Epidemiology
Lp(a) raises heart failure risk in a nonlinear, plateauing dose-response pattern, meta-analysis of 400,631 (Clin Cardiol 2026)
Original title: Lipoprotein(a) and the Risk of Heart Failure: A Dose-Response Meta-Analysis
Dose-response meta-analysis of five prospective cohort studies (400,631 participants), quantifying the association between Lp(a) and incident heart failure (HF). Over a mean 11.0-year follow-up, 10,598 participants (2.6%) developed HF. High Lp(a) was associated with increased HF risk (HR 1.34, 95% CI 1.14-1.59, p<0.001; moderate heterogeneity I2 69%), with a stronger association at an Lp(a) cut-off of 50 mg/dL or more (HR 1.68) than below 50 mg/dL (HR 1.16, p for subgroup difference below 0.01), which fully explained the heterogeneity. Dose-response analysis showed a nonlinear relationship (p for non-linearity=0.001): HF risk rose nearly linearly below 55 mg/dL, then slowed, plateauing around 160 mg/dL. The authors conclude elevated Lp(a) raises HF risk with diminishing marginal risk at higher concentrations.
Original abstract
Background: Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein implicated in cardiovascular disease, but its role in heart failure (HF) remains uncertain. Observational studies indicate a link between elevated Lp(a) and HF risk, but the dose-response relationship remains unexplored. This meta-analysis aimed to quantify the association between circulating Lp(a) levels and HF incidence.
Methods: A systematic search of PubMed, Embase, and Web of Science identified prospective cohort studies reporting hazard ratios (HRs) for HF incidence across different Lp(a) levels. A random-effects model was applied to pool effect estimates while accounting for heterogeneity, and restricted cubic splines assessed dose-response relationships.
Results: Five prospective cohort studies with 400 631 participants were included. During a mean follow-up duration of 11.0 years, 10 598 (2.6%) patients developed HF. A high Lp(a) level was associated with an increased HF risk (HR: 1.34, 95% CI: 1.14-1.59, p < 0.001), with moderate heterogeneity (I² = 69%). Subgroup analysis showed a stronger association in studies using an Lp(a) cutoff of ≥ 50 mg/dL (HR: 1.68) compared to those with a cutoff of < 50 mg/dL (HR: 1.16, p for subgroup difference < 0.01), which completely explained the heterogeneity. The dose-response analysis revealed a nonlinear association (p for non-linearity = 0.001). HF risk increased nearly linearly below 55 mg/dL, then slowed, and plateaued at 160 mg/dL.
Conclusions: Elevated Lp(a) is associated with an increased HF risk in a nonlinear pattern, with risk escalation slowing at higher concentrations.
epidemiologyheart failurerisk prediction
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.