We performed a genome-wide association study (GWAS) of Kawasaki disease in Japanese subjects using data from 428 individuals with Kawasaki disease (cases) and 3,379 controls genotyped at 473,803 SNPs. We validated the association results in two independent replication panels totaling 754 cases and 947 controls. We observed significant associations in the FAM167A-BLK region at 8p22-23 (rs2254546, P = 8.2 × 10(-21)), in the human leukocyte antigen (HLA) region at 6p21.3 (rs2857151, P = 4.6 × 10(-11)) and in the CD40 region at 20q13 (rs4813003, P = 4.8 × 10(-8)). We also replicated the association of a functional SNP of FCGR2A (rs1801274, P = 1.6 × 10(-6)) identified in a recently reported GWAS of Kawasaki disease. Our findings provide new insights into the pathogenesis and pathophysiology of Kawasaki disease.

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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.

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Among patients with ST-segment elevation myocardial infarction, slow gait speed was significantly associated with an increased risk of cardiovascular events. (Gait Speed for Predicting Cardiovascular Events After Myocardial Infarction; NCT01484158).

The effects of jump training on bone hypertrophy were investigated in 3, 6, 12, 20 and 27 month-old female Fischer 344 rats. The rats of all age groups were divided into jump training (height: 40 cm, 100 times/day, 5 days/wk for 8 wk), run training (speed: 30 ml/min, 1 h/day, 5 days/wk for 8 wk) or sedentary group. Fat-free dry weights (FFW) of the femur and the tibia were significantly greater in the jump-trained rats than in the run-trained rats, and were significantly greater in the run-trained rats than in the sedentary rats. Jump training significantly increased FFW of the femur and the tibia not only in young rats but also in old rats, while run training did not increase FFW significantly in old rats. In young rats, both jump training and run training significantly increased the length of the femur and the tibia and the diameter of the femur. The diameter of the tibia was greater in the jump-trained rats than in the sedentary and the run-trained rats in all age groups. The results of the present study indicate that jump training was a more effective training mode than run training for bone hypertrophy and that the effects were not limited by age.