Association of Life's Crucial 9 score with advanced cardiovascular-kidney-metabolic syndrome in U.S. adults

Cardiovascular-kidney-metabolic (CKM) syndrome, a progressively advancing disorder involving metabolic, renal, and cardiovascular dysfunction, was newly defined by the American Heart Association in its latest recommendations. Life's Crucial 9 (LC9) is a novel cardiovascular health (CVH) metric that incorporates depression, thus integrating psychological health into an established framework of lifestyle and clinical factors. It builds upon and extends Life's Essential 8 (LE8). Although LC9 has demonstrated predictive value in other disease contexts, its association with CKM syndrome remains unexamined. A total of 7,776 individuals aged 20 and above were analyzed in this cross-sectional study, based on data collected from NHANES spanning 2005–2018. LC9 included nine components: depression, BMI, non-HDL cholesterol, glucose, blood pressure, sleep, physical activity, diet, and nicotine exposure. According to the American Heart Association's criteria, individuals in CKM stages 3 or 4 were considered to have progressed to advanced syndrome. The analysis used restricted cubic spline models and logistic regression adjusted for survey weights to examine key associations. Weighted quantile sum (WQS) regression was conducted to identify key contributors. To evaluate model performance, we employed the Area Under the Receiver Operating Characteristic Curve (AUROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) as metrics. Additional subgroup and sensitivity analyses assessed result robustness. Elevated LC9 and LE8 scores were both significantly linked to reduced likelihood of advanced CKM syndrome (per 10-point increase: OR = 0.61, 95% CI 0.57–0.66 for LC9; OR = 0.64, 95% CI 0.60–0.69 for LE8). In WQS models, glucose, body mass index, and physical activity emerged as key determinants. The addition of depression to the LE8 framework yielded a modest improvement in predictive accuracy (ΔAUROC = 0.0024, 95% CI 0.0011–0.0036, P < 0.001; IDI = 0.0054, P < 0.001; NRI = 0.0065, P = 0.168). Findings remained consistent across multiple sensitivity and subgroup analyses. Both LC9 and LE8 scores were inversely associated with advanced CKM syndrome. Compared with LE8, adding depression provided only limited incremental discrimination in this cross-sectional analysis, suggesting that incorporating a depression component may not be necessary for CVH scoring in this context and warrants further evaluation in prospective studies.