Associations of NHHR change patterns and cumulative NHHR with incident cardiovascular disease among individuals with CKM stages 0-3

BACKGROUND: Individuals with cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 are free of clinical cardiovascular disease (CVD) but may already have metabolic and renal abnormalities that increase CVD susceptibility. This makes them a distinct target population for early risk stratification. Although non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) potentially reflects atherogenic lipid burden, its association with incident CVD in CKM stages 0-3 remains unclear. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study. K-means clustering identified longitudinal NHHR patterns from 2012 to 2015, and cumulative NHHR (cumNHHR) was calculated as time-weighted exposure. Logistic regression was used to examine associations with incident CVD during 2015-2020 after adjustment for sociodemographic characteristics, lifestyle behaviors, BMI, and kidney function. RESULTS: Among 3996 participants, 764 (19.12%) developed CVD. Compared with the low-stable NHHR pattern, Clusters 2 and 3 had higher odds of incident CVD, with ORs of 1.28 (95% CI, 1.07-1.54) and 1.57 (95% CI, 1.27-1.95). However, these associations were no longer statistically significant after further adjustment for baseline NHHR. Each 1-unit increase in cumNHHR was associated with approximately 7% higher odds of CVD. Restricted cubic spline analyses showed a linear association between cumNHHR and CVD risk in CKM stages 0-3, with an inverted U-shaped association in CKM stages 0-2. CONCLUSIONS: Among adults with CKM stages 0-3, cumNHHR exposure was associated with incident CVD, whereas NHHR change patterns did not show an independent association beyond baseline NHHR. These findings highlight the potential value of cumNHHR assessment for early CVD risk stratification.