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.

Decreased circulating dihomo-gamma-linolenic acid levels are associated with total mortality in patients with acute cardiovascular disease and acute decompensated heart failure.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have important roles in the pathogenesis of cardiovascular diseases. However, the clinical significance of omega-6 PUFAs in acute cardiovascular disease remains unknown. METHODS: We enrolled 417 consecutive patients with acute cardiovascular disease admitted to the cardiac intensive care unit at Juntendo University Hospital between April 2012 and October 2013. We investigated the association between serum PUFA levels and long-term mortality. Blood samples were collected after an overnight fast, within 24 h of admission. We excluded patients who received eicosapentaenoic acid therapy and those with malignancy, end-stage kidney disease, chronic hepatic disease, and connective tissue disease. RESULTS: Overall, 306 patients (mean age: 66.4 ± 15.0 years) were analysed. During the follow-up period of 2.4 ± 1.2 years, 50 patients (16.3%) died. The dihomo-gamma-linolenic acid (DGLA) levels, arachidonic acid (AA) levels, and DGLA/AA ratio were significantly lower in the nonsurvivor group than in the survivor group (DGLA: 23.2 ± 9.8 vs. 31.5 ± 12.0 µg/ml, AA: 151.1 ± 41.6 vs. 173.3 ± 51.6 µg/ml, and DGLA/AA: 0.16 ± 0.05 vs. 0.19 ± 0.06, all p < 0.01). Kaplan-Meier curves showed that survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.01), although omega-3 PUFAs were not associated with prognosis. Furthermore, in patients with acute decompensated heart failure (ADHF), survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.04). However, among patients with acute coronary syndrome, none of the PUFA levels were associated with prognosis. Among patients with ADHF, after controlling for confounding variables, DGLA and DGLA/AA were associated with long-term mortality [DGLA: hazard ratio (HR), 0.94; 95% confidence interval (CI), 0.88-0.99; p = 0.01 and DGLA/AA: HR, 0.87; 95% CI, 0.77-0.97; p < 0.01], whereas AA was not associated with prognosis. CONCLUSION: Low omega-6 PUFA levels, particularly DGLA, and a low DGLA/AA ratio predict long-term mortality in patients with acute cardiovascular disease and ADHF. TRIAL REGISTRATION: UMIN-CTR; UMIN000007555 .

The balance of omega-3 polyunsaturated fatty acids for -reducing residual risks in patients with coronary artery disease.

Residual risk, which cannot be prevented by statins alone, must be controlled for inhibiting the onset of coronary events. Omega-3 polyunsaturated fatty acids (PUFAs) play an important role in controlling residual risk. The Japan eicosapentaenoic acid (EPA) Lipid Intervention Study demonstrated the inhibitory effect of high-purity EPA preparations on the residual risk of cardiovascular events. Omega-3 PUFAs inhibit coronary artery disease (CAD) through various actions, including triglyceride-lowering action. Besides lipid metabolism, platelet aggregation inhibition, anti-inflammatory effects, improved vascular endothelium function, and anti-hypertensive action contribute to arteriosclerosis inhibition. Conversely, several recent studies did not demonstrate the efficacy of omega-3 PUFAs for CAD prevention. PUFAs levels may need to exceed a threshold for anti-arteriosclerotic action. The efficacy of EPA might depend on the baseline value of the EPA/arachidonic acid (AA) ratio prior to EPA administration. This baseline EPA/AA ratio value varies according to country and region as well as changes of dietary habits. More global research in this field is needed to identify an optimal omega-3 PUFAs administration strategy.

Omega 3 Polyunsaturated Fatty Acids Suppress the Development of Aortic Aneurysms Through the Inhibition of Macrophage-Mediated Inflammation.

BACKGROUND: Dietary intake of ω3 polyunsaturated fatty acids (ω3-PUFAs) reduces progression of atherosclerosis and prevents future cardiovascular events. Macrophages are key players in the pathogenesis of aortic aneurysm. The effects of ω3-PUFAs on abdominal aortic aneurysm (AAA) formation and macrophage-mediated inflammation remain unclear. METHODS AND RESULTS: The AAA model was developed by angiotensin II infusion in apolipoprotein E-deficient mice. Mice were supplemented with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). The development of AAA lesions and macrophage infiltration in the aorta were analyzed. Gene expression of inflammatory markers in aortic tissues and peritoneal macrophages were measured by using quantitative polymerase chain reaction. AAA formation and macrophage infiltration were significantly suppressed after EPA and DHA administration. EPA administration and DHA administration significantly decreased the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-ß, matrix metalloproteinases (MMP)-2, MMP-9, and vascular cell adhesion molecule-1 in the aortas. The expression of arginase 2, which is a marker of pro-inflammatory macrophages, was significantly lower and that of Ym1, which is a marker of anti-inflammatory macrophages, and was significantly higher after EPA and DHA administration. The same trends were observed in peritoneal macrophages after EPA and DHA administration. CONCLUSIONS: Dietary intake of EPA and DHA prevented AAA development through the inhibition of aortic and macrophage-mediated inflammation.

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.