TY - JOUR T1 - Omega-3 Fatty Acids and Incident Ischemic Stroke and Its Atherothrombotic and Cardioembolic Subtypes in 3 US Cohorts. JF - Stroke Y1 - 2017 A1 - Saber, Hamidreza A1 - Yakoob, Mohammad Yawar A1 - Shi, Peilin A1 - Longstreth, W T A1 - Lemaitre, Rozenn N A1 - Siscovick, David A1 - Rexrode, Kathryn M A1 - Willett, Walter C A1 - Mozaffarian, Dariush KW - Adult KW - Aged KW - Aged, 80 and over KW - Biomarkers KW - Brain Ischemia KW - Cardiovascular Diseases KW - Case-Control Studies KW - Cohort Studies KW - Fatty Acids, Omega-3 KW - Female KW - Follow-Up Studies KW - Humans KW - Incidence KW - Intracranial Arteriosclerosis KW - Intracranial Embolism KW - Intracranial Thrombosis KW - Male KW - Middle Aged KW - Prospective Studies KW - Random Allocation KW - Risk Factors KW - Stroke KW - United States AB -

BACKGROUND AND PURPOSE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

VL - 48 IS - 10 ER -