Background and Aims: Vascular endothelial dysfunction is the earliest stage of the development of atherosclerosis and recognized as a trigger of cardiovascular events. Eicosapentaenoic acid (EPA) has been reported to ameliorate endothelial dysfunction and reduce cardiovascular events. However, the factors associated with the benefits have not been fully clarified in patients with hypertriglyceridemia and no evidence of coronary artery disease (CAD). We investigated the factors associated with EPA administration that led to improve endothelial function.

Abstract Background Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are well-known for preventing cardiovascular disease. Among n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play key roles in preventing cardiovascular diseases. However, the effects of n-3 PUFAs have been examined under conditions of simultaneous administration of EPA and DHA in the majority of clinical investigations and the effect of purified EPA is still controversial. EPA has been reported to improve endothelial dysfunction. Although several mechanisms underlying the effects of EPA on endothelial function have been demonstrated such as the modulation of lipid metabolism including increases in high-density lipoprotein (HDL) and/or decreases in triglyceride (TG) levels, decreases in cytokine production, and inhibition of inflammatory processes, the main mechanisms ameliorating endothelial function have not been fully determined. Purpose We sought to clarify the main factors associated with EPA administration that led to improved endothelial function. Methods Fifty-one consecutive patients with hypertriglyceridemia (mean ± SD age, 60±13 years) with no evidence of coronary artery disease (CAD) were prospectively enrolled and administered purified EPA (1800 mg/day). Forty-eight patients who were not administered EPA were enrolled as age- and sex-matched controls. Clinical variables such as body mass index, HbA1c, fasting glucose level, HDL, low-density lipoprotein, TG, systolic blood pressure, diastolic blood pressure, heart rate, interleukin-6, baseline diameter of the brachial artery, intima-media thickness of the brachial artery, and flow-mediated dilation (FMD) were examined before and after 6 months of treatment. Univariate and multivariate regression analyses were performed to examine the associations between FMD changes and clinical variables. Results FMD was significantly improved from 4.16% ± 1.88% to 6.30% ± 2.24% (p<0.0001) in the EPA group. The change in FMD was positively correlated with the change in EPA/arachidonic acid (AA) ratio (r=0.34, p=0.014). The multivariate regression analysis showed that the change in EPA/AA ratio alone was significantly associated with the change in FMD (p=0.010). Conclusions EPA treatment improves endothelial dysfunction in patients with hypertriglyceridemia without evidence of CAD. The change in FMD was associated with the change in EPA/AA ratio alone. These finding suggest that a direct effect of EPA on the endothelium may be the predominant factor ameliorating endothelial function. Acknowledgement/Funding This study was supported, in part, by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (15K08649).

BACKGROUND:Varenicline has been reported to achieve high rates of smoking cessation. It remains undetermined whether varenicline therapy improves vascular function in smokers.METHODS:Consecutive Seventy-two smokers (age 57 ± 12 years) who succeeded in complete smoking cessation and 46 normal healthy volunteers (age 24 ± 3 years) with no cardiovascular risk factors were enrolled into this study. Vascular function and structure were assessed by flow-mediated dilation (FMD), nitroglycerin-induced vasodilation, and brachial artery intima-media thickness (baIMT) at baseline and 20 weeks after the initiation of varenicline therapy in smokers. FMD and baIMT were measured simultaneously using a semi-automatic vessel wall-tracking software program. 75 μg dose of a nitroglycerin tablet were sublingually administered for the nitroglycerin-induced vasodilation measurement.RESULTS:Exhaled-carbon monoxide concentration decreased significantly (20.0 ± 11.1 ppm at baseline vs 1.9 ± 1.5 ppm after 20 weeks, p < 0.001). FMD was significantly improved after 20 weeks (4.09% ± 1.83% at baseline vs 4.77% ± 2.33% after 20 weeks, p = 0.010), whereas nitroglycerin-induced vasodilation and baIMT were not significantly changed.CONCLUSIONS:Smoking cessation with varenicline therapy significantly increased FMD without significant changes of nitroglycerin-induced vasodilation or baIMT from baseline to 20 weeks. It appears to improve vascular function in smokers, which depends on endothelial function rather than on vascular smooth muscle function or changes in vascular structure.