RH-PAT indexes were significantly attenuated in women with IHD. Digital RH-PAT can predict patients with IHD, especially NOCAD before angiography. RH-PAT is potentially useful for identifying high-risk women for IHD. (Endothelial Dysfunction and Coronary Artery Spasm; NCT00619294).

Peripheral endothelial dysfunction independently correlated with future cardiovascular events, adding incremental clinical significance for risk stratification in patients with HFNEF. (Endothelial Dysfunction Assessed by Reactive Hyperemia Peripheral Arterial Tonometry and Heart Failure with Preserved Left Ventricular Ejection Fraction; UMIN000002640).

BackgroundEndothelial dysfunction is a key component of vascular vulnerability. Reactive hyperemia index (RHI), as assessed by the peripheral arterial tonometry, can noninvasively evaluate endothelial function. This study was designed to determine the additional prognostic value of endothelial function to the Synergy Between PCI With Taxus and Cardiac Surgery Score (SYNTAXsc) and the Framingham Risk Score (FRS) in predicting cardiovascular events in high‐risk patients.Methods and ResultsWe undertook a two‐center prospective study in 528 stable patients at high‐risk for cardiovascular events from the years 2006–2011. The RHI was measured before coronary angiography and coronary complexity was assessed by SYNTAXsc. After optimal therapies including coronary revascularization, there was follow‐up with patients until August 2012. Cardiovascular events consist of cardiovascular death, myocardial infarction, unstable angina, ischemic stroke, coronary revascularization, heart failure‐induced hospitalization, aortic disease, and peripheral arterial disease. During 1468 person‐years of follow‐up, 105 patients developed cardiovascular events. Multivariate Cox proportional hazards analysis identified B‐type natriuretic peptide (BNP), SYNTAXsc, and RHI as independent cardiovascular event predictors (hazard ratio [95% confidence interval]: natural logarithm of BNP per 0.1: 1.019 [1.002 to 1.037]; P=0.023, SYNTAXsc per tertile: 2.426 [1.825 to 3.225]; P<0.0001, RHI per 0.1: 0.761 [0.673 to 0.859]; P<0.0001). When RHI was added to the FRS, BNP, and SYNTAXsc, net reclassification index was significantly improved (27.5%; P<0.0001), with a significant increase in the C‐statistic (from 0.728 [0.679 to 0.778] to 0.766 [0.726 to 0.806]; P=0.031).ConclusionsAdvanced endothelial dysfunction significantly correlated with near future cardiovascular events in high‐risk patients. This physiological vascular measurement improved risk discrimination when added to the FRS, BNP, and SYNTAXsc.Clinical Trial RegistrationURL: clinicaltrials.gov (http://www.clinicaltrials.gov). Unique identifier: NCT00737945.

Objective-To investigate whether and how the endoplasmic reticulum (ER) stress-induced, CCAAT/enhancer-binding protein-homologous protein (CHOP)-mediated pathway regulates myocardial ischemia/reperfusion injury. Methods and Results-Wild-type and chop-deficient mice underwent 50 minutes of left coronary artery occlusion followed by reperfusion. Expression of chop and spliced x-box binding protein-1 (sxbp1) mRNA was rapidly and significantly increased in reperfused myocardium of wild-type mice. chop-deficient mice exhibited markedly reduced injury size after reperfusion compared with wild-type mice, accompanied by a decreasing number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cardiomyocytes. Interestingly, myocardial inflammation, as assessed by expression of inflammatory cytokines and chemokines and numbers of infiltrated inflammatory cells, was also attenuated in chop-deficient mice. Moreover, expression of interleukin-6 mRNA in response to lipopolysaccharide was enhanced by simultaneous stimulation with thapsigargin, a potent ER stressor, in wild-type cardiomyocytes but not in chop-deficient cardiomyocytes. Finally, we found that superoxide was produced in reperfused myocardium and that intravenous administration of edaravone, a free radical scavenger, immediately before reperfusion significantly suppressed the superoxide overproduction and subsequent expression of sxbp1 and chop mRNA, followed by reduced injury size in wild-type mice. Conclusion-The ER stress-induced, CHOP-mediated pathway, which is activated in part by superoxide overproduction after reperfusion, exacerbates myocardial ischemia/reperfusion injury by inducing cardiomyocyte apoptosis and myocardial inflammation. Key Words: ischemic heart disease Ⅲ reactive oxygen species Ⅲ reperfusion injury Ⅲ CHOP Ⅲ ER stress T he endoplasmic reticulum (ER), one of the largest cellular organelles, is recognized as the principal site of synthesis, folding, assembly, and modification of numerous proteins. Various pathophysiological stimuli, which increase the demand for protein folding or disrupt folding capacity, cause accumulation of unfolded or misfolded proteins within the ER, a condition collectively known as ER stress. To overcome ER stress, cells activate specific signaling pathways in what is termed the ER stress response, the initial intent of which is to restore ER homeostasis and promote cell survival through alteration of cellular transcriptional and translational programs. However, if restoration fails, ER stress triggers a final response, namely, apoptosis, to protect the organism by eliminating damaged cells. Induction of C/EBP-homologous protein (CHOP), a member of the C/EBP transcription factor family, is a signaling event underlying ER stress-induced apoptosis, 1-3 and the involvement of CHOPmediated apoptosis has been demonstrated in various diseases, including diabetes, neurodegenerative diseases, brain ischemia, and even some cardiovascular diseases. [3][4][5] In the setting of acute myocardial infarction, early...

AimThe aim of this study was to evaluate the diagnostic utility of high‐sensitivity cardiac troponin T (hs‐cTnT) levels in discriminating cardiac amyloidosis from patients with cardiac hypertrophy caused by aetiologies other than cardiac amyloidosis.Methods and resultsSerum hs‐cTnT levels were measured in 96 patients with cardiac amyloidosis (light chain: 23, wild‐type transthyretin amyloidosis: 40, and mutated transthyretin amyloidosis: 33), and 91 patients with other causes of cardiac hypertrophy who were confirmed to have no cardiac amyloidosis by endomyocardial biopsy (control group). The diagnostic utility and cut‐off value of hs‐cTnT were evaluated by receiver operating characteristic analysis. The median hs‐cTnT levels were higher in cardiac amyloidosis than the control group [0.048 (0.029–0.073) vs. 0.016 (0.010–0.031) ng/mL; P < 0.001]. High levels of hs‐cTnT were suggestive of cardiac amyloidosis (cut‐off value: 0.0312 ng/mL, sensitivity: 0.74, specificity: 0.76, area under the curve: 0.788; 95% confidence interval: 0.723–0.854, P < 0.001), compared with brain natriuretic peptide and E/e′ ratio. The hs‐cTnT levels were also useful in differentiating each type of amyloidosis from the control group. Multivariate analysis identified log hs‐cTnT as an independent diagnostic factor for cardiac amyloidosis (odds ratio: 2.22; 95% confidence interval: 1.30–3.80; P = 0.004).ConclusionsHigh serum levels of hs‐cTnT are highly suggestive of cardiac amyloidosis, allowing its differentiation from cardiac hypertrophy of other aetiologies. Further refined diagnostic approaches that include imaging modalities and histopathological examination are needed for these patients to avoid underdiagnosis of cardiac amyloidosis.