Takuo Arikawa

Irbesartan, an angiotensin receptor blocker, exhibits metabolic, anti-inflammatory and antioxidative effects in patients with high-risk hypertension

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.

Left ventricular function in pulmonary hypertension

To elucidate left ventricular function in pulmonary hypertension, we measured parameters of left ventricular as well as right ventricular function by echocardiography in 11 patients with pulmonary hypertension (idiopathic pulmonary artery hypertension in 4, chronic thromboembolic pulmonary hypertension in 5, and other pulmonary hypertension in 2). The percent change in these parameters 6 months after treatment with pulmonary artery vasodilators (beraprost in 8 and sildenafil in 3) was assessed. There was a correlation between the relative change in right ventricular systolic pressure (RVSP) and the relative changes in left ventricular outflow tract velocity–time integral (r = −0.730, P = 0.011) and mitral valve velocity–time integral (r = −0.621, P = 0.041). However, there was no correlation between the relative change in RVSP and the relative changes in left ventricular ejection fraction, left ventricular diastolic dimension, and systolic blood pressure. The relative change in RVSP was also correlated with the relative change in early diastolic myocardial velocity at the medial mitral annulus (r = −0.675, P = 0.023). Reduction of RVSP by pulmonary artery vasodilators might increase left ventricular preload, leading to an increase in stroke volume. Right ventricular load reduction might improve left ventricular diastolic function in patients with pulmonary hypertension, possibly through altered interventricular septal performance.

Cardioprotective effects of low-dose combination therapy with a statin and an angiotensin receptor blocker in a rat myocardial infarction model

PURPOSE Statins attenuate angiotensin II-induced myocyte hypertrophy and this might increase the cardioprotective effects of renin-angiotensin system inhibition in the ischemic heart. In this study, we investigated the cardioprotective effects of combination therapy with low-dose simvastatin and low-dose losartan using a rat myocardial infarction model. METHODS Myocardial infarction was created in rats by left anterior descending artery ligation, and the animals were randomly allocated to one of four groups: control (n=8), losartan 3 mg/kg/day (n=8), simvastatin 2 mg/kg/day (n=8), and losartan 3 mg/kg/day plus simvastatin 2 mg/kg/day (n=8). Each treatment was started on the day of coronary ligation, and hemodynamics, myocardial blood flow, and infarct size were measured after 28 days. RESULTS Blood pressure, heart rate, and left ventricular systolic and end-diastolic pressures were not significantly different comparing the control group with the 3 other treatment groups. The peak positive first derivative of left ventricular pressure (peak LV dP/dt) was equivalent comparing the control group with the losartan and simvastatin groups. However, the peak LV dP/dt was greater in the losartan plus simvastatin group than in the control group (p<0.05). Myocardial blood flow, left ventricular weight, and infarct size were not significantly altered by the 3 treatments. CONCLUSIONS Treatment with 3 mg/kg/day losartan plus 2 mg/kg/day simvastatin but not losartan or simvastatin alone improved left ventricular systolic function in a rat myocardial infarction model. The result suggests that statins given in combination with angiotensin receptor blockers might have beneficial cardioprotective effects, even at low-doses for each agent.

Early Surgical Intervention and Optimal Medical Treatment for Candida parapsilosis Endocarditis

We herein report the case of a 72-year-old man with endocarditis of the aortic valve who underwent urgent aortic valve replacement 36 hours after admission due to an aggravation of aortic valve regurgitation. Postoperative cultures of the blood and site of valve vegetation identified Candida parapsilosis as a pathogen. Antifungal therapy with amphotericin B and fluconazole was initiated after surgical treatment. Thereafter, the patient displayed a favorable clinical course. Candida parapsilosis endocarditis involving the native valves is extremely rare and associated with a very high mortality rate. Prompt surgical treatment and the aggressive use of antifungal agents are required to save the patients life.

Pleiotropic effects of ARB on dyslipidemia.

Angiotensin II type 1 (AT1) receptor blockers (ARBs), widely used in the treatment of hypertension, have cardiovascular, cerebral, and renal protective effects beyond blood pressure control. In addition to direct end-organ protection, some ARBs have been suggested to improve abnormalities of glucose and lipid metabolisms, resulting in an anti-atherosclerotic effect in patients with hypertension. In several clinical trials, the effects of ARBs on lipid metabolism have been emerged, although the effects are heterogeneous. Certain subgroups of ARBs such as telmisartan have been identified as partial agonists for the peroxisome proliferators activated receptor (PPAR)-γ, and thus, this class of ARBs has been mostly focused on their effects on lipid metabolism. Based on the pleiotropic effects on lipid metabolism, we can envision that ARBs would provide the promising outcome for hypertensive patients aggregating metabolic risk factors, including dyslipidemia.

Association of serum concentrations of irisin and the adipokines adiponectin and leptin with epicardial fat in cardiovascular surgery patients

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 cardiovascular risk in patients.

Cardiac paraganglioma with a novel germline mutation of succinate dehydrogenase gene D

A 58-year-old woman with a past medical history of a carotid body tumor, resected 4 months prior to presentation, was admitted to our hospital for treatment of a cardiac tumor that was identified on post-operative echocardiography and chest computed tomography. The cardiac tumor was surgically removed and identified pathologically as a paraganglioma, similarly to the carotid body tumor. Genetic analysis of both tumors identified a non-synonymous mutation in the succinate dehydrogenase (SDH) gene D, Exon4, c.320T>C, p.Leu107Pro showing co-segregation with paternal transmission and maternal imprinting among family members. This novel mutation appears to be the cause of familial paraganglioma in this patient.

Protective effects of bisoprolol against myocardial injury and pulmonary dysfunction in patients with chronic heart failure

OBJECTIVES This study was designed to elucidate differences in effects of 2 beta blockers, bisoprolol and carvedilol, in patients with chronic heart failure. BACKGROUND Although the beta blockers bisoprolol and carvedilol are commonly used in patients with chronic heart failure, differences in the efficacy and safety of these medications have not been established in this patient population. METHODS Patients with chronic systolic heart failure, defined as ≤45% ejection fraction, who had received intensive medical therapy with the exception of beta blockers, were randomly assigned to receive either bisoprolol or carvedilol for 24weeks. RESULTS A total of 67 patients were enrolled in the study (bisoprolol: 38 patients, carvedilol: 29 patients). No difference was observed in the improvement of NYHA class, ejection fraction, or N-terminal pro-brain-type natriuretic peptide level between groups. In contrast, the level of high sensitivity troponin T decreased in the bisoprolol group [-4.1±0.9 to -4.5±0.8 log (ng/ml), P=0.003], but did not change in the carvedilol group [-4.4±1.1 to -4.6±0.8 log (ng/ml), P=0.161]. Forced expiratory volume in the first second increased in the bisoprolol group [2.26±0.70 to 2.40±0.70 (L), P=0.014], but did not change in the carvedilol group [2.53±0.71 to 2.59±0.78 (L), P=0.127]. CONCLUSION Bisoprolol might be superior to carvedilol in providing protection from myocardial injury and preserving pulmonary function in patients with chronic systolic heart failure.

Radiation-Induced Coronary Artery Disease Manifested at Very Late Phase

We report the case of a 51-year-old female, in whom coronary artery disease such as occlusion of septal perforators was manifested, on the occasion of hospitalization with congestive heart failure. The patient had a history of radiation therapy for a mediastinal tumor 19 years previously. As she had no conventional coronary risk factors, the cause of the coronary artery disease is thought to have been related to the radiation therapy. As survival rates of cancer patients improve as a consequence of therapeutic advances, we should be aware of the possibility of coronary artery disease as a very late complication of radiation therapy, even in patients who have no coronary risk factors.