Lp(a) Lipoprotein(a)-Related Risk of Heart Failure Is Evident in Whites but Not in Other Racial/Ethnic Groups

Objective- Lp(a) lipoprotein(a) levels vary by race/ethnicity and were recently found to be associated with risk of heart failure (HF). We aimed to determine whether Lp(a)-related risk of HF is similar across different races and whether Lp(a) may further be related to HF with reduced ejection fraction or HF with preserved ejection fraction (HFpEF). Approach and Results- In 6809 participants of the MESA (Multi-Ethnic Study of Atherosclerosis), aged 45 to 84 years and free of cardiovascular disease, 308 incident HF events occurred during a median 13-year follow-up. Baseline Lp(a) concentrations were determined by immunoassay. Incident HF was adjudicated, distinguishing HF with reduced ejection fraction (ejection fraction, <45%) from HFpEF (ejection fraction, ≥45%). Cox regression assessed relations between Lp(a) and HF risk among 4 races/ethnicities. Lp(a) was examined as a continuous variable (per log unit) and using clinical cutoff values, 30 and 50 mg/dL. Lp(a) was related to greater risk of HF in whites alone: per log unit Lp(a) (hazard ratio HR, 1.20; P=0.02); Lp(a) ≥30 mg/dL (HR, 1.69; P=0.01), Lp(a) ≥50 mg/dL (HR, 1.87; P=0.006). No significant relations were found in black, Hispanic, or Chinese participants, and significant race interactions were observed. Lp(a) was additionally related to greater risk of HFpEF in white participants: per log unit Lp(a) (HR, 1.48; P=0.001), Lp(a) ≥30 mg/dL (HR, 2.15; P=0.01), Lp(a) ≥50 mg/dL (HR, 2.60; P=0.004). Lp(a)-related risk of HF and HFpEF in whites was independent of aortic valve disease. Conclusions- In a multiethnic sample, Lp(a)-related risks of HF and HFpEF were only evident in white participants. If confirmed, these findings have implications in further Lp(a) research and clinical practice.