Lipoprotein(a) is associated with ASCVD in individuals with non‐diabetes, prediabetes, or diabetes independent of CRP

AIMS: Conflicting data have explored the association between lipoprotein(a) [Lp(a)] and atherosclerotic cardiovascular disease (ASCVD) among individuals with different glucose metabolism statuses. We aimed to prospectively evaluate this association and to assess whether it is modified by C-reactive protein (CRP). MATERIALS AND METHODS: This population-based cohort study was derived from the UK Biobank database. Lp(a) and CRP were measured between 2006 and 2010. Cox proportional hazards models and restricted cubic spline curves were employed to assess the relationship between Lp(a) levels and time to ASCVD events. RESULTS: A total of 307 269 participants without prevalent ASCVD were included, comprising 253 746 individuals with normal glucose regulation (NGR), 38 020 with prediabetes, and 15 503 with diabetes. The mean age was 57 years (Q1-Q3: 50-63), and 55.3% were female. Over a median follow-up of 13.2 years, 29 521 ASCVD events occurred. Higher Lp(a) levels were associated with an increased risk of ASCVD across all glucose metabolism statuses. In fully adjusted models, the hazard ratio (95% confidence interval) for ASCVD comparing participants in the top 10% of Lp(a) with those in the bottom 33% was 1.28 (1.22-1.34) among those with NGR, 1.23 (1.12-1.35) among those with prediabetes, and 1.16 (1.02-1.31) among those with diabetes. No significant interactions were observed after stratification by CRP (<2/≥2 mg/L) across glucose metabolism groups (P for interaction >0.05). CONCLUSIONS: Elevated Lp(a) levels were associated with a higher risk of ASCVD across different glucose metabolism statuses, particularly among individuals with NGR and prediabetes, independent of baseline CRP levels.