# Non–HDL to HDL cholesterol ratio and coronary outcomes in U.S. adults: a cross-sectional and prospective NHANES analysis

## TL;DR

This study finds that a higher non-HDL to HDL cholesterol ratio is paradoxically linked to lower coronary heart disease prevalence and reduced mortality in U.S. adults.

## Contribution

The study uniquely combines cross-sectional and longitudinal analyses of NHHR with CHD and mortality using nonlinear modeling and subgroup comparisons.

## Key findings

- Higher NHHR was associated with lower odds of self-reported CHD (OR 0.39 in highest vs lowest quartile).
- Longitudinal analysis showed higher NHHR linked to reduced all-cause and cardiovascular mortality hazards.
- Nonlinear U-shaped relationships were observed with mortality nadirs at NHHR ≈3.4 and ≈3.3.

## Abstract

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.

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.

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).

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.

The online version contains supplementary material available at 10.1186/s40001-026-03977-x.