Supplementary Material for: Plasma Fatty Acid Composition and Incident Ischemic Stroke in Middle-Aged Adults: The Atherosclerosis Risk in Communities (ARIC) Study

<b><i>Background:</i></b> The association of individual fatty acids with ischemic stroke has not been thoroughly studied, and results have been inconsistent. Few prospective studies have systematically explored the association of biomarkers of fatty acid intake with stroke. The aim of this study was<b> </b>to explore which individual plasma fatty acids would be associated with higher risk of ischemic stroke among whites. <b><i>Methods:</i></b> We studied 3,870 white men and women from the Minneapolis field center of the Atherosclerosis Risk in Communities (ARIC) Study, aged 45-64 years at baseline (1987-1989), who had plasma cholesterol ester (CE) and phospholipid (PL) fatty acids measured. Participants were followed through 2008 for incident ischemic stroke. Hazard ratios (HRs) with 95% confidence intervals (CIs) across quartiles of each fatty acid, measured as the percentage of total fatty acids, were calculated using the Cox proportional hazards model. <b><i>Results:</i></b> During a maximum of 22 years of follow-up, we identified 168 cases of ischemic stroke. After adjustment for age and sex, plasma levels of saturated fatty acids were associated positively: HR (95% CI) of the highest versus the lowest quartile for CE fraction was 1.93 (1.23-3.04, p for trend = 0.01) and that for PL fraction was 1.64 (1.05-2.57, p for trend = 0.03). There was also a positive linear association with monounsaturated fatty acids, especially with palmitoleic acid: HR (95% CI) of the highest versus the lowest quartile for CE fraction was 1.86 (1.20-2.87, p for trend = 0.003) and that for PL fraction was 1.52 (0.99-2.34, p for trend = 0.005). No associations of ω-3 and ω-6 polyunsaturated fatty acids with ischemic stroke were observed, but linoleic acid was inversely and nonlinearly associated with ischemic stroke: HR (95% CI) of the highest versus the lowest quartile for CE fraction was 0.64 (0.43-0.97, p for trend = 0.13) and that for PL fraction was 0.69 (0.45-1.05, p for trend = 0.24). These associations were generally unchanged after adjustment for cardiovascular risk factors. <b><i>Conclusions:</i></b> In this US cohort of whites, we found significant positive associations of plasma saturated and monounsaturated fatty acids, especially of palmitoleic acid, with ischemic stroke. We also found an inverse nonlinear association between linoleic acid and ischemic stroke.

**背景**：目前针对单一脂肪酸与缺血性脑卒中之间关联的研究尚不够深入，且所得结果并不一致。现有前瞻性研究中，极少有系统探讨脂肪酸摄入生物标志物与脑卒中关联的相关工作。本研究旨在探究白人人群中，哪些血浆脂肪酸与缺血性脑卒中发病风险升高存在关联。
**方法**：本研究纳入来自社区动脉粥样硬化风险（Atherosclerosis Risk in Communities, ARIC）研究明尼阿波利斯分中心的3870名白人男女受试者，基线（1987-1989年）时年龄为45~64岁，所有受试者均完成了血浆胆固醇酯（cholesterol ester, CE）和磷脂（phospholipid, PL）脂肪酸检测。对受试者随访至2008年，记录缺血性脑卒中发病情况。以总脂肪酸占比作为检测指标，将每种脂肪酸按四分位数分组，采用Cox比例风险模型计算风险比（hazard ratio, HR）及95%置信区间（confidence interval, CI）。
**结果**：最长随访时长达22年，本研究共确诊168例缺血性脑卒中病例。校正年龄与性别因素后，血浆饱和脂肪酸水平呈正向关联：胆固醇酯组分中最高四分位数组与最低四分位数组的风险比为1.93（95%CI：1.23~3.04，趋势检验p=0.01），磷脂组分则为1.64（95%CI：1.05~2.57，趋势检验p=0.03）。单不饱和脂肪酸，尤其是棕榈油酸，同样呈现正向线性关联：胆固醇酯组分中最高四分位数组与最低四分位数组的风险比为1.86（95%CI：1.20~2.87，趋势检验p=0.003），磷脂组分则为1.52（95%CI：0.99~2.34，趋势检验p=0.005）。未观察到ω-3与ω-6多不饱和脂肪酸与缺血性脑卒中存在关联，但亚油酸与缺血性脑卒中呈反向非线性关联：胆固醇酯组分中最高四分位数组与最低四分位数组的风险比为0.64（95%CI：0.43~0.97，趋势检验p=0.13），磷脂组分则为0.69（95%CI：0.45~1.05，趋势检验p=0.24）。在校正心血管疾病风险因素后，上述关联基本未发生变化。
**结论**：在这项美国白人队列研究中，我们发现血浆饱和脂肪酸与单不饱和脂肪酸（尤其是棕榈油酸）水平与缺血性脑卒中存在显著正向关联；同时发现亚油酸与缺血性脑卒中呈反向非线性关联。