ABSTRACT Objectives: To evaluate the effect of sitagliptin treatment in early type 2 diabetes mellitus (T2DM) and the impact of different macronutrient compositions on hormones and substrates during meal tolerance tests (MTT). Materials and methods: Half of the drug-naive patients with T2DM were randomly assigned for treatment with 100 mg of sitagliptin, q.d., or placebo for 4 weeks and then submitted to 3 consecutive MTT intercalated every 48 h. The MTTs differed in terms of macronutrient composition, with 70% of total energy from carbohydrates, proteins, or lipids. After 4 weeks of washout, a crossover treatment design was repeated. Both patients and researchers were blinded, and a repeated-measures ANOVA was employed for statistical analysis. Results: Sitagliptin treatment reduced but did not normalize fasting and post-meal glucose values in the three MTTs, with lowered area-under-glucose-curve values varying from 7% to 15%. The sitagliptin treatment also improved the insulinogenic index (+86%) and the insulin/glucose (+25%), glucagon-like peptide-1/glucose (+46%) incremental area under the curves. Patients with early T2DM maintained the lowest glucose excursion after a protein- or lipid-rich meal without any major change in insulin, C-peptide, glucagon, or NEFA levels. Conclusion: We conclude that sitagliptin treatment is tolerable and contributes to better control of glucose homeostasis in early T2DM, irrespective of macronutrient composition. The blood glucose excursion during meal ingestion is minimal in protein- or fat-rich meals, which can be a positive ally for the management of T2DM. Clinical trial no: NCT00881543

OBJECTIVES: To investigate the effect of opioid receptor blockade on the myocardial protection conferred by chronic exercise and to compare exercise training with different strategies of myocardial protection (opioid infusion and brief periods of ischemia-reperfusion) preceding irreversible left anterior descending coronary ligation. INTRODUCTION: The acute cardioprotective effects of exercise training are at least partly mediated through opioid receptor-dependent mechanisms in ischemia-reperfusion models. METHODS: Male Wistar rats (n = 76) were randomly assigned to 7 groups: (1) control; (2) exercise training; (3) morphine; (4) intermittent ischemia-reperfusion (three alternating periods of left anterior descending coronary occlusion and reperfusion); (5) exercise training+morphine; (6) naloxone (a non-selective opioid receptor blocker) plus morphine; (7) naloxone before each exercise-training session. Myocardial infarction was established in all groups by left anterior descending coronary ligation. Exercise training was performed on a treadmill for 60 minutes, 5 times/week, for 12 weeks, at 60% peak oxygen (peak VO2). Infarct size was histologically evaluated. RESULTS: Exercise training significantly increased exercise capacity and ΔVO2 (VO2 peak - VO2 rest) (p<0.01 vs. sedentary groups). Compared with control, all treatment groups except morphine plus naloxone and exercise training plus naloxone showed a smaller infarcted area (p<0.05). No additional decrease in infarct size occurred in the exercise training plus morphine group. No difference in myocardial capillary density (p = 0.88) was observed in any group. CONCLUSIONS: Exercise training, morphine, exercise training plus morphine and ischemia-reperfusion groups had a smaller infarcted area than the control group. The effect of chronic exercise training in decreasing infarct size seems to occur, at least in part, through the opioid receptor stimulus and not by increasing myocardial perfusion

BACKGROUND: Acute myocardial infarction is associated with tissue inflammation. Early coronary reperfusion clearly improves the outcome but may help propagate the inflammatory response and enhance tissue damage. Cyclooxygenase-2 is an enzyme that catalyzes the initial step in the formation of inflammatory prostaglandins from arachidonic acid. Cyclooxygenase-2 levels are increased when ischemic cardiac events occur. The overall function of COX-2 in the inflammatory process generated by myocardial ischemic damage has not yet been elucidated. GOAL: The objective of this study was to determine whether a selective cyclooxygenase-2 inhibitor (rofecoxib) could alter the evolution of acute myocardial infarction after reperfusion. METHODS AND RESULTS: This study was performed with 48 mongrel dogs divided into two groups: controls and those treated with the drug. All animals were prepared for left anterior descending coronary artery occlusion. The dogs then underwent 180 minutes of coronary occlusion, followed by 30 minutes of reperfusion. Blood samples were collected from the venous sinus immediately before coronary occlusion and after 30 minutes of reperfusion for measurements of CPK-MB, CPK-MBm and troponin I. During the experiment we observed the mean blood pressure, heart rate and coronary flow. The coronary flow and heart rate did not change, but in the control group, there was blood pressure instability, in addition to maximal levels of CPK-MB post-infarction. The same results were observed for CPK-MBm and troponin I. CONCLUSION: In a canine model of myocardial ischemia-reperfusion, selective inhibition of Cyclooxygenase-2 with rofecoxib was not associated with early detrimental effects on the hemodynamic profile or the gross extent of infarction; in fact, it may be beneficial by limiting cell necrosis.

There is controversy regarding whether obstructive sleep apnea is responsible for triggering myocardial ischemia, arrhythmias and heart rate variability in patients with coronary artery disease. OBJETIVE: The objective of this study was to identify relationships between sleep apnea, myocardial ischemia and cardiac arrhythmia in patients with coronary artery disease. METHODS: Fifty-three patients with stable coronary disease underwent simultaneous polysomnography and electrocardiographic Holter recording. The apnea-hypopnea index (AHI) was defined as the number of apneas/hypopneas per hour of sleep. Patients were divided into a Control group (AHI15, n=23 pts) and an Apnea group (AHI>15, n=30 pts). A subgroup of 13 patients with an AHI>30 (Severe Apnea group) was also studied. We analyzed ischemic episodes (ST-segment depressions >1 mm, > 1 min), heart rate variability and the occurrence of arrhythmias during wakefulness and sleep. RESULTS: Baseline clinical characteristics among the groups were similar except for higher blood pressure in the Apnea groups (p<0.05). Myocardial ischemia was recorded in 39 (73.6%) patients. The number and duration of ischemic episodes significantly decreased during sleep in all groups; during wakefulness, patients with severe apnea exhibited fewer and shorter episodes in comparison with the controls. There were no significant differences in heart rate variability or in the occurrence of arrhythmias among the groups. Malignant ventricular arrhythmias, atrial fibrillation/flutter, bradycardia and high-degree atrioventricular blocks were not detected. CONCLUSION: Obstructive sleep apnea was not related to myocardial ischemia, heart rate variability or arrhythmias in patients with stable coronary artery disease and did not alter the circadian pattern of myocardial ischemia.

BACKGROUND: Non-invasive detection of atherosclerosis is critical for its prevention. OBJECTIVE: To correlate non-invasively detectable indicators of coronary atherosclerosis, or Coronary Artery Disease (i.e., classical risk factors, hs-CRP test results, carotid intima-media thickness, endothelial function, ankle-brachial index and calcium score by computed tomography) with the extent of coronary disease assessed by the Friesinger index from conventional coronary angiography. METHODS: We conducted a prospective study of 100 consecutive patients, mean age 55.1 ± 10.7 years, 55% men and 45% women. Patients with acute coronary syndrome, renal dialytic insufficiency, collagen disease and cancer were not included. All patients were subjected to clinical evaluation and laboratory tests. Endothelial function of the brachial artery and carotid artery were evaluated by high-resolution ultrasound; ankle-brachial index and computed tomography for coronary determination of calcium score were also performed, and non-HDL cholesterol and TG/HDL-c ratio were calculated. All patients were subjected to coronary angiography at the request of the assistant physician. We considered patients without an obstructive lesion (< 29% stenosis) demonstrated by coronary angiography to be normal. RESULTS: Univariate analysis showed that calcium score, HDL-c, TG/HDL ratio and IMT were significantly correlated with the Friesinger index. However, multivariate analysis indicated that only calcium score and low HDL-c levels correlated significantly with the extension of CAD. On the other hand, hs-CRP, LDL-c, flow-mediated dilation, and Framingham score did not correlate with the Friesinger index. ROC analysis showed that calcium score, HDL-c and TG-HDL ratio accurately predicted extensive CAD in a statistically significant manner. CONCLUSION: It is possible to approximately determine the presence and extent of CAD by non-invasive methods, especially by calcium score, HDL-c and TG/HDL-c ratio assays.

A aterosclerose é uma doença inflamatória crônica que afeta essencialmente todas as artérias incluindo a aorta, coronárias, carótidas e artérias periféricas. É a causa principal de morte no hemisfério ocidental, devido as síndromes cardiovasculares, tais como o infarto do miocárdio, insuficiência cardíaca e acidentes cerebrovasculares. Quantidades enormes de recursos econômicos e humanos são usadas em tratamentos de suas complicações, inclusive estudos de imagem, cirurgias coronárias, intervenções com cateteres, marcapasso e tratamentos médicos. Tratar complicações, entretanto, são ações a posteriori. Uma alternativa melhor seria prevenir o desenvolvimento da aterosclerose, ou pelo menos identificar os pacientes que tenham risco de eventos agudos e intervir antes de sua ocorrência. O objetivo desta revisão é discutir o valor prognóstico dos fatores de riscos tradicionais e emergentes, e o papel dos métodos diagnósticos não invasivos para a doença coronária - teste de esforço, eco estresse, ultra-sonografia dúplex, tomografia computadorizada e a ressonância magnética. A combinação de marcadores biológicos e de métodos não invasivos, é de grande utilidade na identificação precoce da doença aterosclerótica. Futuros desenvolvimentos logo aperfeiçoarão nossa capacidade de identificar o paciente vulnerável e nos permitir um manejo mais individualizado.

Atherosclerosis is a chronic inflammatory disease that affects essentially all arterial beds including the aorta, coronaries, carotids, and peripheral arteries. It is the main cause of death in the western hemisphere, due to cardiovascular syndromes such as myocardial infarction, heart failure, and cerebrovascular accidents. Very substantial economic and human resources have been used on treatments of its complications, including imaging studies, coronary bypass surgery, catheter interventions, pacemakers, and medical treatments. Treating complications, however, are remedial actions. A better alternative is to prevent the development of atherosclerosis, or at least to identify patients who are at risk of acute events and intervene before they occur. The aims of this review are to discuss the predictive value of traditional and emerging risk factors, as well as the role of noninvasive diagnostic methods for coronary atherosclerosis, including exercise stress test, echo stress test, duplex ultrasound, computed tomography, and magnetic resonance. A combination of serum biomarkers and noninvasive approaches is of practical utility for identifying early disease. It is to be expected that future developments will soon perfect our ability to identify the vulnerable patient and allow a more individualized approach.

OBJECTIVE: The aim of this study was to verify whether HDL particles isolated from patients with coronary artery disease (CAD) and low HDL-C had diminished ability to promote cholesterol efflux from cultured cells compared with HDL isolated from subjects without CAD and with normal HDL-C. METHODS: Smooth muscle cells isolated from human aortas cultured and radiolabeled with ³H-cholesterol were loaded with cholesterol and incubated with increasing concentrations of HDL isolated from 13 CAD patients with low HDL-C (CAD group) or from 5 controls without CAD (C group). Efflux of cellular cholesterol was measured by cellular depletion of radiolabeled cholesterol and by the appearance of ³H-cholesterol into experimental medium expressed as a percentage of total labeled cholesterol. RESULTS: Cholesterol efflux increased with the amount of HDL present in the medium, and no difference was found between groups at various HDL protein concentrations: efflux was 28 ± 6.3% (C) and 25.5 ± 8.9% (CAD) with 25 mg/mL; 34 ± 4.3% (C) and 31.9 ± 6.6% (CD) with 50 mg/mL and 39.5 ± 3.5% (C) and 37.1 ± 4.4% (CAD) with 100 mg/mL, HDL. CONCLUSION: Because the HDL fraction of CAD patients with low HDL-C have normal ability to extract cholesterol from cells of the vessel wall, it is suggested that low HDL-C atherogenicity should be ascribed to diminished concentrations of HDL particles rather than to the qualitative properties of the HDL fraction.

OBJECTIVE: To assess the differences between young males and females after acute myocardial infarction. METHODS: We retrospectively studied 236 patients (54 females and 182 males) after acute myocardial infarction and during hospital stay assessed the following parameters: risk factors; the treatment used; the pattern of coronary artery obstruction; left ventricular ejection fraction; complications; and, using a logistic regression model, the factors related to the occurrence of reinfarction and death. RESULTS: No significant difference was observed between the sexes in risk factors, pattern of coronary artery obstruction, and left ventricular function. The time interval between symptom onset and treatment was longer in females (p=0.03), who underwent thrombolysis (p=0.01) and angioplasty (p=0.03) less frequently than males did, but not myocardial revascularization. Female sex (OR = 5.98) and diabetes (OR = 14.52) were independent factors related to the occurrence of reinfarction and death. CONCLUSION: Young males and females after acute myocardial infarction did not differ in coronary risk factors, and clinical and hemodynamic characteristics. Females had their treatment started later, and they underwent chemical thrombolysis and angioplasty less frequently than males did. Female sex and diabetes were related to the occurrence of reinfarction and death.