Association between the non-HDL-c to HDL-c ratio and mortality risk in cardiorenal syndrome

The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a novel biomarker that integrates atherogenic and atheroprotective lipoprotein profiles. We aimed to examine the prognostic significance of NHHR in patients with cardiorenal syndrome (CRS), a vulnerable population with significantly increased risk of mortality. We analyzed data from 1408 US adults with CRS, defined as the coexistence of cardiovascular disease (CVD) and chronic kidney disease, from the 1999 to 2018 National Health and Nutrition Examination Survey. The primary and secondary outcomes were all-cause and CVD mortality, respectively. The relationships between NHHR and mortality outcomes were analyzed using Cox proportional hazards regression analysis, restricted cubic spline modeling, and subgroup analyses. Over a median follow-up of 75 months, 802 deaths (53.63%) occurred, including 373 from CVD. We identified a significant nonlinear, L-shaped association between NHHR and both all-cause and CVD mortality, with inflection points at NHHR = 3.09 and 3.16, respectively. Piecewise regression analysis indicated that the multivariate-adjusted hazard ratios (95% confidence intervals) for all-cause and CVD mortality were 0.64 (0.53–0.76) and 0.60 (0.45–0.79), respectively, below the inflection points, and 0.83 (0.73–0.95) and 0.91 (0.78–1.05), respectively, above the inflection points. Results remained consistent across subgroups stratified by age, sex, body mass index, diabetes status, physical activity, estimated glomerular filtration rate, and urinary albumin-to-creatinine ratio. NHHR demonstrates an independent, L-shaped relationship with all-cause and CVD mortality in a nationally representative cohort of adults with CRS. This simple ratio may serve as a valuable prognostic biomarker to identify high-risk CRS patients.