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

Background and Purpose— We hypothesized that total marine n-3 polyunsaturated fatty acids (PUFA), in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the diet and in adipose tissue (biomarkers of long-term intake and endogenous exposure) were inversely associated with the risk of ischemic stroke and its subtypes. Methods— The Diet, Cancer and Health cohort consisted of 57 053 participants aged 50 to 65 years at enrolment. All participants filled in a food frequency questionnaire and had an adipose tissue biopsy taken at baseline. Information on ischemic stroke during follow-up was obtained from The Danish National Patient Register, and all cases were validated. Cases and a random sample of 3203 subjects from the whole cohort had their fatty acid composition of adipose tissue determined by gas chromatography. Results— During 13.5 years of follow-up 1879 participants developed an ischemic stroke. Adipose tissue content of EPA was inversely associated with total ischemic stroke (hazard ratio [HR], 0.74; 95% CI, 0.62–0.88) when comparing the highest with the lowest quartile. Also, lower rates of large artery atherosclerosis were seen with higher intakes of total marine n-3 PUFA (HR, 0.69; 95% CI, 0.50–0.95), EPA (HR, 0.66; 95% CI, 0.48–0.91) and DHA (HR, 0.72; 95% CI, 0.53–0.99), and higher adipose tissue content of EPA (HR, 0.52; 95% CI, 0.36–0.76). Higher rates of cardioembolism were seen with higher intakes of total marine n-3 PUFA (HR, 2.50; 95% CI, 1.38–4.53) and DHA (HR, 2.12; 95% CI, 1.21–3.69) as well as with higher adipose tissue content of total marine n-3 PUFA (HR, 2.63; 95% CI, 1.33–5.19) and DHA (HR, 2.00; 95% CI, 1.04–3.84). The EPA content in adipose tissue was inversely associated with small-vessel occlusion (HR, 0.69; 95% CI, 0.55–0.88). Conclusions— EPA was associated with lower risks of most types of ischemic stroke, apart from cardioembolism, while inconsistent findings were observed for total marine n-3 PUFA and DHA.

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P4468Dietary plant derived omega-3 fatty acid alpha linolenic acid prevents age-dependent arterial stiffness and improves outcome after stroke in mice

European Heart Journal ◽

10.1093/eurheartj/ehz745.0865 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

N R Bonetti ◽

C Diaz-Canestro ◽

L Pasterk ◽

L Liberale ◽

D Vdovenko ◽

...

Keyword(s):

Ischemic Stroke ◽

Arterial Stiffness ◽

Linolenic Acid ◽

Dietary Intervention ◽

Omega 3 ◽

Alpha Linolenic Acid ◽

Tetrazolium Chloride ◽

Post Stroke ◽

Age Dependent

Abstract Background A fundamental determinant of cardio- and cerebrovascular diseases is vascular aging, characterized by arterial stiffness. Arterial stiffness is an independent predictor of adverse cardio- and cerebrovascular events and mortality. Fish-derived omega-3 fatty acids (n3-FA) have been described to decrease cardiovascular events in high risk populations. Little is known on the effects of the plant-derived n3 FA alpha-linolenic acid (ALA). More insight is urgently needed, because of the low costs and abundant global supply of ALA. Thus, we aimed to investigate the effects of a long-term dietary intervention with ALA on age-dependent arterial stiffness and the magnitude of these effects on a specific vascular endpoint – ischemic stroke – in a mouse model of aging. Methods C57BL/6 wildtype males were either fed an ALA-rich (high ALA, 7.3 g%) or a respective control (0.3 g%) diet for 12 months, starting from 6 months of age. At 9, 15 and 18 months, arterial stiffness was assessed by measuring pulse wave velocity (PWV) in the right common carotid artery using a Vevo 3100 system (VisualSonics, Fig. 1A). At 18 months, ischemic stroke was induced by transient middle cerebral artery occlusion (30 mins/48 h). Stroke size was assessed by triphenyl tetrazolium chloride staining and neurological function by a Bederson based score. Results Arterial stiffness steadily and significantly increased in controls over time, while ALA clearly and effectively prevented it (PWV at 9 vs. 18 months: controls + 95%; p<0,0001 vs. High ALA + 15%; ns) (Fig 1A). Stroke size at 18 months was significantly decreased in ALA-fed animals compared to controls (28.39 mm3 vs. 51.77 mm3 p=0.0017) (Fig. 1B). In line with the morphological changes, controls performed significantly worse neurologically (Fig. 1C). Additionally, post-stroke survival at 48 h was improved in ALA-fed animals compared to controls, with 85% survival compared to 57% (Fig. 1D). Figure 1 Conclusion We demonstrate that long-term dietary supplementation with the plant-derived ALA fully prevents the development of age-dependent arterial stiffness. The magnitude of this effect is clearly reflected in biologically relevant decreased stroke size, improved neurological performance and even post-stroke survival. This study not only demonstrates vasoprotective effects of ALA, but also links them to improved outcome of a specific clinical endpoint. Future analyses will aim at delineating the molecular basis of the observed benefits. This will result in a better understanding of some ambiguous results from clinical trials and likely define the population which benefits from ALA.

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