Yoshitomo Fukuoka

Effects of Combination Therapy With Olmesartan and Azelnidipine on Serum Osteoprotegerin in Patients With Hypertension

Background: Vascular calcification is a potent predictor of plaque instability and cardiac events. Osteoprotegerin (OPG), well-known vascular calcification mediator, is a signaling molecule involved in bone remodeling, which has been implicated in the regulation of vascular calcification and atherogenesis. The purpose of this study was to compare the combination treatments of olmesartan/azelnidipine and olmesartan/diuretics on serum bone-related markers in patients with essential hypertension. Methods and Results: A total of 48 patients with hypertension treated with 20 mg olmesartan were randomized to receive combination treatment with 16 mg azelnidipine (O/A group) or diuretics (1 mg indapamide; O/D group) for 12 months. Osteoprotegerin, matrix metalloproteinase 2 (MMP-2), and high-sensitive CRP (hs-CRP) were measured after 3 and 12 months of treatment. Cardio-ankle vascular index (CAVI) was measured as the arterial stiffness using a VaSera CAVI instrument at the same time points. In both groups, the systolic and diastolic blood pressure reduction is similar. Serum OPG, MMP-2, and hs-CRP were significantly decreased at 12 months in the O/A group (P < .05), while there were no significant reductions in the O/D group. CAVI was significantly improved at 12 months in both the treatment groups. The improvement in CAVI was significantly greater in the O/A group than in the O/D group. Conclusion: Azelnidipine, but not indapamide, combined with olmesartan, improved arterial stiffness and were associated with significant decrease in OPG, MMP-2, and hs-CRP concentrations. These results suggest that the beneficial effects of the combination treatments of olmesartan/azelnidipine on arterial stiffness are mediated by alteration in bone-remodeling and inflammatory markers.

Reduced intensity allogeneic stem cell transplantation for systemic primary amyloidosis refractory to high-dose melphalan.

Complete elimination of the plasma cell dyscrasia is a rational therapeutic goal, as intercepting supply of precursor protein is a necessary condition for a major regression of amyloid deposits. High‐dose melphalan with autologous stem cell transplantation has shown the ability to induce complete hematological response (HR) along with recovery of organ dysfunction. However, the rate of HR with this treatment rarely exceeds 40%. We describe here the first known case of successful reduced intensity allogeneic stem cell transplantation (RIST) for a patient with primary amyloidosis complicated with nephrotic syndrome but without cardiac disease, who had obtained only partial HR by high‐dose melphalan with autologous stem cell transplantation. RIST may be feasible and be capable of achieving complete HR along with recovery from nephrotic syndrome with acceptable toxicity.

Association between matrix metalloproteinase-9 and worsening heart failure events in patients with chronic heart failure: MMP-9 predicts HF events

Matrix metalloproteinase (MMP) is up‐regulated during heart failure (HF) and influences ventricular remodeling. We hypothesized that disparity between MMP‐9 and tissue inhibitors of MMP‐1 (TIMP‐1) results in clinical manifestations and is related to prognostic risk in patients with chronic HF.

Association of CD34/CD133/VEGFR2-Positive Cell Numbers with Eicosapentaenoic Acid and Postprandial Hyperglycemia in Patients with Coronary Artery Disease.

OBJECTIVES Circulating endothelial progenitor cells (EPCs), which have the ability to differentiate into mature endothelial cells, can elicit angiogenesis, vasculogenesis and vessel repair in cardiac ischemia and vascular injuries caused by endothelial damage. Serum 1,5-anhydro-d-glucitol (1,5-AG), which is a useful clinical marker of postprandial hyperglycemia, eicosapentaenoic acid (EPA), and arachidonic acid (AA) are newly identified risk factors for coronary artery disease (CAD). However, no previous study has reported the associations between EPCs and 1,5-AG, EPA, and AA levels in CAD patients with type 2 diabetes mellitus (DM). METHODS Peripheral EPCs, assessed as CD34+ cells co-expressing CD133 and vascular endothelial growth factor receptor-2, were studied in 76 CAD patients (mean age, 69.2±11.3years) with DM. Serum 1,5-AG, EPA, and AA levels were measured. RESULTS EPC numbers showed a significant association with 1,5-AG and HbA1c (r=0.290; p=0.037 and r=-0.328; p=0.011, respectively). In addition, there were significant associations between EPC numbers and EPA and body mass index (BMI) (r=0.354; p=0.027 and r=-0.402; p=0.002, respectively). In multiple linear regression analysis, HbA1c, BMI, and EPA values had significant associations with EPC numbers (β=-0.316, 95% confidence interval (CI) -0.256 to -0.008, p=0.037; β=-0.413, 95% CI -0.099 to -0.017, p=0.007; and β=0.400, 95% CI 0.004 to 0.002, p=0.010, respectively). CONCLUSIONS EPC number is associated with HbA1c, 1,5-AG, EPA, and BMI values, suggesting that postprandial hyperglycemia and n-3 polyunsaturated fatty acids contribute to EPC recruitment in CAD patients with type 2 DM.

ASSOCIATIONS OF BODY MASS INDEX, WASTING SYNDROME AND PROGNOSIS IN PATIENTS WITH CHRONIC HEART FAILURE

Chronic heart failure is one of a number of disorders associated with the development of a wasting syndrome. In patients with chronic heart failure (CHF), previous studies have reported reduced mortality rates in patients with increased body mass index (BMI). The potentially protective effect of

Effect of postprandial hyperglycaemia on coronary flow reserve in patients with impaired glucose tolerance and type 2 diabetes mellitus

Background: This study investigated whether postprandial hyperglycaemia has an adverse effect on coronary microvascular function and left ventricular diastolic function. Methods: In all, 28 patients with type 2 diabetes mellitus with no significant stenosis in left anterior descending artery were enrolled. In all subjects, plasma 1,5-anhydroglucitol was measured, and coronary flow reserve in the left anterior descending artery was evaluated using a Doppler wire. Membrane type-1 matrix metalloproteinase expression on circulating peripheral blood mononuclear cells was measured by flow cytometry. Correlation analyses were performed for coronary flow reserve and 1,5-anhydroglucitol, other coronary risk factors, membrane type-1 matrix metalloproteinase and E/e′. Results: Strong correlations were found only between 1,5-anhydroglucitol and coronary flow reserve and membrane type-1 matrix metalloproteinase. On multiple regression analysis, 1,5-anhydroglucitol remained an independent predictor of coronary flow reserve (β = 0.38, p = 0.048). Conclusion: Postprandial hyperglycaemia appears to have an adverse effect on coronary microvascular function, suggesting that improvement of postprandial hyperglycaemia may contribute to the improvement of coronary microvascular dysfunction.

IMPACT OF SERUM MATRIX METALLOPROTEINASE-2 LEVELS ON PULMONARY VASCULAR RESISTANCE ELEVATION

Pulmonary vascular resistance (PVR) is an important hemodynamic measurement used in the management of patients with heart failure and pulmonary hypertension. The mechanisms of PVR increase are incompletely understood, although pulmonary vasculature remodeling implicated. We evaluated the