Naoki Amaya

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.

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.

Relationship between microcirculatory dysfunction and resolution of ST-segment elevation in the early phase after primary angioplasty in patients with ST-segment elevation myocardial infarction.

BACKGROUNDS AND OBJECTIVES The aim of this study was to evaluate relationships between the degree of resolution of the ST-segment elevation (ST segment resolution; STR) and the extent of microcirculatory dysfunction in infarct-related area (IRA) in patients with ST-segment elevation myocardial infarction (STEMI) using (13)N-ammonia positron emission tomography (N-PET). METHODS The subjects comprised 33 patients with STEMI who underwent successful reperfusion. Serial 12-lead electrocardiography (ECG) was performed at the baseline and at 100 min after reperfusion to calculate STR. The myocardial flow reserve (MFR) was assessed quantitatively using N-PET at 2 weeks after the onset. The summed defect score (SDS) of (99m)Tc-tetrofosmin myocardial perfusion imaging was used as an index of the severity of myocardial infarction. To assess the extent of post-infarct left ventricular remodeling, the changes in the LVEDVI (ΔEDVI) were also calculated. RESULTS A significant correlation of the STR to the MFR in IRA (r = 0.68, p < 0.0001) was observed. A significant correlation was also identified between the SDS and the baseline sum ST-segment elevation (r = 0.65, p < 0.0001), while no correlation was observed between the SDS and the STR. Furthermore, a significant inverse correlation of the STR with the ΔEDVI was also recognized (r = -0.58, p < 0.01). CONCLUSIONS These data indicate that STR after successful reperfusion in STEMI is closely related to the extent of microcirculatory disturbance; in other words, incomplete STR may be a marker of persistent microcirculatory dysfunction after reperfusion therapy.

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.

A multicenter study of the need of additional freezing for cryoballoon ablation in patients with atrial fibrillation: The AD-Balloon study

Pulmonary vein isolation (PVI) is a cornerstone of catheter ablation in patients with paroxysmal atrial fibrillation (PAF), and balloon‐based ablation has been recently performed worldwide. Ablation using the second‐generation cryoballoon (CB2) (Arctic Front AdvanceTM, Medtronic, MN, USA) is useful for PVI; however, there is some debate concerning the optimal freezing time and number of cycles after PVI is achieved.

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

An Aggressive Strategy for Maintenance of Sinus Rhythm Including a Combination of Catheter Ablation and Antiarrhythmic Drug Therapy Benefits Patients with Chronic Atrial Fibrillation

The effects of restoration and maintenance of sinus rhythm by a combination of catheter ablation and antiarrhythmic drugs (AADs) on atrial function in patients with chronic atrial fibrillation (AF) remain unknown. In 15 patients with chronic AF (>1 year), we attempted to restore and maintain sinus rhythm by ablation targeting complex fractionated atrial electrocardiograms (CFAEs) combined with pulmonary vein isolation with or without AADs. Sinus rhythm was restored in all patients. At 17:7 ± 7:2 months after AF ablation, maintenance of sinus rhythm was achieved in 20% of patients without AADs and in 73.3% of patients with AADs. The left atrial diameter decreased significantly by 9:5 ± 8:1% (P < 0:05) during the 12‐month followup. AADs did not have any adverse effects. The aggressive strategy for maintenance of sinus rhythm involving AF ablation and AADs potentially led to recovery of structural changes in the LA in patients with chronic AF.