Abstract 15873: Association of Heart Failure With Lipoprotein (a) Level: A Systematic Review and Meta-Analysis of Observational and Mendelian Randomization Studies

Abstract

Background and Aims: The rising incidence of heart failure (HF) in the Western world, despite advancing clinical care, necessitates further exploration of preventive tools and strategies. Lipoprotein(a) [Lp(a)], a recognized cardiovascular risk factor, has been implicated in heart failure. However, existing evidence is inconclusive, which is the impetus for this meta-analysis. Methods: We systematically searched PubMed/Medline, EMBASE, and Scopus for studies on the association of Lp(a) with heart failure occurrence until February 2023. Pooled hazard ratios (HR) and odds ratios (OR) were estimated using random effects models, and heterogeneity was assessed using I2 statistics. Leave-one-out sensitivity analyses were performed by sequentially removing one study at a time. Results: After screening, 11 study populations were included, consisting of 7 mendelian randomization (MR) and 2 adjusted observational studies. MR analysis showed a significant association between increasing Lp(a) levels and heart failure risk (OR 1.064, 95% CI: 1.043-1.086, I2= 97.59%, p<0.001) (Fig 1a). However, in the observational studies, Lp(a) ≥30mg/dL was not associated with increased heart failure risk after adjusting for confounders (OR 0.97, 95% CI: 0.64-1.47, I2=62.01%, p=0.894) (Fig 1b). Leave-one-out sensitivity analysis confirmed the robustness of the MR findings (Fig 1b). Conclusions: Our meta-analysis of mendelian randomization data demonstrates an association between increasing Lp(a) levels and increased risk of heart failure. The underlying mechanisms, whether direct effects on heart muscle contraction or increased risk of ischemic cardiac disease, require further elucidation.