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Eicosapentaenoic acid (EPA) has been reported to reduce cardiovascular risk in patients with hypertriglyceridemia. Although several mechanisms underlying the effects of EPA have been demonstrated, those responsible for its beneficial role in patients with hypertriglyceridemia without evidence of coronary artery disease (CAD) have not been fully elucidated. We sought to clarify the main factors associated with EPA administration that led to improved endothelial function.Forty-seven consecutive patients with mild hypertriglyceridemia (mean age, 59 ± 13 years) without evidence of CAD were prospectively enrolled and administered purified EPA (1800 mg/day). Forty-four patients who were not administered EPA were enrolled as age- and sex-matched controls. Clinical variables and flow-mediated dilation (FMD) were examined before and after 6 months of treatment. Univariate and multivariate regression analyses were performed between FMD changes and clinical variables.EPA treatment decreased triglyceride levels (from 224.6 ± 58.8 to 151.8 ± 54.5 mg/dl, p 0.001) and increased FMD (from 4.21% ± 1.91% to 6.21% ± 2.30%, p 0.001). Multivariate analysis showed that the change in FMD was associated with the baseline high-density lipoprotein cholesterol (HDL-C) level (β = -0.331, p = 0.027) and the change in EPA/arachidonic acid (AA) ratio (β = 0.301, p = 0.048).EPA treatment improved triglyceride levels and FMD in patients with mild hypertriglyceridemia and without evidence of CAD. The baseline HDL-C level and the change in EPA/AA ratio predicted FMD improvement. The beneficial effects of EPA on triglyceride-rich lipoproteins and vascular endothelium may help improve endothelial function.

Baseline brachial artery (BBA) diameter has been reported to be a potential confounding factor of flow-mediated vasodilation (FMD). The purpose of this study was to evaluate the relationships between BBA diameter and cardiovascular risk factors and compare the diagnostic accuracy of BBA diameter in subjects without cardiovascular risk factors and patients with cardiovascular disease (CVD) with that of FMD.We measured BBA diameter and FMD in 5695 male subjects. In addition, we retrospectively investigated the incidence of cardiovascular events using another population sample consisting of 440 male subjects, to compare the accuracy of BBA diameter with that of FMD in predicting cardiovascular events.BBA diameter and FMD significantly correlated with age, body mass index, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, and glucose as well as Framingham risk score. The prevalence of cardiovascular risk factors and CVD increased with the increase in BBA diameter and FMD. Area under the curve (AUC) value of the receiver operating characteristic (ROC) curve for BBA diameter to diagnose subjects without cardiovascular risk factors (0.59 vs. 0.62, p = 0.001) or patients with CVD (0.58 vs. 0.64, p 0.001) was significantly lower than that for FMD. In the retrospective study, the AUC value of the ROC curve for BBA diameter to predict first major cardiovascular events was significantly lower than that of FMD (0.50 vs. 0.62, p = 0.03).In men, BBA diameter was inferior to FMD for assessment of cardiovascular risk.

Aims: For the standardization of flow-mediated vasodilatation (FMD) assessment as a clinical tool, validation of its reliability across multiple institutions and the establishment of normal/reference values based on reliable data from multiple institutions are needed. Methods and results: In Study 1, assessment of FMD (scan recording and analysis) using an ultrasonographic semi-automatic measuring system (sFMD) was conducted at 18 participating institutions (sFMD-INST) (n = 981). All of the brachial arterial scans were also analyzed at a core laboratory (sFMD-COLB). After 111 subjects with inadequate sFMD recordings were excluded (n = 880), the correlation between the sFMD-INST and sFMD-COLB improved from R = 0.725 to R = 0.838 (p < 0.001). In Study 2, based on good-quality sFMD data obtained from 6660 subjects without cardiovascular disease (CVD) and 729 subjects with CVD from 27 institutions, reference values of sFMD are proposed by the Framingham risk score (FRS)-based risk categories and according to gender and age. The receiver-operating characteristic curve analysis revealed a significant power of sFMD values in reference ranges to discriminate between subjects with and without CVD (e.g., area under curve = 0.64 in the FRS-low risk group). Conclusions: When the analysis was limited to cases with clear sFMD recordings, the reliability of the sFMD assessment (scan and its analysis) conducted in individual institutions appeared to be acceptable. Reference sFMD values (lower cuff occlusion) for the Japanese population are proposed based on reliable data derived from multiple institutions, and the reference values may identify patients without advanced vascular damage., Atherosclerosis, 242(2), pp.433-442; 2015

Background and aims Low-flow-mediated constriction (L-FMC), the endothelial response to reduced blood flow by forearm compression, is present in some smokers. The differences between smokers with and without L-FMC are unclear. It is also unknown whether flow-mediated total dilation (FMTD) or modified flow-mediated dilation (mFMD), both of which incorporate information concerning L-FMC, could be used to estimate cardiovascular risk. We sought to clarify the clinical factors associated with the presence of L-FMC in smokers according to sex and examine whether L-FMC incorporated indices would be better than a conventional index to estimate cardiovascular risk in smokers. Methods In total, 140 consecutive smokers (58 ± 13 years old) with no coronary heart disease and 48 non-smokers, who comprised the age- and sex-matched control group, were enrolled. Results L-FMC was demonstrated in 33.6% (47/140) and 25% (12/48) of the smokers and non-smokers, respectively. In male smokers, the predictors of the presence of L-FMC were age ( p = 0.014), body mass index (BMI) ( p = 0.045), and baseline brachial arterial diameter (D base ) ( p = 0.048). In female smokers, there were no predictors of the presence of L-FMC. The correlations between the Framingham risk score (FRS) and %FMTD (r = −0.34) and between FRS and %mFMD (r = −0.33) were stronger than that between FRS and conventional flow-mediated dilation (%cFMD) (r = −0.20). Conclusions Independent predictors of the presence of L-FMC were age, BMI, and D base in male smokers. L-FMC incorporated indices may be good alternatives to cFMD to estimate cardiovascular risk.