Abstract Aims To evaluate the association between longitudinal non‐HDL‐C exposure and the risks of major adverse cardiovascular events (MACEs) and all‐cause mortality in type 2 diabetes patients on lipid‐lowering therapy. Materials and Methods This post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial included patients with type 2 diabetes who had non‐HDL‐C measured at baseline and four subsequent visits over 24 months. Longitudinal exposure was assessed using cumulative load, variability (standard deviation) and trajectory (slope). Outcomes were MACEs and all‐cause mortality. Cox proportional hazard models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). Results Among 4673 participants with a median follow‐up of 7.5 years, 695 MACEs and 842 deaths occurred. After adjusting for baseline and mean non‐HDL‐C levels, the highest quartile of cumulative load (HR, 1.81; 95% CI, 1.41–2.32), variability (HR, 1.27; 95% CI, 1.00–1.60) and the most rapidly increasing slope (HR, 1.26; 95% CI, 1.02–1.56) were each associated with increased risks of MACEs, compared to the lowest quartile. The association with all‐cause mortality followed a similar pattern, except for the non‐HDL‐C slope. Stratified analyses showed that cumulative load and variability were associated with MACEs among participants with baseline non‐HDL‐C < 130 mg/dL, and with all‐cause mortality among those with baseline ≥130 mg/dL. No significant associations with slope were observed within strata of baseline non‐HDL‐C. Conclusions Longitudinal non‐HDL‐C exposure showed associations with both MACEs and mortality, independent of baseline non‐HDL‐C, underscoring the need for sustained and stable non‐HDL‐C control over time.
Lv et al. (2026) studied this question.