Specific 5-HT2A receptor blockade with sarpogrelate immediately after MCT inhibited PAH and prolongs survival in rats. These effects were accompanied by anti-inflammatory and anti-proliferative effects in the lung tissue and marked improvement of pulmonary vascular endothelial dysfunction and activation.

We investigated whether nicorandil might prevent and reverse monocrotaline (MCT)-induced pulmonary arterial hypertension. Rats were injected with 50 mg/kg of MCT subcutaneously and randomized to either 7.5 mg/kg/d of nicorandil in drinking water or placebo for 3 weeks. Animals that were treated with MCT and survived for 3 weeks were assigned to either nicorandil or placebo. Nicorandil markedly attenuated pulmonary arterial hypertension with severe structural remodeling of the pulmonary vessels. The survival rate at 3 weeks after treatment was significantly increased in the nicorandil group compared with the placebo group (73% versus 39%, P<0.05). In the placebo group, endothelial nitric oxide synthase (eNOS) protein was significantly decreased, the numbers of the CD45-positive cells and those of the proliferating cell nuclear antigen-positive cells were increased in the lung tissue, and P-selectin was intensely expressed on the endothelium of the pulmonary arteries. These features were prevented by nicorandil. Late treatment with nicorandil did not palliate established pulmonary arterial hypertension nor improved survival. Thus, nicorandil inhibited development of MCT-induced pulmonary arterial hypertension but failed to reverse it. These effects were associated with marked up-regulation of diminished lung eNOS protein along with improvement of pulmonary vascular endothelial activation and anti-inflammatory and anti-proliferative effects in the lung tissue.

ObjectiveLittle is known about the relationship between body composition indicators, including body mass index (BMI), fat mass index (FMI) and lean BMI (LBMI), and adverse outcomes after percutaneous coronary intervention (PCI) in Asian populations. The aim of this study was to clarify this relationship.MethodsThe SHINANO registry is a prospective, observational, multicenter cohort registry that enrolled 1923 consecutive patients with coronary heart disease (CHD) from August 2012 to July 2013; 66 patients were excluded because of missing data. We evaluated 1857 patients with CHD who underwent PCI (aged 70±11 years; 23% women; BMI 23.8±3.5 kg/m2; LBMI 18.3±1.8 kg/m2; FMI 5.4±2.2 kg/m2). Patients were divided into three groups, based on BMI, LBMI and FMI tertiles, to assess the prognostic value of the three indicators. The primary endpoint was major adverse cardiac events (MACE), including all cause death, non-fatal myocardial infarction and ischaemic stroke at 1 year.ResultsOver a 1 year follow-up period (1776 patients, 95.6%), the cumulative MACE incidence was 8.7% (161 cases). Using Kaplan–Meier analysis, the MACE incidence was significantly higher in patients with lower BMI values (13.4–22.2 kg/m2) (p=0.002) and lower LBMI values (11.6–17.6 kg/m2) (p<0.001); this trend was not observed for FMI. Multivariate Cox regression analysis showed that lower LBMI but not lower BMI values were predictive of a higher MACE incidence (HR 1.55; 95% CI 1.05 to 2.30).ConclusionsLower LBMI values are associated with adverse outcomes in an Asian population with CHD undergoing PCI. LBMI is a better predictor of MACE than BMI or FMI.Clinical trial registrationUMIN-ID; 000010070.

easurements of pulse wave velocity (PWV) are useful for evaluating aortic stiffness, which has been shown to be associated with traditional risk factors. [1][2][3][4][5] Aortic stiffness, but not stiffness of peripheral muscular arteries, also has been noted to predict not only primary coronary events and fatal stroke in a variety of disease conditions, such as end-stage renal disease, 6 hypertension 7 and diabetes, 8 but also cardiovascular mortality in the general population. 9-11 Although conventional techniques for measuring carotid-femoral PWV are non-invasive, sophisticated methods, they are inconvenient, particularly in large clinical trials. Recently, brachial-ankle (ba) PWV has been developed as a more simple, practical, reproducible procedure to assess both the central elastic and peripheral muscular arterial stiffness. 12,13 It has been reported that the baPWV is closely correlated with aortic PWV and leg PWV, 13 is associated with risk factors and organ damage in the presence of cardiovascular diseases, [14][15][16] and has a prognostic value for future cardiovascular events in patients with acute coronary syndrome. 17 Thus, the measurement of baPWV is suitable, especially for screening vascular damage in a large population and when assessing vascular damage in long-term follow-up studies.Recent studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (ie, statins) act to exert direct beneficial effects on myocardial ischemia and hypertrophy, coronary vasomotion and vascular smooth muscle cell proliferation, and reduce adverse cardiovascular events in patients at risk through not only the lipid-lowering action but also the lipid-independent anti-atherogenic properties; that is, the so-called pleiotropic effects. Although fluvastatin, but not pravastatin or non-statin antihyperlipidemic agents, has been noted to improve aortic stiffness in association with decreased serum lipid and C-reactive protein (CRP) levels over a treatment period of 12 months, 18 its effect over longer treatment periods has not yet been clarified. Thus, the present study was designed to test the hypothesis that fluvastatin might improve arterial stiffness assessed by PWV in patients with coronary artery disease (CAD) and hyperlipidemia over a much longer treatment period. We also investigated whether arterial stiffness improved in patients whose drugs had been switched from non-statin antihyperlipidemic agents to fluvastatin. Background The present study was designed to test the hypothesis that fluvastatin might improve arterial stiffness, as assessed with pulse wave velocity (PWV), in patients with coronary artery disease (CAD) and hyperlipidemia over the long term. Methods Protocol Methods and ResultsNinety-three patients were randomly assigned to either fluvastatin (group A, n=50) or bezafibrate (group B, n=43) and followed for 5 years. There was no difference in the clinical findings between the 2 groups. In group A, there was a progressive reduction in the brachial-ankle PWV along with a decrease in...

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