Determinação da Idade Vascular em Homens Através do Escore de Cálcio Coronariano e seu Impacto na Reestratificação do Risco Cardiovascular / Determination of Vascular Age in Men Using the Coronary Calcium Score and its Impact on Restratification of Cardiovascular Risk

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.

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.

The effects of macronutrients composition on hormones and substrates during a meal tolerance test in drug-naive and sitagliptin-treated individuals with type 2 diabetes: a randomized crossover study

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

Medicina translacional - nova fronteira / A new frontier in translacional medicine

O conceito de Medicina Translacional abrange três aspectos: a) a aceleração de transmissão de conhecimentos de pesquisa básica à aplicação clínica; b) aprofundamento de observações clínicas, em busca de melhor entendimento fisiopatológico pela interação com ciência básica; c) aplicação à população geral de conhecimentos básicos e conceitos oriundos de pesquisas clínicas. Assim, no geral, a medicina translacional procura acelerar a transmissão de conhecimento gerado em pesquisa, transformando tais conhecimentos em instrumentos práticos de investigação diagnóstica e/ou tratamentos. Para tanto, necessitam-se estruturas técnicas/administrativas que incluem: pesquisadores, instituições, orçamento e cultura de integração entre as diferentes equipes de trabalho. Pela complexidade desse conjunto, apenas instituições de excelência podem se engajar com sucesso em tais programas. O Brasil já conta com algumas instituições de prestação de serviços médicos e pesquisa que atendem esses requisitos. Crucial ao desenvolvimento de programas translacionais, as universidades devem atender dentro do princípio de meritocracia. Neste ponto, universidades brasileiras precisam de transformações profundas. Por fim, a medicina translacional, ao visar o progresso científico e a melhoria da saúde populacional, também contribui para diminuir as desigualdades sociais, entre essas, a saúde da população esta em destaque

The concept of Translational Medicine covers three aspects: a) acceleration of the transmission of basic research knowledge to clinical application; b) in-depth investigation of clinical observations in search of a better pathophysiological understanding, through interaction with basic science; and c) application of basic knowledge and concepts from clinical research, to the general population. Thus, essentially, translational medicine seeks to speed up the transmission of knowledge generated by research, transforming it into practical tools for diagnosis and/or treatment. For this purpose, appropriate technical and administrative structures are needed, including researchers, institutions, funds, and a culture of integration between the different research teams. Given the complexity of such structures, only institutions of excellence can successfully undertake programs of this type. Brazil already has several medical service and research institutions that meet these requirements. It is critical to the development of translational programs that universities adhere to the principle of meritocracy. In this aspect, radical change is needed in Brazilian universities. Finally, translational medicine, by striving for scientific advancement and improvement in the health of the population, also plays its part in reducing social inequalities, and among these the health of the population is paramount

Endotélio e aterosclerose / Endothelium and atherosclerosis

Endotélio é um órgão secretor que recobre a face interna de todos os vasos, atua como barreira entre o meio circulante e a parede arterial, secreta substâncias vasodilatadoras e vasoconstritoras por meio das quais regula a vasomotricidade arterial, protege contra a coagulação do sangue e é antiproliferativo. Desempenha papel fundamental na aterosclerose: esta começa pela disfunção endotelial, a qual permite a entrada de partículas lipídicas na região subendotelial. A partir daí, formam-se as placas ateroscleróticas, sob a influência de células inflamatórias. A progressão das placas é em parte também mediada pelo endotélio: igualmente, a instabilização das placas, fenômeno responsável pelos eventos coronários agudos, também depende em grande parte de lesões endoteliais. A disfunção endotelial precede fenômenos clínicos da aterosclerose, como a angina. Neste artigo, resumimos os aspectos mais relevantes da participação do endotélio na aterosclerose...

The endothelium is a secretory organ that covers lhe inner surface of ali vessels. It acts as a barrier separati ng the circulating millieu from the arterial wall, produces several vasoconstrictive and vasodilating subsumce s through which blood circulation and arterial di l ation are preserved. It plays pivotal roles in atherosclerosis: the latter begins with endothelial dysfunction which permits that lipid particles penetrate the sub-endothclial space thus initiating a cascade of events mainly mcdiatcd by inflammatory cells. Atherosclerosis prngressi on and plaque instability are both endothelium dependem phenomena. Endothelial dysfunction precedes cl inicul manifestations of atherosclerosis, such as in angina. 111 this article we review the main features of endothelial participation in atherosclerosis...

Ecocardiografia com contraste miocárdico e cintilografia de perfusão miocárdica sincronizada ao eletrocardiograma na avaliação de pacientes com torácica / Contrast echocardiography and gated perfusion imaging in the evaluation of patients with chest pain

Introdução: A avaliação de pacientes com dor torácica é muitas vezes problemática. O desafio em diagnosticar corretamente a etiologia da dor torácica é dificultado pela baixa sensibilidade dos métodos diagnósticos disponíveis. Neste estudo, avaliou-se a utilidade diagnóstica da ecocardiografia com contraste miocárdico (MCE) e da cintilografia de perfusão miocárdica sincronizada ao eletrocardiograma (G-SPECT) para detecção de isquemia miocárdica. Métodos e Resultados: Dezoito pacientes atendidos no pronto socorro, para avaliação da dor torácica sugestiva de angina, foram submetidos à MCE e G-SPECT. Para ambos os métodos, a perfusão miocárdica e a mobilidade foram avaliados nos mesmos sete segmentos do ventrículo esquerdo. As imagens foram classificadas como positivas ou negativas para isquemia. Um segmento era considerado positivo na presença de um defeito da perfusão ou uma anomalia do movimento da parede. A cinecoronariografia foi realizada se MCE ou G-SPECT foram classificados como positivos para isquemia. Se ambos os exames foram negativos, o paciente foi submetido ao SPECT de estresse no dia seguinte. Sensibilidade e especificidade para detecção de isquemia miocárdica foram, respectivamente: A) G-SPECT: 1. avaliação de perfusão: 100 por cento e 75 por cento; 2. avaliação de contração: 66 por cento e 91,6 por cento; 3. associação perfusão+contração: 66 por cento e 91,6 por cento. B) MCE: 1. avaliação de perfusão: 20 por cento e 76 por cento; 2. avaliação de contração: 33,3 por cento e 83,3 por cento; 3. associação perfusão...

Cardioprotection conferred by exercise training is blunted by blockade of the opioid system

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 percent 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 ...

Comparison of non-invasive methods for the detection of coronary atherosclerosis

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...

Evidence that the degree of obstructive sleep apnea may not increase myocardial ischemia and arrhythmias in patients with stable coronary artery disease

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 percent) 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.

Selective cyclooxygenase-2 inhibition protects against myocardial damage in experimental acute ischemia

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.

Short-term red wine consumption promotes differential effects on plasma levels of high-density lipoprotein cholesterol, sympathetic activity, and endothelial function in hypercholesterolemic, hypertensive, and healthy subjects

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 percent (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.

High ratio of triglycerides to hdl-cholesterol predicts extensive coronary disease

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...