Key result
Elevated Lp(a) is linked to increased HF risk, with escalation slowing at higher concentrations.
Why the study?
The role of lipoprotein(a) in heart failure risk remains uncertain, and the dose-response relationship has not been explored.
Does elevated Lipoprotein(a) increase the incidence of heart failure?
Meta-Analysis (n=400,631)
Does elevated Lipoprotein(a) increase the incidence of heart failure?
Hazard Ratio: 1.34 (95% CI 1.14–1.59)
p-value: p=<0.001
Elevated Lipoprotein(a) is nonlinearly associated with an increased risk of incident heart failure, with risk increasing nearly linearly below 55 mg/dL and plateauing at 160 mg/dL.
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.
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He et al. (2026) conducted a meta-analysis in Heart Failure (n=400,631). High Lipoprotein(a) level vs. Lower Lipoprotein(a) level was evaluated on Heart failure incidence (HR 1.34, 95% CI 1.14-1.59, p=<0.001). High Lipoprotein(a) levels were associated with an increased risk of heart failure (HR 1.34; 95% CI 1.14-1.59; p<0.001), with risk increasing nonlinearly and plateauing at 160 mg/dL.
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