非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值与中国中老年人脑卒中风险的关联

The Association between the Non-High-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol Ratio and Stroke Risk among Middle-Aged and Elderly Chinese Adults

摘要: 背景：脑卒中是中国成人死亡和致残的重要原因，脂质代谢异常是其重要危险因素。非高密度脂蛋白胆固醇比值(NHHR)是近年来提出的新型复合脂质参数，整合了致动脉粥样硬化与非高密度脂蛋白胆固醇与保护性高密度脂蛋白胆固醇的信息，理论上能更全面评估动脉粥样硬化负荷，但其与中国中老年人群脑卒中风险的前瞻性关联尚缺乏大规模证据。目的：利用中国健康与养老追踪调查(CHARLS)数据，分析NHHR与中国中老年人群脑卒中风险的关联。方法：本研究采用了CHARLS 2011~2020年的纵向数据，共纳入了10,983名≥45岁基线无脑卒中史的研究对象。通过多因素Cox回归模型、Kaplan-Meier分析、限制性立方样条(RCS)、亚组分析及敏感性分析探讨NHHR与中国中老年人脑卒中风险之间的关联。结果：随访9年后，新发脑卒中960例(发生率8.74%)。调整后的多变量Cox回归分析显示，NHHR每增加1单位，脑卒中风险上升5% [HR = 1.05, 95% CI (1.00~1.10), P = 0.048)]。与NHHR的最低四分位数相比，第三四分位数[HR = 1.28, 95% CI (1.05~1.56)]和最高四分位数[HR = 1.48, 95% CI (1.19~1.83)]脑卒中风险显著升高(均P < 0.05)。完全调整后的RCS显示NHHR与脑卒中风险之间整体显著关联(P for overall = 0.001)且存在显著的非线性关系(P for non-linearity = 0.003)。在拐点以下的参与者NHHR每增加1单位，脑卒中发病风险升高16%。亚组分析表明二者的关系不受不受年龄、性别、教育、婚姻、高血压、糖尿病、吸烟、饮酒、BMI的影响(交互作用P > 0.05)。结论：在中国中老年人群中，较高的NHHR水平与增加的脑卒中风险相关，且呈现非线性关联。研究结果提示NHHR可作为脑卒中患者风险分层及血脂管理的潜在指标。

Abstract: Background: Stroke is a significant cause of mortality and disability among adults in China, with dyslipidemia constituting a key risk factor. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a recently proposed composite lipid index that integrates atherogenic non-high-density lipoprotein cholesterol and anti-atherogenic high-density lipoprotein cholesterol. In theory, NHHR provides a more comprehensive assessment of atherosclerotic burden; however, robust large-scale prospective evidence on its association with stroke risk in middle-aged and older Chinese populations remains insufficient. Objective: Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS), this study examined the association between NHHR and stroke risk in middle-aged and older Chinese adults. Methods: This study analyzed data from the China Health and Retirement Longitudinal Study (2011~2020), including 10,983 participants aged ≥ 45 years without prior stroke. Multivariable Cox regression, Kaplan-Meier analysis and restricted cubic splines (RCS) were used to assess the association with stroke risk, and sensitivity analyses, subgroup analyses were performed to test robustness. Results: During the 9-year follow-up, 960 incident stroke cases (8.74%) were recorded. Each 1-unit increase in NHHR was associated with a 5% elevated stroke risk (HR = 1.05, 95% CI: 1.00~1.10, P = 0.048). Compared with the lowest quartile (Q1), the risk was significantly higher in Q3 (HR = 1.28, 95% CI: 1.05~1.56) and Q4 (HR = 1.48, 95% CI: 1.19~1.83). RCS demonstrated a nonlinear association between NHHR and stroke (Overall P = 0.001, Nonlinear P = 0.003). Among participants with NHHR values below the inflection point, each 1-unit increase in NHHR was associated with a 16% increase in the risk of incident stroke. Subgroup analyses indicated that this association was not modified by age, sex, education level, marital status, hypertension, diabetes, smoking status, alcohol consumption, or body mass index (all interaction P values > 0.05). Conclusion: Elevated NHHR serves as a risk factor for stroke risk in middle-aged and older Chinese adults, demonstrating a nonlinear association. These findings suggest that this ratio may serve as a potential early-warning indicator for lipid management in populations at risk of stroke.