Lipoprotein (a) in patients with diabetes and high atherosclerotic cardiovascular risk: risk enhancer or risk modifier?

We read with great interest the recent article by de Mira et al., reporting that elevated lipoprotein(a) [Lp(a)] was associated with greater coronary plaque burden, but not with long-term cardiovascular events or mortality in patients with established atherosclerotic cardiovascular disease (ASCVD).1 Emerging evidence suggests that, among individuals at high ASCVD risk, Lp(a) may function less as a universal ‘risk enhancer’ and more as a context-dependent risk modifier, particularly in the presence of type 2 diabetes mellitus (DM). In a cohort of more than 25 000 patients with established ASCVD, Kim et al. demonstrated that the association between elevated Lp(a) and major adverse cardiovascular events was significantly stronger in patients with than in those without DM.2 Likewise, the Mass General Brigham Lp(a) Registry showed markedly higher ASCVD event rates among individuals with both DM and elevated Lp(a).3 More recently, analyses from the CIN-II and RED-CARPET cohorts also demonstrated a synergistic association between elevated Lp(a) and DM with cardiovascular and all-cause mortality in patients with coronary artery disease.4