Impact of diabetes on risk of major adverse cardiovascular events associated with lipoprotein(a) levels in patients with established atherosclerotic cardiovascular disease

Abstract Aims Lipoprotein(a) [Lp(a)] is an emerging risk factor for major adverse cardiovascular events (MACE). However, evidence on MACE risk according to Lp(a) level in atherosclerotic patients is insufficient, and more data is needed about whether type 2 diabetes (T2DM) additionally contributes to this risk. We aimed to investigate the association between Lp(a) and MACE in atherosclerotic patients and compare the magnitude of Lp(a)-MACE association in the patients with and without T2DM. Methods and results Using a retrospective cohort study of atherosclerotic patients with and without T2DM who were screened for Lp(a) between 1 January 2000 to 31 December 2020, we estimated the risk of MACE according to Lp(a) level stratified by quintiles and compared the difference in magnitude of Lp(a)-MACE association according to presence of T2DM with partial likelihood ratio test. The study included 25 826 patients with established atherosclerotic cardiovascular disease, of whom 7535 had T2DM (29.2%) and 18 291 did not (70.8%). During 160 174 person-years (PY) of follow-up, a total of 4836 MACE were observed. Compared to the lowest quintile (Q) of Lp(a) levels, multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for MACEs across Q2 to Q5 were 1.10 (95% CI: 0.94–1.30), 0.98 (95% CI: 0.83–1.16), and 1.25 (95% CI: 1.06–1.46), 1.29 (95% CI: 1.10–1.51) in patients with T2DM, and 0.99 (95% CI: 0.88–1.12), 1.10 (95% CI: 0.98–1.23), 1.01 (95% CI: 0.90–1.13), and 1.13 (95% CI: 1.01–1.27) for those without T2DM. The strength of Lp(a)-MACE association was stronger among the patients with T2DM (P < 0.001). Conclusion Among atherosclerotic patients with and without T2DM, elevated Lp(a) level was significantly associated with a higher risk of MACE. Compared to those without T2DM, the patients with T2DM showed an excess MACE risk, suggesting the need for clinical interventions concerning both Lp(a) level and glycemic control.