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

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 16771 White and Black participants in ARIC (N=10347), 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 ≥30mg/dL and ≥50mg/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) ≥50mg/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) ≥50mg/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.