Predictive Value of the High-Sensitivity C-Reactive Protein/HDL-Cholesterol Ratio for Cardiovascular and Cancer-Specific Mortality in Cancer Survivors: A Study from NHANES 2015-2018.
TL;DR
With distinct predictive effects for the two competing fatal outcomes, CHR could act as a convenient auxiliary biomarker for long-term mortality risk evaluation and lay a foundation for future large-cohort validation of clinical thresholds.
Abstract
Background
Although inflammation and lipid metabolism disorders have been confirmed to affect the risk of cardiovascular disease (CVD)-specific mortality and cancer-specific mortality in cancer survivors, the predictive value of the high-sensitivity C-reactive protein/high-density lipoprotein cholesterol ratio (CHR) for these outcomes remains unclear, with a paucity of relevant research evidence.
Methods
Based on data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018, a total of 1,064 cancer survivors aged ≥20 years were enrolled and followed up for 61 months. Inverse probability of treatment weighting (IPTW)-weighted Fine-Gray competing risk models, restricted cubic splines, and subgroup analyses were used to systematically explore the association between CHR and CVD-specific mortality as well as cancer-specific mortality.
Results
During the follow-up period, 127 deaths occurred, including 52 cancer-specific deaths and 27 CVD-specific deaths. The level of high-sensitivity C-reactive protein (hs-CRP) was significantly higher in the CVD-specific death group, while the level of high-density lipoprotein cholesterol (HDL-C) was significantly lower in the cancer-specific death group; CHR was significantly elevated in both death groups compared with their corresponding non-death groups. After IPTW-weighted Fine-Gray competing risk adjustment, each 1-unit increment in CHR was associated with a 5.0% higher subdistribution hazard of CVD-specific mortality among cancer survivors (adjusted SHR = 1.050, P < 0.05). A weak but statistically significant overall linear association was also observed between CHR and cancer-specific mortality (P < 0.05). Restricted cubic spline (RCS) competing risk models further revealed a distinct threshold-dependent nonlinear relationship for cancer-specific mortality, with an inflection point at 3.02 mg/mmol. The hazard of cancer death increased sharply with rising CHR below this cutoff and remained stable without additional risk elevation at higher CHR levels.
Conclusions
CHR independently predicts higher subdistribution hazard of CVD-specific mortality in cancer survivors, with a 5.0% risk increase per unit elevation. While CHR shows a weak overall linear association with cancer-specific mortality, their relationship exhibits a segmented nonlinear pattern with an exploratory inflection point at 3.02 mg/mmol; this value is not a validated clinical cutoff due to limited outcome events. With distinct predictive effects for the two competing fatal outcomes, CHR could act as a convenient auxiliary biomarker for long-term mortality risk evaluation and lay a foundation for future large-cohort validation of clinical thresholds.