These two new vascular indexes might be useful in actual clinical settings to evaluate cardiovascular risks with various clinical backgrounds.

The interaction between atherosclerosis and commensal microbes through leaky gut syndrome (LGS), which is characterized by impaired intestinal permeability and the introduction of undesired pathogens into the body, has not been fully elucidated. Our aim was to investigate the potential role of a ClC-2 chloride channel activator, lubiprostone, which is reported to have beneficial effects on LGS, in the development of atherosclerosis in apolipoprotein E–deficient (ApoE-/-) mice. After a 15-week feeding period of a Western diet (WD), ApoE-/- mice were treated with a Western-type diet (WD) alone or WD with oral supplementation of lubiprostone for 10 weeks. This feeding protocol was followed by experimental evaluation of LGS and atherosclerotic lesions in the aorta. In mice with lubiprostone, in vivo translocation of orally administered 4-kDa FITC-dextran was significantly improved, and RNA expression of the epithelial tight junction proteins, Zo-1 and occludin, was significantly up-regulated in the ileum, compared to the WD alone group, suggesting a possible reversal of WD-induced intestinal barrier dysfunction. As a result, WD-induced exacerbation of atherosclerotic lesion formation was reduced by 69% in longitudinally opened aortas and 26% in aortic root regions. In addition, there was a significant decrease in circulating immunoglobulin level, followed by an attenuation of inflammatory responses in the perivascular adipose tissue, as evidenced by reduced expression of pro-inflammatory cytokines and chemokines. Lubiprostone attenuates atherosclerosis by ameliorating LGS-induced inflammation through the restoration of the intestinal barrier. These findings raise the possibility of targeting LGS for the treatment of atherosclerosis.

Objectives: Earlier detection of vascular stiffness and endothelial dysfunction will be useful in preventing atherosclerotic catastrophic conditions. Individuals with high risks for future cardiovascular (CV) events should be recognized by physicians to strengthen preventive therapeutic procedures, such as antihypertensive therapy, antidiabetic therapy, and antidyslipidemic therapy. As such, various non-invasive devices have been developed and are currently applied in clinical settings. Among them, we previously reported arterial velocity pulse index (AVI) and arterial pressure volume index (API) measured using a cuff-oscillometric-based medical electronic blood pressure monitor. These are significantly correlated with arterial stiffness and cardiac overload; therefore, these indexes might be useful in predicting future CV events. Materials and methods: We performed survival and CV event analyses in a total of 180 subjects with various clinical implications who visited Yokohama City University Hospital between May 2013 and March 2015 and followed them up until March 2016. The mean age was 66±13 years, and 101 subjects (56.1%) were men. A total of 116 subjects (64.4%) had hypertension, 87 subjects (48.3%) had dyslipidemia, and 39 subjects (21.7%) had diabetes mellitus. The mean AVI and API were 23.3±7.7 and 31.8±8.4, respectively. Results: The mean follow-up duration was 769±275 days. A total of 13 major adverse cardiac events (MACEs) occurred during the observational period, which consisted of 1 cardiac death, 8 CV events, and 4 hospitalizations owing to heart failure. After we performed Kaplan-Meier analysis, univariate Cox proportional hazard regression analysis, and multivariate Cox proportional hazard regression analysis, we found that AVI is significantly correlated with the risk of MACE. Therefore, we successfully revealed the clinical implications of the new non-invasive indexes for CV mortality and morbidity. Conclusion: The new non-invasive vascular index, AVI, was significantly correlated with the CV outcomes in our Japanese cohort.