Remnant Cholesterol and Its Visit-to-visit Variability Predict Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus: Findings from the ACCORD Cohort

Objective: Remnant cholesterol (remnant-C) predicts atherosclerotic cardiovascular disease, regardless of LDL cholesterol (LDL-C) levels. This study assessed the associations between remnant-C and cardiovascular outcomes in type 2 diabetes mellitus. Research design and methods: This post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial used patient (type 2 diabetes >3 months) remnant-C and major adverse cardiovascular event (MACE) data from the study database. The associations between remnant-C and MACEs were evaluated using Cox proportional hazards regression analyses. We examined the relative MACE risk in remnant-C versus LDL-C discordant/concordant groups using clinically relevant LDL-C targets by discordance analyses. Results: The baseline analysis included 10,196 participants, with further visit-to-visit variability analysis including 9650 participants. During follow-up (median, 8.8 years), 1815 (17.8%) patients developed MACEs. After adjusting for traditional cardiovascular risk factors, each 1-SD increase in remnant-C was associated with a 7% higher MACE risk (HR=1.07, 95% CI: 1.02-1.12; P=0.004). In the fully adjusted model, the visit-to-visit remnant-C variability calculated using logSD (HR=1.41, 95% CI: 1.18-1.69, P<0.001) and logARV (HR=1.45, 95% CI: 1.22-1.73, P<0.001) was associated with MACEs. Residual lipid risk (remnant-C ³31 mg/dL) recognized individuals at a higher MACE risk, regardless of LDL-C concentrations. Within each LDL-C subgroup (>100 or ≤100 mg/dL), high baseline remnant-C was associated with a higher MACE risk (HR=1.37, 95% CI: 1.09-1.73; P=0.007; HR=1.22, 95% CI: 1.04-1.41; P=0.015, respectively). Conclusions: Remnant-C levels were associated with MACEs in type 2 diabetic patients independent of LDL-C, and visit-to-visit remnant-C variability helped identify those with higher cardiovascular risk.