BackgroundEndothelial dysfunction plays a pivotal role in cardiovascular disease progression, and is associated with adverse events. The purpose of this systematic review and meta‐analysis was to investigate the prognostic magnitude of noninvasive peripheral endothelial function tests, brachial artery flow‐mediated dilation (FMD), and reactive hyperemia–‐peripheral arterial tonometry (RH‐PAT) for future cardiovascular events.Methods and ResultsDatabases of MEDLINE, EMBASE, and the Cochrane Library were systematically searched. Clinical studies reporting the predictive value of FMD or RH‐PAT for cardiovascular events were identified. Two authors selected studies and extracted data independently. Pooled effects were calculated as risk ratio (RR) for continuous value of FMD and natural logarithm of RH‐PAT index (Ln_RHI) using random‐effects models. Thirty‐five FMD studies of 17 280 participants and 6 RH‐PAT studies of 1602 participants were included in the meta‐analysis. Both endothelial function tests significantly predicted cardiovascular events (adjusted relative risk [95% CI]: 1% increase in FMD 0.88 [0.84–0.91], P<0.001, 0.1 increase in Ln_RHI 0.79 [0.71–0.87], P<0.001). There was significant heterogeneity in the magnitude of the association across studies. The magnitude of the prognostic value in cardiovascular disease subjects was comparable between these 2 methods; a 1 SD worsening in endothelial function was associated with doubled cardiovascular risk.ConclusionsNoninvasive peripheral endothelial function tests, FMD and RH‐PAT, significantly predicted cardiovascular events, with similar prognostic magnitude. Further research is required to determine whether the prognostic values of these 2 methods are independent of each other and whether an endothelial function–guided strategy can provide benefit in improving cardiovascular outcomes.

Despite the greater reduction of platelet reactivity by addition of cilostazol to conventional DAT, TAT did not show superiority in reducing the composite of adverse cardiovascular outcomes after DES implantation. (The Efficacy of CILostazol ON Ischemic Complications After DES Implantation [CILON-T]; NCT00776828).

Objective Endothelial dysfunction is an early manifestation of atherosclerosis. Inflammation and vasa vasorum play a pivotal role in the pathophysiology of plaque initiation, development and complications. Optical coherence tomography (OCT) allows high-resolution imaging of tissue microstructure. Therefore, the aim of this study was to test the hypothesis that segments with endothelial dysfunction show macrophages and/or vasa vasorum in patients with early coronary artery disease. Approach and Results OCT images were obtained from 40 patients with mild coronary atherosclerosis who underwent coronary endothelial function assessment. OCT findings including macrophages and micorchannels were evaluated in 76 coronary segments corresponding to those in endothelial response to acetylcholine. Coronary artery diameter (CAD) change in response to acetylcholine was more severe in segments showing macrophages (−17.7±14.7% vs. −6.3±13.9%, p<0.01) and microchannels (−15.9±15.9% vs. −6.4±13.5%, p<0.01) than those without. There were increasing trends of the prevalence of macrophages and microchannels with endothelial dysfunction as stratified by quartiles of CAD change (p<0.01 and p=0.02 for trend, respectively). In particular, segments with both macrophages and microchannels (n=12) tended to have worse endothelial function than those with macrophages alone (n=15) and microchannels alone (n=15) (−22.1±14.6% vs.−10.9±15.6% and −10.9±15.6%, p=0.07 and p=0.06, respectively). Conclusion Epicardial endothelial dysfunction was associated with OCT-identified macrophages and microchannels in mild coronary atherosclerosis. The current study further supports the role of inflammation and vasa vasorum proliferation in the early stage of coronary atherosclerosis.

This study suggests that slow flow may be dependent on the tissue characterisation (fibrofatty volume) of the underlying lesion at the time of the primary PCI for acute myocardial infarction.

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Ischemic heart disease is the leading cause of morbidity and mortality throughout the world. Many clinical trials have suggested that lifestyle and pharmacologic interventions are effective in attenuating atherosclerotic disease progression and events development. However, an individualized approach with careful consideration to comprehensive vascular health is necessary to perform successful intervention strategies. Endothelial dysfunction plays a pivotal role in the early stage of atherosclerosis and is also associated with plaque progression and occurrence of atherosclerotic complications. The assessment of endothelial function provides us with important information about individual patient risk, progress and vulnerability of disease, and guidance of therapy. Thus, the application of endothelial function assessment might enable clinicians to innovate ideal individualized medicine. In this review, we summarize the current knowledge on the impact of pharmacological therapies for atherosclerotic cardiovascular disease on endothelial dysfunction, and argue for the utility of non-invasive assessment of endothelial function aiming at individualized medicine.

Background:Patients with heart failure (HF) have abnormal endothelial function. Although use of a continuous flow left ventricular assist device (CF-LVAD) results in significant hemodynamic improvement, the effects on systemic endothelial function are unclear. Methods and Results:Eighteen HF patients with CF-LVAD implantation were included in this prospective observational study. We measured reactive hyperemia index (RHI) before and after CF-LVAD implantation to evaluate sequential changes in endothelial function. Patients were followed clinically for the occurrence of adverse cardiovascular events, a composite of death, thrombosis, bleeding, HF, renal failure, and arrhythmia. Preoperative RHI was 1.77±0.39. Early in the postoperative period (7-14 days after operation) RHI significantly decreased to 1.19±0.31 (P<0.001, compared with preoperative RHI). At first and second follow-up (4-6 weeks and 3-7 months after operation) RHI remained lower at 1.48±0.50 (P=0.030) and 1.26±0.37 (P=0.002), respectively, compared with preoperative RHI. The decrease in early postoperative RHI relative to preoperative RHI was significantly associated with adverse cardiovascular events after CF-LVAD (age-adjusted risk ratio for 0.25 decrease in RHI, 1.35; 95% confidence interval: 1.13-1.62, P=0.001). Conclusions:Peripheral endothelial function had a significant and persistent decline up to 5 months following implantation of CF-LVAD, and this decline was associated with adverse cardiovascular events. These findings may provide insight into some of the vascular complications following CF-LVAD in HF patients. (Circ J 2015; 79: 770 -777)