Longitudinal exposure to non-HDL-C and cardiovascular events, all-cause mortality in type 2 diabetes: A post hoc analysis of the ACCORD trial

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.