Kentaro Ishida

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.

Predictive Utility of the Changes in Matrix Metalloproteinase‐2 in the Early Phase for Left Ventricular Reverse Remodeling After an Acute Myocardial Infarction

Background The relationship between the serum levels of matrix metalloproteinase (MMP) and tissue inhibitors of MMP (TIMP) and left ventricular (LV) reverse remodeling (LV‐RR) after an acute myocardial infarction (AMI) has not been sufficiently examined. Methods and Results In 25 patients with successful reperfusion after an AMI and 15 normal control subjects, the serum MMP‐2 and TIMP‐2 levels were measured on days 1, 2, 3, and 7 and at 1 and 6 months after the AMI onset. LV‐RR was defined as a >15% decrease in the LV end‐systolic volume index at 6 months after the AMI. The MMP‐2 level on day 1 and TIMP‐2 levels throughout the study period were comparable between the patients with and without LV‐RR. The MMP‐2 on day 7 (P<0.05) and the changes in the MMP‐2 from day 1 to day 7 (∆MMP‐2; P<0.01) were lower in patients with than in those without LV‐RR. The ∆MMP‐2 was strongly correlated with the changes in the LV volume and ejection fraction from 1 month to 6 months after the AMI. The ∆MMP‐2 value of <−158.5 ng/mL predicted LV‐RR with a high accuracy (91.7% sensitivity and 76.9% specificity; area under the curve=0.82). Conclusions Changes in MMP‐2 are associated with LV‐RR after an AMI. The ΔMMP‐2 might be a useful predictor of subsequent LV‐RR.

Beneficial effects of statin treatment on coronary microvascular dysfunction and left ventricular remodeling in patients with acute myocardial infarction

BACKGROUND Statin treatment has been shown to improve coronary endothelial function, irrespective of lipid-lowering effects. This studys aim was to elucidate the effects of statin treatment on coronary microvascular dysfunction and left ventricular remodeling in acute myocardial infarction (AMI) patients. METHODS Thirty-five patients undergoing successful reperfusion following AMI were assigned to a statin-treated (Group S, 16) or a non-statin-treated (Group NS, 19) group, according to fasting serum low-density lipoprotein-cholesterol. (13)N-ammonia positron emission tomography was performed to assess myocardial flow reserve (MFR) in the infarct area. RESULTS Infarct sizes and lipid profiles during the chronic period were similar between the two groups. At 2 weeks after AMI onset, mean MFR in the infarct area was significantly higher in Group S than in Group NS (2.34 ± 0.63 vs. 1.91 ± 0.43, p=0.0214). At 6 months post-AMI, Group S had a smaller left-ventricular end-diastolic volume index (69.4 ± 11.7 mL/m(2) vs. 88.5 ± 32.5 mL/m(2), p=0.0328) and higher left-ventricular ejection fraction (67.7 ± 9.2% vs. 59.2 ± 13.3%, p=0.0394) than Group NS. Serum asymmetric dimethylarginine was significantly increased in Group NS at 1 month post-AMI (0.43 ± 0.12 μmol/L (baseline) vs. 0.52 ± 0.14 μmol/L, p=0.0186), but unchanged in Group S. CONCLUSIONS Statin treatment appears to beneficially attenuate left ventricular remodeling after AMI, which may be associated with restoring coronary endothelial function via endogenous nitric oxide.

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.

Successful treatment of primary central nervous system lymphoma in an elderly patient

The successful treatment of an elderly patient with primary central nervous system lymphoma is described. A 74‐year‐old Japanese man with left hemiplegia and consciousness disturbance presented in December 2001. His performance status was Grade 4. Computed tomography of the brain revealed a tumor in the right paraventricle. A biopsy of the brain confirmed the diagnosis of non‐Hodgkin lymphoma (diffuse large, B cell type). Radiographic examinations did not detect any other lesions outside the brain. Primary central nervous system lymphoma was diagnosed. Chemotherapy was initiated in January 2002 using intravenous administration of methotrexate (600 mg/m2, 6‐h infusion, day 1) combined with etoposide (25 mg/m2, continuous infusion, day 2–5), doxorubicin (5 mg/m2, continuous infusion, day 2–5), vincristine (0.2 mg/m2, continuous infusion, day 2–5), cyclophosphamide (350 mg/m2, 2‐h infusion, day 6) and dexamethazone (6 mg/body, 1‐h infusion, day 1–6), with intrathecal administration of methotrexate (15 mg/body, day 8) and prednisolone (10 mg/body, day 8). Four courses of chemotherapy were completed without severe toxicities, followed by whole‐brain radiotherapy (25 Gy). Complete remission was achieved, and the patient became alert with normalized movement of the left extremities. Despite poor prognostic factors (old age, low performance status), the patient was successfully treated as such and was still in remission without neurotoxicity in May 2004. The combination of methotrexate‐based chemotherapy and radiotherapy with appropriate dose modification may improve the outcome in elderly patients with this disease since supportive therapy; CHOP, a combination of cyclophosphamide, doxorubicin, vincristine and prednisolone; and solo radiotherapy are usually not effective.

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