cardiovascular events and increasing quartiles of systolic BPV (Kaplan-Meier estimates for quartiles 1-4: 6.1% vs 8.5% vs 10.1% vs 12.0%, respectively; log-rank P <.001). These distinct stepwise associations were not seen with diastolic BPV or pulse pressure variability. Conclusions and Relevance:Greater BPV, particularly systolic BPV, is significantly associated with coronary atheroma progression and adverse clinical outcomes. These data suggest maintaining stable blood pressure levels may be important to further improve outcomes in patients with coronary disease.
10.1001/jamacardio.2019.0751
Diastolic Blood Pressure, Subclinical Myocardial Damage, and Cardiac Events: Implications for Blood Pressure Control.
McEvoy John W,Chen Yuan,Rawlings Andreea,Hoogeveen Ron C,Ballantyne Christie M,Blumenthal Roger S,Coresh Josef,Selvin Elizabeth
Journal of the American College of Cardiology
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 prospective 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 subclinical 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.
10.1016/j.jacc.2016.07.754
Diastolic Blood Pressure and Heart Rate Are Independently Associated With Mortality in Chronic Aortic Regurgitation.
Yang Li-Tan,Pellikka Patricia A,Enriquez-Sarano Maurice,Scott Christopher G,Padang Ratnasari,Mankad Sunil V,Schaff Hartzell V,Michelena Hector I
Journal of the American College of Cardiology
BACKGROUND:The prognostic significance of diastolic blood pressure (DBP) and resting heart rate (RHR) in patients with hemodynamically significant aortic regurgitation (AR) is unknown. OBJECTIVES:This study sought to investigate the association of DBP and RHR with all-cause mortality in patients with AR. METHODS:Consecutive patients with ≥ moderate to severe AR were retrospectively identified from 2006 to 2017. The association between all-cause mortality and routinely measured DBP and RHR was examined. RESULTS:Of 820 patients (age 59 ± 17 years; 82% men) followed for 5.5 ± 3.5 years, 104 died under medical management, and 400 underwent aortic valve surgery (AVS). Age, symptoms, left ventricular ejection fraction (LVEF), LV end-systolic diameter-index (LVESDi), DBP, and RHR were univariable predictors of all-cause mortality (all p ≤ 0.002). When adjusted for demographics, comorbidities, and surgical triggers (symptoms, LVEF, and LVESDi), baseline DBP (adjusted-hazard ratio [HR]: 0.79 [95% confidence interval: 0.66 to 0.94] per 10 mm Hg increase, p = 0.009) and baseline RHR (adjusted HR: 1.23 [95% confidence interval: 1.03 to 1.45] per 10 beat per min [bpm] increase, p = 0.01) were independently associated with all-cause mortality. These associations persisted after adjustment for presence of hypertension, medications, time-dependent AVS, and using average DBP and RHR (all p ≤ 0.02). Compared with the general population, patients with AR exhibited excess mortality (relative risk of death >1), which rose steeply in inverse proportion (p nonlinearity = 0.002) to DBP starting at 70 mm Hg and peaking at 55 mm Hg and in direct proportion to RHR starting at 60 bpm. CONCLUSIONS:In patients with chronic hemodynamically significant AR, routinely measured DBP and RHR demonstrate a robust association with all-cause death, independent of demographics, comorbidities, guideline-based surgical triggers, presence of hypertension, and use of medications. Therefore, DBP and RHR should be integrated into comprehensive clinical decision-making for these patients.
10.1016/j.jacc.2019.10.047
Linear and Nonlinear Mendelian Randomization Analyses of the Association Between Diastolic Blood Pressure and Cardiovascular Events: The J-Curve Revisited.
Arvanitis Marios,Qi Guanghao,Bhatt Deepak L,Post Wendy S,Chatterjee Nilanjan,Battle Alexis,McEvoy John W
Circulation
BACKGROUND:Recent clinical guidelines support intensive blood pressure treatment targets. However, observational data suggest that excessive diastolic blood pressure (DBP) lowering might increase the risk of myocardial infarction (MI), reflecting a J- or U-shaped relationship. METHODS:We analyzed 47 407 participants from 5 cohorts (median age, 60 years). First, to corroborate previous observational analyses, we used traditional statistical methods to test the shape of association between DBP and cardiovascular disease (CVD). Second, we created polygenic risk scores of DBP and systolic blood pressure and generated linear Mendelian randomization (MR) estimates for the effect of DBP on CVD. Third, using novel nonlinear MR approaches, we evaluated for nonlinearity in the genetic relationship between DBP and CVD events. Comprehensive MR interrogation of DBP required us to also model systolic blood pressure, given that the 2 are strongly correlated. RESULTS:Traditional observational analysis of our cohorts suggested a J-shaped association between DBP and MI. By contrast, linear MR analyses demonstrated an adverse effect of increasing DBP increments on CVD outcomes, including MI (MI hazard ratio, 1.07 per unit mm Hg increase in DBP; <0.001). Furthermore, nonlinear MR analyses found no evidence for a J-shaped relationship; instead confirming that MI risk decreases consistently per unit decrease in DBP, even among individuals with low values of baseline DBP. CONCLUSIONS:In this analysis of the genetic effect of DBP, we found no evidence for a nonlinear J- or U-shaped relationship between DBP and adverse CVD outcomes; including MI.
10.1161/CIRCULATIONAHA.120.049819
Systolic blood pressure levels among adults with hypertension and incident cardiovascular events: the atherosclerosis risk in communities study.
Rodriguez Carlos J,Swett Katrina,Agarwal Sunil K,Folsom Aaron R,Fox Ervin R,Loehr Laura R,Ni Hanyu,Rosamond Wayne D,Chang Patricia P
JAMA internal medicine
IMPORTANCE:Studies document a progressive increase in heart disease risk as systolic blood pressure (SBP) rises above 115 mm Hg, but it is unknown whether an SBP lower than 120 mm Hg among adults with hypertension (HTN) lowers heart failure, stroke, and myocardial infarction risk. OBJECTIVE:To examine the risk of incident cardiovascular (CV) events among adults with HTN according to 3 SBP levels: 140 mm Hg or higher; 120 to 139 mm Hg; and a reference level of lower than 120 mm Hg. DESIGN, SETTING, AND PARTICIPANTS:A total of 4480 participants with HTN but without prevalent CV disease at baseline (years 1987-1989) from the Atherosclerosis Risk in Communities Study were included. Measurements of SBP were taken at baseline and at 3 triennial visits; SBP was treated as a time-dependent variable and categorized as elevated (≥140 mm Hg), standard (120-139 mm Hg), and low (<120 mm Hg). Multivariable Cox regression models included baseline age, sex, diabetes status, BMI, high cholesterol level, smoking status, and alcohol intake. MAIN OUTCOMES AND MEASURES:Incident composite CV events (heart failure, ischemic stroke, myocardial infarction, or death related to coronary heart disease). RESULTS:After a median follow-up of 21.8 years, a total of 1622 incident CV events had occurred. Participants with elevated SBP developed incident CV events at a significantly higher rate than those in the low BP group (adjusted hazard ratio [HR], 1.46; 95% CI, 1.26-1.69). However, there was no difference in incident CV event-free survival among those in the standard vs low SBP group (adjusted HR, 1.00; 95% CI, 0.85-1.17). Further adjustment for BP medication use or diastolic BP did not significantly affect the results. CONCLUSIONS AND RELEVANCE:Among patients with HTN, having an elevated SBP carries the highest risk for cardiovascular events, but in this categorical analysis, once SBP was below 140 mm Hg, an SBP lower than 120 mm Hg did not appear to lessen the risk of incident CV events.
10.1001/jamainternmed.2014.2482
Use of Long-term Cumulative Blood Pressure in Cardiovascular Risk Prediction Models.
Pool Lindsay R,Ning Hongyan,Wilkins John,Lloyd-Jones Donald M,Allen Norrina B
JAMA cardiology
Importance:Long-term cumulative systolic blood pressure (SBP) is significantly associated with increased rates of atherosclerotic cardiovascular disease (ASCVD) development independent of single SBP levels. However, published ASCVD risk prediction algorithms only include currently measured SBP. Objective:To determine whether including long-term (5- and 10-year) cumulative SBP in risk equations improves the predictive ability compared with single SBP measurements. Design, Setting, and Participants:Adults aged 45 to 65 years at the time of risk estimation with at least 20 years of follow-up (5 and 10 years prior to risk estimation and 10 years of event follow-up). The Lifetime Risk Pooling Project included data from the following cohorts: Coronary Artery Risk Development in Young Adults Study, Atherosclerosis Risk in Communities Study, and Framingham Heart Study (both the original and offspring). Exposures:Ten-year ASCVD risk, calculated using the approach of the 2013 American College of Cardiology/American Heart Association 10-year ASCVD risk equations, first with current SBP and then substituting 5- and 10-year cumulative SBP levels. Main Outcomes and Measures:Incident ASCVD events that occurred over 10 years of follow-up, compared with the predicted risks, using the C statistic, net reclassification index at event rate, and the integrated discrimination index. Results:This study included 11 767 participants with a mean (SD) age of 59.1 (4.7) years at risk estimation. A total of 6873 participants (58%) were women, and 1499 (13%) were African American. In the 10 years of follow-up from risk estimation, 1887 participants (16%) had an ASCVD event. There were no significant improvements in the C statistic when including 5- or 10-year cumulative SBP. However, the addition of cumulative SBP resulted in significant improvements in the net reclassification index at event rate (10-year net reclassification index for men, 0.04 [95% CI, 0.02-0.06]; 10-year net reclassification index for women, 0.03 [95% CI, 0.01-0.06]) and the relative integrated discrimination index (10-year relative integrated discrimination index for men, 0.12; 10-year relative integrated discrimination index for women, 0.10). Conclusions and Relevance:Using long-term measures of cumulative blood pressure, instead of single measurements, can modestly improve the ability of cardiovascular disease risk prediction models to correctly classify individuals in terms of their risk for cardiovascular disease.
10.1001/jamacardio.2018.2763
Carotid atherosclerosis in relation to systolic and diastolic blood pressure: Kuopio Ischaemic Heart Disease Risk Factor Study.
Salonen R,Salonen J T
Annals of medicine
We investigated the association of systolic and diastolic blood pressure and hypertension with two different manifestations of carotid atherosclerosis in a random population sample of 1165 Eastern Finnish men aged 42, 48, 54 or 60 years, examined in the Kuopio Ischaemic Heart Disease Risk Factor Study. Carotid atherosclerosis was assessed with high-resolution B-mode ultrasonography. Men with a casual sitting systolic blood pressure of 175 mmHg or more had a 3.17-fold (95% confidence interval 1.79-5.61) prevalence of intima-media thickening--adjusted for age, smoking, S-LDL-cholesterol, IHD history and diabetes--compared to men with lower systolic pressures. The relative prevalence of carotid plaques in men with raised systolic pressures. The relative prevalence of carotid plaques in men with raised systolic blood pressure was 2.61 (95% confidence interval 1.44-4.72) in relation to men with no lesions. Our findings suggest that systolic but not diastolic hypertension is associated with an increased prevalence of both early and advanced atherosclerotic lesions in carotid arteries.
J-shaped relation between change in diastolic blood pressure and progression of aortic atherosclerosis.
Witteman J C,Grobbee D E,Valkenburg H A,van Hemert A M,Stijnen T,Burger H,Hofman A
Lancet (London, England)
The J-shaped relation between diastolic blood pressure and mortality from coronary heart disease continues to provoke controversy. We examined the association between diastolic blood pressure and progression of aortic atherosclerosis in a population-based cohort of 855 women, aged 45-64 years at baseline. The women were examined radiographically for calcified deposits in the abdominal aorta, which have been shown to reflect intimal atherosclerosis. After 9 years of follow-up, slight progression of atherosclerosis was noted in 19% of women and substantial progression in 16%. The age-adjusted relative risk of substantial atherosclerotic progression in women with a decrease in diastolic pressure of 10 mm Hg or more was 2.5 (95% CI 1.3-5.6), compared with the reference group of women who had a smaller decrease or no change. The excess risk in this group was confined to women whose increase in pulse pressure was above the median (3.9 [1.5-9.9] vs 1.1 [0.3-4.2] in women with an increase in pulse pressure below the median). The relative risks for women with rises in diastolic pressure of 1-9 mm Hg and 10 mm Hg or more were 2.2 (1.1-4.3) and 3.5 (1.6-8.0), respectively. These findings suggest that a decline in diastolic blood pressure indicates vessel wall stiffening associated with atherosclerotic progression. They support the hypothesis that in low-risk subjects progression of atherosclerosis may be accompanied by a decrease in diastolic blood pressure rather than the opposing idea that low diastolic blood pressure precipitates the occurrence of atherosclerotic events.
10.1016/s0140-6736(94)91459-1
Low diastolic blood pressure and atherosclerosis in elderly subjects. The Rotterdam study.
Bots M L,Witteman J C,Hofman A,de Jong P T,Grobbee D E
Archives of internal medicine
BACKGROUND:A low diastolic blood pressure has been associated with increased cardiovascular risk. The following proposed mechanisms underlie this phenomenon: a low diastolic pressure that compromises coronary blood flow, a low diastolic pressure that is due to deteriorating health, and a low diastolic pressure that is a consequence of stiffening of the large arteries. Atherosclerosis may be the link between stiffening of the arteries, a low diastolic pressure, and an increased cardiovascular risk. OBJECTIVE:To study whether a low diastolic blood pressure in older subjects is a reflection of atherosclerosis. METHODS:The Rotterdam (the Netherlands) Study is a population-based follow-up study of 7983 subjects (age, > or = 55 years) who are living in the suburb of Ommoord of Rotterdam. Baseline measurements included ultrasonographic evaluation of the carotid arteries, measurement of blood pressure, and determination of other cardiovascular risk factors. The main cross-sectional analyses were performed among 930 subjects who currently were not using blood pressure-lowering drugs. RESULTS:A J-shaped association of the intima-media thickness of the common carotid artery with diastolic blood pressure was found with a nadir from 60 to 69 mm Hg. The intima-media thickness was increased in subjects with a diastolic pressure that was less than 60 mm Hg compared with that in subjects with a diastolic pressure that was between 60 and 69 mm Hg (a difference of 0.033 mm [95% confidence limits; 0.001, 0.065]). Beyond a diastolic pressure of 70 mm Hg, a gradual increase in the intima-media thickness was observed. The association was most pronounced among subjects with relatively high pulse pressures. CONCLUSIONS:Results of the present study indicate the existence of a J-shaped association between carotid atherosclerosis and diastolic pressure. These findings support the hypothesis that in elderly subjects, a low diastolic pressure may be a reflection of widespread atherosclerosis.