RCT: Lipoprotein(a) and LDL-C as Independent Cardiovascular Risk Factors in Statin Trials
5 Nov, 2024 | 17:50h | UTCBackground: Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] are both known risk factors for atherosclerotic cardiovascular disease (ASCVD). However, the interaction between Lp(a) and LDL-C levels in relation to ASCVD risk, especially in the context of LDL-C-lowering treatments like statins, remains unclear. This study aimed to clarify if LDL-C reduction impacts Lp(a)-associated ASCVD risk.
Objective: This meta-analysis examined whether LDL-C reduction with statins affects ASCVD risk mediated by elevated Lp(a) levels.
Methods: Data from 27,658 participants across six statin trials were analyzed, including both placebo and statin groups. ASCVD risk was assessed using multivariable Cox proportional hazards models with adjustments for various cardiovascular risk factors. The study evaluated continuous associations between Lp(a) levels, LDL-C levels, and ASCVD risk.
Results: Elevated Lp(a) levels were associated with higher ASCVD risk across all LDL-C levels, even among patients with the lowest LDL-C achieved through statin therapy. Statin-treated patients with Lp(a) >50 mg/dL exhibited a significantly higher ASCVD risk, even in the lowest quartile of achieved LDL-C (HR 1.38, 95% CI 1.06–1.79). The highest risk was observed in individuals with both elevated Lp(a) and LDL-C levels (HR 1.90, 95% CI 1.46–2.48).
Conclusions: Lp(a) and LDL-C are independent risk factors for ASCVD, with LDL-C lowering alone insufficient to mitigate the risk associated with elevated Lp(a).
Implications for Practice: These findings underscore the need for distinct strategies to manage patients with elevated Lp(a), particularly as LDL-C reduction alone does not fully address the associated ASCVD risk.
Study Strengths and Limitations: This study’s strength lies in its large participant pool and robust statistical analysis; however, variability in Lp(a) measurement methods across trials may limit precision.
Future Research: Investigations into therapies specifically targeting Lp(a) may offer additional ASCVD risk reduction beyond LDL-C lowering alone.