Association of Sickle Cell Trait with Risk of Coronary Heart Disease in African Americans

• Published in: Blood 2016-12, Vol.128 (22), p.11-11
• Main Authors: Hyacinth, Hyacinth I, Cara, Carty L, Seals, Samantha R, Irvin, Marguerite R., Naik, Rakhi P., Caughey, Melissa, Winkler, Cheryl, Franceschini, Nora, Burke, Gregory L, Zakai, Neil A, Kopp, Jeffrey B, Judd, Suzanne E, Adams, Robert J., Gee, Beatrice E., Longstreth, WT, Egede, Leonard E, Lackland, Daniel T, Greenberg, Charles S., Herman, Taylor, Manson, JoAnn E, Key, Nigel S., Derebail, Vimal K., Kshirsagar, Abhijit V, Folsom, Aaron R, Konety, Suma H, Howard, Virginia J, Allison, Mattthew, Wilson, James G., Correa, Adolfo, Zhi, Degui, Arnett, Donna, Howard, George, Cushman, Mary, Reiner, Alexander, Safford, Monika M
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.11.11

Background The incidence of and mortality from coronary heart disease (CHD) is significantly higher among African Americans (AAs) compared to Whites, even after adjusting for traditional CHD risk factors. Studies suggests that the unexplained excess risk might be the result of genetic modifiers associated with African ancestry conferring a higher risk of CHD. One such gene variant is the sickle cell mutation. The heterozygous state, or sickle cell trait (SCT), with a prevalence of 8 - 12% among AAs, was previously deemed clinically benign; however, recent evidence indicates that SCT is associated with increased risk of chronic kidney disease venous thromboembolism and sudden death following exertion. Individuals with SCT have higher circulating levels of C-reactive protein, fibrinogen, prothrombin fragment 1.2 and D-dimer. We hypothesized that AAs with SCT have a higher risk for myocardial infarction (MI) and coronary heart disease (CHD) than AAs who are homozygous for wild-type hemoglobin. Methods We obtained genotype and phenotype data from the Women's Health Initiative (WHI) REasonsfor Geographic and Racial Differences in Stroke (REGARDS), Multi-Ethnic Study of Atherosclerosis (MESA), Jackson Heart Study (JHS) and Atherosclerosis Risk In Communities (ARIC) cohorts. The outcomes were incident MI or CHD. Incident MI was defined as adjudicated non-fatal or fatal MI, while incident CHD was defined as 1) adjudicated non-fatal MI, 2) fatal MI, 3) documented coronary revascularization procedures or 4) non-MI CHD death. SCT status was determined by either direct genotyping or imputation for rs334 using the 1000Genome reference panel. Homozygous individuals and those with a prior history of CHD were excluded. Individuals with incident “micro MI”, only defined in REGARDS, were also excluded from the analysis. Analysis was performed separately in each cohort using a Cox proportional hazard models to estimate the hazard ratio (HR) for incident MI or CHD comparing SCT carriers to non-carriers. Models in each cohort were adjusted for age, sex, study site or region of residence, hypertension or systolic blood pressure, diabetes, serum LDL or HDL or total cholesterol, and population stratification (using principal components of global ancestry). The results from each cohorts were then meta-analyzed using a random effect model due to significant heterogeneity between studies (I2 = 39.1%, p = 0.02 for MI meta-analysis and I2 = 56%, p = 0.01 for CHD meta-analysis). Result