Low Serum n-3 Polyunsaturated Fatty Acid/n-6 Polyunsaturated Fatty Acid Ratio Predicts Neurological Deterioration in Japanese Patients with Acute Ischemic Stroke

Abstract

Background: Epidemiological and clinical trials have shown that n-3 polyunsaturated fatty acids (PUFAs) reduce the incidence of coronary heart disease or stroke. However, the association between PUFAs and acute-phase stroke has not yet been thoroughly studied. We investigated the impact of serum PUFAs on early neurological deterioration (END) in patients with acute ischemic stroke. Methods: In this retrospective study, we enrolled 281 Japanese patients (mean age: 75 ± 13 years; 165 males) with acute ischemic stroke diagnosed within 24 h of onset. General blood examinations, including PUFAs (n-3 PUFAs: eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA, and n-6 PUFAs: arachidonic acid, AA), were performed on admission. Other risk factors and comorbidities were also examined. END was defined as a ≥2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within a 72-hour period. Statistical significance between the END and non-END group was assessed using Wilcoxon rank sum tests or Student's t tests for categorical variables. Multiple logistic regression analyses were performed to identify predictors of END. Results: END was observed in 75 patients (26.7%). Diabetes mellitus (p = 0.003), high-sensitivity C-reactive protein (hs-CRP) level (p < 0.001), prior stroke (p = 0.035), ischemic heart disease (p = 0.029), EPA/AA ratio (p = 0.003), DHA/AA ratio (p = 0.002), EPA+DHA/AA ratio (p = 0.002), diagnosis of small vessel disease (p = 0.004) and admission NIHSS score (p < 0.001) were significantly associated with END. We used separate multiple logistic regression analyses for the EPA/AA, DHA/AA and EPA+DHA/AA ratios, because EPA and DHA are considered covariant factors (r = 0.544; p < 0.0001). Multiple logistic regression analyses showed that END was positively associated with diabetes mellitus, hs-CRP level and NIHSS score on admission, and negatively associated with the EPA/AA ratio (odds ratio, OR: 0.18; 95% confidence interval, CI: 0.05-0.58; p = 0.003), DHA/AA ratio (OR: 0.045; 95% CI: 0.006-0.30; p = 0.001), EPA+DHA/AA ratio (OR: 0.45; 95% CI: 0.26-0.74; p = 0.002) and diagnosis of small vessel disease. Conclusions: Our data suggest that a low serum n-3 PUFA/n-6 PUFA ratio on admission may predict neurological deterioration in Japanese patients with acute ischemic stroke. Large-scale prospective studies are further required to clarify the role of PUFAs in the acute phase of ischemic stroke.