Do elevated lipoprotein(a) and diabetes mellitus together identify patients with coronary artery disease (CAD) at greater risk of death? An observational cohort analysis published in Diabetes, Obesity and Metabolism evaluated their combined association with cardiovascular and all-cause mortality.

The study included 65,547 patients with CAD from the CIN-II and RED-CARPET cohorts, with a mean age of 62.6 ± 10.7 years and 27.7% women, followed for a median of 5.5 years. Patients were stratified into four groups according to lipoprotein(a) [Lp(a)] level (<30 mg/dL or ≥30 mg/dL) and diabetes mellitus (DM) status. Multivariable Cox regression models estimated associations with cardiovascular and all-cause mortality and assessed additive and multiplicative interactions. During follow-up, 10,686 patients (16.3%) died from any cause, and 5,106 (7.8%) died from cardiovascular causes.

Elevated Lp(a) ≥30 mg/dL and DM were each independently associated with cardiovascular mortality (adjusted hazard ratio [aHR] 1.28; 95% confidence interval [CI] 1.20-1.35; and aHR 1.53; 95% CI 1.44-1.62; both p < 0.001). Compared with patients with Lp(a) <30 mg/dL without DM, the aHRs for cardiovascular mortality were 1.26 (95% CI 1.16-1.36; p<0.001) for elevated Lp(a) without DM, 1.51 (95% CI 1.40-1.62; p<0.001) for DM with Lp(a) <30 mg/dL, and 2.00 (95% CI 1.83-2.18; p < 0.001) for those with both elevated Lp(a) and DM. A significant additive interaction was observed, with 12% of the excess cardiovascular mortality attributed to their joint presence. Similar associations were observed for all-cause mortality.

In patients with CAD, elevated Lp(a) and DM were jointly associated with higher risks of cardiovascular and all-cause mortality. The coexistence of both factors corresponded to a greater mortality risk than either factor alone within the studied population.