Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Jun 2025)
Lipoprotein(a) and Heart Failure Among Black and White Participants in Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and Multi‐Ethnic Study of Atherosclerosis: The Pooling Project
Abstract
Background This study investigated Lp(a) (lipoprotein(a)) levels with heart failure (HF) incidence overall and ejection fraction (EF) subtypes among Black and White participants in a pooled analysis of MESA (Multi‐Ethnic Study of Atherosclerosis), FOS (Framingham Offspring Study), and ARIC (Atherosclerosis Risk in Communities Study). Methods This study was conducted among 16 771 White and Black participants in ARIC (N=10 347), MESA (N=4150), and FOS (N=2274). Baseline was time of Lp(a) measurement (ARIC Visit 4: 1996–1998; MESA Visit 1: 2000–2002; FOS Cycle 6: 1995–1998). HF with reduced EF (HFrEF) was defined as EF <50% and ≥50% as HF with preserved EF (HFpEF). Cox proportional hazards regression was used to evaluate associations between Lp(a) (log‐transformed continuous, dichotomized at ≥30 mg/dL and ≥50 mg/dL, and quartiles) and HF (overall, HFpEF, HFrEF) in the overall population and stratified by race. Analyses were replicated excluding prior history of myocardial infarction. Results There were 2759 HF cases (HFpEF N=859; HFrEF N=649; EF unknown N=1251) through 2019. Among White participants, Lp(a) ≥50 mg/dL was associated with HF risk overall (hazard ratio [HR], 1.19 [95% CI, 1.07–1.34]) and by EF subtype (HFpEF HR, 1.32 [95% CI, 1.08–1.59]; HFrEF HR, 1.33 [95% CI, 1.05–1.67]). Among Black participants, Lp(a) ≥50 mg/dL was not associated with HF risk overall (HR, 0.93 [95% CI, 0.78–1.11]) or by EF subtype (HFpEF HR, 0.97 [95% CI, 0.69–1.35]; HFrEF HR, 0.89 [95% CI, 0.63–1.26]). Associations were no longer significant after excluding prior myocardial infarction. Conclusions Elevated Lp(a) levels are associated with HF risk among White, but not Black individuals, and associations appears to be mostly mediated by a history of myocardial infarction.
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