Resumo Fundamento Identificar os indivíduos assintomáticos sob risco de desenvolver doenças cardiovasculares é um dos principais objetivos da cardiologia preventiva. O escore de cálcio coronariano (ECC) permite estimar a idade vascular, que se mostrou mais fidedigna que a idade cronológica na determinação do risco cardiovascular. Objetivos Reclassificar o risco cardiovascular com base na idade arterial e avaliar a progressão do escore de cálcio durante o seguimento. Métodos 150 homens assintomáticos foram submetidos a avaliação clínica e do ECC em 2 avaliações com intervalo de 7,6 anos. Classificamos os pacientes pelos escores de risco tradicionais e pela idade arterial. Avaliamos quais variáveis se associaram a maior progressão do ECC durante o período. O nível de significância estatística considerado foi de 5% (p < 0,05). Resultados A utilização da idade arterial na estratificação do risco cardiovascular em comparação ao escore de risco de Framingham (ERF) reclassificou 29% dos indivíduos para uma categoria de risco superior e 37% para uma categoria inferior. Em relação ao escore da AHA e ACC (ASCVD), 31% passaram para um risco maior e 36% para um risco menor. A classificação inicial pela idade arterial teve relação direta com a progressão do ECC ao longo do seguimento (p < 0,001), fato que não foi observado para o ERF (p = 0,862) e ASCVD (p = 0,153). As variáveis individuais que mais se associaram à progressão do ECC foram a pressão arterial sistólica e o HDL baixo. Conclusão A estratificação de risco cardiovascular utilizando a idade arterial apresentou melhor associação que o ERF e ASCVD na identificação de indivíduos com maior risco de progressão da aterosclerose. preventiva (ECC vascular 15 76 7 6 7, anos período 5 p 0,05. 005 0,05 . 0 05 0,05) (ERF 29 37 inferior ASCVD, , (ASCVD) 31 36 menor 0,001, 0001 0,001 001 0,001) 0,862 0862 862 0,153. 0153 0,153 153 0,153) baixo aterosclerose 1 00 0,0 3 (ASCVD 000 0,00 0,86 086 86 015 0,15 0, 0,8 08 8 01 0,1

Abstract Background Identifying asymptomatic individuals at risk of developing cardiovascular disease is one of the main goals of preventive cardiology. The coronary calcium score (CCS) makes it possible to estimate vascular age, which has shown to be more reliable than chronological age for determining cardiovascular risk. Objectives To reclassify cardiovascular risk based on arterial age and evaluate CCS progression during follow-up. Methods We included 150 asymptomatic men who underwent clinical and CCS evaluation in 2 evaluations with an interval of 7.6 years. We classified patients by traditional risk scores and arterial age. We evaluated which variables were associated with greater CCS progression during the period, considering a statistical significance level of 5% (p < 0.05). Results The use of arterial age in the stratification of cardiovascular risk in comparison with the Framingham risk score (FRS) reclassified 29% of individuals to a higher risk category and 37% to a lower risk category. Regarding the American Heart Association and American College of Cardiology score (ASCVD), 31% were reclassified as higher risk and 36% as lower risk. The initial classification by arterial age was directly related to the progression of CCS throughout follow-up (p < 0.001). This was not observed for the FRS (p = 0.862) or ASCVD (p = 0.153). The individual variables most associated with CCS progression were high systolic blood pressure and low HDL. Conclusion Cardiovascular risk stratification using arterial age showed a better association than the FRS and ASCVD in identifying individuals with higher risk of atherosclerosis progression. cardiology (CCS followup. followup follow up. up 15 76 7 6 7. years period 5 p 0.05. 005 0.05 . 0 05 0.05) (FRS 29 37 ASCVD, , (ASCVD) 31 36 0.001. 0001 0.001 001 0.001) 0.862 0862 862 0.153. 0153 0.153 153 0.153) HDL 1 00 0.0 3 (ASCVD 000 0.00 0.86 086 86 015 0.15 0. 0.8 08 8 01 0.1

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 TDM T DM (T2DM MTT. . (MTT) methods drugnaive drug naive 10 qd q d q.d. h composition 70 carbohydrates proteins lipids washout repeated blinded repeatedmeasures measures analysis Results postmeal post areaunderglucosecurve curve 7 15 15% +86% 86 (+86% insulinglucose insulin +25%, 25 +25% , (+25%) glucagonlike glucagon like peptide1/glucose peptide1glucose peptideglucose peptide 1/glucose 1 +46% 46 (+46% curves protein lipidrich lipid rich Cpeptide, Cpeptide C peptide, C-peptide levels Conclusion fatrich fat meals no NCT NCT0088154 (MTT q.d +86 8 (+86 +25 (+25% peptide1 1glucose +46 (+46 NCT008815 +8 (+8 +2 (+25 +4 (+4 NCT00881 + (+ (+2 NCT0088 ( NCT008 NCT00 NCT0

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

OBJECTIVES: To compare the metabolic, hemodynamic, autonomic, and endothelial responses to short-term red wine consumption in subjects with hypercholesterolemia or arterial hypertension, and healthy controls. METHODS: Subjects with hypercholesterolemia (n=10) or arterial hypertension (n=9), or healthy controls (n=7) were given red wine (250 mL/night) for 15 days. Analyses were performed before and after red wine intake. RESULTS: Red wine significantly increased the plasma levels of HDL-cholesterol in the controls, but not in the other groups. The effects on hemodynamic measurements were mild, non-significantly more prominent in healthy subjects, and exhibited high interindividual variability. Across all participants, mean blood pressure decreased 7 mmHg (p <0.01) and systemic vascular resistance decreased 7% (p = 0.05). Heart rate and cardiac output did not significantly change in any group. Red wine enhanced muscle sympathetic fibular nerve activity in hypercholesterolemic and hypertensive patients, but not in controls. At baseline, brachial artery flow-mediated dilation was impaired in patients with hypercholesterolemia and arterial hypertension; red wine restored the dilation in the hypercholesterolemic group but not in the hypertensive group. CONCLUSIONS: Red wine elicits different metabolic, autonomic, and endothelial responses among individuals with hypercholesterolemia or arterial hypertension and healthy controls. Our findings highlight the need to consider patient characteristics when evaluating the response to red wine.

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.

An abnormal ratio of triglycerides to HDL-cholesterol (TG/HDL-c) indicates an atherogenic lipid profile and a risk for the development of coronary disease. OBJECTIVE: To investigate the association between lipid levels, specifically TG/HDL-c, and the extent of coronary disease. METHODS: High-risk patients (n = 374) submitted for coronary angiography had their lipid variables measured and coronary disease extent scored by the Friesinger index. RESULTS: The subjects consisted of 220 males and 154 females, age 57.2 ± 11.1 years, with total cholesterol of 210± 50.3 mg/dL, triglycerides of 173.8 ± 169.8 mg/dL, HDL-cholesterol (HDL-c) of 40.1 ± 12.8 mg/dL, LDL-cholesterol (LDL-c) of 137.3 ± 46.2 mg/dL, TG/HDL-c of 5.1 ± 5.3, and a Friesinger index of 6.6 ± 4.7. The relationship between the extent of coronary disease (dichotomized by a Friesenger index of 5 and lipid levels (normal vs. abnormal) was statistically significant for the following: triglycerides, odds ratio of 2.02 (1.31-3.1; p = 0.0018); HDL-c, odds ratio of 2.21 (1.42-3.43; p = 0.0005); and TG/HDL-c, odds ratio of 2.01(1.30-3.09; p = 0.0018). However, the relationship was not significant between extent of coronary disease and total cholesterol [1.25 (0.82-1.91; p = 0.33)] or LDL-c [1.47 (0.96-2.25; p = 0.0842)]. The chi-square for linear trends for Friesinger > 4 and lipid quartiles was statistically significant for triglycerides (p = 0.0017), HDL-c (p = 0.0001), and TG/HDL-c (p = 0.0018), but not for total cholesterol (p = 0.393) or LDL-c (p = 0.0568). The multivariate analysis by logistic regression OR gave 1.3 ± 0.79 (p = .0001) for TG/HDL-c, 0.779 ± 0.074 (p = .0001) for HDL-c, and 1.234 ± 0.097 (p = 0.03) for LDL. Analysis of receiver operating characteristic curves showed that only TG/HDL-c and HDL-c were useful for detecting extensive coronary disease, with the former more strongly associated with disease. CONCLUSIONS: Although some lipid variables were associated with the extent of coronary disease, the ratio of triglycerides to HDL-cholesterol showed the strongest association with extent.