Prospective Atherosclerosis Risk in Communities (ARIC) Study Connects Differences in Lipoprotein(a) With Racial Disparities in Atherosclerotic Cardiovascular Disease

In a prospective study of 9519 adults with no baseline atherosclerotic cardiovascular disease (ASCVD), investigators concluded that differences in plasma lipoprotein(a) (Lp[a]) distributions between White and Black participants probably contribute to racial disparities in ASCVD.^1,2 Study authors added that investigational therapies aimed at lowering Lp(a) could help to address these disparities.²

The findings were presented as a poster, “Assessing the Contribution of Racial Difference in Elevated Lipoprotein(a) Levels to Disparities in Atherosclerotic Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study,” at the American Heart Association (AHA) Scientific Sessions 2023, which convened from November 11 to 13, 2023, in Philadelphia, Pennsylvania.² Acknowledging that higher levels of Lp(a) had been reported in Black adults relative to White adults, investigators sought to compare the relative risk of higher Lp(a) levels on incident ASCVD in these 2 populations and to estimate the percentage of cases of ASCVD in each population attributable to higher Lp(a) levels.¹ The investigation used data from the Atherosclerosis Risk in Communities (ARIC) study, which in 1987 recruited 15,792 Black and White adults aged 45 to 64 years from 4 US communities (Forsyth County, North Carolina; Jackson, Mississippi; suburban Minneapolis, Minnesota; and Washington County, Maryland).^2,3 The ARIC study has followed active participants to the present by means of regular clinical exams and telephone follow-ups.⁴

Authors of the present study measured Lp(a) levels in stored plasma samples drawn between 1996 and 1999 from participants during the fourth clinical visit of the ARIC study (baseline). Samples were classified into the following categories based on Lp(a) levels: below 30 mg/dL, at least 30 mg/dL to 50 mg/dL, at least 50 mg/dL to 100 mg/dL, or at least 100 mg/dL. Using follow-up clinical data from the subsequent 20 to 25 years, the investigators assessed associations between higher Lp(a) levels ( ≥ 30 mg/dL) and incident ASCVD (defined as coronary heart disease or ischemic stroke) both overall and by race and assessed whether differences by race were significant. Finally, the investigators estimated the percentage of incident (post-baseline) ASCVD attributable to higher Lp(a) levels—the population-attributable fraction (PAF)—for the study population and for Black and White subpopulations.^1,2

The mean (SD) age of study participants at baseline was 63.1 (5.6) years.² Overall, patients were mostly White (77.5%) and female (58.8%). Of White patients, 24% had plasma Lp(a) levels of at least 30 mg/dL; of Black patients, 53.5% had elevated plasma Lp(a) levels. When adjusted for biologic and social cofounders (age, sex, race, education, smoking, alcohol, low-density lipoprotein cholesterols, triglycerides, systolic blood pressure, antihypertensive medications, diabetes mellitus, and body mass index), higher Lp(a) levels were associated with higher risk of ASCVD among all participants; patients with plasma Lp(a) of at least 100 mg/dL were 1.7 times more likely to have a subsequent ASCVD event (95% CI, 1.4-2.1).^1,2

Associations between Lp(a) level and ASCVD risk did not differ significantly by race.^1,2 Among White participants, 4.7% of all incident ASCVD was estimated to be attributable to higher Lp(a) levels (95% CI, 2.3%-7.0%); among Black participants, the estimate was 10.7% (95% CI, 5.8-15.4).²

The study expands the limited body of literature and data estimating how differences in Lp(a) contribute to race-based disparities in ASCVD. Also, use of the PAF enabled evaluation of higher Lp(a) levels upon ASCVD at the population level. Investigators noted several limitations to the study. The patient population was limited to only Black and White participants, excluding patients of other races and ethnicities (and Asian, Hispanic, or Native American patients). Moreover, the analysis did not include genetic data related to Lp(a).²

According to the investigators, genetic heritage may inform health disparities associated with race. Future research examining the role that biology plays in ASCVD could inform public health solutions addressing the racial disparities associated with this disease.²

References

1. Grant JK, Martin SS, Zhang S, et al. Abstract 14629. Assessing the contribution of racial differences in elevated lipoprotein (a) levels to disparities in atherosclerotic cardiovascular disease: the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 2023;148(suppl 1): A14629. doi:10.1161/circ.148.suppl_1.14629
2. Grant JK, Martin SS, Zhang S, et al. Assessing the contribution of racial differences in elevated lipoprotein (a) levels to disparities in atherosclerotic cardiovascular disease: the Atherosclerosis Risk in Communities (ARIC) study. Poster presented at: American Heart Association Scientific Sessions 2023; November 11-13, 2023; Philadelphia, PA. PR.APS.P1
3. Wright JD, Folsom AR, Coresh J, et al. The ARIC (Atherosclerosis Risk In Communities) study: JACC focus seminar 3/8. J Am Coll Cardiol. 2021;77(23):2939-2959. doi:10.1016/j.jacc.2021.04.035
4. Project overview. Atherosclerosis Risk in Communities (ARIC). Accessed February 7, 2024. https://aric.cscc.unc.edu/aric9/about/project_overview