Non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol is a predictor for cardiovascular mortality in patients with diabetes mellitus.

Background: The non-high-density lipoprotein cholesterol (non-HDL-C)/HDL-C ratio (NHHR) is linked to cardiovascular event risk, but its prognostic value in diabetes mellitus (DM) patients remains unclear.

Aim: To explore the association of NHHR and cardiovascular mortality in patients with DM and generate predictive model.

Methods: This cohort study analyzed data from 8425 DM patients in National Health and Nutrition Examination Survey. NHHR was calculated as (total cholesterol - HDL-C)/HDL-C. Cardiovascular mortality was determined via the National Death Index. Feature selection was performed using the Boruta algorithm and least absolute shrinkage and selection operator regression, followed by Cox proportional hazards models to evaluate NHHR's relationship with cardiovascular mortality. Stratified and sensitivity analyses assessed the findings' robustness. A nomogram was developed to predict cardiovascular mortality, with model performance evaluated using receiver operating characteristic curves and calibration plots.

Results: Over an average follow-up of 94.2 months, 671 cardiovascular deaths (8.0%) occurred. Six key features including age, education, ethnicity, poverty-income ratio, history of heart failure, and NHHR, were selected. A non-linear association was found, with the highest NHHR quartile showing a 39% higher risk of cardiovascular death compared to the lowest quartile (Q4, hazard ratio: 1.39, 95% confidence interval: 1.11-1.73). Stratified analyses confirmed the increased risk across all subgroups. Sensitivity analyses supported the stability of the results. The nomogram for predicting cardiovascular mortality demonstrated high accuracy.

Conclusion: Elevated NHHR is associated with increased cardiovascular mortality risk in DM patients. NHHR could be a valuable prognostic marker, aiding in identifying high-risk patients and guiding targeted lipid management strategies.