Association of the total cholesterol to high-density lipoprotein cholesterol ratio with all-cause mortality risk in the migraine population.

BACKGROUND

Migraine, a prevalent neurological disorder, is associated with dyslipidemia and increased cardiovascular morbidity; however, the prognostic value of lipid biomarkers, particularly the total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio, remains inadequately explored.

OBJECTIVE

This study aims to explore the potential relationship between the TC/HDL-C ratio and all-cause mortality in patients with migraine and determine optimal thresholds for prognostic prediction.

METHODS

Data from the 1999–2004 National Health and Nutrition Examination Surveys, encompassing 654 patients with migraine, were analyzed. A restricted cubic spline (RCS) was employed to delineate the dose-response relationship between the TC/HDL-C ratio and mortality risk. TC/HDL-C ratio was categorized into two groups based on thresholds derived from RCS and the maximally selected rank statistics method (MSRSM). Weighted multivariate Cox regression models were used to assess associations, adjusting for demographic variables, comorbidities, and inflammatory markers. Kaplan-Meier survival curves and time-dependent receiver operating characteristic (ROC) analysis were conducted to evaluate survival prognosis and prediction accuracy.

RESULTS

Over a median follow-up of 16.33 years, 126 (19.27%) of the 654 patients died. RCS analysis revealed a U-shaped relationship between TC/HDL-C ratio and all-cause mortality. In the multivariable model, higher TC/HDL-C ratio (MSRSM-derived threshold of 5.15) were associated with a significantly increased risk of all-cause mortality (Hazard ratio = 2.986, 95% confidence interval = 1.495–5.967,  < 0.001), compared to the lower TC/HDL-C ratio cohort. Conversely, dichotomous stratification based on the RCS-derived inflection point (4.23) indicated no significance in the higher TC/HDL-C ratio group. Both two-piecewise linear regression and Kaplan–Meier survival curve analyses demonstrated significantly worse overall survival for the higher TC/HDL-C ratio cohort (≥ 5.15). Time-dependent ROC analysis revealed area under the curve of 0.865, 0.880, 0.891, and 0.889 for 5-, 10-, 15-, and 20-year survival rates, respectively, for all-cause mortality.

CONCLUSION

This study reveals a nonlinear, U-shaped relationship between the TC/HDL-C ratio and all-cause mortality in patients with migraine, with higher TC/HDL-C ratio emerging as a robust, independent predictor of mortality. These findings underscore the potential of the TC/HDL-C ratio as a clinically actionable biomarker for personalized migraine management.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s10194-025-02077-1.