Association between the ratio of serum n-3 to n-6 polyunsaturated fatty acids and acute coronary syndrome in non-obese patients with coronary risk factor: a multicenter cross-sectional study.

BACKGROUND: Previous studies have reported that being overweight, obese, or underweight is a risk factor for ischemic cardiovascular disease (CVD); however, CVD also occurs in subjects with ideal body mass index (BMI). Recently, the balance of n-3/n-6 polyunsaturated fatty acids (PUFAs) has received attention as a risk marker for CVD but, so far, no study has been conducted that investigates the association between BMI and the balance of n-3/n-6 PUFAs for CVD risk. METHODS: We evaluated the association between n-3/n-6 PUFA ratio and acute coronary syndrome (ACS) in three BMI-based groups (< 25: low BMI, 25-27.5: moderate BMI, and ≥ 27.5: high BMI) that included 1666 patients who visited the cardiovascular medicine departments of five hospitals located in urban areas in Japan. RESULTS: The prevalence of ACS events was 9.2, 7.3, and 10.3% in the low, moderate, and high BMI groups, respectively. We analyzed the relationship between ACS events and several factors, including docosahexaenoic acid/arachidonic acid (DHA/AA) ratio by multivariate logistic analyses. In the low BMI group, a history of smoking (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.40-4.35) and low DHA/AA ratio (OR: 0.30, 95% CI: 0.12-0.74) strongly predicted ACS. These associations were also present in the moderate BMI group but the magnitude of the association was much weaker (ORs are 1.47 [95% CI: 0.54-4.01] for smoking and 0.63 [95% CI: 0.13-3.10] for DHA/AA). In the high BMI group, the association of DHA/AA (OR: 1.98, 95% CI: 0.48-8.24) was reversed and only high HbA1c (OR: 1.46, 95% CI: 1.03-2.08) strongly predicted ACS. The interaction test for OR estimates (two degrees of freedom) showed moderate evidence for reverse DHA/AA ratio-ACS associations among the BMI groups (P = 0.091). CONCLUSIONS: DHA/AA ratio may be a useful marker for risk stratification of ACS, especially in non-obese patients.

Significance of imbalance in the ratio of serum n-3 to n-6 polyunsaturated fatty acids in patients with acute coronary syndrome.

This study aimed to assess the balance of serum n-3 to n-6 polyunsaturated fatty acids (PUFAs) in patients with acute coronary syndrome (ACS). We enrolled 1,119 patients who were treated and in whom serum PUFA level was evaluated in 5 divisions of cardiology in a metropolitan area in Japan. Serum levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA), were compared between patients with and without ACS. We also evaluated the balance of serum n-3 to n-6 PUFAs, including EPA/AA and DHA/AA ratios. EPA/AA values were 0.46 ± 0.32 and 0.50 ± 0.32 in the ACS and non-ACS groups, respectively. DHA/AA values were 0.95 ± 0.37 and 0.96 ± 0.41 in the ACS and non-ACS groups, respectively. Next, we divided the patients into 3 groups based on the tertiles of EPA/AA or tertiles of DHA/AA to determine the independent risk factors for ACS. According to multivariate logistic regression analysis, the group with the lowest EPA/AA (≤0.33) had a greater probability of ACS (odds ratio 3.14, 95% confidence interval 1.16 to 8.49), but this was not true for DHA/AA. In conclusion, an imbalance in the ratio of serum EPA to AA, but not in the ratio of DHA to AA, was significantly associated with ACS.

Effects of dietary fish oil on lipid peroxidation and serum triacylglycerol levels in psychologically stressed mice.

OBJECTIVE: The intake of omega-3 polyunsaturated fatty acids and psychological stress can each induce tissue lipid peroxidation. In our present study, we investigated their combined effects on the oxidative status of mouse tissues. METHODS: Mice were group-housed (four mice/cage) and fed a diet containing fish oil (as a source of omega-3 polyunsaturated fatty acids), soybean oil, or olive oil for 3 wk. These animals were then 1) housed under the same conditions (four per cage, control group) or 2) individually housed to generate psychological stress conditions (isolation stress). After 2 wk of isolation stress, the levels of thiobarbituric acid-reactive substances (an index of lipid peroxidation) and antioxidants in the liver and kidney and the serum levels of triacylglycerol were measured. RESULTS: Fish oil-fed mice showed increased levels of thiobarbituric acid-reactive substances in their livers and kidneys compared with soybean oil- or olive oil-fed mice. These increases in thiobarbituric acid-reactive substance levels in the fish oil-fed mice were less profound under isolation stress conditions when compared with the group-housed animals on the same diet. In the fish oil-fed mice, isolation stress led to an increase in liver vitamin E levels when compared with their group-housed counterparts. The fish oil-fed mice exhibited lower serum triacylglycerol levels compared with the soybean oil- or olive oil-fed mice, and this decrease was more profound under conditions of isolation stress when compared with group-housing conditions. CONCLUSION: Dietary fish oil combined with isolation stress results in lower levels of lipid peroxidation in the liver and kidney compared with dietary fish oil alone.

A relative high dose of vitamin E does not attenuate unweighting-induced oxidative stress and ubiquitination in rat skeletal muscle.

We previously reported that intragastric administration of cysteine could be beneficial to prevent unweighting-induced ubiquitination and degradation of muscle protein in association with redox regulation [Ikemoto et al., Biol. Chem., 383 (2002), 715-721]. In this study, we investigated whether vitamin E, another potent antioxidative nutrient, also had beneficial effects on the muscle protein catabolism. However, daily intragastric supplementation of 1.5 or 15 mg/rat of alpha-tocopherol did not prevent weight loss of hindlimb skeletal muscle in tail-suspended rats. To elucidate the reason for the non-effectiveness of vitamin E, we further examined concentrations of oxidative stress markers, ubiquitination of muscle proteins and fragmentation of myosin heavy chain in gastrocnemius muscle of rats daily treated with 15 mg of alpha-tocopherol. Unexpectedly, vitamin E increased concentrations of glutathione disulfide and thiobarbituric acid-reactive substance and decreased glutathione level in the muscle, compared with those of vehicle treatment, indicating that vitamin E enhanced unweighting-induced oxidative stress in skeletal muscle. The vitamin E supplementation did not suppress the ubiquitination of muscle proteins and fragmentation of myosin heavy chain caused by tail-suspension. Our results suggest that supplementation of a relative high dose of vitamin E could not inhibit ubiquitin-dependent degradation of muscle protein in tail-suspended rats possibly due to its prooxidant action.