Adipose tissue content of alpha-linolenic acid and the risk of ischemic stroke and ischemic stroke subtypes: A Danish case-cohort study

BACKGROUND: The plant-derived omega-3 fatty acid alpha-linolenic acid (ALA) may reduce the risk of cardiovascular disease. OBJECTIVE: We have investigated associations between the content of ALA in adipose tissue and the risk of ischemic stroke and its subtypes. METHODS: Incident cases of ischemic stroke among participants enrolled into the Danish Diet, Cancer and Health cohort (n = 57,053) were identified by linkage with the Danish National Patient Register. Subsequently, all potential cases were validated and classified into ischemic stroke subtypes. The fatty acid composition of adipose tissue was determined by gas chromatography in cases and in a randomly drawn sub-cohort (n = 3500). Statistical analyses were performed using weighted Cox regression. RESULTS: During a median of 13.4 years of follow-up, 1735 cases of total ischemic stroke were identified including 297 cases of large artery atherosclerosis, 772 cases of small-vessel occlusion, 99 cases of cardio-embolism, 91 cases with stroke of other etiology and 476 cases with stroke of undetermined etiology. The median content of ALA in adipose tissue within the sub-cohort was 0.84% (95% central range: 0.53–1.19%). Multivariable analyses showed a U-shaped association between adipose tissue content of ALA and the rate of total ischemic stroke, but this association was not statistically significant (p = 0.172). In analyses of ischemic stroke subtypes, we observed a statistically significant U-shaped association between ALA and the rate of ischemic stroke due to large artery atherosclerosis (p = 0.017), whereas no appreciable association was observed between ALA and the rate of small-vessel occlusion (p = 0.427). A positive but statistically non-significant association was observed between ALA and the rate of ischemic stroke due to cardio-embolism (p = 0.162). CONCLUSIONS: The content of ALA in adipose tissue was statistically non-significantly U-shaped associated with risk of total ischemic stroke. For ischemic stroke subtypes a statistically significant, U-shaped association with large artery atherosclerosis was observed.