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

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.

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.

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

Value of adenosine infusion for infarct size determination using real-time myocardial contrast echocardiography.

BACKGROUND: Myocardial contrast echocardiography has been used for determination of infarct size (IS) in experimental models. However, with intermittent harmonic imaging, IS seems to be underestimated immediately after reperfusion due to areas with preserved, yet dysfunctional, microvasculature. The use of exogenous vasodilators showed to be useful to unmask these infarcted areas with depressed coronary flow reserve. This study was undertaken to assess the value of adenosine for IS determination in an open-chest canine model of coronary occlusion and reperfusion, using real-time myocardial contrast echocardiography (RTMCE). METHODS: Nine dogs underwent 180 minutes of coronary occlusion followed by reperfusion. PESDA (Perfluorocarbon-Exposed Sonicated Dextrose Albumin) was used as contrast agent. IS was determined by RTMCE before and during adenosine infusion at a rate of 140 mcg.Kg(-1).min(-1). Post-mortem necrotic area was determined by triphenyl-tetrazolium chloride (TTC) staining. RESULTS: IS determined by RTMCE was 1.98 +/- 1.30 cm2 and increased to 2.58 +/- 1.53 cm2 during adenosine infusion (p = 0.004), with good correlation between measurements (r = 0.91; p < 0.01). The necrotic area determined by TTC was 2.29 +/- 1.36 cm2 and showed no significant difference with IS determined by RTMCE before or during hyperemia. A slight better correlation between RTMCE and TTC measurements was observed during adenosine (r = 0.99; p < 0.001) then before it (r = 0.92; p = 0.0013). CONCLUSION: RTMCE can accurately determine IS in immediate period after acute myocardial infarction. Adenosine infusion results in a slight better detection of actual size of myocardial damage.

Cellular cholesterol efflux mediated by HDL isolated from subjects with low HDL levels and coronary artery disease.

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 H-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 H-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 microg/mL; 34 +/- 4.3% (C) and 31.9 +/- 6.6% (CD) with 50 micro g/mL and 39.5 +/- 3.5% (C) and 37.1 +/- 4.4% (CAD) with 100 micro g/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.

Electrocardiographic and blood pressure alterations during electroconvulsive therapy in young adults.

OBJECTIVE: To study cardiovascular alterations in young patients with no apparent organic disease who underwent electroconvulsive therapy. METHODS: The study comprised 47 healthy patients (22 males and 25 females) with a mean age of 30.3 years, who underwent electroconvulsive therapy. Ambulatory blood pressure monitoring and continuous electrocardiographic monitoring (Holter monitor) were performed during 24 hours. Blood pressure and heart rate were assessed 4 hours prior to electric shock administration, during electric shock administration, and 3 hours after electric shock administration. Arrhythmias and alterations in the ST segment in 24 hours were recorded. RESULTS: On electroconvulsive therapy, a significant increase in blood pressure and heart rate was observed and the measurements returned to basal values after 25 minutes. Three females had tracings with depression of the ST segment suggesting myocardial ischemia prior to and after electroconvulsive therapy. Coronary angiography was normal. No severe cardiac arrhythmias were diagnosed. CONCLUSION: 1) Electroconvulsive therapy is a safe therapeutic modality in psychiatry; 2) it causes a significant increase in blood pressure and heart rate; 3) it may be associated with myocardial ischemia in the absence of coronary obstructive disease; 4) electroconvulsive therapy was not associated with the occurrence of severe cardiac arrhythmias.

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

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% 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.