Lipoprotein(a) as a Risk Factor for Myocardial Infarction, Cardiovascular, and All-Cause Mortality in Patients with Type 2 Diabetes Mellitus

Background: Lipoprotein(a) (Lp(a)) is a genetically determined lipoprotein associated with atherosclerotic cardiovascular disease (ASCVD). Its prognostic role in type 2 diabetes mellitus (T2DM) remains unclear. We aimed to evaluate the association of Lp(a) with first myocardial infarction (MI), cardiovascular (CV) mortality, and all-cause mortality, with a focus on sex differences. Methods: We retrospectively analysed patients with T2DM and no prior MI who were hospitalised between 2000 and 2018 and had baseline Lp(a) measurements. Patients were followed until MI, death, or the end of 2023. Lp(a) was categorised as ≤50, 51–90, and >90 mg/dL. Cox proportional hazards models were adjusted for low-density lipoprotein cholesterol, arterial hypertension, and estimated glomerular filtration rate < 60 mL/min/1.73 m2, with attained age used as the time scale. Results: A total of 2967 patients (37.5% women) were included. During follow-up, 12.5% of patients experienced MI, 36.4% died from CV causes, and 68.8% died from any cause. A significant interaction between Lp(a) and sex was observed for MI. In sex-specific analyses, Lp(a) > 50 mg/dL was associated with a higher risk of first MI in women (51–90 mg/dL: HR 1.79, 95% CI 1.07–2.99; >90 mg/dL: HR 2.67, 95% CI 1.66–4.32), whereas no significant association was observed in men. Elevated Lp(a) ≥ 50 mg/dL was also associated with higher CV mortality overall (51–90 mg/dL: HR 1.42, 95% CI 1.07–1.89; >90 mg/dL: HR 1.38, 95% CI 1.01–1.91), without a significant interaction with sex. No significant associations were observed for all-cause mortality. Conclusions: In patients with T2DM, elevated Lp(a) > 50 mg/dL was associated with increased risk of first MI, predominantly in women, and with higher CV mortality overall. Lp(a) may serve as a valuable marker for CV risk stratification in this population.