The predictive role of the hs-CRP/HDL-C ratio for long-term mortality in the general population: evidence from a cohort study

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.

Keywords: Correlational analysis; HDL-C; Long-term mortality; NHANES; hs-CRP.

Fig. 1

Flow diagram of study selection. NHANES, National Health and Nutrition Examination Survey

Fig. 2

Restricted cubic spline plots of the association between the hs-CRP/HDL-C ratio ratio with long-term all-cause mortality (A) and cardiovascular mortality (B) in the general population. Analysis was adjusted for age, sex, race, drinking, smoking, BMI, hypertension, diabetes, heart failure, coronary artery disease, stroke and lipid-lowering drugs. HR, hazard ratio

Fig. 3

Subgroup analysis of restricted cubic spline plots for the association between the hs-CRP/HDL-C ratio and long-term all-cause mortality by sex (A), age (B), drinking (C) and smoking (D). Adjusted for age, sex, race, drinking, smoking, BMI, hypertension, diabetes, heart failure, coronary artery disease, stroke and lipid-lowering drugs except the subgroup variable

Fig. 4

Subgroup analysis of restricted cubic spline plots for the association between the hs-CRP/HDL-C ratio and long-term cardiovascular mortality by sex (A), age (B), drinking (C) and smoking (D). Adjusted for age, sex, race, drinking, smoking, BMI, hypertension, diabetes, heart failure, coronary artery disease, stroke and lipid-lowering drugs except the subgroup variable

Fig. 5

K-M survival analysis for long-term all-cause mortality (hs-CRP/HDL-C ratio ≤ 1.094 vs. > 1.094) (A) and cardiovascular mortality (hs-CRP/HDL-C ratio ≤ 0.154 vs. > 0.154) (B)