**4. Conclusion**

*New Insights into Metabolic Syndrome*

reported that low D5D predict the development of type 2 diabetes [49–51] and the risk of CVD [39]. In a Swedish population-based prospective cohort study of 2009 50-year old men, D5D was reported to have an inverse correlation with CVD mortality over a follow-up of 30 years [52]. The association of lower D5D with accumulation of atherogenic sdLDL, MDA-LDL, and RL-C in our study may provide the

Previous studies reported that statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, have differential effects on the activities of D5D, D6D, and elongase, and any statins increased AA [53]. It is suggested that EPA/AA may better reflect the residual risk for CHD following statin treatment than DHA / AA. Some previous cross-sectional studies have demonstrated that EPA/AA but not DHA/AA was significantly associated with ACS [54, 55]. A cohort study of CHD patients underwent nonemergency percutaneous coronary intervention (PCI) found that lower EPA/AA (but not lower DHA/AA) was significantly associated with the incidence of major adverse cardiac events [56]. Our study showed that the EPA/AA is a superior risk marker than DHA/AA in terms of correlation with

Multiple studies have demonstrated that EPA and DHA have different effects on cardiometabolic risk factors [57, 58]. Innes and Calder reviewed 18 randomized controlled trials that compare EPA or DHA (>2 g/day and purity ≥90%) and placebo on cardiometabolic risk factors [57]. The study durations were between 4 and 10 weeks. They reported the following results: (1) both EPA and DHA lowered triglycerides with DHA having a greater triglyceride-lowering effects than EPA; (2) while total cholesterol was largely unchanged by EPA and DHA, DHA increased HDL-C, particularly HDL2 and increased LDL-C and LDL particle size; (3) both EPA and DHA inhibited platelet activity while DHA improved vascular function and lowered heart rate and blood pressure to a greater extent than EPA; and

association between lower D5D and atherosclerotic CVD.

atherogenic lipid profiles in ACS patients.

**164**

**Figure 7.**

*Relative changes in the expression of specific genes determined by quantitative real-time polymerase chain reaction (Q-PCR) in olive oil, EPA and DHA supplementation groups. Data are expressed as mean ± standard error. Differences within each group were determined by paired t test (\*\*p < 0.01, \*p < 0.05). Brackets indicate differences between two groups as determined with a 2-factor ANOVA with Tukey honestly significant difference correction. CCR6, chemokine (C-C motif) receptor 6; CREB1, cAMP responsive element binding protein 1; HIF1A, hypoxia-inducible factor 1-alpha; HMGB1, high mobility group box 1; IL1RN, interleukin 1 receptor antagonist; IL2RB, interleukin 2 receptor, beta; IRF7, interferon regulatory factor 7; STAT3, signal* 

*transducer and activator of transcription. Reproduced from [58].*

IP-TFA intake (estimated from plasma levels) is low in Japan, and accordingly, there is a little difference in IP-TFA levels between Japanese ACS patients and healthy controls. However, a certain IP-TFA is associated with the increased risk of CHD even in Japan. Although it is not clear whether R-TFA are cardioprotective or not, the ACS patients, especially middle-aged patients showed significantly lower levels of R-TFA and omega-3 FA. Although average EPA and DHA levels in Japan are much higher than in the United States [59], still higher levels of the marine omega-3 PUFA are associated with the lower cardiovascular disease risk. However, the Japanese dietary style has changed markedly in the younger generation since 1990 [37, 60]. The lack of fish intake and excessive oils and meat and poultry intakes have been recognized in subjects <60 years old in the present Japanese. Decreased biosynthesis of long-chain PUFA and imbalance of omega-3 and omega-6 FA are clearly associated with atherogenic lipid profiles in Japanese ACS patients. Multiple studies have demonstrated that EPA and DHA have different effects on cardiometabolic risk factors. The EPA/AA may be a superior risk marker than DHA/AA in terms of correlation with atherogenic lipid profiles in clinical practice.
