Elevated Lp(a) predicts heart failure in White but not Black participants, pooled 16,771-person ARIC/MESA/FOS analysis finds, largely via prior heart attack (J Am Heart Assoc 2025)

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.