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Metabolic syndrome (MetS) is an important predictor of mortality in older adulthood, but it is not reliably related to measures of body composition such as body mass index in older adults, as opposed to those in earlier life stages. Previous research suggests that skeletal muscle mass is related to cardiovascular risk in older adulthood, but it is difficult to measure muscle mass accurately and independently of body fat. This study aimed to examine the relationship between body composition and cardiovascular risk factors among women in older adulthood. A cross-sectional observational clinical study was conducted at a single medical clinic in Tokyo, Japan. Participants included 90 healthy Japanese women aged 65 years and older. MetS risk factors were assessed. Appendicular skeletal muscle mass (ASM) was assessed using dual-emission X-ray absorptiometry. Visceral fat area (VFA) was measured using computed tomography. VFA positively correlated with ASM and MetS, whereas ASM and MetS did not correlate with each other. Using VFA and ASM data in a MetS multiple linear regression model, the association between VFA and MetS remained positive, whereas a significant negative relationship emerged between ASM and MetS. Lower muscle mass was independently associated with higher cardiovascular risk after controlling for VFA. Clinical interventions to reduce muscle loss in older adulthood may be beneficial for reducing the risk of MetS and improving cardiovascular health. [ABSTRACT FROM AUTHOR]

Aim To investigate the relationship between physical function, mortality and autonomic nervous activity measured by heart rate variability of elderly in long-term care. Methods Cross-sectional and longitudinal studies were carried out at hospitals and health service facilities for the elderly in Nagano prefecture, Japan, from July 2007 to March 2011. A total of 105 long-term care older adults and 17 control older adults with independent physical function were included. The Functional Independence Measure ( FIM) and Barthel Index were determined as indices of physical function. Twenty-four-hour Holter monitoring was carried out. From RR intervals in electrocardiograms, heart rate and standard deviations of all NN intervals in all 5-min segments of the entire recording, power spectral density, low frequency, high frequency and low frequency/high frequency ( LF/ HF) were calculated. Results FIM score and Barthel Index were 46 ± 26 and 30 ± 31, respectively, in long-term care elderly. FIM and Barthel index were significantly correlated with heart rate and the standard deviations of all NN intervals after adjustment for age, sex, cardiovascular risk factors and FIM. Furthermore, LF/ HF was significantly decreased in long-term care elderly compared with control elderly after adjustment for covariates. In addition, decrease in LF/ HF was an independent risk factor for mortality. Conclusion Low LF/ HF activity was observed in long-term care elderly and was related to an increase of overall mortality. Geriatr Gerontol Int 2014; 14: 159-166. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which is concerned with sleep apnea in patients with metabolic syndrome.

Abstract: Hyperphosphatemia has emerged as a cardiovascular risk factor that stimulates calcification in vessels. We explored molecules that were induced by inorganic phosphate (Pi) at an early stage in vascular smooth muscle cells (VSMC). In the present study, we examined the role of thrombomodulin (TM) in Pi-induced VSMC calcification based on the results of DNA microarray analysis. Both mRNA and protein expression of TM were markedly augmented in Pi-induced calcification. Conversely, knockdown of TM by siRNA significantly inhibited calcification, in addition to Pi-induced apoptosis which plays critical roles in VSMC calcification. We further found that TM suppressed both of mRNA and protein expression of growth arrest-specific gene 6 (Gas6), a key molecule regulating apoptosis. Recombinant extracellular epidermal growth factor (EGF)-repeat domain of TM exaggerated calcification and this effect was abrogated by a neutralizing antibody for EGF receptor, suggesting that the cleaved and secreted form of TM may activate EGF receptor. We also found that downregulation of Gas6 by TM/EGF receptor axis was mediated by ERK in VSMC calcification. In the aorta of adenine-fed rat, a typical medial calcification model with hyperphosphatemia, we found that TM expression was increased. Furthermore, in human calcified aorta, increased TM expression was also observed. These results indicate that TM is a novel molecule that promotes apoptosis and vascular calcification by regulation of Gas6, presumably via EGF receptor/ERK axis. [Copyright &y& Elsevier]

Abstract: Objective: Recent epidemiological studies have found that testosterone deficiency is associated with higher mortality largely due to cardiovascular (CV) disease in community-dwelling older men. We investigated whether a low plasma testosterone level could predict cardiovascular events in middle-aged Japanese men with coronary risk factors. Methods: One hundred and seventy-one male outpatients (30–69 years old, mean±SD=48±13 years) who had any coronary risk factor (hypertension, diabetes, dyslipidemia, smoking, and obesity) without a previous history of CV disease were followed up. At baseline, the subjects underwent examination of coronary risk factors, measurement of flow-mediated dilation (FMD) of the brachial artery as an indicator of vascular endothelial function and assays of plasma total testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol and cortisol. Results: During the mean follow-up period of 77 months, a total of 20 CV events occurred. Kaplan–Meier survival analysis by tertile of plasma hormone levels revealed that the subjects with the lowest testosterone tertile were more likely to develop CV events than those with the highest tertile (P <0.01 by log-rank test). Cox proportional hazards models showed that the subjects with the lowest tertile of plasma testosterone (<14.2nmol/L) had an approximately 4-fold higher CV event risk compared to those with the higher testosterone tertiles after adjustment for coronary risk factors including medication and FMD (unadjusted hazard ratio, 3.61; 95% CI, 1.47–8.86: multivariate-adjusted hazard ratio, 4.61; 95% CI, 1.02–21.04). Multivariate analysis did not show any significant association of DHEA-S, estradiol or cortisol with CV events. Conclusions: A low plasma testosterone level is associated with CV events in middle-aged Japanese men, independent of coronary risk factors and endothelial function. This is the first report to show the relationship between endogenous testosterone and CV events in Asian population. [Copyright &y& Elsevier]

Abstract: Objectives: Arterial calcification makes the management of hemodynamics more difficult. Some reports have previously shown that simple assessment of aortic calcification using plain radiography is associated with cardiovascular (CV) events; however, these studies simply assessed whether aortic calcification was present or absent only, without considering its extent. Here, we evaluated validity of grading aortic arch calcification (AAC) to predict new CV events. Methods and results: We retrospectively reviewed chest X-rays in 239 asymptomatic out-patients who underwent measurement of endothelial function at the 1994–2000 without past history of CV events. The extent of AAC was divided into four grades (0–3). Among these subjects, the follow-up of CV events in 209 patients was completed. At baseline, AAC grade was positively related to age, pulse pressure, diabetes and renal dysfunction. Impairment of endothelial function, as determined by flow-mediated dilation (FMD), was also correlated to increasing AAC grade. Fifty-seven CV events in total occurred during a mean follow-up period of 69±45 months. With multivariate adjustment, Kaplan–Meier analysis showed that the incidence was significantly higher in patients with higher AAC grade (grades 2 and 3) than in those with grade 0 or 1 (p <0.01, log-rank test). Two kinds of multivariate Cox-proportional hazards analyses showed the predictive values of AAC grade were significant (hazard ratio, 2.49; p =0.01, 2.56; p <0.01, respectively), and the predictive power was superior to that of renal dysfunction or FMD. In addition, the prediction was valuable even in patients without CKD. Conclusions: AAC detectable on chest X-ray is a strong independent predictor of CV events beyond traditional risk factors including endothelial dysfunction. Risk stratification by assessment of AAC may provide important information for management of atherosclerotic disease. [Copyright &y& Elsevier]

Recent epidemiological studies have found that androgen deficiency is associated with a higher incidence of cardiovascular disease in men. However, little is known about the mechanism underlying the cardioprotective effects of androgens. Here we show the inhibitory effects of testosterone on vascular calcification and a critical role of androgen receptor (AR)-dependent transactivation of growth arrest-specific gene 6 (Gas6), a key regulator of inorganic phosphate (P,)induced calcification of vascular smooth muscle cells (VSMC). Testosterone and nonaromatizable androgen dihydrotestosterone inhibited Pi-induced calcification of human aortic VSMC in a concentration-dependent manner. Androgen inhibited Pi-induced VSMC apoptosis, an essential process for VSMC calcification. The effects on VSMC calcification were mediated by restoration of Pi-induced down-regulation of Gas6 expression and a subsequent reduction of Akt phosphorylation. These effects of androgen were blocked by an AR antagonist, flutamide, but not by an estrogen receptor antagonist, ICI 182,780. We then explored the mechanistic role of the AR in Gas6 expression and found an abundant expression of AR predominantly in the nucleus of VSMC and two consensus ARE sequences in the Gas6 promoter region. Dihydrotestosterone stimulated Gas6 promoter activity, and this effect was abrogated by flutamide and by AR siRNA. Sitespecific mutation revealed that the proximal ARE was essential for androgen-dependent transactivation of Gas6. Furthermore, chromatin immunoprecipitation assays demonstrated ligand-dependent binding of the AR to the proximal ARE of Gas6. These results indicate that AR signaling directly regulates Gas6 transcription, which leads to inhibition of vascular calcification, and provides a mechanistic insight into the cardioprotective action of androgens. [ABSTRACT FROM AUTHOR]

Aging is an independent risk factor for the development of cardiovascular disease. Vascular aging is mainly characterized by endothelial dysfunction, which, in turn, is primarily attributable to increased superoxide (O2⋅−) formation with age. To date, the source of this age-associated increased O2⋅− production remains obscure. We investigated whether like in hyperglycemia or hypertension protein kinase C (PKC)-mediated activation of the NAD(P)H oxidase system is involved. Here we show that both PKC translocation, necessary for its activation, and expression of the cytosolic subunits of the NAD(P)H oxidase, p47phox and p67phox, remain unchanged with age. Therefore, we suggest that oxidative stress-associated vascular aging mechanistically differs from endothelial dysfunction seen in the context of other cardiovascular risk factors, for which the PKC/NAD(P)H oxidase pathway has been shown responsible. [Copyright &y& Elsevier]