Medicine (Baltimore). 2026 Aug 14;105(33):e50306. doi: 10.1097/MD.0000000000050306.
ABSTRACT
Dyslipidemia is a major contributor to adverse outcomes in patients with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a comprehensive lipid marker, but its prognostic value in this high-risk population remains unclear. This study aimed to investigate the association between NHHR and the risks of all-cause and cardiovascular mortality, as well as its correlations with metabolic, renal, and inflammatory markers in patients with CHD and T2DM. A total of 1058 patients with CHD and T2DM were identified from the National Health and Nutrition Examination Survey 2005 to 2018 database. NHHR was calculated and categorized into quartiles. The primary outcomes were all-cause and cardiovascular mortality, determined via linkage to the National Death Index. Cox proportional hazards models, adjusted for multiple confounders, were used to assess associations. Restricted cubic spline analyses were performed to investigate nonlinear relationships, and subgroup analyses evaluated effect modifications. Pearson correlation analyses assessed associations between NHHR and baseline clinical parameters. During a median follow-up of 59 months, 414 deaths occurred, including 177 cardiovascular deaths. Each unit increase in NHHR was independently associated with a 13% higher risk of all-cause mortality (hazard ratio: 1.13; 95% confidence interval: 1.09-1.17) and a 16% higher risk of cardiovascular mortality (hazard ratio: 1.16; 95% confidence interval: 1.12-1.19). Compared with the lowest quartile, participants in the highest NHHR quartile had markedly elevated mortality risks. Restricted cubic spline analyses revealed significant nonlinear associations between NHHR and both outcomes (P-nonlinearity < .001 for all-cause mortality; P = .002 for cardiovascular mortality), with a threshold effect observed around NHHR = 2.69. Subgroup analyses showed stronger associations among individuals with normal renal function and higher inflammatory markers. NHHR correlated positively with triglycerides, total cholesterol, body mass index, glycated hemoglobin, and inflammatory indices, and negatively with high-density lipoprotein cholesterol. Elevated NHHR is independently associated with increased risks of all-cause and cardiovascular mortality in patients with CHD and T2DM, with a clear nonlinear threshold effect. NHHR also reflects metabolic, renal, and inflammatory status, highlighting its potential as a simple, cost-effective biomarker for risk stratification and personalized management in this high-risk population.
PMID:42601761 | DOI:10.1097/MD.0000000000050306