Abstract
BACKGROUND: The high-sensitivity C-reactive protein (hs-CRP) to high-density lipoprotein cholesterol (HDL-C) ratio, a composite marker of low-grade inflammation and lipid metabolism, is reportedly associated with the occurrence of new cardiovascular diseases (CVDs) in certain people. However, the predictive value of the hs-CRP/HDL-C ratio for long-term mortality in the general population remains unclear. METHODS: This retrospective cohort study included data from 9,492 adults obtained from the National Health and Nutrition Examination Survey (NHANES) (2015-2018) in the United States. Multivariate Cox regression, two-piecewise linear regression, restricted cubic spline (RCS) models and subgroup analysis by age, sex, smoking status and drinking status were applied to evaluate the associations of the hs-CRP/HDL-C ratio with long-term all-cause and cardiovascular mortality. RESULTS: The overall median age of the cohort was 47.0 years (interquartile range (IQR) 32.0-62.0), and 4,585 (48.30%) patients were male. During a median follow-up period of 37.0 months, 239 (2.52%) all-cause deaths occurred, 59 (0.62%) of which were attributed to cardiovascular events. Participants with all-cause and cardiovascular mortality presented a higher hs-CRP/HDL-C ratio than did those without events [0.56 (0.24-1.38) vs. 0.37 (0.14-0.94) and 0.60 (0.23-1.60) vs. 0.37 (0.14-0.95), P < 0.001 and P = 0.002]. According to multivariate Cox regression models, the hs-CRP/HDL-C ratio was found to be an independent risk factor for both long-term all-cause mortality [hazard ratio (HR) = 1.09, 95% confidence interval (CI): 1.05-1.13] and cardiovascular mortality (HR = 1.11, 95% CI: 1.05-1.19). A two-piecewise linear regression model indicated that the risk of all-cause mortality increased more prominently when the hs-CRP/HDL-C ratio was less than 1.21. In addition, a significant interaction effect with smoking status was discovered (P = 0.006), indicating that the association of the hs-CRP/HDL-C ratio with all-cause mortality was stronger in nonsmokers. The RCS curve revealed a positive linear association of the hs-CRP/HDL-C ratio with long-term mortality after adjustment for potential confounders. CONCLUSIONS: The hs-CRP/HDL-C ratio is a crucial predictor of long-term mortality in the general population, independent of potential confounding factors.