Inflammation
Meta-analysis of 562,301 participants confirms Lp(a) raises MACE risk independent of hs-CRP in both primary and secondary prevention (JACC Adv 2024)
Original title: Association of Lipoprotein(a) With Major Adverse Cardiovascular Events Across hs-CRP: A Systematic Review and Meta-Analysis
This systematic review and meta-analysis pooled nine publications encompassing 11 studies and 562,301 participants (39.9% female, weighted mean age 61.2 years) to clarify whether Lp(a)'s association with major adverse cardiovascular events (MACE) depends on high-sensitivity C-reactive protein (hs-CRP) level. Elevated Lp(a) was significantly associated with MACE risk in both low hs-CRP (below 2 mg/L, pooled hazard ratio 1.26, 95% CI 1.11-1.42) and high hs-CRP (2 mg/L or above, pooled hazard ratio 1.33, 95% CI 1.20-1.47) groups. In primary prevention, hazard ratios were 1.33 (95% CI 1.06-1.66) and 1.43 (95% CI 1.13-1.82) for low and high hs-CRP respectively (subgroup difference P = 0.65), while in secondary prevention they were 1.13 (95% CI 1.00-1.27) and 1.31 (95% CI 1.12-1.52) respectively (subgroup difference P = 0.13). The findings resolve prior conflicting evidence, confirming Lp(a) predicts MACE independent of inflammatory status in both primary and secondary prevention settings.
Original abstract
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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.