Rie Matsumori

Single Administration of α-Glucosidase Inhibitors on Endothelial Function and Incretin Secretion in Diabetic Patients With Coronary Artery Disease - Juntendo University Trial: Effects of Miglitol on Endothelial Vascular Reactivity in Type 2 Diabetic Patients With Coronary Heart Disease (J-MACH) -

Background: Post-prandial hyperglycemia, hyperlipidemia, and endothelial dysfunction play an important role in the pathogenesis of atherosclerosis. Improvement in post-prandial hyperglycemia on α-glucosidase inhibitors (α-GIs) is associated with a risk reduction of cardiovascular diseases, but the post-prandial effects of α-GIs on endothelial function and incretin secretion in type 2 diabetic patients with coronary artery disease (CAD) remain unclear. Methods and Results: The post-prandial effects of a single administration of miglitol and voglibose on endothelial function and changing levels of glucose, insulin, lipids, glucagon-like peptide (GLP)-1, and gastric inhibitory polypeptide (GIP) were compared after a standard meal loading in 11 diabetic patients with CAD, using a placebo-controlled cross-over design. The changing levels of glucose, insulin and triglycerides at 60 min were significantly lower in the miglitol group than in the voglibose and placebo groups (all P<0.01). GLP-1 levels were significantly higher at 120 min (P<0.05) and GIP levels were significantly lower at 30 min and 60 min (P<0.05) in the miglitol group compared to other treatments. The reactive hyperemia duration at 120 min was significantly maintained in the miglitol group compared to the other groups. Conclusions: A single administration of miglitol significantly improved post-prandial glucose/lipid metabolism, incretin secretion, and endothelial dysfunction in diabetic patients with CAD, suggesting that miglitol may be a useful anti-atherogenic agent (UMIN000002264).  (Circ J 2010; 74: 1471 - 1478)

Effects of calcium channel blockers on glucose tolerance, inflammatory state, and circulating progenitor cells in non-diabetic patients with essential hypertension: a comparative study between azelnidipine and amlodipine on glucose tolerance and endothelial function--a crossover trial (AGENT).

BackgroundHypertension is associated with impaired glucose tolerance and insulin resistance. Medical treatment that interferes with various steps in the renin-angiotensin system improves glucose tolerance and insulin resistance. However, it remains unclear if long-acting calcium channel blockers (CCBs) such as azelnidipine and amlodipine affect glucose tolerance and insulin resistance in clinical practice.MethodsSeventeen non-diabetic patients with essential hypertension who had controlled blood pressure levels using amlodipine (5 mg/day) were enrolled in this study. After randomization, either azelnidipine (16 mg/day) or amlodipine (5 mg/day) was administered in a crossover design for 12-weeks. At baseline and the end of each CCB therapy, samples of blood and urine were collected and 75 g oral glucose tolerance test (OGTT) was performed. In addition, hematopoietic progenitor cells (HPCs) were measured at each point by flow cytometry and endothelial functions were measured by fingertip pulse amplitude tonometry using EndoPAT.ResultsAlthough blood pressure levels were identical after each CCB treatment, the heart rate significantly decreased after azelnidipine administration than that after amlodipine administration (P < 0.005). Compared with amlodipine administration, azelnidipine significantly decreased levels of glucose and insulin 120 min after the 75 g OGTT (both P < 0.05). Serum levels of high-sensitivity C-reactive protein (P = 0.067) and interleukin-6 (P = 0.035) were decreased. Although endothelial functions were not different between the two medication groups, the number of circulating HPCs was significantly increased after azelnidipine administration (P = 0.016).ConclusionsThese results suggest that azelnidipine treatment may have beneficial effects on glucose tolerance, insulin sensitivity, the inflammatory state, and number of circulating progenitor cells in non-diabetic patients with essential hypertension.

Omega 3 Polyunsaturated Fatty Acids Suppress the Development of Aortic Aneurysms Through the Inhibition of Macrophage-Mediated Inflammation

BACKGROUND Dietary intake of ω3 polyunsaturated fatty acids (ω3-PUFAs) reduces progression of atherosclerosis and prevents future cardiovascular events. Macrophages are key players in the pathogenesis of aortic aneurysm. The effects of ω3-PUFAs on abdominal aortic aneurysm (AAA) formation and macrophage-mediated inflammation remain unclear. METHODS AND RESULTS: The AAA model was developed by angiotensin II infusion in apolipoprotein E-deficient mice. Mice were supplemented with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). The development of AAA lesions and macrophage infiltration in the aorta were analyzed. Gene expression of inflammatory markers in aortic tissues and peritoneal macrophages were measured by using quantitative polymerase chain reaction. AAA formation and macrophage infiltration were significantly suppressed after EPA and DHA administration. EPA administration and DHA administration significantly decreased the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-β, matrix metalloproteinases (MMP)-2, MMP-9, and vascular cell adhesion molecule-1 in the aortas. The expression of arginase 2, which is a marker of pro-inflammatory macrophages, was significantly lower and that of Ym1, which is a marker of anti-inflammatory macrophages, and was significantly higher after EPA and DHA administration. The same trends were observed in peritoneal macrophages after EPA and DHA administration. CONCLUSIONS Dietary intake of EPA and DHA prevented AAA development through the inhibition of aortic and macrophage-mediated inflammation.

High levels of very long-chain saturated fatty acid in erythrocytes correlates with atherogenic lipoprotein profiles in subjects with metabolic syndrome

AIM Very long chain saturated fatty acid (VLCFA) levels in erythrocytes are associated with metabolic syndrome (MS). However, the relationship between levels of the VLCFA ligonoceric acid (C24:0) in erythrocytes and the atherogenic lipoprotein profiles and inflammatory state in MS remain unclear. METHODS Based on the International Diabetes Federation (IDF) definition of MS, 195 apparently healthy males were assigned to either an MS group (n=38) or a non-MS group (n=157). Fatty acid composition of erythrocytes was determined by gas liquid chromatography. RESULTS Erythrocytes from the MS group had a significantly higher level of C24:0 than cells from the non-MS group (4.06±0.48% versus 3.88±0.34%; p=0.03). C24:0 levels were significantly correlated with several components of MS. The C24:0 levels showed a significant negative correlation with LDL and HDL particle size. Multivariate linear regression analysis showed that C24:0 levels were independently correlated with LDL particle size after adjusting for age and each MS criterion. C24:0 levels were also positively correlated with log-transformed high-sensitivity CRP levels (p=0.04). CONCLUSION C24:0 levels in erythrocytes are associated with specific atherogenic lipoprotein profiles and inflammation status in subjects with MS.

Disease Duration and Severity Impacts on Long-term Cardiovascular Events in Japanese Patients with Rheumatoid Arthritis

BACKGROUND Rheumatoid arthritis (RA) increases the mortality and morbidity of cardiovascular disease (CVD). However, the relationship between RA and the risk of CVD in the Japanese population remains unclear. METHODS AND RESULTS This study comprised 571 RA patients who were admitted to Juntendo University Hospital from January 1990 to December 2000. Cardiovascular events (CVEs) were defined as cardiac death, acute coronary syndrome (ACS), symptomatic stroke, and congestive heart failure. During follow-up (mean 11.7 ± 5.8 years), 7.5% of the patients died from all causes and 11.0% experienced CVEs. The morbidity of stroke and ACS was 3.6 and 2.5 per 1000 person-years, respectively. The mean RA disease duration at enrolment was significantly longer in patients who experienced CVEs than in those who did not experience CVEs (15.0 ± 12.7 years vs. 10. 8 ± 9.7 years; p = 0.01). Physical disabilities due to RA were more severe in patients who experienced CVEs than in those who did not experience CVEs. Patients with a long RA disease duration showed significantly higher event rates (p = 0.033). Cox proportional hazards analysis identified a longer RA duration as an independent risk factor for CVD (hazard ratio 1.57, 95% CI 1.09-2.30, p = 0.02). CONCLUSION Japanese RA patients showed a relatively high incidence of CVD, despite the fact that they had few coronary risk factors. The RA disease duration was an independent risk factor for CVEs.

Clinical significance of the measurements of urinary liver-type fatty acid binding protein levels in patients with acute coronary syndrome

BACKGROUND Recently, much attention has been focused on cardio-renal interaction. Urinary liver-type fatty acid binding protein (U-L-FABP), which is produced in the proximal tubule by renal hypoxia and oxidative stress, has been identified as a useful marker for diagnosis of acute kidney disease and a predictor of future events in chronic kidney disease. However, the clinical significance of U-L-FABP measurements in patients with acute coronary syndrome (ACS) has not been completely evaluated. METHODS AND RESULTS This study included 50 consecutive patients with ACS [37 with acute myocardial infarction (AMI) and 13 with unstable angina pectoris (UAP)] and 47 subjects without coronary artery disease (control group). U-L-FABP levels, urinary albumin (U-Alb), and other serum parameters were measured at admission and at 24 h after percutaneous coronary intervention. RESULTS U-L-FABP levels in patients with AMI were significantly higher (p=0.0019), than in control subjects, while patients with UAP did not exhibit such an increase. U-L-FABP levels at admission were positively correlated with brain natriuretic protein levels (p=0.001) and duration of hospitalization (p=0.025). At follow-up angiography, patients with restenosis had significantly higher U-L-FABP (p=0.047) and U-Alb levels (p<0.0001) than those without restenosis. After a median follow-up of 42 months, U-L-FABP levels at second measurement in patients with major adverse cardiocerebrovascular events (MACCEs) were significantly higher than those in patients without MACCEs (p=0.028). After adjusting for confounding factors, high U-L-FABP levels at second measurement were found to be independent factors for MACCEs (p=0.019). CONCLUSIONS These data suggest that patients with ACS, especially those with AMI, have high U-L-FABP levels, and that U-L-FABP measurements may be useful in identifying high-risk patients for future cardiovascular events after ACS.

Prognostic Value of Coronary Computed Tomography (CT) Angiography and Coronary Artery Calcium Score Performed Before Revascularization

Background Cardiac events after revascularization are equally attributable to recurrence at site of culprit lesions and development of nonculprit lesions. We evaluated the hypothesis that coronary computed tomography (CT) angiography and coronary artery calcium score (CACS) performed before revascularization predicts cardiac events after treatment. Methods and Results Among 2238 consecutive patients without known coronary artery disease who underwent coronary CT angiography and CACS, 359 patients underwent revascularization within 30 days after CT; in 337 of 359 (93.9%) follow-up clinical information was available. In addition to known cardiac risk factors, CT findings were evaluated as predictors of cardiac events after revascularization: CACS and the presence of CT-verified high-risk plaque (CT-HRP). Improvement of predictive accuracy by including CT findings was evaluated from a discrimination (Harrell’s C-statistics) standpoint. During the follow-up period (median: 673, interquartile range: 47 to 1529 days), a total of 98 cardiac events occurred. Cox proportional hazard model revealed that age, diabetes, triglyceride, CACS, and nonculprit CT-HRP were significant predictors of overall cardiac events. Although not statistically significant, discriminatory power was greater for the model with CACS (C-stat: 63.2%) and the model with both CACS and CT-HRP (65.8%) compared to the model including neither CACS nor CT-HRP (60.7%). Conclusions High CACS and the presence of nonculprit CT-HRP performed before revascularization are significant predictors of cardiac events after revascularization.

High hexacosanoic acid levels are associated with coronary artery disease

AIMS Levels of saturated very long chain fatty acids (VLCFAs) are associated with coronary risk factors, including metabolic syndrome (MS), atherogenic lipoproteins, and systemic inflammation. However, the relationship between circulating levels of saturated VLCFA and coronary artery disease (CAD) remains unclear. METHOD We enrolled 100 consecutive CAD patients and 40 age-, gender-, and body mass index (BMI)-matched healthy control subjects. The levels of hexacosanoic acid (C26:0), a VLCFA, in whole blood were measured by gas-liquid chromatography mass spectrometry. RESULTS C26:0 levels were significantly higher in the CAD group than in the control group (2.42±0.32 vs. 2.27±0.24 μg/ml, P=0.01) and positively correlated with BMI (r=0.23, P=0.008), triglyceride levels (r=0.22, P=0.01), and hypertension (P=0.01). CAD patients with MS showed the highest C26:0 levels adjusted by hematocrit. Furthermore, adjusted C26:0 levels in CAD patients without MS were higher than those in controls (P=0.02), suggesting that C26:0 levels increased with the presence of CAD independent of MS. Our multivariate analysis revealed that high C26:0 levels in whole blood is an independent marker for CAD even after adjustment for age, gender, BMI, lipid profiles, fasting plasma glucose, and blood pressure. CONCLUSION High C26:0 levels in whole blood may be an independent marker for identifying the risks of CAD.

Incremental prognostic value of coronary computed tomographic angiography high-risk plaque characteristics in newly symptomatic patients

BACKGROUND The incremental prognostic value of the plaque features in coronary computed tomographic angiography (CTA) has not been well assessed. This study was designed to determine whether CTA high-risk plaques have prognostic value incremental to the Framingham risk score (FRS) and the severity of luminal obstruction. METHODS A total of 628 newly symptomatic patients without known coronary artery disease underwent CTA. They were followed for a median of 677 days during which there were 26 cardiac events, including cardiac death, acute myocardial infarction, and hospitalization for unstable angina. Incremental prognostic value of adding plaque characteristics to the number of diseased vessels and the FRS was evaluated using 3 Cox models and net reclassification indexes. RESULTS The discrimination index was significantly increased by adding the number of diseased vessels to the FRS (change in c-statistic from 65.8% to 78.6%, p=0.028) but not significantly by further adding plaque characteristics (change in c-statistic from 78.6% to 80.0%, p=0.812). However, improved model-fitting by adding plaque characteristics into the linear combination with risk score and the number of diseased vessels (p=0.007 from likelihood ratio test) and the lowest value of Akaikes information criteria of that model indicated that plaque characteristics improved both predictive accuracy and discrimination perspective. More subjects reclassified by plaque characteristics were moved to directions consistent with their subsequent cardiac event status than in an inconsistent direction. CONCLUSIONS Evaluation of CTA plaque characteristics may provide incremental prognostic value to the number of diseased vessels and the FRS.

An adult case of polysplenia syndrome associated with sinus node dysfunction, dextrocardia, and systemic venous anomalies.

A 54-year-old woman was referred to our hospital for symptomatic sinus bradyarrhythmia with a sinus pause of 8 seconds. She was diagnosed with dextrocardia during childhood and discovered to have heterotaxy syndrome when she had an appendectomy during her teenager years. Chest and abdominal examinations by computed tomography showed multiple spleens located on the right side and abnormal drainages of the superior and inferior vena cava. Left isomerism was diagnosed by bilaterally bilobed lungs. Because of a patent bilateral superior vena cava, pacemaker leads were implanted using the right cephalic vein approach. Her fainting symptoms disappeared after pacemaker implantation.