Postchallenge responses of nitrotyrosine and TNF-alpha during 75-g oral glucose tolerance test are associated with the presence of coronary artery diseases in patients with prediabetes.

BACKGROUND: Meta-analysis has demonstrated an exponential relationship between 2-hr postchallenge hyperglycemia and coronary artery disease (CAD). Pulsatile hyperglycemia can acutely increase proinflammatory cytokines by oxidative stress. We hypothesized that postchallenge proinflammatory and nitrosative responses after 75 g oral glucose tolerance tests (75 g-OGTT) might be associated with CAD in patients without previously recognized type 2 diabetes mellitus (T2DM). METHODS: Serial changes of plasma glucose (PG), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitrotyrosine levels were analyzed during 75 g-OGTT in 120 patients (81 male; age 62 ± 11 years) before coronary angiography. Patients were classified as normal (NGT; 42%), impaired (IGT; 34%) and diabetic (T2DM; 24%) glucose tolerance by 75 g-OGTT. RESULTS: Postchallenge hyperglycemia elicited TNF-α, IL-6 and nitrotyrosine levels time-dependently, and 2-hr median levels of TNF-α (7.1 versus 6.4 pg/ml; P < 0.05) and nitrotyrosine (1.01 versus 0.83 µmol/l; P < 0.05), but not IL-6 or PG, were significantly higher in patients with CAD in either IGT or T2DM groups. After adjusting risk factors and glucose tolerance status, 2-hr nitrotyrosine in highest quartiles (OR: 3.1, P < 0.05) remained an independent predictor of CAD by logistic regression analysis. CONCLUSIONS: These results highlight postchallenge proinflammatory and nitrosative responses by 75 g-OGTT, rather than hyperglycemia per se, are associated with CAD in patients without previous recognized diabetes.

Effects of verapamil and procainamide on acute atrial electrical remodeling induced by short-term rapid atrial pacing in humans.

Atrial electrical remodeling (ER) after spontaneous or pacing-induced atrial fibrillation has been previously described in humans. We investigated atrial ER induced by a 5-minute period of rapid atrial pacing and the pharmacologic effects of verapamil and procainamide on this atrial ER phenomenon. The atrial effective refractory periods (ERPs) at drive cycle lengths of 400 (ERP 400 ) and 600 (ERP 600 ) ms, at five representative atrial sites (high right atrium [HRA]; proximal, middle and distal coronary sinus; interatrial septum), were determined in 20 patients at baseline and immediately after cessation of a 5-minute period of rapid pacing from the HRA at a rate of 150 bpm. The degrees of atrial ERP 400 and ERP 600 shortening after pacing were calculated as acute atrial ER. The same protocol was repeated in another 15 patients after intravenous administration of verapamil (0.15 mg/kg) and in another 15 patients after intravenous administration of procainamide (15 mg/kg). The results demonstrated that, in the control state acute atrial ER can be significantly demonstrated at each atrial representative site ( p < 0.001). The mean ERP 400 and ERP 600 shortenings were 9 +/- 4% and 8 +/- 4%, respectively. After procainamide infusion, but not after verapamil, baseline ERP 400 and ERP 600 values were significantly prolonged at the five representative atrial sites ( p < 0.01). Acute atrial ER could still be demonstrated at each atrial site after procainamide or verapamil infusion ( p < 0.001). In conclusion, acute atrial ER can be demonstrated after only a 5-minute period of rapid atrial pacing in humans. Intravenous verapamil or procainamide does not abolish this ER process.

Validation of a new index for estimating arterial stiffness: measurement of the QPV interval by Doppler ultrasound.

BACKGROUND: Pulse wave velocity (PWV), a relevant indicator of arterial stiffness, can be measured noninvasively with a variety of automatic devices, but most are complexly equipped. We developed a novel index for estimating arterial stiffness as "QPV interval," which was determined by means of surface electrocardiogram and Doppler ultrasound of the brachial artery simultaneously. HYPOTHESIS: This study aimed to validate the QPV interval as an exact and convenient index for estimation of arterial stiffness. METHODS: Forty-seven patients with untreated essential hypertension and 19 normotensive subjects were enrolled. Brachial-ankle PWV (baPWV) was measured using an automatic volume-plethysmographic apparatus, and Doppler ultrasound was implemented sequentially to measure the QPV interval in each subject. Clinical biochemistry and echocardiography were performed on the same day. RESULTS: Mean baPWV was significantly higher in hypertensive patients than in normotensive subjects (p = 0.002), whereas mean QPV interval was significantly shorter in hypertensive patients than in the normotensive group (p = 0.019). A simple regression analysis demonstrated an inverse correlation between the QPV interval and baPWV (r = -0.671, p < 0.001) in all enrolled subjects. In a stepwise regression model that adjusted for age, systolic blood pressure, and other determinants of baPWV, the negative association remained between the QPV interval and baPWV (p < 0.001). CONCLUSION: The QPV interval correlates inversely with baPWV, independent of age and other determinants of baPWV; hence, the QPV interval can serve as a simple and convenient index for assessing arterial stiffness in clinical practice.

Plasma renin level and aldosterone to renin ratio are associated with presence of carotid plaques in patients with stable coronary artery disease.

INTRODUCTION: We aimed to determine the association between plasma aldosterone and renin levels as well as their ratios with carotid plaques in patients with coronary artery disease (CAD). MATERIALS AND METHODS: Carotid intima-media thickness (IMT) and plaque score were evaluated in 111 patients with stable CAD. Plasma renin and aldosterone levels were measured in all patients. Aldosterone to renin ratio (ARR) was calculated. All patients were categorized into: Group 1 (normal coronary angiography), Group 2 (patients had CAD but without carotid plaque) and Group 3 (patients had CAD and at least one carotid plaque). RESULTS: Renin levels are significantly higher in Group 3 than in Group 1 and 2. ARR was significantly lower in Group 3 than in Group 1 and 2. Renin levels were found to be positively correlated with carotid IMT and plaque score but ARR was inversely associated with carotid IMT and plaque score. Renin levels and ARR are independently associated with presence of carotid plaque in CAD patients (OR 1.124, CI 1.021-1.237, p = 0.017 and OR 0.906, CI 0.839-0.978, p = 0.011, adjusted for age, respectively). CONCLUSIONS: Plasma renin and ARR but not aldosterone are independently associated with presence of carotid plaques in CAD patients. Hence, the linkage between aldosterone and renin plays a more important role than aldosterone alone in carotid atherosclerosis.

Clinical proteomics identifies urinary CD14 as a potential biomarker for diagnosis of stable coronary artery disease.

Inflammation plays a key role in coronary artery disease (CAD) and other manifestations of atherosclerosis. Recently, urinary proteins were found to be useful markers for reflecting inflammation status of different organs. To identify potential biomarker for diagnosis of CAD, we performed one-dimensional SDS-gel electrophoresis followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Among the proteins differentially expressed in urine samples, monocyte antigen CD14 was found to be consistently expressed in higher amounts in the CAD patients as compared to normal controls. Using enzyme-linked immunosorbent assays to analyze the concentrations of CD14 in urine and serum, we confirmed that urinary CD14 levels were significantly higher in patients (n = 73) with multi-vessel and single vessel CAD than in normal control (n = 35) (P < 0.001). Logistic regression analysis further showed that urinary CD14 concentration level is associated with severity or number of diseased vessels and SYNTAX score after adjustment for potential confounders. Concomitantly, the proportion of CD14+ monocytes was significantly increased in CAD patients (59.7 ± 3.6%) as compared with healthy controls (14.9 ± 2.1%) (P < 0.001), implicating that a high level of urinary CD14 may be potentially involved in mechanism(s) leading to CAD pathogenesis. By performing shotgun proteomics, we further revealed that CD14-associated inflammatory response networks may play an essential role in CAD. In conclusion, the current study has demonstrated that release of CD14 in urine coupled with more CD14+ monocytes in CAD patients is significantly correlated with severity of CAD, pointing to the potential application of urinary CD14 as a novel noninvasive biomarker for large-scale diagnostic screening of susceptible CAD patients.

Terlipressin-related acute myocardial infarction: a case report and literature review.

Acute ST-segment elevation myocardial infarction after the administration of terlipressin in patients with hemorrhagic esophageal varices is a rare but life-threatening complication. We report the case of a 73-year-old female patient with esophageal variceal bleeding complicated with acute ST-segment elevation myocardial infarction after intravenous injection of terlipressin. We discuss the underlying mechanisms of terlipressin-related acute myocardial infarction and review the literature.

Association between wall shear stress and carotid atherosclerosis in patients with never treated essential hypertension.

BACKGROUND: Wall shear stress (WSS) has been shown to be a critical determinant of vessel diameter implicated in vascular remodeling and atherogenesis. Carotid intima-media thickness (IMT), resistive index (RI), and pulsatility index (PI) have been used as relevant indictors for carotid atherosclerosis. The study aimed to investigate the relationship between hemodynamic parameters in the common carotid artery (CCA) and the severity of carotid atherosclerosis in untreated hypertensive patients. METHODS: Duplex ultrasound was performed in 64 untreated hypertensive patients and 16 age-matched normotensive control subjects. Morphologic and hemodynamic parameters of CCA, including peak and mean WSS, RI, PI, and IMT were calculated after measuring internal diameter (ID) and flow velocity of CCA. RESULTS: Subjects with hypertension had lower peak and mean WSS than did normotensive control subjects (P < 0.05). Both carotid RI and PI were found to correlate inversely with mean WSS in hypertensive subjects. There was no correlation between carotid IMT and WSS. Stepwise multiple regression analysis for carotid RI and PI after adjustment for age, carotid IMT, and high sensitivity C-reactive protein (hsCRP) showed that mean WSS was an independent determinant of RI and PI. CONCLUSIONS: High carotid atherosclerotic indexes as expressed by both RI and PI are associated with low WSS in CCA. These findings indicate that local shear stress is associated with altered vascular pulsatility and resistance. Consequent alteration in local vascular dynamics could be an underlying mechanism for the progression of atherosclerosis.

Reactive hyperemic pre-ejection shear stress of brachial artery determines endothelial function in patients with untreated essential hypertension.

The aim of this study was to identify which phase of wall shear stress (SS) augmentation during reactive hyperemia (RH) is the crucial determinant of endothelial reactivity. Fifty-three patients with untreated essential hypertension were enrolled. A 7.5-MHz linear array transducer was used to record the 2D images and Doppler flow signals of brachial artery at baseline and during RH. Wall SS and flow-mediated vasodilation were calculated sequentially. The result of this study demonstrated that augmentation of wall SS at end-diastolic phase during peak RH is the main rheologic determinant of endothelial function in patients with untreated essential hypertension.