UC San Diego

BACKGROUND: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. The relationship between Lp(a) and major adverse cardiovascular events (MACE) in the context of high-sensitivity C-reactive protein (hs-CRP) levels remains controversial due to conflicting results from previous studies. OBJECTIVES: This systematic review and meta-analysis aimed to clarify the association between Lp(a) and risk of MACE across different hs-CRP levels in both primary and secondary prevention settings. METHODS: We performed a systematic review by searching MEDLINE (PubMed), Embase (Ovid), Cochrane CENTRAL (Wiley), and Web of Science (Clarivate) from their inception to February 2024. Eligible studies reported the association of Lp(a) with MACE stratified by hs-CRP level. Data extraction and quality assessment were systematically conducted. Meta-analyses used random-effects models to compute pooled HRs for individuals with low (<2 mg/L) and high (≥2 mg/L) hs-CRP levels. Subgroup analyses were performed in primary and secondary prevention populations. RESULTS: Nine publications encompassing 11 studies that involved 562,301 participants met the inclusion criteria. The mean proportion of females was 39.9% and the weighted mean age for the entire cohort was 61.2 years. Elevated Lp(a) was significantly associated with MACE risk in both low and high hs-CRP groups, with pooled HR of 1.26 (95% CI: 1.11-1.42) and 1.33 (95% CI: 1.20-1.47), respectively. In the primary prevention group, the pooled HR for low and high hs-CRP groups was 1.33 (95% CI: 1.06-1.66) and 1.43 (95% CI: 1.13-1.82), respectively (subgroup difference, P = 0.65). The corresponding HRs for the secondary prevention population were 1.13 (95% CI: 1.00-1.27) and 1.31 (95% CI: 1.12-1.52), respectively (subgroup difference P = 0.13). CONCLUSION: Elevated Lp(a) is associated with an increased risk of MACE independent of hs-CRP levels in both primary and secondary prevention populations.