Cumulative remnant cholesterol and major adverse cardiovascular events among adults with type 2 diabetes

Background Individuals with type 2 diabetes are prone to dyslipidemia. The relationship of cumulative exposure to elevated remnant cholesterol (RC) with major adverse cardiovascular events (MACEs) remains unclear for individuals with type 2 diabetes, especially for those with intensive lipid-lowering treatment. Methods This study included 5143 participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes trial, who had at least four lipid measurements over the first three years of the trial and did not have MACEs across the measurements. Cumulative RC (cumRC) was calculated considering RC levels at each measurement and the between-measurement time interval. Cox proportional hazards regression models were used to estimate HRs and 95% CIs of MACEs associated with cumRC levels. Results During a median follow-up of 6.3 years, 472 participants developed MACEs, including 154 cardiovascular deaths, 211 with nonfatal myocardial infarction, and 148 with nonfatal stroke. After multivariable adjustment for conventional risk factors, higher levels of cumRC were associated with a higher risk of MACEs (HR Q4 vs. Q1 = 1.71, 95% CI: 1.31-2.22; P-trend <0.001), with similar associations for cardiovascular death (P-trend = 0.013) and nonfatal myocardial infarction (P-trend <0.001), but no association for nonfatal stroke (P-trend = 0.114). The association of cumRC with the risk of MACEs was consistent across age, sex, and lipid trial assignment groups and remained after further adjusting for baseline RC. Conclusion Among adults with type 2 diabetes, cumulative exposure to elevated RC is associated with a higher risk of MACEs, even in the context of intensive lipid management.