Development and Validation of Risk Prediction Models for Cardiovascular Events in Black Adults: The Jackson Heart Study Cohort.

IMPORTANCE: Cardiovascular risk assessment is a fundamental component of prevention of cardiovascular disease (CVD). However, commonly used prediction models have been formulated in primarily or exclusively white populations. Whether risk assessment in black adults is dissimilar to that in white adults is uncertain. OBJECTIVES: To develop and validate risk prediction models for CVD incidence in black adults, incorporating standard risk factors, biomarkers, and subclinical disease. DESIGN, SETTING, AND PARTICIPANTS: The Jackson Heart Study (JHS), a longitudinal community-based study of 5301 black adults in Jackson, Mississippi. Inclusive study dates were the date of a participant's first visit (September 2000 to March 2004) to December 31, 2011. The median (75th percentile) follow-up was 9.1 (9.7) years. The dates of the analysis were August 2013 to May 2015. Measurements included standard risk factors, including age, sex, body mass index, systolic and diastolic blood pressure, ratio of fasting total cholesterol to high-density lipoprotein cholesterol, estimated glomerular filtration rate, antihypertensive therapy, diabetes mellitus, and smoking; blood biomarkers; and subclinical disease measures, including ankle-brachial index, carotid intimal-medial thickness, and echocardiographic left ventricular hypertrophy and systolic dysfunction. MAIN OUTCOMES AND MEASURES: Incident CVD event was defined as the first occurrence of myocardial infarction, coronary heart disease death, congestive heart failure, stroke, incident angina, or intermittent claudication. Model performance was compared with the American College of Cardiology/American Heart Association (ACC/AHA) CVD risk algorithm and the Framingham Risk Score (FHS) refitted to the JHS data and evaluated in the Atherosclerosis Risk in Communities (ARIC) and Multi-Ethnic Study of Atherosclerosis cohorts. RESULTS: The study cohort comprised 3689 participants with mean (SD) age at baseline was 53 (11) years, and 64.8% (n = 2390) were female. Over a median of 9.1 years, 270 participants (166 women) experienced a first CVD event. A simple combination of standard CVD risk factors, B-type natriuretic peptide, and ankle-brachial index (model 6) yielded modest improvement over a model without B-type natriuretic peptide and ankle-brachial index (C statistic, 0.79; 95% CI, 0.75-0.83 [relative integrated discrimination improvement, 0.22; 95% CI, 0.15-0.30]). However, the reclassification improvement was not substantially different between model 6 and the ACC/AHA CVD Pooled Cohort risk equations or between model 6 and the FHS. The models discriminated reasonably well in the ARIC and Multi-Ethnic Study of Atherosclerosis data (C statistic range, 0.70-0.77). CONCLUSIONS AND RELEVANCE: Our findings using the JHS data in the present study are valuable because they confirm that current FHS and ACC/AHA risk algorithms work well in black individuals and are not easily improved on. A unique risk calculator for black adults may not be necessary.

Stem-cell angiogenesis and regeneration of the heart: review of a saga of 2 decades.

Advances in the novel approach to control ischemic heart disease and heart failure using stem cells or progenitor cells from bone marrow, mesenchyme, or myocardial tissue itself have demonstrated efficacy for increasing left ventricular function, decreasing infarct scar tissue, improving exercise tolerance and heart failure symptoms, and, in some studies, decreasing mortality and reducing rehospitalization for intractable angina or subsequent myocardial infarction. The most common techniques utilize injections of cells into the coronary vasculature or directly into specific areas of vulnerable myocardium. Although few adverse effects have been noted in clinical trials of these procedures, further clinical trials over the next decade should provide further advances in interventional techniques, ancillary supporting technologies to enhance cell regeneration, and applications in ischemic heart disease, cardiomyopathies, and cardiac genetic disorders.

Relations between subclinical disease markers and type 2 diabetes, metabolic syndrome, and incident cardiovascular disease: the Jackson Heart Study.

OBJECTIVE: The presence of subclinical disease measures has been directly associated with the development of cardiovascular disease (CVD) in whites. African Americans (AAs) in the U.S. are at higher risk of CVD compared with non-Hispanic whites; however, data on the prevalence of subclinical disease measures in AAs and their association to CVD remain unclear and may explain the higher CVD risk in this group. RESEARCH DESIGN AND METHODS: We evaluated 4,416 participants attending the first examination of the Jackson Heart Study (mean age 54 years; 64% women) with available subclinical disease measures. RESULTS: There were 1,155 participants (26%) with subclinical disease, defined as the presence of one or more of the following: peripheral arterial disease, left ventricular hypertrophy, microalbuminuria, high coronary artery calcium (CAC) score, and low left ventricular ejection fraction. In cross-sectional analyses using multivariable-adjusted logistic regression, participants with metabolic syndrome (MetS) or diabetes (DM) had higher odds of subclinical disease compared with those without MetS and DM (odds ratios 1.55 [95% CI 1.30-1.85] and 2.86 [95% CI 2.32-3.53], respectively). Furthermore, the presence of a high CAC score and left ventricular hypertrophy were directly associated with the incidence of CVD (265 events) in multivariable-adjusted Cox proportional hazards regression models (P < 0.05). In prospective analyses, having MetS or DM significantly increased the hazard of incident CVD, independent of the presence of subclinical disease (P < 0.001). CONCLUSIONS: In our community-based sample of AAs, we observed a moderately high prevalence of subclinical disease, which in turn translated into a greater risk of CVD, especially in people with MetS and DM.

Clinical correlates and prognostic significance of change in standardized left ventricular mass in a community-based cohort of African Americans.

BACKGROUND: Though left ventricular mass (LVM) predicts cardiovascular events (CVD) and mortality in African Americans, limited data exists on factors contributing to change in LVM and its prognostic significance. We hypothesized that baseline blood pressure (BP) and body mass index (BMI) and change in these variables over time are associated with longitudinal increases in LVM and that such increase is associated with greater incidence of CVD. METHODS AND RESULTS: We investigated the clinical correlates of change in standardized logarithmically transformed-LVM indexed to height2.7 (log-LVMI) and its association with incident CVD in 606 African Americans (mean age 58±6 years, 66% women) who attended serial examinations 8 years apart. Log-LVMI and clinical covariates were standardized within sex to obtain z scores for both visits. Standardized log-LVMI was modeled using linear regression (correlates of change in standardized log-LVMI) and Cox proportional hazards regression (incidence of CVD [defined as coronary heart disease, stroke, heart failure and intermittent claudication]). Baseline clinical correlates (standardized log-LVM, BMI, systolic BP) and change in systolic BP over time were significantly associated with 8-year change in standardized log-LVMI. In prospective analysis, change in standardized LVM was significantly (P=0.0011) associated with incident CVD (hazards ratio per unit standard deviation change log-LVMI 1.51, 95% CI 1.18 to 1.93). CONCLUSIONS: In our community-based sample of African Americans, baseline BMI and BP, and change in BP on follow-up were key determinants of increase in standardized log-LVMI, which in turn carried an adverse prognosis, underscoring the need for greater control of BP and weight in this group.

The relation of diabetes, impaired fasting blood glucose, and insulin resistance to left ventricular structure and function in African Americans: the Jackson Heart Study.

OBJECTIVE: We assessed the relation of diabetes and insulin resistance (IR) on left ventricular (LV) structure and function in African Americans. RESEARCH DESIGN AND METHODS: Among those receiving echocardiograms in cycle 1 of the Jackson Heart Study, we assessed the sex-specific relation of fasting blood glucose (FBG), diabetes, and IR to LV structure and function, adjusting for age, systolic blood pressure, antihypertensive medications, and BMI. RESULTS: Among 2,399 participants, LV mass index (P(women) = 0.0002 and P(men) = 0.02), posterior wall thickness (P(women) = 0.01 and P(men) = 0.05), and interventricular septal wall thickness (P(women) = 0.01) were related to FBG categories. Among those with normal FBG and no diabetes, concentric remodeling and low ejection fraction in women and LV mass index and posterior wall thickness in men were related to IR. CONCLUSIONS: In the largest study of its kind in a community-based cohort of African Americans, we found a relation of FBG category and IR to LV structure and function.

Distribution and determinants of Doppler-derived diastolic flow indices in African Americans: the Jackson Heart Study (JHS).

OBJECTIVES: The objective of this study is to investigate the distribution and determinants of diastolic function in a middle-aged cohort of African Americans (AA). BACKGROUND: The distribution and determinants of left ventricular (LV) diastolic function in AA are not well-described despite high rates of AA with diastolic heart failure and a five-fold higher risk of death in those with diastolic dysfunction (DD) compared to normal diastolic function. METHODS: Four categories of diastolic function were defined in JHS participants undergoing echocardiograms at the first examination (2001-2004) using mitral and pulmonary vein velocities. Investigators used logistic regression to assess the independent relation of DD to traditional risk factors and LV systolic dysfunction. RESULTS: Of the 3,571 study participants (mean age, 56 +/- 12 years; 63.9% female), 70.4% had normal diastolic function, and 18.0%, 10.6%, and 0.9% had mild, moderate, and severe DD, respectively. In the multivariable analysis, DD was significantly related to age (OR 1.2, 95% CI 1.1-1.4), male sex (OR 1.3 CI 1.0-1.5), LV systolic dysfunction (OR 1.5, CI 1.2-2.0), body mass index (OR 0.8, CI 0.8-0.9), and heart rate (OR 1.2; CI 1.1-1.2). The severity of DD was significantly related with age (OR 0.3; CI 0.3, 0.4), male sex (OR 1.6; CI 1.2-2.2), hypertension (OR 0.6, CI 0.4-0.8), and heart rate (OR 0.7; CI 0.6-0.8). CONCLUSION: This is the largest community-based analysis of LV diastolic function in middle-aged AA. DD was present in 29.5% and independently related to several traditional risk factors and LV systolic dysfunction.

Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET): implications for reduced cardiovascular risk.

The recently published Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) in patients with vascular disease or high-risk diabetes, as the largest published comparative trial of these agent classes, provides further evidence concerning the comparison between the angiotensin-receptor blockers (ARBs) and the angiotensin-converting enzyme inhibitors (ACEIs). In this trial, telmisartan (an ARB) was non-inferior to ramipril (an ACEI) in reducing fatal and nonfatal cardiovascular events. Moreover, ONTARGET is an example of a high-quality noninferiority trial. However, the combination of the 2 agents was associated with more adverse effects without an increase in benefit. The study differed from several other comparative studies in which the dose and choice of ACEI was left to individual physicians. Further, in ONTARGET, the ACEI was not titrated to the maximum dose and patients with heart failure were excluded.