Irbesartan, an angiotensin II receptor blocker (ARB), acts as a selective PPAR-γ (peroxisome proliferator-activated receptor-γ) modulator, and thus may have anti-inflammatory and antioxidative effects, as well as beneficial effects on glucose and lipid metabolism. We enrolled 118 high-risk hypertensive outpatients, defined as those with the presence of at least one complication such as coronary artery disease, cerebrovascular disease or diabetes, and who were receiving any ARB except for irbesartan (67±10 years, 80% male subjects). After a 4-week control period, all ARBs were switched to an equivalent dose of irbesartan. We evaluated changes in lipid parameters, inflammatory markers and derivatives of reactive oxygen metabolites (d-ROMs) as an oxidative stress index. After 12 weeks of irbesartan, there were significant decreases in triglycerides (138±73 versus 123±65 mg dl(-1), P<0.05), high-sensitivity C-reactive protein (hs-CRP) (2.80±0.53 versus 2.66±0.50, log (ng ml(-1)), P<0.05) and d-ROMs (338±74 versus 305±62 U.CARR, P<0.001). There were significant increases in high-density lipoprotein cholesterol (50±13 versus 52±14 mg dl(-1), P<0.01) and adiponectin (9.4±6.2 versus 16.6±13.4 ng ml(-1), P<0.05). There were no significant changes in systolic and diastolic blood pressure. The change in d-ROMs from baseline to 12 weeks was positively correlated with the change in hs-CRP (R=0.34, P<0.01). Irbesartan appears to exert beneficial effects on oxidative stress, inflammation, lipid metabolism and metabolic syndrome, indicating that it may be useful in high-risk hypertensive patients.

Frailty and sarcopenia increase the risk of complications and mortality when invasive treatment such as cardiac surgery is performed. Growth differentiation factor-15 (GDF-15) involves various pathophysiological conditions including renal dysfunction, heart failure and cachexia. We investigated the pathophysiological roles of preoperative GDF-15 levels in cardiovascular surgery patients. Preoperative skeletal muscle index (SMI) determined by bioelectrical impedance analysis, hand-grip strength, 4 m gait speed, and anterior thigh muscle thickness (TMth) measured by echocardiography were assessed in 72 patients (average age 69.9 years) who underwent cardiovascular surgery. The preoperative serum GDF-15 concentration was determined by enzyme-linked immunosorbent assay. Circulating GDF-15 level was correlated with age, brain natriuretic peptide, and estimated glomerular filtration rate (eGFR). It was also negatively correlated with SMI, hand-grip strength, and anterior TMth. In multivariate analysis, eGFR and anterior TMth were the independent determinants of GDF-15 concentration even after adjusting for age, sex, and body mass index. Alternatively, the GDF-15 level was an independent determinant of eGFR and anterior TMth. We concluded that preoperative GDF-15 levels reflect muscle wasting as well as renal dysfunction in preoperative cardiovascular surgery patients. GDF-15 may be a novel biomarker for identify high-risk patients with muscle wasting and renal dysfunction before cardiovascular surgery.

Obstructive sleep apnoea, even when treated appropriately, may worsen long-term cardiac function and outcomes in patients who have heart failure with preserved ejection fraction.

The effects of beta-blockers on long-term morbidity and mortality have been established in patients with chronic heart failure (CHF) with reduced left ventricular function [1][2][3][4]. Among various beta-blockers, only carvedilol and bisoprolol are approved by Japanese guidelines for the treatment of patients with CHF [5]. Bisoprolol is highly selective for the beta-1 receptor, whereas carvedilol is a non-selective beta-blocker with simultaneous alpha-receptor antagonism [6]. However, there is no established clinical evidence on how to properly use these two agents. Our previous clinical trial, the Bisoprolol Improvement Group for Chronic Heart Failure Treatment Study in Dokkyo Medical University (BRIGHT-D), reported that bisoprolol is superior to carvedilol for myocardial protection in patients with CHF, as demonstrated by a greater reduction in high-sensitivity cardiac troponin T (hsTnT) [7].

Epicardial fat located adjacent to the heart and coronary arteries is associated with increased cardiovascular risk. Irisin is a myokine produced by skeletal muscle after physical exercise, and originally described as a molecule able to promote the browning of white adipose tissue and energy expenditure. In order to decrease cardiovascular risk, it has been proposed as a promising therapeutic target in obesity and type 2 diabetes. We investigated the relationships between serum concentrations of irisin and the adipokines adiponectin and leptin and body fat including epicardial fat in patients undergoing cardiovascular surgery. We obtained serum samples from 93 patients undergoing cardiovascular surgery (age 69.6 (SD 12.8) years, BMI 24.1 ± 4.8 kg/m2). Computed tomography (CT) and echocardiographic data were obtained from the routine preoperative examination. Subcutaneous fat area (SFA, cm2) and visceral fat area (VFA, cm2) near the umbilicus were automatically measured using the standard fat attenuation range. Epicardial fat area (EFA, cm2) was measured at the position where the heart became a long axis image with respect to the apex of the heart in the coronal section image. Total body fat mass, body fat percentage, and skeletal muscle volume (SMV) were estimated using bioelectrical impedance analysis (BIA). Serum irisin concentration was measured by enzyme-linked immunosorbent assay, and compared with adiponectin and leptin concentrations. The data were also compared with the clinical biochemical data. EFA was strongly correlated with BMI (P = 0.0001), non-HDL-C (P = 0.029), TG (P = 0.004), body fat mass (P = 0.0001), and body fat percentage (P = 0.0001). Serum leptin concentration showed a significant positive correlation with BMI (P = 0.0001) and TG (P = 0.001). Adiponectin, but not irisin, showed a significant negative correlation with BMI (P = 0.006) and TG (P = 0.001). Serum leptin level had a significant positive correlation with EFA, VFA, and SFA. In contrast, the serum adiponectin level was significantly negatively correlated with EFA, VFA, and SFA. The serum irisin level was also negatively correlated with EFA (r = -0.249, P = 0.015), and SFA (r = -0.223, P = 0.039), and tended to correlate with VFA (r = -0.198, P = 0.067). The serum level of adiponectin was negatively correlated with that of leptin (r = -0.296, P = 0.012), but there were no significant correlations between irisin and either adiponectin or leptin. Multivariate linear regression demonstrated that EFA showed a positive association with serum leptin level (β = 0.438, P = 0.0001) and a negative correlation with serum irisin level (β = -0.204, P = 0.038) and serum adiponectin level (β = -0.260, P = 0.015) after adjusting for age, sex, and BMI. The present study provided the first evidence of associations of the serum irisin and adipokines (adiponectin and leptin) concentrations with epicardial fat in cardiovascular surgery patients. Irisin may play a role in preventing excess adiposity including epicardial fat, and consequently cardiovascul...