Association of non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio with cardiovascular outcomes in patients with type 2 diabetes mellitus: Evidence from the ACCORD cohort.

Aim: To explore the association between the non-high-density lipoprotein cholesterol (HDL-C)/HDL-C ratio (NHHR) and the risk of major adverse cardiovascular events (MACEs) and overall mortality in patients with type 2 diabetes mellitus (T2DM).

Materials and methods: NHHR, calculated as (total cholesterol - HDL-C)/HDL-C, was evaluated in 10,188 participants. Cox proportional hazard regression models were employed to assess the association of NHHR with future risk of MACEs and overall mortality. Restricted cubic spline analysis, smooth curve fitting and piecewise regression models were utilized to explore the non-linear correlation and establish the threshold. Subgroup and interaction analyses verified the robustness of the findings. The area under the receiver operating characteristic area under the curve assessed the additional predictive value of NHHR beyond conventional risk factors.

Results: After adjusting for confounding factors, each 1-unit increase in NHHR was associated with a 12% increased risk of MACEs (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.07-1.16; p < 0.0001), a 5% increase in overall mortality (HR: 1.05, 95% CI: 1.01-1.10; p = 0.0256), a 10% increase in cardiovascular disease mortality (HR 1.10, 95% CI: 1.03-1.18; p = 0.0074), an 12% increase in non-fatal myocardial infarction (HR: 1.12, 95% CI: 1.05-1.18; p = 0.0002), and an 11% increase in non-fatal stroke (HR: 1.11, 95% CI: 1.02-1.20; p = 0.0123). Analyses showed a non-linear relationship between NHHR and MACEs in patients with T2DM (non-linearity p < 0.001). A two-stage linear regression model identified a threshold for MACEs at 6.28. Integration NHHR into the conventional model significantly enhanced predictive accuracy for MACEs.

Conclusions: NHHR is a predictor of the risk of developing MACEs and overall mortality in patients with T2DM, with higher NHHR values independently associated with increased future MACE risks after full adjustment for confounders.