Minoru Wakasa

Increased levels of the oxidative stress marker, nitrotyrosine in patients with provocation test-induced coronary vasospasm

BACKGROUND Endothelial dysfunction of the coronary arteries caused by oxidative stress plays an important role in the pathogenesis of coronary vasospasm. However, it is not clear whether circulating biomarkers for oxidative stress are altered after coronary vasospasm. We investigated temporal changes in the levels of oxidative stress biomarkers after coronary vasospasm induced by intracoronary acetylcholine provocation testing, resulting in transient myocardial ischemia. METHODS AND RESULTS Thirty consecutive patients with suspected vasospastic angina pectoris (VSAP) were enrolled in the study. Patients were categorized into the VSAP-positive group (n=14) and the VSAP-negative group (n=16) on the basis of test results. Serum samples were examined for the levels of the oxidative stress markers 4-hydroxynonenal (HNE) and nitrotyrosine (NT) before, and 15min, 3h, and 12h after the provocation test. The serum HNE levels did not change in either group after the test. The serum NT levels in the VSAP-positive group significantly increased at 3h and 12h after the test (11.3±3.3μg/ml at 3h, p=0.015, and 12.1±5.7μg/ml at 12h, p=0.03), as compared with baseline (8.1±3.2μg/ml). In the VSAP-negative group, the serum NT levels significantly decreased from baseline at each of the 3 time points. CONCLUSIONS Serum NT significantly increased after coronary vasospasm induced by acetylcholine provocation, suggesting that serum NT could be a biomarker of transient myocardial ischemia and could contribute to the development of VSAP.

Serum deoxyribonuclease I activity can be a useful diagnostic marker for the early diagnosis of unstable angina pectoris or non–ST-segment elevation myocardial infarction

BACKGROUND AND PURPOSE Recently, serum deoxyribonuclease I (DNase I) activity has been highlighted as a potential diagnostic marker for transient myocardial ischemia. To evaluate whether serum DNase I activity can be a useful biomarker for diagnosing unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI), we investigated serial changes in DNase I levels after chest pain in UAP and NSTEMI (UAP/NSTEMI) patients. METHODS AND RESULTS Thirty-three and ten patients classified into the UAP/NSTEMI and the chest pain syndrome (CPS) group, respectively, were enrolled. The serum DNase I activity levels within 3h after chest pain and the absolute median value of percentage differences in serum DNase I activity levels from admission to 3h after hospitalization in the UAP/NSTEMI patients was significantly higher than those in the CPS patients. We evaluated the patients to show positive results for DNase I activity if the serum levels or percentage differences exceeded the corresponding cut-off values. The sensitivity and specificity of DNase I within 6h after chest pain in the UAP/NSTEMI patients without elevated levels of cardiac troponin T and the MB isoenzyme of creatine kinase were 89% and 88%, respectively. CONCLUSIONS Serum DNase I activity can be a useful marker for the early diagnosis of UAP/NSTEMI after the onset of chest pain, irrespective of the evidence of myocardial injury.

Diurnal glycemic fluctuation is associated with severity of coronary artery disease in prediabetic patients: Possible role of nitrotyrosine and glyceraldehyde-derived advanced glycation end products.

BACKGROUND Glucose fluctuation (GF) is a risk factor for coronary artery disease (CAD). However, it remains unknown whether specific indices of GF are risk factors for CAD. Therefore, we evaluated the relationship between GF, as determined by a continuous glucose monitoring system (CGMS) or the glucose level at 2h after a 75-g oral glucose tolerance test (75g OGTT 120), and the severity of CAD in prediabetic patients. We also evaluated whether nitrotyrosine (NT) and glyceraldehyde-derived advanced glycation end-products (Glycer-AGE) were induced by GF. METHODS Twenty-eight prediabetic patients underwent coronary angiography (CAG), and the Gensini score and the SYNTAX score were evaluated as the severity of CAD, while the mean amplitude of glycemic excursions (MAGE) by CGMS and 75g OGTT 120 were evaluated. Serum NT and Glycer-AGE were measured. RESULTS The MAGE was closely associated with the Gensini score (r=0.742, p<0.001) and the SYNTAX score (r=0.776, p<0.001), respectively. The 75g OGTT 120 was not associated with the Gensini score (r=0.36, p=0.06), but it was significantly associated with the SYNTAX score (r=0.413, p=0.036). Multiple linear regression analysis showed that the MAGE was the only independent determinant for the severity of CAD. The levels of NT and Glycer-AGE were significantly higher in the high MAGE group than in the low MAGE group. CONCLUSIONS Diurnal GF is associated with the severity of CAD, even in prediabetic patients. GF, NT, and Glycer-AGE may play a pathological role in the progression of CAD.

18F-FDG PET/CT for Detecting Sarcoma of the Aorta in a Patient with Takayasu Arteritis

Sarcoma of the aorta is extremely rare; however, 18Ffluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) imaging is a useful modality for detectingmalignant tumors, including various sarcomas. We report on a case of sarcoma of the aorta associated concomitantly with Takayasu arteritis. The 18F-FDG PET/CT detected an abnormal increased uptake in an aortic mass of the descending thoracic aorta, thoracic vertebra, and ilium. The standardized uptake value (SUV) of 18F-FDG in the aortic mass was 21.7, suggesting that 18F-FDG PET/CT imaging may be useful for detecting sarcoma of the aorta associated concomitantly with Takayasu arteritis and bone metastases during treatment (Figs. 1 and 2). Fig. 1 Before (a) and after (b) contrast enhanced computed tomography (CT). Primary malignancies such as angiosarcoma of the aorta are extremely rare. They occur more frequently in men with a male-tofemale ratio of 2:1 [1–3]. The average age of those affected is in their 60s [1–3]. At the time of initial presentation, >50 % of patients have metastatic disease [3–5]. Sarcomas of the aorta are classified into intimal angiosarcomas of endothelial origin, intimal myofibroblastic sarcomas of mesenchymal origin, and mural sarcomas of medial or adventitial origin of the aorta, depending on the immunohistochemical pattern of the tumors [3]. The majority of cases are believed to arise in the intima as an intraluminal growth, which forms a plaque-like structure along the intima or presents with a polypoid intraluminal growth [5, 6]. Mural sarcomas are defined as extra-aortic soft tissue sarcomas [3]. Mural sarcomas behave less aggressively than intimal sarcomas, despite the very similar overall and average survival (mean range, 8–14 months) [3, 6, 7]. A 32-year-old woman with Takayasu arteritis during treatment presented with persistent fever, general fatigue, and elevated inflammatory blood markers. The CT demonstrated a heterogeneous enhanced mass surrounding the distal portion of the thoracic aorta. No portion of the mass extended into the aorta. A thoracoscopic biopsy was performed, and the tumor was histopathologically confirmed as a sarcoma of the aorta (intraluminal and mural type) * Tomoko Takahashi tomoko-t@kanazawa-med.ac.jp

Circulating Glutamate and Taurine Levels Are Associated with the Generation of Reactive Oxygen Species in Paroxysmal Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, but its proarrhythmic mechanism remains to be elucidated. Glutamate (Glu) and taurine (Tau) are present in the myocardium at substantially higher concentrations than in the plasma, suggesting their active role in myocardium. Here, we tested the hypothesis that the metabolism of Glu and Tau is altered in association with the generation of reactive oxygen species (ROS) in patients with AF. Fifty patients with paroxysmal AF and 50 control subjects without a history of AF were consecutively enrolled. Circulating Glu and Tau levels were measured and correlations between Glu/Tau and ROS levels were examined. Glu/Tau content was significantly higher in patients with AF versus controls (Glu: 79.2 ± 23.9 versus 60.5 ± 25.2 nmol/L; Tau: 78.8 ± 19.8 versus 68.5 ± 20.8 nmol/L; mean ± standard deviation (SD), p < 0.001 for both). Glu/Tau levels also showed an independent association with AF by multiple logistic regression analysis. Glu and Tau levels both showed significant positive associations with plasma hydroperoxide concentrations. These data suggest a novel pathophysiological role of Glu and Tau in association with ROS production in paroxysmal AF, providing new insights into the elevated amino acid content in cardiac disease.

Chronic total occlusions of the right coronary and left anterior descending coronary arteries in a young adult patient with antiphospholipid syndrome

A 36-year-old male appeared to have an old myocardial infarction on electrocardiogram, and coronary angiography (CAG) was performed. The CAG showed total occlusions of the right coronary artery and left anterior descending artery. He was successfully treated with drug-eluting stent implantation for both occluded coronary arteries. Such serious coronary lesions are uncommon for his young age. The patient was diagnosed as having antiphospholipid syndrome (APS) based on elevation of anticardiolipin antibody and anti-β2 glycoprotein I antibody. Two years after stent implantation, the patient was well without ischemia or thrombosis. APS should be considered a potential cause of serious coronary disease in young adults. <Learning objective: Antiphospholipid syndrome (APS) should be considered a potential cause of serious coronary disease in young adults. Although there is a high risk of acute stent thrombosis and restenosis after multiple stents implantation, percutaneous coronary intervention with drug-eluting stent implantation could be an appropriate therapy for chronic total occlusion in APS patients.>.