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.

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.

Red wine (RW) consumption has been proposed to have a potential health benefit. However, the effect of RW consumption on the brain is not entirely known, mainly when associated with aging. Regular red wine consumers (n = 30) and abstainers (ABST; n = 27) without cognitive impairment were evaluated for brain structural characteristics (Fazekas score and voxel-based morphometry) and for functional adaptations assessed by fMRI (using the Word Tasks Color Stroop (WCST) and Two-Back (TBT)), as well as by neuropsychological tests in different domains. There were no significant differences regarding brain morphological features. RW consumers showed greater activation in the thalamus during WCST and in paracingulate/anterior cingulate cortices, left superior frontal gyrus and frontal pole during TBT. ABST required higher activation of different cortical areas in the left parietal lobe during WCST. Age and intelligence quotient influenced those activations. In Stroop and trail-making neuropsychological tests, RW consumers performed slightly better than ABST. This study should be viewed as hypothesis-generating rather than conclusive.

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

Background Gut microbiota profiles are closely related to cardiovascular diseases through mechanisms that include the reported deleterious effects of metabolites, such as trimethylamine N-oxide (TMAO), which have been studied as diagnostic and therapeutic targets. Moderate red wine (RW) consumption is reportedly cardioprotective, possibly by affecting the gut microbiota. Objectives To investigate the effects of RW consumption on the gut microbiota, plasma TMAO, and the plasma metabolome in men with documented coronary artery disease (CAD) using a multiomics assessment in a crossover trial. Methods We conducted a randomized, crossover, controlled trial involving 42 men (average age, 60 y) with documented CAD comparing 3-wk RW consumption (250 mL/d, 5 d/wk) with an equal period of alcohol abstention, both preceded by a 2-wk washout period. The gut microbiota was analyzed via 16S rRNA high-throughput sequencing. Plasma TMAO was evaluated by LC-MS/MS. The plasma metabolome of 20 randomly selected participants was evaluated by ultra-high-performance LC-MS/MS. The effect of RW consumption was assessed by individual comparisons using paired tests during the abstention and RW periods. Results Plasma TMAO did not differ between RW intervention and alcohol abstention, and TMAO concentrations showed low intraindividual concordance over time, with an intraclass correlation coefficient of 0.049 during the control period. After RW consumption, there was significant remodeling of the gut microbiota, with a difference in beta diversity and predominance of Parasutterella, Ruminococcaceae, several Bacteroides species, and Prevotella. Plasma metabolomic analysis revealed significant changes in metabolites after RW consumption, consistent with improved redox homeostasis. Conclusions Modulation of the gut microbiota may contribute to the putative cardiovascular benefits of moderate RW consumption. The low intraindividual concordance of TMAO presents challenges regarding its role as a cardiovascular risk biomarker at the individual level. This study was registered at clinical trials.gov as NCT03232099.

O ensino e a prática médica brasileiros sofrem de inúmeras limitações, entre as quais destaca-se a deficiente formação científica. Ultimamente surgiu a figura do médico-pesquisador como elemento capaz de suprir, em parte, tal deficiência. Aqui procuro avaliar seu papel. A medicina tradicional ocupa-se da aplicação do conhecimento médico. Portanto, lida com as características gerais das doenças, isto é, sintomas, evolução, comprometimento fisiopatológico de órgãos e sistemas, etiologia, métodos diagnósticos e terapêutica. […] Médico-Pesquisador, Prática Médica e Pesquisa: A Importância do [...]

A Medicina Translacional engloba basicamente três áreas: 1) a aceleração de transmissão de conhecimentos de pesquisa básica à aplicação clínica; 2) análise causal e da fisiopatologia de observações clínicas, pela interação com ciência básica; e 3) implementação, na população geral, de conhecimentos básicos e conceitos oriundos de pesquisas clínicas e experimentais, também chamada Ciência da Implementação. No passado, muitas descobertas fundamentais ficaram apenas no domínio das ciências básicas, levando-se muitos anos até se transformarem em instrumentos diagnósticos ou tratamentos aplicáveis [...]

Colcorona was a multicenter, international study promoted by the Montreal Heart Institute, Canada, whose main objective was to test the effects of colchicine in non-hospitalized patients with COVID-19 [1]. So far, the majority of studies addressed hospitalized patients which is understandable since mortality occurs mainly among those individuals.

Background Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission. Methods The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0middot5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97middot9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants. Findings Trial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53middot9% women; median age 54middot0 years, IQR 47middot0-61middot0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4middot7%) of 2235 patients in the colchicine group and 131 (5middot8%) of 2253 patients in the placebo group (odds ratio [OR] 0middot79, 95middot1% CI 0middot61-1middot03; p=0middot081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4middot6%) of 2075 patients in the colchicine group and 126 (6middot0%) of 2084 patients in the placebo group (OR 0middot75, 0middot57-0middot99; p=0middot042). Serious adverse events were reported in 108 (4middot9%) of 2195 patients in the colchicine group and 139 (6middot3%) of 2217 patients in the placebo group (p=0middot051); pneumonia occurred in 63 (2middot9%) of 2195 patients in the colchicine group and 92 (4middot1%) of 2217 patients in the placebo group (p=0middot021). Diarrhoea was reported in 300 (13middot7%) of 2195 patients in the colchicine group and 161 (7middot3%) of 2217 patients in the placebo group (p<0middot0001). Interpretation In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended. Funding The Government of Quebec, the Bill & Melinda Gates Foundation, the National Heart, Lung, and Blood Institute of the US National Institutes of Health, the Montreal Heart Institute Foundation, the NYU Grossman School of Medicine, the Rudin Family Foundation, and philanthropist Sophie Desmarais. Copyright (c) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Background Evidence suggests the role of an inflammatory storm in COVID-19 complications. Colchicine is an orally administered, anti-inflammatory medication beneficial in gout, pericarditis and coronary disease. Methods We performed a randomized, double-blind trial involving non-hospitalized patients with COVID-19 diagnosed by polymerase chain reaction (PCR) testing or clinical criteria. The patients were randomly assigned to receive colchicine (0.5 mg twice daily for 3 days and once daily thereafter) or placebo for 30 days. The primary efficacy endpoint was the composite of death or hospitalization for COVID-19. Results A total of 4488 patients were enrolled. The primary endpoint occurred in 4.7% of the patients in the colchicine group and 5.8% of those in the placebo group (odds ratio, 0.79; 95.1% confidence interval (CI), 0.61 to 1.03; P=0.08). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 4.6% and 6.0% of patients in the colchicine and placebo groups, respectively (odds ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04). In these patients with PCR-confirmed COVID-19, the odds ratios were 0.75 (95% CI, 0.57 to 0.99) for hospitalization due to COVID-19, 0.50 (95% CI, 0.23 to 1.07) for mechanical ventilation, and 0.56 (95% CI, 0.19 to 1.66) for death. Serious adverse events were reported in 4.9% and 6.3% in the colchicine and placebo groups (P=0.05); pneumonia occurred in 2.9% and 4.1% of patients (P=0.02). Diarrhea was reported in 13.7% and 7.3% in the colchicine and placebo groups (P<0.0001). Conclusion Among non-hospitalized patients with COVID-19, colchicine reduces the composite rate of death or hospitalization. (COLCORONA ClinicalTrials.gov number: NCT04322682)

Neste editorial especial gostaríamos de prestar homenagens a um ícone da Cardiologia brasileira e responsável direto pelo desenvolvimento de uma das maiores instituições da Cardiologia mundial, o Instituto do Coração (InCor), do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (USP). Nas palavras de 3 pessoas muito próximas a ele (Professores Kalil, Mady e Protásio da Luz), vamos relembrar sua trajetória e traços de personalidade tão característicos deste líder inconteste de uma geração de cardiologistas. Como residente do InCor, tive a honra de conhecer e interagir com Professor Fúlvio que teve papel fundamental na minha carreira acadêmica. Primeiro, uma aparente barreira para entrar na pós-graduação: “para se inscrever na pós tem que ter estágio fora do país”, associada ao fato de que quase todas as bolsas de estudo no exterior exigiam como pré-requisito estar inscrito em um programa de pós, pareceu colocar uma barreira intransponível. Mas na verdade só me estimulou ainda mais a procurar alternativas para transpô-la. E de fato, ele abriu todas as portas para que eu realizasse o estágio na Universidade de Johns Hopkins. Depois disso, minha jornada já era história. Uma dívida eterna e um aprendizado para vida.

Dietary factors may influence the process of atherosclerosis and coronary artery calcification (CAC). This study assessed CAC and its association with dietary intake in asymptomatic men. We evaluated 150 asymptomatic men with mean age of 58.2±5.3 years. The dietary intake was assessed by the Food Consumption Register method. CAC was measured through multidetector computed tomography (MDCT) and assessed in accordance with the Agatston score. Modified Poisson regression model was used to estimate the effects of intake of different nutrients that are prevalent in moderate/severe CAC, adjusted for calorie intake and CAC risk factors by means of prevalence ratios and 95% confidence intervals [95%CI]. An association was found between the intake of some nutrients and moderate/severe CAC. Lower carbohydrate intake (P=0.021) and higher lipid intake (P=0.006) were associated with moderate/severe CAC. After adjustment, the nutrients associated with the prevalence of moderate/severe CAC were carbohydrates (P=0.040), lipids (P=0.005), and saturated fatty acids (SFA) (P=0.013). A 1% increase in lipids and SFA intake caused an increase of 4% [95%CI: 1-7%] and 8% [95%CI: 2-14%] in the prevalence of moderate/severe CAC, respectively. A 1% increase of carbohydrate intake led to a 2% decrease in the likelihood of moderate/severe CAC [95%CI: 1-4%]. These conclusions showed that the higher intake of total lipids and SFA was associated with higher CAC scores, whereas higher carbohydrate intake was associated with lower CAC scores in asymptomatic men.