Association of Sickle Cell Trait With Incidence of Coronary Heart Disease Among African American Individuals

• Type of Material: Article
• Authors: Hyacinth Hyacinth, Emory University; Nora Franceschini, University of North Carolina; Samantha R. Seals, University of West Florida; Marguerite R. Irvin, University of Alabama, Birmingham; Ninad Chaudhary, University of Alabama, Birmingham; Rakhi P. Naik, Johns Hopkins University; Alvaro Alonso, Emory University; Cara L. Carty, Fred Hutchinson Cancer Research Center; Greg Burke, Emory University; Neil A. Zakai, University of Vermont; Cheryl A. Winkler, National Cancer Institute and Frederick National Laboratory; Victor A. David, National Cancer Institute and Frederick National Laboratory; Jeffrey B. Kopp, National Institute of Diabetes and Digestive and Kidney Diseases; Suzanne E. Judd, University of Alabama, Birmingham; Robert J. Adams, Medical University of South Carolina; Beatrice Gee, Emory University; W. T. Longstreth, University of Washington; Leonard Egede, Medical College of Wisconsin; Daniel T. Lackland, Medical University of South Carolina; Charles S. Greenberg, Medical University of South Carolina; Herman Taylor, Emory University; JoAnn E. Manson, Harvard Medical School; Nigel S. Key, University of North Carolina; Vimal K. Derebail, University of North Carolina; Abhijit V. Kshirsagar, University of North Carolina; Aaron R. Folsom, University of Minnesota; Suma H. Konety, University of Minnesota; Virginia Howard, University of Alabama, Birmingham; Matthew Allison, University of California, San Diego; James G. Wilson, University of Mississippi; Adolfo Correa, Emory University; Degui Zhi, University of Alabama, Birmingham; Donna K. Arnett, University of Kentucky; George Howard, University of Alabama, Birmingham; Alexander P. Reiner, University of Washington; Mary Cushman, University of Vermont; Monika M. Safford, Weill Cornell Medicine
• Language: English
• Date: 2021-01-05
• Publisher: AMER MEDICAL ASSOC
• Publication Version: Final Published Version
• Copyright Statement: 2021 Hyacinth HI et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1001/jamanetworkopen.2020.30435
• Title of Journal or Parent Work: JAMA NETWORK OPEN
• Volume: 4
• Issue: 1
• Start Page: e2030435
• End Page: e2030435
• Grant/Funding Information: The Multi-Ethnic Study of Atherosclerosis (MESA) and the MESA SHARe project are conducted and supported by the NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-001079, UL1-TR-000040, and DK063491. Funding for SHARe genotyping was provided by NHLBI contract N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, California) and the Broad Institute of Harvard and MIT (Boston, Massachusetts) using the Affymetrix Genome-Wide Human SNP Array 6.0. The Jackson Heart Study is supported and conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I), and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I) contracts from the NHLBI and the National Institute on Minority Health and Health Disparities. The Women’s Health Initiative program is funded by the NHLBI, NIH, US Department of Health and Human Services, through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The Reasons for Geographic and Racial Differences in Stroke study is co-funded by the NINDS and the NIA. This research project is supported by cooperative agreement U01NS041588 co-funded by the NINDS and the NIA, NIH, US Department of Health and Human Services. The Atherosclerosis Risk in Communities study has been funded in whole or in part with federal funds from the NHLBI, NIH, US Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700005I), R01HL087641, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200625226C. Infrastructure was partly supported by grant number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. This study was supported in part by grant R01HL080477 from the NHLBI, NIH (Dr Safford); grants 3U01HL117721, R01HL138423, and R01HL156024 from the NHLBI, NIH (Dr Hyacinth); grant 1K08HL125100 from the NHLBI, NIH (Dr Naik); grant K08HL096841 from the NHLBI, NIH (Dr Zakai); grants R01HL136574, R01HL132947, and R01HL130733 from the NHLBI, NIH (Dr Reiner); grants R56 DK104806 and R21HL123677 from the NHLBI, NIH (Dr Franceschini); and grant K24HL148521 (Dr Alonso) from the NHLBI, NIH and grant 00051285 (Dr Hyacinth) from the Emory Pediatrics Children's Heart Research and Outcomes Center. The project has been supported in part by the NIH and the National Cancer Institute Intramural Research Program (Dr Winkler) and under contract HHSN26120080001E.
• Keywords: RENAL-INSUFFICIENCY COHORT; CHRONIC KIDNEY-DISEASE; Medicine, General & Internal; RACIAL-DIFFERENCES; Science & Technology; VENOUS THROMBOEMBOLISM; MEDULLARY CARCINOMA; General & Internal Medicine; Life Sciences & Biomedicine; ETHNIC-DIFFERENCES; STROKE; CARDIOVASCULAR-DISEASE; RISK-FACTOR; APOL1 VARIANTS
• Research Categories: Health Sciences, Medicine and Surgery; Engineering, Biomedical

Abstract

Importance: The incidence of and mortality from coronary heart disease (CHD) are substantially higher among African American individuals compared with non-Hispanic White individuals, even after adjusting for traditional factors associated with CHD. The unexplained excess risk might be due to genetic factors related to African ancestry that are associated with a higher risk of CHD, such as the heterozygous state for the sickle cell variant or sickle cell trait (SCT). Objective: To evaluate whether there is an association between SCT and the incidence of myocardial infarction (MI) or composite CHD outcomes in African American individuals. Design, Setting, and Participants: This cohort study included 5 large, prospective, population-based cohorts of African American individuals in the Women's Health Initiative (WHI) study, the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, the Multi-Ethnic Study of Atherosclerosis (MESA), the Jackson Heart Study (JHS), and the Atherosclerosis Risk in Communities (ARIC) study. The follow-up periods included in this study were 1993 and 1998 to 2014 for the WHI study, 2003 to 2014 for the REGARDS study, 2002 to 2016 for the MESA, 2002 to 2015 for the JHS, and 1987 to 2016 for the ARIC study. Data analysis began in October 2013 and was completed in October 2020. Exposures: Sickle cell trait status was evaluated by either direct genotyping or high-quality imputation of rs334 (the sickle cell variant). Participants with sickle cell disease and those with a history of CHD were excluded from the analyses. Main Outcomes and Measures: Incident MI, defined as adjudicated nonfatal or fatal MI, and incident CHD, defined as adjudicated nonfatal MI, fatal MI, coronary revascularization procedures, or death due to CHD. Cox proportional hazards regression models were used to estimate the hazard ratio for incident MI or CHD comparing SCT carriers with noncarriers. Models were adjusted for age, sex (except for the WHI study), study site or region of residence, hypertension status or systolic blood pressure, type 1 or 2 diabetes, serum high-density lipoprotein level, total cholesterol level, and global ancestry (estimated from principal components analysis). Results: A total of 23 197 African American men (29.8%) and women (70.2%) were included in the combined sample, of whom 1781 had SCT (7.7% prevalence). Mean (SD) ages at baseline were 61.2 (6.9) years in the WHI study (n = 5904), 64.0 (9.3) years in the REGARDS study (n = 10 714), 62.0 (10.0) years in the MESA (n = 1556), 50.3 (12.0) years in the JHS (n = 2175), and 53.2 (5.8) years in the ARIC study (n = 2848). There were no significant differences in the distribution of traditional factors associated with cardiovascular disease by SCT status within cohorts. A combined total of 1034 participants (76 with SCT) had incident MI, and 1714 (137 with SCT) had the composite CHD outcome. The meta-analyzed crude incidence rate of MI did not differ by SCT status and was 3.8 per 1000 person-years (95% CI, 3.3-4.5 per 1000 person-years) among those with SCT and 3.6 per 1000 person-years (95% CI, 2.7-5.1 per 1000 person-years) among those without SCT. For the composite CHD outcome, these rates were 7.3 per 1000 person-years (95% CI, 5.5-9.7 per 1000 person-years) among those with SCT and 6.0 per 1000 person-years (95% CI, 4.9-7.4 per 1000 person-years) among those without SCT. Meta-analysis of the 5 study results showed that SCT status was not significantly associated with MI (hazard ratio, 1.03; 95% CI, 0.81-1.32) or the composite CHD outcome (hazard ratio, 1.16; 95% CI, 0.92-1.47). Conclusions and Relevance: In this cohort study, there was not an association between SCT and increased risk of MI or CHD in African American individuals. These disorders may not be associated with sickle cell trait-related sudden death in this population.