Association of Lipoprotein(a) With Adverse Clinical Outcomes Among Patients With Heart Failure: A Systematic Review and Meta-Analysis

Lipoprotein(a) (Lp(a)) is a genetically determined, causal risk factor for atherosclerotic cardiovascular disease, but its prognostic significance in patients with established heart failure (HF) remains poorly quantified despite growing evidence linking it to incident HF.We conducted a systematic review and metaanalysis to evaluate the association between Lp(a) levels and adverse outcomes, including composite cardiovascular events and all-cause mortality, in patients with prevalent HF.PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to August 31, 2026, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.Cohort studies reporting adjusted hazard ratios (HRs) for Lp(a) and outcomes in patients with HF were included; study quality was assessed using the Newcastle-Ottawa Scale.Pooled HRs were calculated using random-effects models on the log-HR scale, with heterogeneity quantified by the I² statistic.Of 681 records, seven cohort studies met the inclusion criteria (five from China and two from the United States).Elevated Lp(a) was independently associated with a significantly increased risk of composite cardiovascular outcomes (pooled HR, 1.32; 95% confidence interval (CI), 1.20-1.46;four studies; I² = 14%) and all-cause mortality (pooled HR, 1.20; 95% CI, 1.06-1.35;6 studies; I² = 51%), with low and moderate heterogeneity, respectively.Sensitivity analyses confirmed the robustness of the mortality finding across leave-one-out exclusions.These findings indicate that elevated Lp(a) is an independent prognostic biomarker for adverse cardiovascular events and mortality in patients with established HF, extending its recognized role beyond incident HF risk.Given the emergence of effective Lp(a)-lowering therapies, routine Lp(a) assessment may aid risk stratification in HF populations, and dedicated outcome trials evaluating Lp(a) reduction in this population are warranted.