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

TitleAssociation of Sickle Cell Trait With Incidence of Coronary Heart Disease Among African American Individuals.
Publication TypeJournal Article
Year of Publication2021
AuthorsHyacinth HI, Franceschini N, Seals SR, Irvin MR, Chaudhary N, Naik RP, Alonso A, Carty CL, Burke GL, Zakai NA, Winkler CA, David VA, Kopp JB, Judd SE, Adams RJ, Gee BE, Longstreth WT, Egede L, Lackland DT, Greenberg CS, Taylor H, Manson JAE, Key NS, Derebail VK, Kshirsagar AV, Folsom AR, Konety SH, Howard V, Allison M, Wilson JG, Correa A, Zhi D, Arnett DK, Howard G, Reiner AP, Cushman M, Safford MM
JournalJAMA Netw Open
Volume4
Issue1
Paginatione2030435
Date Published2021 01 04
ISSN2574-3805
KeywordsAfrican Americans, Aged, Cohort Studies, Coronary Disease, Female, Humans, Incidence, Male, Middle Aged, Sickle Cell Trait
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.

DOI10.1001/jamanetworkopen.2020.30435
Alternate JournalJAMA Netw Open
PubMed ID33399855
PubMed Central IDPMC7786247
Grant ListU01 NS041588 / NS / NINDS NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
HHSN271201100004C / AG / NIA NIH HHS / United States
HHSN261201800010I / CA / NCI NIH HHS / United States
R01 HL080477 / HL / NHLBI NIH HHS / United States
N02 HL64278 / HL / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
R01 HL132947 / HL / NHLBI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
HHSN261201800014I / CA / NCI NIH HHS / United States
K08 HL096841 / HL / NHLBI NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
R01 HL156024 / HL / NHLBI NIH HHS / United States
R56 DK104806 / DK / NIDDK NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
R21 HL140385 / HL / NHLBI NIH HHS / United States
L60 MD013112 / MD / NIMHD NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201800015I / HB / NHLBI NIH HHS / United States
R01 DK117445 / DK / NIDDK NIH HHS / United States
R01 HL130733 / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
R21 HL123677 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States
R01 HL136574 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
K24 HL148521 / HL / NHLBI NIH HHS / United States
HHSN268201500003I / HL / NHLBI NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
HHSN268201100003C / WH / WHI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
R01 HL138423 / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
R01 MD012765 / MD / NIMHD NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
HHSN268201800013I / MD / NIMHD NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States