Lu Zhao-Xuan, Dong Bing-Qing, Chen Liang, Wei Heng-Le
Department of Interventional and Vascular Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Department of Radiology, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, China.
J Headache Pain. 2025 Jun 5;26(1):135. doi: 10.1186/s10194-025-02077-1.
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.
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.
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.
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.
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.
The online version contains supplementary material available at 10.1186/s10194-025-02077-1.
偏头痛是一种常见的神经系统疾病，与血脂异常和心血管疾病发病率增加有关；然而，脂质生物标志物的预后价值，尤其是总胆固醇与高密度脂蛋白胆固醇（TC/HDL-C）比值，仍未得到充分研究。
本研究旨在探讨偏头痛患者TC/HDL-C比值与全因死亡率之间的潜在关系，并确定预后预测的最佳阈值。
分析了1999 - 2004年国家健康和营养检查调查中的数据，其中包括654例偏头痛患者。采用受限立方样条（RCS）来描述TC/HDL-C比值与死亡风险之间的剂量反应关系。根据RCS和最大选择秩统计方法（MSRSM）得出的阈值，将TC/HDL-C比值分为两组。使用加权多变量Cox回归模型评估相关性，并对人口统计学变量、合并症和炎症标志物进行调整。进行Kaplan-Meier生存曲线和时间依赖性受试者工作特征（ROC）分析，以评估生存预后和预测准确性。
在中位随访16.33年期间，654例患者中有126例（19.27%）死亡。RCS分析显示TC/HDL-C比值与全因死亡率之间呈U形关系。在多变量模型中，与较低TC/HDL-C比值队列相比，较高的TC/HDL-C比值（MSRSM得出的阈值为5.15）与全因死亡率风险显著增加相关（风险比 = 2.986，95%置信区间 = 1.495 - 5.967，P < 0.001）。相反，基于RCS得出的拐点（4.23）进行二分分层，在较高TC/HDL-C比值组中无显著性差异。两段式线性回归和Kaplan-Meier生存曲线分析均表明，较高TC/HDL-C比值队列（≥ 5.15）的总体生存率显著更差。时间依赖性ROC分析显示，全因死亡率的5年、10年、15年和20年生存率的曲线下面积分别为0.865、0.880、0.891和0.889。
本研究揭示了偏头痛患者TC/HDL-C比值与全因死亡率之间存在非线性U形关系，较高的TC/HDL-C比值是死亡率的一个强有力的独立预测指标。这些发现强调了TC/HDL-C比值作为个性化偏头痛管理的临床可操作生物标志物的潜力。
在线版本包含可在10.1186/s10194-025-02077-1获取的补充材料。
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