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.

Diabetes, gender, and left ventricular structure in African-Americans: the atherosclerosis risk in communities study.

BACKGROUND: Cardiovascular risk associated with diabetes may be partially attributed to left ventricular structural abnormalities. However, the relations between left ventricular structure and diabetes have not been extensively studied in African-Americans. METHODS: We studied 514 male and 965 female African-Americans 51 to 70 years old, in whom echocardiographic left ventricular mass measurements were collected for the ARIC Study. In these, we investigated the independent association of diabetes with left ventricular structural abnormalities. RESULTS: Diabetes, hypertension and obesity prevalences were 22%, 57% and 45%, respectively. Unindexed left ventricular mass was higher with diabetes in both men (238.3 +/- 79.4 g vs. 213.7 +/- 58.6 g; p < 0.001) and women (206.4 +/- 61.5 g vs. 176.9 +/- 50.1 g; p < 0.001), respectively. Prevalence of height-indexed left ventricular hypertrophy was higher in women while increased relative wall thickness was similar in men and women. Those with diabetes had higher prevalences of height-indexed left ventricular hypertrophy (52% vs. 32%; p < 0.001), and of increased relative wall thickness (73% vs. 64%; p = 0.002). Gender-adjusted associations of diabetes with left ventricular hypertrophy (OR = 2.29 95% CI:1.79-2.94) were attenuated after multiple adjustments in logistic regression (OR = 1.50 95% CI:1.12-2.00). Diabetes was associated with higher left ventricle diameter (OR = 2.13 95% CI:1.28-3.53) only in men and with higher wall thickness (OR = 1.89 95% CI:1.34-2.66) only in women. Attenuations in diabetes associations were frequently seen after adjustment for obesity indices. CONCLUSION: In African-Americans, diabetes is associated with left ventricular hypertrophy and, with different patterns of left ventricular structural abnormalities between genders. Attenuation seen in adjusted associations suggests that the higher frequency of structural abnormalities seen in diabetes may be due to factors other than hyperglycemia.

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.

Left ventricular mass indexed to height and prevalent MRI cerebrovascular disease in an African American cohort: the Atherosclerotic Risk in Communities study.

BACKGROUND AND PURPOSE: Previous studies have demonstrated that echocardiographic left ventricular mass (LVM) is an independent risk factor for stroke in whites. Despite the greater burden of stroke, the echocardiographic predictors of stroke in African Americans remain poorly understood. METHODS: This investigation is a retrospective analysis of prospectively collected data from the Jackson, Miss (all African American), cohort of the Atherosclerotic Risk in the Communities study. Between 1993 and 1995, 2445 participants received an echocardiogram, and a random subset (n=778) received cerebral MRI evaluating presence of infarcts or white matter disease (WMD; >3 on a scale of 0 to 9). Compared with the entire Jackson cohort, the random subset was older, had a lower body mass index (BMI), and a higher systolic blood pressure (SBP). Logistic regression models examined the relations of LVM indexed by height (LVM/height) to MRI findings adjusted for age, gender, BMI, SBP, hypertensive medications, diabetes, total/high-density lipoprotein cholesterol, smoking status, and history of myocardial infarction. RESULTS: The 667 participants (63% women; 62+/-4 years of age) had a high prevalence of hypertension (68%), obesity (46%), echocardiographic left ventricular hypertrophy (49%), MRI stroke (n=133), and WMD (n=92). Adjusted LVM/height was significantly associated with prevalent MRI stroke (odds ratio [OR], 1.3; 95% CI, 1.1 to 1.7; P=0.02) and WMD (OR, 1.5; 95% CI, 1.1 to 1.9; P=0.006; OR expressed per 1 SD LVM/height, 45 g/m). CONCLUSIONS: In this randomized subset of a population-based cohort of African American adults, LVM/height was related to MRI evidence of prevalent cerebrovascular disease. The current study supports the hypothesis that LVM/height is an important risk factor for stroke in multiple ethnicities.

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.

Comparison of the prognostic value of left ventricular hypertrophy in African-American men versus women.

Echocardiographically determined left ventricular (LV) hypertrophy may be a stronger risk factor of cardiovascular disease (CVD) for women than for men, although it is unclear whether reported gender differences are real or attributable to confounding. We evaluated echocardiographic LV hypertrophy (defined as LV mass/height(2.7) >/=51 g/m(2.7)) collected from the African-American population of the Atherosclerosis Risk in Communities Study. Incident CVD events (57 in men, 62 in women) were determined during a median follow-up of 4.9 years (interquartile range 4.3 to 5.6) and included nonfatal myocardial infarction, cardiac death, coronary revascularization, and stroke. We conducted 2 analyses. First, we created matched samples of 340 men and 812 women who had LV hypertrophy based on propensity score and estimated the gender-specific incidence rate ratios and population-attributable risks. Second, we evaluated the complete cohort (604 men and 1,113 women) with Poisson's regression after adjusting for age, body mass index, hypertension, diabetes mellitus, ratio of total cholesterol to high-density lipoprotein cholesterol, current smoking, and education level. LV hypertrophy was significantly predictive of incident CVD, and the association shown by analyses of matched propensity scores was similar in men and women (incidence rate ratio 1.88 vs 1.92, p = 0.97 for men, population-attributable risk 0.22 vs 0.26, p <0.07 for women). In the multivariate analysis, we found comparable effect estimates for LV hypertrophy (incidence rate ratio 1.66 vs 2.09, p = 0.55 for men; population-attributable risk 0.24 vs 0.32, p <0.07 for women). Thus, LV hypertrophy is a strong predictor of CVD in African-Americans, and the effect of LV hypertrophy on CVD is similar in men and women.

Role of surrogate markers in assessing patients with diabetes mellitus and the metabolic syndrome and in evaluating lipid-lowering therapy.

Diabetes mellitus and the metabolic syndrome (MS) are reaching epidemic proportions in the United States, and cardiovascular disease continues to be the leading cause of death among patients with diabetes. A range of noninvasive screening tools may help reduce the morbidity and mortality of patients with diabetes because of early detection of subclinical cardiovascular disease and active monitoring of the effectiveness of therapy. Surrogate markers of subclinical disease include conventional and contrast-enhanced ultrasound imaging of carotid artery intima-media thickness (c-IMT), 2-dimensional echocardiography, coronary artery calcium imaging, cardiac magnetic resonance imaging, ankle-brachial indices, and brachial artery reactivity testing. Because these noninvasive imaging tools are relatively comfortable and entail relatively low risk to the patient, they are ideal for initial screening and for the repeated imaging that is required for monitoring the effectiveness of therapy. Moreover, when used in large numbers of patients with diabetes, prediabetes, and the MS, these imaging tools may be useful in developing and validating thresholds for the use of lipid-lowering therapy as well as clear therapeutic goals for this population. In addition, contrast-enhanced c-IMT scans now produce real-time images of the vasa vasorum and neovascularization of atherosclerotic plaque, potentially causing a paradigm shift in our view of the genesis of atherosclerosis and affecting treatment options for all populations. Thus, surrogate markers may not only help improve individual patient outcomes, they also may help direct scarce medical resources to maximize medical benefits, improve overall medical care, and minimize costs and untoward side effects.

Comparison of m-mode echocardiographic left ventricular mass measured using digital and strip chart readings: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Epidemiological and clinical studies frequently use echocardiography to measure LV wall thicknesses and chamber dimension for estimating quantitative measures of LV mass. While echocardiographic M-mode LV images have traditionally been measured using hand-held calipers and strip-chart paper tracings, digitized M-mode LV image measurements made directly on the computer screen using electronic calipers have become standard practice. We sought to determine if systematic differences in LV mass occur between the two methods by comparing LV mass measured from simultaneous M-mode strip chart recordings and digitized recordings. METHODS: The Atherosclerosis Risk in Communities study applied the latter method. To determine if systematic differences in LV mass occur between the two methods, LV mass was measured from simultaneous M-mode strip chart recordings and digitized recordings. RESULTS: We found no difference in LV mass (p > .25) and a strong correlation in LV mass between the two methods (r = 0.97). Neither age, sex, nor hypertension status affected the correlation of LV mass between the two methods. CONCLUSIONS: We conclude that digital estimates of LV mass provide unbiased estimates comparable to the strip-chart method.

Hormone therapy and selective estrogen receptor modulators for prevention of coronary heart disease in postmenopausal women estrogen replacement from the cardiologist's perspective.

Coronary heart disease is the leading cause of morbidity and mortality in women older than the age of 50 in the United States today. Traditional cardiovascular risk factors (hyperlipidemia, glucose intolerance, and hypertension) are more clearly associated with significant cardiovascular risk after menopause. The increased incidence of cardiovascular events in postmenopausal women and the evidence that cardiovascular disease on average manifests a decade later in women compared with men suggests that estrogen deficiency may predispose women to a higher cardiovascular risk. Numerous biologic mechanisms have been proposed that relate use of hormone therapy (HT) to improved lipid profiles, insulin sensitivity, and vascular reactivity. Early observational trials in the last 2 decades showed a significant decrease in cardiovascular events. Recently published randomized clinical trial results, however, have led to uncertainty about the earlier established cardiovascular benefits of HT. To complicate issues further, alternative estrogenlike compounds, selective estrogen receptor modulators, are being introduced that appear to convey similar cardiovascular benefit and notably less cancer risk than HT. The newly released randomized trials on hormone and nonhormonal agents are reviewed.

Left ventricular structure and systolic function in African Americans: the Atherosclerosis Risk in Communities (ARIC) study.

OBJECTIVES: To estimate prevalence of left ventricular (LV) hypertrophy and its relation to systolic function in a population-based sample of African Americans. DESIGN: A baseline 2D guided M-mode echocardiogram was conducted as part of a longitudinal cohort study to assess prevalence and cross-sectional relationships between echocardiographic and clinical parameters. SETTING: Data were collected as part of the Atherosclerosis Risk in Communities study. PARTICIPANTS: Analysis is limited to 1543 African Americans, aged 51-70 years, without clinically apparent cardiovascular or echocardiographically determined valvular disease. MAIN OUTCOME MEASURES: LV hypertrophy prevalence was defined as LV mass/ height2.7 > or = 51 g/m2.7. LV systolic chamber function was assessed at the midwall using the ratio of observed midwall fractional shortening (MWS%) to the value predicted from circumferential end-systolic stress. RESULTS: The prevalence of LV hypertrophy was 33% in men, 38% in women. The prevalence of concentric hypertrophy (LV hypertrophy with relative wall thickness > or = 0.45) was greater than that of eccentric hypertrophy (men: 24% vs 9%; women: 27% vs 11% women). Observed/predicted (O/P) MWS% was strongly and inversely related to LV mass/ height2.7 (P<.001) and LV hypertrophy (P<.001). The O/P MWS% was inversely related to LV mass/height2.7 quartile: O/P MWS% was 106% and 99% in the first and 97% and 89% in the fourth quartile of LV mass/height2.7 for men and women, respectively. Adjusting for age, adiposity, diabetes, blood pressure, antihypertensive medication use, and smoking did not remove association between O/P MWS% and LV mass/height2.7. CONCLUSIONS: LV hypertrophy was highly prevalent in this population-based middle-aged sample of African Americans and was associated with poorer LV systolic chamber function.