Sickle Cell Trait Has No Link to Coronary Heart Disease, Myocardial Infarction

Hyacinth Hyacinth, MD, PhD, MPH

Findings from a new study suggest that sickle cell trait may not increase the risk of myocardial infarction or coronary heart disease.

As such, the investigators indicated there was no association between these cardiovascular conditions and sickle cell-related sudden death.

The cohort study, led by Hyacinth Idu Hyacinth MD, PhD, MPH, Assistant Professor, Pediatrics, Emory University, evaluated prospective, population-based cohorts of African American individuals taken from the Women’s Heath Initiative (WHI) study, the Reasons for Geographic and Racial Differences in Stroke (REGARDS), the Multi-Ethnic Study of Atherosclerosis (MESA), the Jackson Heart Study (JHS), and the Atherosclerosis Risk in Communities (ARIC) study.

The team sought to further understand the increased incidence of coronary heart disease among African American populations.

“The burden of cardiovascular disease in general and coronary heart disease in particular is disproportionately high among African American individuals, resulting in a substantial health disparity,” they noted.

“Approximately 60% of this disparity is associated with the excess burden of classical factors associated with CVD among African American individuals compared with non-Hispanic White individuals.”

Cardiovascaulr Disease and Sickle Cell Trait

In all 5 trials, sickle cell trait status was determined by either direct genotyping or high-quality imputation of rs334.

Hyacinth and colleagues excluded from their analysis those with sickle cell disease as well as those with a history of coronary heart disease.

Thus, they evaluated a total of 23,197 African American—29.8% of which were men. Furthermore, 1781 were determined to have the sickle cell trait.

Mean ages at baseline were 61.2 years in WHI trial, 64.0 years in the REGARDS trial, 62.0 years in the MESA trial, 50.3 in the JHS, and 53.2 years in the ARIC trial.

Across all cohorts, the investigators assessed incident myocardial infarction and incident coronary heart disease.

Further, they used cox proportional hazards regression models to estimate hazard ratios comparing the sickle cell trait with non-carriers.

The Results

Overall, a total of 1034 participants—76 with the sickle cell trait—had incident myocardial infarction.

Furthermore, as many as 1714—137 with sickle cell trait—had a composite coronary heart disease outcome, which consisted of adjudicated nonfatal myocardial infarction, fatal myocardial infarction, coronary revascularization procedures, or death due to coronary heart disease.

The meta-analyzed crude incidence rate of myocardial infarction among those with the sickle cell trait was 3.8 per 1000 person-years (95% CI, 3.3-4.5 per 1000 person-years).

Among those without the sickle cell trait, the crude incidence rate was 3.6 per 1000 person-years (95% CI, 2.7-5.1 per 1000 person-years) among those without the sickle cell trait.

As for the composite coronary heart disease outcome, crude incidence rate among individuals with the sickle cell trait was 7.3 per 1000 person-years (95% CI, 5.5-9.7 per 1000 person-years) — versus 6.0 per 1000 person-years (95% CI, 4.9-7.4 per 1000 person-years) among those without the trait.

And finally, meta-analysis showed that the sickle cell trait had no significant association with risk for myocardial infarction (hazard ratio [HR], 1.03; 95% CI, 0.81-1.32) or the composite coronary heart disease outcomes (HR, 1.16; 95% CI, 0.92-1.47).

Conclusions and Perspective

“Our study is, to our knowledge, the largest to examine the association between sickle cell trait and incidence of and coronary heart disease and, as such, adds to the current literature,” Hyacinth and team wrote. 

“The findings may provide useful information leading to a closer examination and a more thorough workup for a patient with sickle cell trait who presents with a coronary heart disease symptom.”

They noted that a few of the limitations included the inability to account for the modifying effect of other genetic factors, such as alpha-thalassemia.

Furthermore, their study was not well-powered enough to stratify analysis by sex differences and the individual components of the coronary heart disease outcomes. 

The study, “Association of Sickle Cell Trait With Incidence of Coronary Heart Disease Among African American Individuals,” was published online in JAMA Network Open.