Associations of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio with all-cause and cardiovascular mortality among general population

The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a novel lipid indicator for predicting mortality across populations, but its link to mortality in the general population is underestimated. A total of 17,334 participants from the US National Health and Nutrition Examination Survey (2005-2018) were analyzed. Weighted Cox proportional hazards models were employed to investigate the association between NHHR and all-cause and cardiovascular (CVD) mortality. We employed restricted cubic splines (RCS) to assess potential nonlinear relationships. Over a median follow-up of 88 months, we documented 1878 deaths. According to the RCS analysis, NHHR exhibited an L-shaped association with all-cause and CVD mortality. Inflection points were identified at NHHR = 2.30 for all-cause mortality and NHHR = 2.64 for CVD mortality. Below these thresholds, each unit increase in NHHR was associated with a 39% reduction in all-cause mortality (HR: 0.61, 95% CI 0.50-0.75) and a 34% reduction in CVD mortality (HR: 0.66, 95% CI 0.50-0.88). Above these thresholds, no significant associations were observed. Subgroup analyses revealed stronger inverse associations in adults aged ≥ 60 years (P for interaction < 0.0001) and those with underweight or overweight statuses (P = 0.0032). Our findings highlight an L-shaped association between NHHR and both all-cause and cardiovascular disease (CVD) mortality. NHHR demonstrates potential as a novel biomarker for personalized mortality risk stratification, particularly in high-risk subgroups.