Sickle cell trait not tied to higher risk for MI, CHD in Bla
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Sickle cell trait was not associated with increased risk for MI or CHD in Black individuals, according to a cohort study published in JAMA Network Open.

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).

This study aimed to evaluate whether there is an association between SCT and the incidence of myocardial infarction (MI) or composite CHD outcomes in African American individuals.

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.

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.

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).

-- A total of 23197 African American men (29.8%) and women (70.2%) were included in the combined sample, of whom 1781 had SCT.

-- Mean ages at baseline were 61.2 years in the WHI study (n=5904), 64.0 years in the REGARDS study (n=10714), 62.0 years in the MESA (n=1556), 50.3 years in the JHS (n=2175), and 53.2 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 among those with SCT and 3.6 per 1000 person-years among those without SCT.

-- For the composite CHD outcome, these rates were 7.3 per 1000 person-years among those with SCT and 6.0 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 or the composite CHD outcome.

Conclusively, 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.