Saber Hamidreza, Yakoob Mohammad Yawar, Shi Peilin, Longstreth W T, Lemaitre Rozenn N, Siscovick David, Rexrode Kathryn M, Willett Walter C, Mozaffarian Dariush
From the Department of Neurology, Wayne State University School of Medicine, Detroit, MI (H.S.); Department of Epidemiology (H.S., M.Y.Y., W.C.W.) and Department of Nutrition (W.C.W.), Harvard T.H. Chan School of Public Health, Boston, MA; Tufts Friedman School of Nutrition Science and Policy, Boston, MA (P.S., D.M.); Departments of Neurology and Epidemiology (W.T.L.) and Departments of Medicine and Epidemiology (R.N.L.), University of Washington, Seattle; New York Academy of Medicine (D.S.); and Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA (K.M.R.).
Stroke. 2017 Oct;48(10):2678-2685. doi: 10.1161/STROKEAHA.117.018235. Epub 2017 Aug 22.
The associations of individual long-chain n-3 polyunsaturated fatty acids with incident ischemic stroke and its main subtypes are not well established. We aimed to investigate prospectively the relationship of circulating eicosapentaenoic acid, docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with risk of total ischemic, atherothrombotic, and cardioembolic stroke.
We measured circulating phospholipid fatty acids at baseline in 3 separate US cohorts: CHS (Cardiovascular Health Study), NHS (Nurses' Health Study), and HPFS (Health Professionals Follow-Up Study). Ischemic strokes were prospectively adjudicated and classified into atherothrombotic (large- and small-vessel infarctions) or cardioembolic by imaging studies and medical records. Risk according to fatty acid levels was assessed using Cox proportional hazards (CHS) or conditional logistic regression (NHS, HPFS) according to study design. Cohort findings were pooled using fixed-effects meta-analysis.
A total of 953 incident ischemic strokes were identified (408 atherothrombotic, 256 cardioembolic, and 289 undetermined subtypes) during median follow-up of 11.2 years (CHS) and 8.3 years (pooled, NHS and HPFS). After multivariable adjustment, lower risk of total ischemic stroke was seen with higher DPA (highest versus lowest quartiles; pooled hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.58-0.92) and DHA (HR, 0.80; 95% CI, 0.64-1.00) but not eicosapentaenoic acid (HR, 0.94; 95% CI, 0.77-1.19). DHA was associated with lower risk of atherothrombotic stroke (HR, 0.53; 95% CI, 0.34-0.83) and DPA with lower risk of cardioembolic stroke (HR, 0.58; 95% CI, 0.37-0.92). Findings in each individual cohort were consistent with pooled results.
In 3 large US cohorts, higher circulating levels of DHA were inversely associated with incident atherothrombotic stroke and DPA with cardioembolic stroke. These novel findings suggest differential pathways of benefit for DHA, DPA, and eicosapentaenoic acid.
个体长链n-3多不饱和脂肪酸与缺血性卒中及其主要亚型的关联尚未明确。我们旨在前瞻性研究循环中的二十碳五烯酸、二十二碳五烯酸（DPA）和二十二碳六烯酸（DHA）与全缺血性、动脉粥样硬化血栓形成性和心源性栓塞性卒中风险之间的关系。
我们在美国3个独立队列中测量了基线时循环中的磷脂脂肪酸：心血管健康研究（CHS）、护士健康研究（NHS）和卫生专业人员随访研究（HPFS）。通过影像学研究和医疗记录对缺血性卒中进行前瞻性判定并分类为动脉粥样硬化血栓形成性（大血管和小血管梗死）或心源性栓塞性。根据研究设计，使用Cox比例风险模型（CHS）或条件逻辑回归（NHS、HPFS）评估脂肪酸水平相关的风险。使用固定效应荟萃分析汇总队列研究结果。
在CHS队列11.2年的中位随访期以及NHS和HPFS队列合并后的8.3年中位随访期内，共识别出953例缺血性卒中事件（408例动脉粥样硬化血栓形成性、256例心源性栓塞性和289例亚型未确定）。多变量调整后，较高的DPA（最高四分位数与最低四分位数相比；合并风险比[HR]，0.74；95%置信区间[CI]，0.58 - 0.92）和DHA（HR，0.80；95% CI，0.64 - 1.00）与全缺血性卒中风险降低相关，但二十碳五烯酸无此关联（HR，0.94；95% CI，0.77 - 1.19）。DHA与动脉粥样硬化血栓形成性卒中风险降低相关（HR，0.53；95% CI，0.34 - 0.83），DPA与心源性栓塞性卒中风险降低相关（HR，0.58；95% CI，0.37 - 0.92）。每个单独队列的研究结果与汇总结果一致。
在美国3个大型队列中，较高的循环DHA水平与动脉粥样硬化血栓形成性卒中事件呈负相关，DPA与心源性栓塞性卒中呈负相关。这些新发现提示DHA、DPA和二十碳五烯酸的获益途径存在差异。
