Participants in the highest quartile of non-HDL to HDL cholesterol ratio had paradoxically lower odds of self-reported coronary heart disease (OR 0.39) compared to the lowest quartile.
Observational (n=27,091)
Is the non-HDL to HDL cholesterol ratio (NHHR) associated with coronary heart disease and long-term mortality in U.S. adults?
Paradoxically, a higher non-HDL to HDL cholesterol ratio was associated with lower odds of self-reported CHD and a U-shaped relationship with mortality, likely reflecting reverse causality or residual confounding in this observational cohort.
Odds Ratio: 0.39 (95% CI 0.31–0.5)
p-value: p=<0.0001
Abstract Background Coronary heart disease (CHD) remains a leading global cause of morbidity and mortality. Dyslipidemia—particularly elevated non-high-density lipoprotein cholesterol (non–HDL-C) and reduced high-density lipoprotein cholesterol (HDL-C)—is a key risk factor for CHD. The ratio of non–HDL-C to HDL-C (NHHR) has been proposed as an integrative marker of lipid-related risk. We separately examined the cross-sectional association of NHHR with CHD status and its prospective association with long-term mortality in a nationally representative U.S. cohort. Methods We analyzed data from adults (aged ≥ 18 years) in NHANES 2005–2016. NHHR was calculated as non–HDL-C divided by HDL-C. Cross-sectional associations between NHHR and self-reported CHD were assessed using multivariable logistic regression. Prospective associations of baseline NHHR with all-cause and cardiovascular mortality were examined using Cox proportional hazards models. Restricted cubic splines (3 knots) were used to explore potential nonlinear relationships. Results Among ~ 20,000 adults, higher NHHR was paradoxically associated with lower odds of self-reported CHD. In fully adjusted models, participants in the highest NHHR quartile had an odds ratio of 0.39 (95% CI, 0.31–0.50; p < 0.0001) compared to the lowest quartile. In longitudinal analyses over a median follow-up of 7–10 years, higher NHHR was associated with lower hazard of all-cause and cardiovascular mortality. Spline analyses suggested a U-shaped relationship, with nadirs at NHHR ≈3.4 for all-cause and ≈3.3 for cardiovascular mortality ( P for nonlinearity < 0.001). Conclusions In this large NHANES-based observational study, NHHR was cross-sectionally associated with lower CHD prevalence and longitudinally associated with reduced mortality. While similar patterns have been reported in prior NHANES studies, our analysis contributes additional insight by jointly modeling both CHD and mortality outcomes using nonlinear spline approaches and subgroup analyses. The paradoxical inverse association with CHD may reflect residual confounding or reverse causality. These findings remain exploratory and require cautious interpretation and further validation.
Xu et al. (2026) conducted an observational in Coronary heart disease and mortality (n=27,091). Non-HDL to HDL cholesterol ratio (NHHR) vs. Lowest NHHR quartile (Q1) was evaluated on Self-reported coronary heart disease (CHD) (OR 0.39, 95% CI 0.31-0.50, p=<0.0001). Participants in the highest quartile of non-HDL to HDL cholesterol ratio had paradoxically lower odds of self-reported coronary heart disease (OR 0.39) compared to the lowest quartile.