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To investigate the relationship between asymptomatic target organ damage (TOD) and different somatotypes in a population of elderly from Chinese communitydwelling. Methods: A total of 2098 Chinese senior residents from northern Shanghai older than 65 years were recruited in the research. The following somatotype parameters were recorded and analyzed: body mass index, waist circumference, hip circumference, and waist-hip ratio were recorded and calculated. Asymptomatic TOD, including urine albumin/creatinine ratio, estimated glomerular filtration rate (eGFR), intima-media thickness (IMT), left ventricular mass index (LVMI), left ventricular diastolic function, and carotid-femoral pulse wave velocity (PWV) was recorded using the MyLab30 Gold CV system and SphygmoCor. Results: Of all 2098 residents, 817 (38.9%) were overweight and 289 (13.8%) were obese. All somatotype measures were significantly correlated with TOD parameters (p<0.05). After adjustment for age and male gender, in total population, LVMI (p<0.001), cardiac diastolic function (E/Ea, p<0.001), PWV (p<0.001), eGFR (p=0.03), and urine albumin/creatinine ratio (p<0.001) changed gradually and significantly correlated with increasing BMI values. Obesity and overweight were independently related to the incidence of LVH, LVDD, artery stiffness, carotid arterial plaque, and microalbuminuria. Conclusion:The incidence of asymptomatic TOD was significantly correlated with overweight and obesity, especially in women, whereas the underweight may favor in the prevention of TOD.

Background and Aims The ryanodine receptor (RyR2) is essential for cardiac muscle excitation-contraction coupling, dysfunctional RyR2 participates in the development of inherited arrhythmogenic cardiac disease. In this study, a novel RyR2 mutation A690E is identified from a patient with family inheritance of sudden cardiac death, and we investigated the pathogenic basis of the mutation. Methods and Results We generated a mouse model that carried the A690E mutation. Mice were characterized by adrenergic-induced ventricular arrhythmias similar to clinical manifestation of the patient. Optical mapping studies revealed that isolated A690E hearts were prone to arrhythmogenesis and displayed frequency-dependence calcium transient alternans. Upon β-adrenoceptor challenge, the concordant alternans was shifted towards discordant alternans that favor triggering ectopic beats and Ca2+ re-entry, similar phenomenon was also found in the A690E cardiomyocytes. In addition, we found that A690E cardiomyocytes manifested abnormal Ca2+ release and electrophysiological disorders, including an increased sensitivity to cytosolic Ca2+, an elevated diastolic RyR2-mediated Ca2+ leak, and an imbalance between Ca2+ leak and reuptake. Structural analyses reveal that the mutation directly impacts RyR2-FKBP interaction. Conclusions In this study, we have identified a novel mutation in RyR2 that is associated with sudden cardiac death. By characterizing the function defects of mutant RyR2 in animal, whole heat, and cardiomyocytes, we demonstrated the pathogenic basis of the disease-causing mutation and provided a deeper mechanistic understanding of a life-threatening cardiac arrhythmia.