Association Between NHHR and Future Cardiovascular Disease Among Patients With CKM Stages 0-3: A Nationwide Prospective Cohort Study.

The American Heart Association recently proposed the concept of Cardiovascular-kidney-metabolic (CKM) syndrome, emphasizing the interconnections among cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders. The ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) has emerged as a novel lipid marker associated with CVD, but its relevance in individuals with CKM syndrome remains unclear. This study aimed to examine the association between NHHR and incident CVD among adults with CKM stages 0-3 using data from the China Health and Retirement Longitudinal Study (CHARLS). CVD events were defined as self-reported heart disease or stroke. Cox proportional hazards models and restricted cubic spline (RCS) analyses were applied to assess associations, and receiver operating characteristic (ROC) curves evaluated predictive performance. Among 7445 participants (mean follow-up: 80 months), 1476 developed CVD. Each one-unit increase in NHHR was associated with a 4% higher risk of CVD (95% CI: 1.00-1.08). Participants in the highest quartile (Q4) had a 23% higher risk compared with Q1 (HR = 1.23, 95% CI: 1.03-1.47). RCS analysis showed a significant positive linear relationship (P overall = 0.018). NHHR demonstrated the strongest predictive ability for CVD, with consistent results across subgroups. Higher NHHR levels were independently linked to increased CVD risk among individuals with CKM stages 0-3, suggesting NHHR may serve as a simple marker to identify high-risk populations.