Medication adherence and visit-to-visit variability of systolic blood pressure in African Americans with chronic kidney disease in the AASK trial

Lower adherence to antihypertensive medications may increase visit-to-visit variability of blood pressure (VVV of BP), a risk factor for cardiovascular events and death. We used data from the African American Study of Kidney Disease and Hypertension (AASK) trial to examine whether lower medication adherence is associated with higher systolic VVV of BP in African Americans with hypertensive chronic kidney disease (CKD). Determinants of VVV of BP were also explored. AASK participants (n=988) were categorized by self-report or pill count as having perfect (100%), moderately high (75–99%), moderately low (50–74%) or low ( < 50%) proportion of study visits with high medication adherence over a 1-year follow-up period. We used multinomial logistic regression to examine determinants of medication adherence, and multivariable-adjusted linear regression to examine the association between medication adherence and systolic VVV of BP, defined as the coefficient of variation or the average real variability (ARV). Participants with lower self-reported adherence were generally younger and had a higher prevalence of comorbid conditions. Compared with perfect adherence, moderately high, moderately low and low adherence was associated with 0.65% (±0.31%), 0.99% (±0.31%) and 1.29% (±0.32%) higher systolic VVV of BP (defined as the coefficient of variation) in fully adjusted models. Results were qualitatively similar when using ARV or when using pill counts as the measure of adherence. Lower medication adherence is associated with higher systolic VVV of BP in African Americans with hypertensive CKD; efforts to improve medication adherence in this population may reduce systolic VVV of BP

Depressive Symptoms and Cardiovascular Health by the American Heart Association’s Definition in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Background Depressive symptoms are associated with increased incident and recurrent cardiovascular events. In 2010, the American Heart Association published the Life’s Simple 7, a metric for assessing cardiovascular health as measured by 4 health behaviors (smoking, physical activity, body mass index, diet) and 3 biological measures (cholesterol, blood pressure, glucose). The association between depressive symptoms and the Life’s Simple 7 has not yet been explored. Methods Data from 20,093 participants ≥45 years of age who enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007 and who had complete data available on Life’s Simple 7 components were used for these analyses. The prevalence of ideal, intermediate, and poor health on each Life’s Simple 7 component and total Life’s Simple 7 scores were compared between participants with and without depressive symptoms. Depressive symptoms were measured using the 4-item Centers for Epidemiologic Studies of Depression scale. Results Participants with depressive symptoms were more likely to have poor levels on each of the Life’s Simple 7 components other than cholesterol [adjusted prevalence ratios (95% CI): smoking 1.41 (1.29–1.55); physical activity 1.38 (1.31–1.46); body mass index 1.09 (1.04–1.15); diet 1.08 (1.06–1.10); blood pressure 1.11 (1.02–1.21); glucose 1.24 (1.09–1.41)]. There was a graded association between increasing depressive symptoms and lower total Life’s Simple 7 score. Conclusion Depressive symptoms are associated with worse cardiovascular health on the overall Life’s Simple 7 and on individual components representing both health behaviors and biological factors

Are two commonly used self-report questionnaires useful for identifying antihypertensive medication nonadherence?

Objective: Medication nonadherence is a major cause of uncontrolled hypertension, but clinicians are poor at judging adherence, and the gold standard for measuring adherence, electronic monitoring, is rarely available in clinical settings. Self-report questionnaires (SRQs), by contrast, are inexpensive, easy to administer, and hence, may be useful for ‘diagnosing’ nonadherence. In this study, we evaluated the validity of two commonly used medication adherence SRQs among patients with uncontrolled hypertension, using electronic pillbox measurement as the gold standard. Methods: A total of 149 patients with uncontrolled hypertension had adherence to their antihypertensive medication regimen monitored using a four-compartment electronic pillbox (MedSignals) between two primary care visits (median 50 days). Participants completed the 8-item Morisky Medication Adherence Scale (MMAS-8) and the Visual Analog Scale (VAS) at the second visit. Likelihood ratios were calculated using less than 80% correct dosing adherence by electronic measurement as the gold standard. Results: SRQ scores indicating low adherence (MMAS-8 <6 and VAS <80%, 23 and 9% of participants, respectively) had likelihood ratios of 2.00 [95% confidence interval (CI) 1.10–3.65] and 7.72 (95% CI 1.77–33.6), respectively, for detecting nonadherence compared to electronic measurement. SRQ scores indicating highest adherence (MMAS-8 = 8 and VAS = 100%, 43 and 61% of participants, respectively) had likelihood ratios of 0.55 (95% CI 0.35–0.85) and 0.76 (95% CI 0.57–1.01), respectively, for detecting nonadherence. Conclusion: The MMAS-8 and VAS are modestly useful in identifying antihypertensive medication nonadherence. Other tools, including electronic measurement, may be needed to guide titration of antihypertensive medications among patients with uncontrolled hypertension

Projected impact of polypill use among US adults: Medication use, cardiovascular risk reduction, and side effects

Background Polypills, which include multiple medications for reducing cardiovascular disease (CVD) risk in a single pill, have been proposed for population-wide use. The number of US adults eligible for polypills and potential benefits are unknown. Methods The National Health and Nutrition Examination Survey 2003-2004 and 2007-2008 were analyzed to estimate treatment rates for medications proposed for inclusion in polypills (aspirin, statin, an angiotensin-converting enzyme [ACE] inhibitor, and a thiazide-type diuretic for those without and a β-blocker for those with a history of myocardial infarction) among US adults. The number of coronary heart disease (CHD) and stroke events potentially prevented through polypill use was projected by published meta-analyses and 3 large population-based cohort studies. Two polypill eligibility criteria were analyzed: (1) US adults ≥55 years and (2) US adults with a history of CVD. Results There are 67.6 million US adults ≥55 years and 15.4 million US adults with a history of CVD and, thus, eligible for polypills using the 2 outlined criteria. In 2007 to 2008, 37.3% of US adults ≥55 years and 57.0% of those with a history of CVD were taking statins. Use of other polypill medications was also low. Polypill use by US adults aged ≥55 years is projected to potentially prevent 3.2 million CHD events and 1.7 million strokes over 10 years. Among those with a history of CVD, the potential to prevent of 0.9 million CHD events and 0.5 million strokes is projected. Conclusions Polypills have the potential to lower CVD incidence substantially among US adults

Generalizability of SPRINT Results to the U.S. Adult Population

Background In SPRINT (Systolic Blood Pressure Intervention Trial), a systolic blood pressure (SBP) goal of <120 mm Hg resulted in lower cardiovascular disease (CVD) risk compared with an SBP goal of <140 mm Hg. Objectives The purpose of this study was to estimate the prevalence, number, and characteristics of U.S. adults meeting SPRINT eligibility criteria and determine the broader population to whom SPRINT could be generalized. Methods We conducted a cross-sectional, population-based study using data from the National Health and Nutrition Examination Survey, 2007 to 2012. The SPRINT inclusion criteria were age ≥50 years, SBP 130 to 180 mm Hg depending on the number of antihypertensive medication classes being taken, and high CVD risk (history of coronary heart disease, estimated glomerular filtration rate of 20 to 59 ml/min/1.73 m2, 10-year CVD risk ≥15%, or age ≥75 years). Exclusion criteria were diabetes, history of stroke, >1 g in 24 h of proteinuria daily, heart failure, estimated glomerular filtration rate <20 ml/min/1.73 m2, or receiving dialysis. Treated hypertension was defined by self-reported use of medication to lower blood pressure with ≥1 class of antihypertensive medication identified through a pill bottle review. Results Overall, 7.6% (95% confidence interval [CI]: 7.0% to 8.3%) or 16.8 million (95% CI: 15.7 to 17.8 million) U.S. adults, and 16.7% (95% CI: 15.2% to 18.3%) or 8.2 million (95% CI: 7.6 to 8.8 million) adults with treated hypertension met the SPRINT eligibility criteria. Among both the overall U.S. population and adults with treated hypertension, the percentage meeting SPRINT eligibility criteria increased with older age, was higher among males than females, and was higher among non-Hispanic whites compared with non-Hispanic blacks or Hispanics. Of U.S. adults eligible for SPRINT, 51.0% (95% CI: 47.8% to 54.1%) or 8.6 million (95% CI: 8.0 to 9.1 million) were not treated for hypertension. Conclusions A substantial percentage of U.S. adults meet the eligibility criteria for SPRINT

Association between 24-hour blood pressure variability and chronic kidney disease: a cross-sectional analysis of African Americans participating in the Jackson heart study

Background Studies suggest 24-h blood pressure (BP) variability has prognostic value for cardiovascular disease. Several factors associated with high 24-h BP variability are also common among individuals with chronic kidney disease (CKD). We hypothesized 24-h BP variability would be higher for individuals with versus without CKD. Methods We analyzed 1,022 Jackson Heart Study participants who underwent ambulatory blood pressure monitoring (ABPM). Twenty-four hour BP variability was defined by two metrics: day-night standard deviation (SDdn) and average real variability (ARV). CKD was defined as ACR ≥30 mg/g or eGFR <60 mL/min/1.73 m2. Results The mean SDdn of systolic BP (SBP) was 10.2 ± 0.2 and 9.1 ± 0.1 mmHg and the mean ARV of SBP was 9.2 ± 0.2 and 8.6 ± 0.1 mmHg for those with and without CKD, respectively (each p ≤ 0.001). After adjustment for age and sex, SDdn and ARV were 0.98 mmHg (95 % CI 0.59, 1.38) and 0.52 mmHg (95 % CI 0.18, 0.86), respectively, higher among participants with versus without CKD. These differences were not statistically significant after further multivariable adjustment including 24-h mean SBP. Older age, and higher total cholesterol and 24-h mean SBP were associated with higher SDdn and ARV of SBP among participants with CKD. Mean SDdn and ARV of diastolic BP (DBP) were higher for participants with versus without CKD but these associations were not present after multivariable adjustment. Conclusion Data from the current study suggest that CKD is associated with higher 24-h BP variability, but the association is primarily explained by higher mean BP among those with CKD

Behavioral Mechanisms, Elevated Depressive Symptoms, and the Risk for Myocardial Infarction or Death in Individuals With Coronary Heart Disease The REGARDS (Reason for Geographic and Racial Differences in Stroke) Study

ObjectivesThe aim of this study was to determine whether behavioral mechanisms explain the association between depressive symptoms and myocardial infarction (MI) or death in individuals with coronary heart disease (CHD).BackgroundDepressive symptoms are associated with increased morbidity and mortality in individuals with CHD, but it is unclear how much behavioral mechanisms contribute to this association.MethodsThe study included 4,676 participants with a history of CHD. Elevated depressive symptoms were defined as scores ≥4 on the Center for Epidemiologic Studies Depression 4-item Scale. The primary outcome was definite/probable MI or death from any cause. Incremental proportional hazards models were constructed by adding demographic data, comorbidities, and medications and then 4 behavioral mechanisms (alcohol use, smoking, physical inactivity, and medication non-adherence).ResultsAt baseline, 638 (13.6%) participants had elevated depressive symptoms. Over a median 3.8 years of follow up, 125 of 638 (19.6%) participants with and 657 of 4,038 (16.3%) without elevated depressive symptoms had events. Higher risk of MI or death was observed for elevated depressive symptoms after adjusting for demographic data (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 1.15 to 1.72) but was no longer significant after adjusting for behavioral mechanisms (HR: 1.14, 95% CI: 0.93 to 1.40). The 4 behavioral mechanisms together significantly attenuated the risk for MI or death conveyed by elevated depressive symptoms (−36.9%, 95% CI: −18.9 to −119.1%), with smoking (−17.6%, 95% CI: −6.5% to −56.0%) and physical inactivity (−21.0%, 95% CI: −9.7% to −61.1%) having the biggest explanatory roles.ConclusionsOur findings suggest potential roles for behavioral interventions targeting smoking and physical inactivity in patients with CHD and comorbid depression

Relations Between QRS|T Angle, Cardiac Risk Factors, and Mortality in the Third National Health and Nutrition Examination Survey (NHANES III)

On the surface electrocardiogram, an abnormally wide QRS|T angle reflects changes in the regional action potential duration profiles and in the direction of the repolarization sequence, which is thought to increase the risk of ventricular arrhythmia. We investigated the relation between an abnormal QRS|T angle and mortality in a nationally representative sample of subjects without clinically evident heart disease. We studied 7,052 participants ≥40 years old in the third National Health and Nutrition Examination Survey with 12-lead electrocardiograms. Those with self-reported or electrocardiographic evidence of a previous myocardial infarction, QRS duration of ≥120 ms, or history of heart failure were excluded. Borderline and abnormal spatial QRS|T angles were defined according to gender-specific 75th and 95th percentiles of frequency distributions. All-cause (1,093 women and 1,191 men) and cardiovascular (462 women and 455 men) mortality during the 14-year period was assessed through linkage with the National Death Index. On multivariate analyses, an abnormal spatial QRS|T angle was associated with an increased hazard ratio (HR) for cardiovascular mortality in women (HR 1.82, 95% confidence interval 1.05 to 3.14) and men (HR 2.21, 95% confidence interval 1.32 to 3.68). Also, the multivariate adjusted HR for all-cause mortality associated with an abnormal QRS|T angle was 1.30 (95% confidence interval 0.95 to 1.78) for women and 1.87 (95% confidence interval 1.29 to 2.7) for men. A borderline QRS|T angle was not associated with an increased risk of all-cause or cardiovascular mortality. In conclusion, an abnormal QRS|T angle, as measured on a 12-lead electrocardiogram, was associated with an increased risk of cardiovascular and all-cause mortality in this population-based sample without known heart disease

Concurrent Stress and Depressive Symptoms Increase Risk of Myocardial Infarction or Death

BACKGROUND: Depression and stress have each been found to be associated with poor prognosis in patients with coronary heart disease. A recently offered psychosocial perfect storm conceptual model hypothesizes amplified risk will occur in those with concurrent stress and depressive symptoms. We tested this hypothesis in a large sample of US adults with coronary heart disease. METHODS AND RESULTS: Participants included 4487 adults with coronary heart disease from the Reasons for Geographic and Racial Differences in Stroke study, a prospective cohort study of 30,239 black and white adults. We conducted Cox proportional hazards regression with the composite outcome of myocardial infarction or death and adjustment for demographic, clinical, and behavioral factors. Overall, 6.1% reported concurrent high stress and high depressive symptoms at baseline. During a median 5.95 years of follow-up, 1337 events occurred. In the first 2.5 years of follow-up, participants with concurrent high stress and high depressive symptoms had increased risk for myocardial infarction or death (adjusted hazard ratio, 1.48 [95% confidence interval, 1.08-2.02]) relative to those with low stress and low depressive symptoms. Those with low stress and high depressive symptoms (hazard ratio, 0.92 [95% confidence interval, 0.66-1.28]) or high stress and low depressive symptoms (hazard ratio, 0.86 [95% confidence interval, 0.57-1.29]) were not at increased risk. The association on myocardial infarction or death was not significant after the initial 2.5 years of follow-up (hazard ratio, 0.89 [95% confidence interval, 0.65-1.22]). CONCLUSIONS: Our results provide initial support for a psychosocial perfect storm conceptual model; the confluence of depressive symptoms and stress on medical prognosis in adults with coronary heart disease may be particularly destructive in the shorter term

Evaluation of Criteria to Detect Masked Hypertension

The prevalence of masked hypertension, out-of-clinic daytime systolic/diastolic blood pressure (SBP/DBP)≥135/85 mmHg on ambulatory blood pressure monitoring (ABPM) among adults with clinic SBP/DBP<140/90 mmHg, is high. It is unclear who should be screened for masked hypertension. We derived a clinic blood pressure (CBP) index to identify populations for masked hypertension screening. Index cut-points corresponding to 75% to 99% sensitivity and prehypertension were evaluated as ABPM testing criterion. In a derivation cohort (n=695), the index was clinic SBP+1.3*clinic DBP. In an external validation cohort (n=675), the sensitivity for masked hypertension using an index ≥190 mmHg and ≥217 mmHg and prehypertension status was 98.5%, 71.5% and 82.5%, respectively. Using NHANES data (n=11,778), we estimated that these thresholds would refer 118.6, 44.4 and 59.3 million US adults, respectively, to ABPM screening for masked hypertension. In conclusion, the CBP index provides a useful approach to identify candidates for masked hypertension screening using ABPM