Publications (38) View all
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Article: Heart Failure with Preserved Ejection Fraction in African-Americans - The Atherosclerosis Risk in Communities (ARIC) Study.
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ABSTRACT: In an entirely African-American cohort, we compared clinical characteristics, cardiac structure and function, and all cause mortality in heart failure (HF) with preserved ejection fraction (HFpEF) in relation to HF with reduced ejection fraction (HFrEF) and those without HF. African-Americans are at increased risk for HF. Nevertheless, there are limited phenotypic and prognostic data in African-Americans with HFpEF compared to those with HFrEF and those without HF. Middle-aged African-Americans from the Jackson cohort of the Atherosclerosis Risk in Communities study (n=2,445) underwent echocardiography between 1993 and 1995. HF prevalence was available in 1,962 for whom left ventricular ejection fraction (LVEF) could be quantified. Participants with HF were categorized as having HFpEF (LVEF ≥ 50%) or HFrEF (LVEF < 50%), or no HF, with comparisons made between groups. HF was identified in 116 (5.9%) participants (n=85 [73%] HFpEF; n=31 [27%] HFrEF). Compared to those without HF, those with HFpEF were older, more likely to be female, had more frequent comorbidities, and concentric hypertrophy. In relation to HFrEF, those with HFpEF were more likely female, but less likely to have coronary heart disease, diabetes mellitus, chronic kidney disease, left atrial enlargement, and eccentric hypertrophy. Over a median 13.7 years of follow up, risk of death differed between groups, with age and sex adjusted hazard ratios of 1.51 (95%CI 1.01-2.25) for HFpEF vs. those without HF, and 2.50 (95%CI 1.37-4.58) for HFrEF vs. HFpEF. In this cohort of middle-aged African-Americans, HFpEF was the most common form of HF, and was associated with a substantially better prognosis than HFrEF, but worse than those without HF.JACC. Heart failure. 04/2013; 1(2):156-163. -
Article: Gender differences in the association of visceral and subcutaneous adiposity with adiponectin in African Americans: the Jackson Heart Study.
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ABSTRACT: Adiponectin, paradoxically reduced in obesity and with lower levels in African Americans (AA), modulates several cardiometabolic risk factors. Because abdominal visceral adipose tissue (VAT), known to be reduced in AA, and subcutaneous adipose tissue (SAT) compartments may confer differential metabolic risk profiles, we investigated the associations of VAT and SAT with serum adiponectin, separately by gender, with the hypothesis that VAT is more strongly inversely associated with adiponectin than SAT. Participants from the Jackson Heart Study, an ongoing cohort of AA (n = 2,799; 64% women; mean age, 55 ± 11 years) underwent computer tomography assessment of SAT and VAT volumes, and had stored serum specimens analyzed for adiponectin levels. These levels were examined by gender in relation to increments of VAT and SAT. Compared to women, men had significantly lower mean levels of adiponectin (3.9 ± 3.0 μg/mL vs. 6.0 ± 4.4 μg/mL; p < 0.01) and mean volume of SAT (1,721 ± 803 cm3 vs. 2,668 ± 968 cm3; p < 0.01) but significantly higher mean volume of VAT (884 ± 416 cm3 vs. 801 ± 363 cm3; p < 0.01). Among women, a one standard deviation increment in VAT was inversely associated with adiponectin (β = - 0.13; p < 0.0001) after controlling for age, systolic blood pressure, fasting plasma glucose, high-density lipoprotein cholesterol, triglycerides, education, pack-years of smoking and daily intake of alcohol. The statistically significant inverse association of VAT and adiponectin persisted after additionally adjusting for SAT, body mass index (BMI) and waist circumference (WC), suggesting that VAT provides significant information above and beyond BMI and WC. Among men, after the same multivariable adjustment, there was a direct association of SAT and adiponectin (β = 0.18; p = 0.002) that persisted when controlling for BMI and WC, supporting a beneficial effect of SAT. Insulin resistance mediated the association of SAT with adiponectin in women. In African Americans, abdominal visceral adipose tissue had an inverse association with serum adiponectin concentrations only among women. Abdominal subcutaneous adipose tissue appeared as a protective fat depot in men.BMC Cardiovascular Disorders 01/2013; 13:9. · 1.52 Impact Factor -
Article: Genome-Wide Association Study of Cardiac Structure and Systolic Function in African Americans: The Candidate Gene Association Resource (CARe) Study.
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ABSTRACT: BACKGROUND: -Using data from four community-based cohorts of African Americans (AA), we tested the association between genome-wide markers (SNPs) and cardiac phenotypes in the Candidate-gene Association REsource (CARe) study. METHODS AND RESULTS: -Among 6,765 AA, we related age, sex, height and weight-adjusted residuals for nine cardiac phenotypes (assessed by echocardiogram or MRI) to 2.5 million SNPs genotyped using Genome-Wide Affymetrix Human SNP Array 6.0 (Affy6.0) and the remainder imputed. Within cohort genome-wide association analysis was conducted followed by meta-analysis across cohorts using inverse variance weights (genome-wide significance threshold=4.0 x10(-07)). Supplementary pathway analysis was performed. We attempted replication in 3 smaller cohorts of African ancestry and tested look-ups in one consortium of European ancestry (EchoGEN). Across the 9 phenotypes, variants in 4 genetic loci reached genome-wide significance: rs4552931 in UBE2V2 (p=1.43x10(-07)) for left ventricular mass (LVM); rs7213314 in WIPI1 (p=1.68 x10(-07)) for LV internal diastolic diameter (LVIDD); rs1571099 in PPAPDC1A (p= 2.57 x10(-08)) for interventricular septal wall thickness (IVST); and rs9530176 in KLF5 (p=4.02 x10(-07)) for ejection fraction (EF). Associated variants were enriched in three signaling pathways involved in cardiac remodeling. None of the 4 loci replicated in cohorts of African ancestry were confirmed in look-ups in EchoGEN. CONCLUSIONS: -In the largest GWAS of cardiac structure and function to date in AA, we identified 4 genetic loci related to LVM, IVST, LVIDD and EF that reached genome-wide significance. Replication results suggest that these loci may represent unique to individuals of African ancestry. Additional large-scale studies are warranted for these complex phenotypes.Circulation Cardiovascular Genetics 12/2012; · 6.11 Impact Factor -
Article: Association of Plasma B-Type Natriuretic Peptide Concentrations With Longitudinal Blood Pressure Tracking in African Americans: Findings From the Jackson Heart Study.
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ABSTRACT: Water and sodium retention precedes the development of high blood pressure (BP) and explains a compensatory rise in B-type natriuretic peptide (BNP) concentrations. It is unclear whether BNP concentrations antedate the BP progression. We hypothesized that higher BNP concentrations in our African American cohort will be associated with longitudinal increases in BP, progression of BP stage, and incident hypertension. Our study sample consisted of 888 normotensive (based on BP at examination 1 [2000-2004]) participants of the Jackson Heart Study (mean age, 47±12 years; 61% women). We examined the relation of BNP concentrations at the baseline examination to change in systolic and diastolic BPs, BP progression (an increase by 1 BP stage as defined by THE sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) and incident hypertension by examination 2 (2005-2008) adjusting for baseline BP stages, systolic and diastolic BPS, traditional risk factors, and echocardiographic left ventricular mass. Over a median follow-up period of 5.0±0.8 years, 36.9% progressed to a higher BP stage and 19.3% developed hypertension. In multivariable regression models, higher log-BNP concentrations at examination 1 were significantly and positively associated with changes in systolic and diastolic BPs (P<0.05 for both). Baseline log-BNP was significantly associated with BP progression (P=0.046). Every SD increase in baseline log BNP was associated with a 12% increased risk of BP progression. Log-BNP was not significantly associated with incident hypertension (P=0.12). In our community-based sample of African Americans, higher BNP concentrations predicted a longitudinal increase in systolic and diastolic BPs and progression of BP stage.Hypertension 11/2012; · 6.21 Impact Factor -
Article: Common genetic variation near the Connexin-43 gene is associated with resting heart rate in African Americans: A Genome-wide Association Study of 13,372 participants.
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ABSTRACT: BACKGROUND: Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE: We sought to identify novel genetic variants associated with resting heart rate in African Americans. METHODS: Ten cohort studies participating in the CARe and COGENT consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from ten-second resting 12-lead ECGs and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (p≤ 2.5x10(-8)). RESULTS: Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele, p=4.98 x 10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European GWAS, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSION: An intergenic region downstream of GJA1, the gene encoding Connexin-43, the major protein of the human myocardial gap junction and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.Heart rhythm: the official journal of the Heart Rhythm Society 11/2012; · 4.56 Impact Factor
