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

Abstract 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 inadequatel...

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Main Authors: Zhao-Xuan Lu, Bing-Qing Dong, Liang Chen, Heng-Le Wei
Format: Article
Language:English
Published: BMC 2025-06-01
Series:The Journal of Headache and Pain
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Online Access:https://doi.org/10.1186/s10194-025-02077-1
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author Zhao-Xuan Lu
Bing-Qing Dong
Liang Chen
Heng-Le Wei
author_facet Zhao-Xuan Lu
Bing-Qing Dong
Liang Chen
Heng-Le Wei
author_sort Zhao-Xuan Lu
collection DOAJ
description Abstract 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, p < 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.
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spelling doaj-art-72b5409190524f59836ea244aff4618f2025-08-20T02:30:42ZengBMCThe Journal of Headache and Pain1129-23772025-06-0126111410.1186/s10194-025-02077-1Association of the total cholesterol to high-density lipoprotein cholesterol ratio with all-cause mortality risk in the migraine populationZhao-Xuan Lu0Bing-Qing Dong1Liang Chen2Heng-Le Wei3Department of Interventional and Vascular Radiology, Nanjing First Hospital, Nanjing Medical UniversityDepartment of Radiology, Kunshan Hospital of Traditional Chinese MedicineDepartment of Interventional and Vascular Radiology, Nanjing First Hospital, Nanjing Medical UniversityDepartment of Radiology, The Affiliated Jiangning Hospital of Nanjing Medical UniversityAbstract 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, p < 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.https://doi.org/10.1186/s10194-025-02077-1MigraineTotal cholesterol/High-density lipoprotein cholesterol ratioAll-cause mortalityDyslipidemia
spellingShingle Zhao-Xuan Lu
Bing-Qing Dong
Liang Chen
Heng-Le Wei
Association of the total cholesterol to high-density lipoprotein cholesterol ratio with all-cause mortality risk in the migraine population
The Journal of Headache and Pain
Migraine
Total cholesterol/High-density lipoprotein cholesterol ratio
All-cause mortality
Dyslipidemia
title Association of the total cholesterol to high-density lipoprotein cholesterol ratio with all-cause mortality risk in the migraine population
title_full Association of the total cholesterol to high-density lipoprotein cholesterol ratio with all-cause mortality risk in the migraine population
title_fullStr Association of the total cholesterol to high-density lipoprotein cholesterol ratio with all-cause mortality risk in the migraine population
title_full_unstemmed Association of the total cholesterol to high-density lipoprotein cholesterol ratio with all-cause mortality risk in the migraine population
title_short Association of the total cholesterol to high-density lipoprotein cholesterol ratio with all-cause mortality risk in the migraine population
title_sort association of the total cholesterol to high density lipoprotein cholesterol ratio with all cause mortality risk in the migraine population
topic Migraine
Total cholesterol/High-density lipoprotein cholesterol ratio
All-cause mortality
Dyslipidemia
url https://doi.org/10.1186/s10194-025-02077-1
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AT liangchen associationofthetotalcholesteroltohighdensitylipoproteincholesterolratiowithallcausemortalityriskinthemigrainepopulation
AT henglewei associationofthetotalcholesteroltohighdensitylipoproteincholesterolratiowithallcausemortalityriskinthemigrainepopulation