Table_1_Interaction Analysis of Abnormal Lipid Indices and Hypertension for Ischemic Stroke: A 10-Year Prospective Cohort Study.docx

BackgroundDyslipidemia and hypertension are two important independent risk factors for ischemic stroke (IS); however, their combined effect on IS remains uncertain.
ObjectivesThis present study aimed to evaluate the interaction effect of hypertension and abnormal lipid indices on IS in a 10-year prospective cohort in Chinese adults.
MethodsThe cohort study of 4,128 participants was conducted in May 2009 and was followed up to July 2020. All qualified participants received a questionnaire survey, physical examination, and blood sample detection. Cox regression was used to evaluate the association of dyslipidemia and hypertension with IS, and calculate the hazard ratio (HR) and 95% confidence interval (CI). The relative excess risk of interaction (RERI) and the HR (95%CI) of interaction terms were used to examine additive and multiplicative interactions.
ResultsIn the hypertensive population, Non-HDL-C ≥190 mg/dl, LDL-C/HDL-C ≥2 and HDL-C ≥60 mg/dl were statistically associated with IS, and after adjusting for covariates, HRs (95%CIs) were 1.565 (1.007–2.429), 1.414 (1.034–1.933) and 0.665 (0.450–0.983), respectively. While in the non-hypertension population, no significant association of Non-HDL-C ≥190 mg/dl, LDL-C/HDL-C ≥2, and HDL-C ≥60 was detected with IS (P > 0.05). There was a significant association between TC/HDL-C ≥ 3.6 and the decreased risk of IS in the non-hypertension population, and the HR (95%CI) was 0.479 (0.307–0.750). Whereas, a similar association was not observed in the hypertensive population. HDL-C ≥ 60 mg/dl, Non-HDL-C ≥ 190 mg/dl, TC/HDL-C ≥ 3.6, and TG/HDL-C ≥ 1 have additive and multiplicative interactions with hypertension (P < 0.05). The RERIs (95% CIs) of the additive interaction are −0.93 (−1.882–0.044), 1.394 (0.38–2.407), 0.752 (0.354–1.151) and 0.575 (0.086–1.065), respectively. The HRs (95% CIs) of the multiplicative interaction terms were 0.498 (0.272–0.911), 4.218 (1.230–14.464), 2.423 (1.437–4.086) and 1.701 (1.016–2.848), respectively.
ConclusionHigh concentration of HDL-C reduces the impact of hypertension on IS, while the high concentration of Non-HDL-C, TC/HDL-C, and TG/HDL-C positively interact with hypertension affecting the incidence of IS. This study provides useful evidence for the combined effects of dyslipidemia and hypertension in predicting IS.

研究背景：血脂异常与高血压是缺血性脑卒中(ischemic stroke, IS)的两大重要独立危险因素，但二者联合对缺血性脑卒中的影响仍不明确。
研究目的：本研究旨在基于中国成人10年前瞻性队列，评估高血压与异常血脂指标对缺血性脑卒中的交互作用效应。
研究方法：本队列研究于2009年5月启动，共纳入4128名受试者，随访至2020年7月。所有合格受试者均接受问卷调查、体格检查及血液样本检测。采用Cox回归分析评估血脂异常、高血压与缺血性脑卒中的关联，并计算风险比(hazard ratio, HR)及95%置信区间(confidence interval, CI)。通过交互相对超额危险度(relative excess risk of interaction, RERI)与交互项的风险比(95%CI)，分别检验相加交互作用与相乘交互作用。
研究结果：在高血压人群中，非高密度脂蛋白胆固醇(non-high-density lipoprotein cholesterol, Non-HDL-C)≥190 mg/dl、低密度脂蛋白胆固醇/高密度脂蛋白胆固醇(low-density lipoprotein cholesterol/high-density lipoprotein cholesterol, LDL-C/HDL-C)≥2及高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)≥60 mg/dl与缺血性脑卒中存在统计学关联；校正混杂因素后，对应的风险比(95%置信区间)分别为1.565(1.007–2.429)、1.414(1.034–1.933)及0.665(0.450–0.983)。而在非高血压人群中，未检测到Non-HDL-C≥190 mg/dl、LDL-C/HDL-C≥2及HDL-C≥60 mg/dl与缺血性脑卒中存在显著关联(P > 0.05)。在非高血压人群中，总胆固醇/高密度脂蛋白胆固醇(total cholesterol/high-density lipoprotein cholesterol, TC/HDL-C)≥3.6与缺血性脑卒中发病风险降低存在显著关联，对应的风险比(95%置信区间)为0.479(0.307–0.750)，但该关联在高血压人群中未观察到。HDL-C≥60 mg/dl、Non-HDL-C≥190 mg/dl、TC/HDL-C≥3.6及三酰甘油/高密度脂蛋白胆固醇(triglyceride/high-density lipoprotein cholesterol, TG/HDL-C)≥1与高血压存在显著的相加及相乘交互作用(P < 0.05)。上述相加交互作用的相对超额危险度(95%置信区间)分别为−0.93(−1.882–0.044)、1.394(0.38–2.407)、0.752(0.354–1.151)及0.575(0.086–1.065)；相乘交互作用项的风险比(95%置信区间)分别为0.498(0.272–0.911)、4.218(1.230–14.464)、2.423(1.437–4.086)及1.701(1.016–2.848)。
研究结论：高浓度HDL-C可削弱高血压对缺血性脑卒中的影响，而高浓度Non-HDL-C、TC/HDL-C及TG/HDL-C则与高血压存在正向交互作用，共同升高缺血性脑卒中的发病风险。本研究为血脂异常与高血压联合预测缺血性脑卒中提供了有价值的证据。