Effects of sitagliptin beyond glycemic control: focus on quality of life.

Background: Recently, incretin hormones, including glucagon-like peptide-1 (GLP-1) analogue and dipeptidyl peptidase-4 (DPP-4) inhibitor, have been found to regulate glucose metabolism. The aim of this study was to elucidate the efficacy and safety of the clinical usage of DPP-4 inhibitors in Japan.

Methods: This study was designed as a prospective, open-label, multi-center trial.

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.

Evaluation of serial changes in tissue characteristics during statin-induced plaque regression using virtual histology-intravascular ultrasound studies.

Treatment of all coronary arteries is important to improve the prognosis of acute coronary syndrome after early reperfusion of the culprit lesion. Early statin treatment has been reported to cause regression of plaques away from the site of the culprit lesion in patients with acute coronary syndrome. However, the precise mechanism of coronary plaque regression is not well understood.

A multicenter study design to assess the clinical usefulness of semi-automatic measurement of flow-mediated vasodilatation of the brachial artery.

Flow-mediated vasodilatation of the brachial artery (FMD) is a marker which is related to endothelial nitric oxide bioavailability. Commercially available ultrasound machines equipped with online computer-assisted semi-automatic analysis software to measure FMD have recently become available in Japan. These devices enable more convenient examination, enhanced reproducibility of FMD measurement, and a shortened examination time.

Repetitive hyperthermia attenuates progression of left ventricular hypertrophy and increases telomerase activity in hypertensive rats.

We investigated the hypothesis that repetitive hyperthermia (RHT) attenuates the progression of cardiac hypertrophy and delays the transition from hypertensive cardiomyopathy to heart failure in Dahl salt-sensitive (DS) hypertensive rats. Six-week-old DS rats were divided into the following five groups: a normal-salt diet (0.4% NaCl) (NS group), a normal-salt diet plus RHT by daily immersion for 10 min in 40°C water (NS+RHT group), a high-salt diet (8% NaCl) (HS group), a high-salt diet (8% NaCl) plus RHT (HS+RHT group), and high-salt diet (8% NaCl) plus RHT with 17-DMAG (HSP90 inhibitor) administration (HS+RHT+17-DMAG group).

The glucagon-like peptide 1 analog liraglutide reduces TNF-α-induced oxidative stress and inflammation in endothelial cells.

Objective: Glucagon-like peptide 1 (GLP-1), one of the incretin hormones, has been reported to increase positive inotropic activity in cardiac myocytes and protect against myocardial injury. However, the effects upon endothelial cells and the mechanisms involved are not fully understood. We assessed the hypothesis that GLP-1 has protective effects against inflammation and oxidative stress on human endothelial cells.

Continuous positive airway pressure therapy improves vascular dysfunction and decreases oxidative stress in patients with the metabolic syndrome and obstructive sleep apnea syndrome.

Background: Patients with obstructive sleep apnea syndrome (OSAS) are always exposed to intermittent hypoxia and reoxygenation. The metabolic syndrome (MetS) and OSAS are also known to accelerate atherosclerosis, diabetes, and dyslipidemia. Therefore, nasal continuous positive airway pressure (CPAP) therapy may have beneficial effects in patients with the MetS and OSAS.

Hyperthermia by bathing in a hot spring improves cardiovascular functions and reduces the production of inflammatory cytokines in patients with chronic heart failure.

Balneotherapy has been shown to reduce systemic blood pressure in healthy volunteers. Hyperthermia might ameliorate the inflammatory status in heart failure through improving cardiac function. The purpose of this study was to examine the beneficial effects of balneotherapy in patients with chronic heart failure (CHF).

Endothelial dysfunction as a cellular mechanism for vascular failure.

The regulation of vascular tone, vascular permeability, and thromboresistance is essential to maintain blood circulation and therefore tissue environments under physiological conditions. Atherogenic stimuli, including diabetes, dyslipidemia, and oxidative stress, induce vascular dysfunction, leading to atherosclerosis, which is a key pathological basis for cardiovascular diseases such as ischemic heart disease and stroke. We have proposed a novel concept termed "vascular failure" to comprehensively recognize the vascular dysfunction that contributes to the development of cardiovascular diseases.

Vascular inflammation and repair: implications for re-endothelialization, restenosis, and stent thrombosis.

The cellular and molecular processes that control vascular injury responses after percutaneous coronary intervention involve a complex interplay among vascular cells and progenitor cells that control arterial remodeling, neointimal proliferation, and re-endothelialization. Drug-eluting stents (DES) improve the efficacy of percutaneous coronary intervention by modulating vascular inflammation and preventing neointimal proliferation and restenosis. Although positive effects of DES reduce inflammation and restenosis, negative effects delay re-endothelialization and impair endothelial function.

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).

IL-27 inhibits hyperglycemia and pancreatic islet inflammation induced by streptozotocin in mice.

Inflammation driven by immune cells and pro-inflammatory cytokines is implicated in pancreatic β-cell injury, leading to the development of diabetes mellitus. IL-27, a cytokine consisting of IL-27p28 and Epstein-Barr virus-induced gene 3 (EBI3), binds a membrane-bound heterodimeric receptor consisting of the IL-27 receptor α chain (WSX-1) and gp130. IL-27 has anti-inflammatory properties that regulate T-cell polarization and cytokine production.

Renovascular protective effects of erythropoietin in patients with chronic kidney disease.

Background/aims: Erythropoietin (EPO) has been widely used for the treatment of anemia in chronic kidney disease (CKD). A growing body of evidence indicates that the therapeutic benefits of EPO could extend beyond the improvement of anemia. The aim of the present study was to determine whether EPO affects renovascular and oxidative stress biomarkers in pre-dialysis CKD patients with anemia.

Antihypertensive treatment using an angiotensin receptor blocker and a thiazide diuretic improves patients' quality of life: the Saga Challenge Antihypertensive Study (S-CATS).

The aim of the Saga Challenge Antihypertensive Study (S-CATS), a single-arm, prospective and multi-center trial, was to evaluate the effectiveness of combined antihypertensive treatment with losartan and hydrochlorothiazide (HCTZ). Enrolled in the study were a total of 161 patients with hypertension, who in spite of treatment with an angiotensin receptor blocker (ARB) alone or an ARB and calcium channel blocker (CCB), had not been able to reach blood pressure control goals set by the Japanese Society of Hypertension Guidelines (JSH 2004). The ARBs were replaced with a combination pill containing losartan (50 mg) and HCTZ (12.

Prediction of acute coronary syndrome by using multislice computed tomography. -Can we predict the onset of acute coronary syndrome? (Pro)-.

Predicting the occurrence of acute coronary syndrome (ACS) is a major clinical challenge for cardiologists. Multi-slice computed tomography (CT) has enabled easy detection and assessment of atherosclerotic coronary plaque, and therefore has considerable potential in the prevention of ACS. The recent development of 64-slice cardiac CT enables detailed information on both plaque properties and characteristics to be obtained with excellent diagnostic accuracy.

Angiotensin II induces microtubule reorganization mediated by a deacetylase SIRT2 in endothelial cells.

Angiotensin II has been implicated in vascular remodeling. Microtubule composed of tubulins regulates cell shape, migration and survival. Tubulin acetylation has an important role in the control of microtubule structure and microtubule-based cellular functions.

Potential benefit of statin therapy for dyslipidemia with chronic kidney disease: Fluvastatin Renal Evaluation Trial (FRET).

Background: Dyslipidemia is a common complication of chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality of CKD patients.

Aim: The aim of the present study was to determine whether fluvastatin, which is mostly characterized by its pleiotropic anti-oxidant effects, has renoprotective effects in dyslipidemic patients with CKD.

Methods: In 43 dyslipidemic patients with CKD taking fluvastatin 10 mg/day, 20 mg/day or 30 mg/day, renal functions as well as lipid profiles were assessed.

Design and rationale of Japanese evaluation between Formula of Azelnidipine and amlodipine add on olmesartan to Get antialbuminuric effect study (J-FLAG) : evaluation of the antialbuminuric effects between calcium channel blocker with sympatholytic action in hypertensive patients with diabetes and albuminuria.

Purpose: Calcium channel blockers (CCBs) are recommended second-line antihypertensives for renin-angiotensin system (RAS) inhibitor-treated patients with chronic kidney disease (CKD), but they do not always ameliorate the progression of CKD. However, small clinical studies suggest that sympatholytic CCBs may protect against kidney injury. Therefore, a clinical trial was designed to test whether the sympatholytic CCB azelnidipine decreases the urinary albumin levels of CKD patients treated with the angiotensin receptor blocker olmesartan more potently than the widely-used non-sympatholytic CCB amlodipine.

[Effects of incretin on cardiovascular disease and risk factors].

Diabetes is an important poor prognostic factor for ischemic heart disease and other cardiovascular diseases. Various study results have previously shown that new diabetes therapeutic agents including GLP-1 agonists and DPP-4 inhibitors have been suggested to be able to not only improve the pathology of diabetes, but also improve cardiovascular risk and be useful in prognosis. This report describes the effects of incretin on the cardiovascular system and its expected efficacy in reducing cardiovascular risk.

Relationships among hyperuricemia, metabolic syndrome, and endothelial function.

Background: We evaluated the relationship of the severity of hyperuricemia and the flow-mediated vasodilatation of the brachial artery (FMD) in patients with and without the metabolic syndrome (MetS).

Methods: In a cross-sectional study, FMD was obtained in 2,732 Japanese healthy men (49 ± 8 years) who had no cardiovascular (CV) disease and were not on any medication for CV risk factors. MetS was defined according to Japanese criteria, and serum uric acid (UA) levels in the upper half of the fifth (highest) quintile range were defined as severe hyperuricemia, whereas those in the lower half of this quintile range were defined as mild hyperuricemia.