Lipoprotein(a) as a cardiovascular risk factor among patients with and without diabetes Mellitus: the Mass General Brigham Lp(a) Registry

Background: Diabetes mellitus (DM) and Lp(a) are well-established predictors of coronary artery disease (CAD) outcomes. However, their combined association remains poorly understood. Objective: To investigate the relationship between elevated Lp(a) and DM with CAD outcomes. Methods: Retrospective analysis of the MGB Lp(a) Registry involving patients ≥ 18 years who underwent Lp(a) measurements between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasms, and prior atherosclerotic cardiovascular disease (ASCVD). The primary outcome was a combination of cardiovascular death or myocardial infarction (MI). Elevated Lp(a) was defined as > 90th percentile (≥ 216 nmol/L). Results: Among 6,238 patients who met the eligibility criteria, the median age was 54, 45% were women, and 12% had DM. Patients with DM were older, more frequently male, and had a higher prevalence of additional cardiovascular risk factors. Over a median follow-up of 12.9 years, patients with either DM or elevated Lp(a) experienced higher rates of the primary outcome. Notably, those with elevated Lp(a) had a higher incidence of the primary outcome regardless of their DM status. The annual event rates were as follows: No-DM and Lp(a) < 90th% − 0.6%; No-DM and Lp(a) > 90th% − 1.3%; DM and Lp(a) < 90th% − 1.9%; DM and Lp(a) > 90th% − 4.7% (p < 0.001). After adjusting for confounders, elevated Lp(a) remained independently associated with the primary outcome among both patients with DM (HR = 2.66 [95%CI: 1.55–4.58], p < 0.001) and those without DM (HR = 2.01 [95%CI: 1.48–2.74], p < 0.001). Conclusions: Elevated Lp(a) constitutes an independent and incremental risk factor for CAD outcomes in patients with and without DM.