Consumo de carnes por adultos e idosos de uma cidade de colonização alemã do sul do Brasil: estudo de base populacional / Meat consumption by adults and the elderly in a city colonized by Germans in the south of Brazil: a population-based study

Resumo O consumo excessivo de carnes, em especial as vermelhas e processadas, está associado ao aumento da morbi-mortalidade. O padrão de consumo de carnes varia no Brasil e no mundo influenciado por fatores econômicos e culturais. O estudo buscou analisar o consumo de carnes por adultos e idosos de uma cidade de colonização alemã do sul do Brasil. Trata-se de estudo populacional seccional. Foram coletados dados sociodemográficas e de consumo de carne por Questionário de Frequência Alimentar previamente validado. Foram analisadas as frequências, e as quantidades por tipo de carne e processamento. A associação entre o consumo excessivo de carne e as variáveis de estudo foi estimada por Razão de Prevalência. Entre os 1.941 participantes, a média de carne consumida foi de 250 g/dia, sendo a carne não processada branca (138 g/dia) a mais consumida, com destaque para as aves (80 g/dia). A prevalência de consumo excessivo de carne vermelha e processada (mais que 500 g/semana) foi de 63%, principalmente entre os homens (RP=1,6; IC95% 1,5-1,8), de 20 a 29 anos (RP=1,4; IC95% 1,2-1,5), e mais alta classe econômica (RP=1,2; IC95% 1,0-1,3). O consumo excessivo de carne vermelha e processada entre homens jovens de classe econômica alta deve ser alvo de ações de saúde pública para a adequação no consumo alimentar.

Abstract Excessive meat consumption, especially red and processed meats, is associated with increased morbidity and mortality. The pattern of meat consumption varies in Brazil and is influenced by economic and cultural factors in the world. The study aimed to analyze the consumption of meat by adults and the elderly in a city colonized by Germans in the south of Brazil. It involved a cross-sectional population study. Sociodemographic and meat consumption data were collected using a previously validated Food Frequency Questionnaire. Frequencies and amounts were analyzed by type of meat and processing. The association between excessive meat consumption and the study variables was estimated by Prevalence Ratio. Among the 1,941 participants, the average amount of meat consumed was 250 g/day, the most consumed being white unprocessed meat (138 g/day), especially poultry (80 g/day). The prevalence of excessive consumption of red and processed meat (more than 500 g/week) was 63%, mainly among men (PR=1.6; 95%CI 1.5-1.8), aged 20 to 29 years (PR=1.4; 95%CI 1.2-1.5), and higher economic class (PR=1.2; 95%CI 1.0-1.3). Excessive consumption of red and processed meat among young men of upper economic class should be the target of public health actions for the adequacy of food consumption.

Determinando Percentis do Risco Cardiovascular Aterosclerótico de acordo com Sexo e Idade numa População Saudável Brasileira / Determining Percentiles of Atherosclerotic Cardiovascular Risk According to Sex and Age in a Healthy Brazilian Population

Resumo Fundamento Expressar o risco de doença cardiovascular aterosclerótica (DCVA) em percentis da distribuição por sexo e idade pode proporcionar uma melhor percepção do risco. Objetivos Determinar os percentis da distribuição do risco de DCVA em 10 anos segundo sexo e idade em uma amostra da população brasileira; caracterizar indivíduos com baixo risco em 10 anos, mas em alto percentil de risco. Métodos Analisamos indivíduos de 40 a 75 anos que realizaram avaliações de saúde de rotina de 2010 a 2020. Foram excluídos indivíduos com DCVA clínica conhecida, diabetes mellitus, doença renal crônica ou LDL-colesterol ≥ 190 mg/dL. O risco de DCVA em 10 anos foi calculado pelas equações das coortes agrupadas do American College of Cardiology/American Heart Association. Foi utilizada a regressão polinomial local para determinar os percentis de risco. Valores de p bilateral < 0,050 foram considerados estatisticamente significativos. Resultados Nossa amostra incluiu 54.145 atendimentos (72% do sexo masculino, idade mediana [intervalo interquartil] 48 [43; 53] anos). Construímos gráficos específicos por sexo traçando a idade contra o risco de DCVA correspondente aos percentis 10, 25, 50, 75 e 90. A maioria dos homens até 47 anos e mulheres até 59 anos acima do percentil 75 apresentaram risco em 10 anos < 5%. Indivíduos com baixo risco em 10 anos e percentil de risco ≥ 75 apresentaram alta prevalência de excesso de peso e níveis medianos (intervalos interquartis) de LDL-colesterol de 136 (109; 158) mg/dL (sexo masculino) e 126 (105; 147) mg/dL (sexo feminino). Conclusões Estabelecemos percentis de risco de DCVA segundo sexo e idade em uma grande amostra da população brasileira. Essa abordagem pode aumentar a conscientização sobre o risco e ajudar a identificar pessoas mais jovens com baixo risco em 10 anos que podem se beneficiar de um controle mais agressivo dos fatores de risco.

Abstract Background Expressing the risk of atherosclerotic cardiovascular disease (ASCVD) as percentiles of the distribution according to sex and age may provide a better perception of the risk. Objectives To determine percentiles of the 10-year ASCVD risk distribution according to sex and age in a sample of the Brazilian population; to characterize individuals at low 10-year risk but high risk percentile. Methods We analyzed individuals aged 40 to 75 years who underwent routine health evaluations from 2010 to 2020. Persons with known clinical ASCVD, diabetes mellitus, chronic kidney disease, or LDL-cholesterol ≥ 190 mg/dL were excluded. The 10-year ASCVD risk was calculated by the ACC/AHA pooled cohort equations. Local polynomial regression was used to determine risk percentiles. Two-sided p-values < 0.050 were considered statistically significant. Results Our sample comprised 54,145 visits (72% male, median age [interquartile range] 48 [43, 53] years). We constructed sex-specific graphs plotting age against ASCVD risk corresponding to the 10th, 25th, 50th, 75th, and 90th percentiles. Most males up to 47 years and females up to 59 years above the 75th percentile had a 10-year risk < 5%. Individuals at low 10-year risk and risk percentile ≥ 75th had a high prevalence of excess weight and median (interquartile range) LDL-cholesterol levels 136 (109, 158) mg/dL (males) and 126 (105, 147) mg/dL (females). Conclusions We established ASCVD risk percentiles according to sex and age in a large sample of the Brazilian population. This approach may increase risk awareness and help identify younger persons at low 10-year risk who may benefit from more aggressive risk factor control.

Inclisiran, ARN interferente pequeño: un nuevo enfoque para el tratamiento del colesterol / Inclisiran, small interfering RNA: a new approach to cholesterol treatment

Resumen: La hiperlipidemia es altamente prevalente y contribuye de forma sustancial a la enfermedad cardiovascular aterosclerótica, que es una de las principales causas de morbilidad y mortalidad en Colombia. La reducción del colesterol LDL (c-LDL) produce una disminución del riesgo de enfermedad cardiovascular aterosclerótica y de eventos cardiovasculares adversos. La terapia dirigida a la proproteína convertasa subtilisina/kexina tipo 9 (PCSK9; su sigla en inglés) ha surgido como una herramienta novedosa para el tratamiento de la hiperlipidemia. Inclisiran es un ARN pequeño de doble hebra, que actúa inhibiendo la transcripción de PCSK-9 en los hepatocitos, lo que conduce a una reducción marcada y sostenida del c-LDL. En contraste con otras terapias hipolipemiantes, como estatinas, ezetimibe y anticuerpos monoclonales (MAbs; su sigla en inglés) e inhibidores de PCSK9, inclisiran propone un régimen de dosificación infrecuente de dos o tres veces al año. Su efecto prolongado representa una ventaja frente al incumplimiento del tratamiento, que es una de las principales causas por las que no se alcanzan los objetivos de c-LDL con la terapia estándar. Esta revisión tiene como objetivo presentar y discutir los datos científicos actuales con relación a la eficacia, tolerabilidad y seguridad del inclisiran en el tratamiento de la hipercolesterolemia.

Abstract: Hyperlipidemia is a highly prevalent condition and contributes substantially to atherosclerotic cardiovascular disease (ASCVD), which is one of the main causes of morbidity and mortality in Colombia. The reduction of LDL cholesterol (LDL-C) decreases the risk of ASCVD and adverse cardiovascular events. Targeted therapy for the proprotein convertase subtilisin/kexin type 9 (PCSK-9) has emerged as a novel tool for the treatment of hyperlipidemia. Inclisiran is a small double-stranded small interfering RNA that acts by blocking PCSK-9 transcription in hepatocytes, leading to a marked and sustained reduction in circulating LDL-C levels. In contrast to other lipid-lowering therapies such as statins, ezetimibe and monoclonal antibodies (MAbs) PCSK-9 inhibitors, Inclisiran proposes an infrequent dosing regimen of twice or three times a year. Its prolonged effect represents an advantage over non-compliance of the treatment, which is one of the main reasons why LDL-C goals are not achieved with standard therapy. This review aims to present and discuss current scientific data regarding the efficacy, tolerability and safety of Inclisiran in the treatment of hypercholesterolemia.

Rastreamento para Hipercolesterolemia Familiar em Pequenos Municípios: A Experiência do Programa HipercolBrasil em 11 Municípios Brasileiros / Screening for Familial Hypercholesterolemia in Small Towns: Experience from 11 Brazilian Towns in the Hipercolbrasil Program

Resumo Fundamento A hipercolesterolemia familiar (HF) é uma doença genética dominante que se caracteriza por níveis sanguíneos elevados de colesterol de lipoproteína de baixa densidade (LDL-C), e está associada à ocorrência de doença cardiovascular precoce. No Brasil, o HipercolBrasil, que é atualmente o maior programa de rastreamento em cascata para HF, já identificou mais de 2.000 indivíduos com variantes genéticas causadoras de HF. A abordagem padrão baseia-se no rastreamento em cascata de casos índices referidos, indivíduos com hipercolesterolemia e suspeita clínica de HF. Objetivos Realizar rastreamento direcionado de 11 pequenos municípios brasileiros com suspeita de alta prevalência de indivíduos com HF. Métodos A seleção dos municípios ocorreu de 3 maneiras: 1) municípios em que houve suspeita de efeito fundador (4 municípios); 2) municípios em uma região com altas taxas de infarto do miocárdio precoce, conforme descrito pelo banco de dados do Sistema Único de Saúde (2 municípios); e 3) municípios geograficamente próximos a outros municípios com alta prevalência de indivíduos com HF (5 municípios). A significância estatística foi considerada como valor p < 0,05. Resultados Foram incluídos 105 casos índices e 409 familiares de primeiro grau. O rendimento dessa abordagem foi de 4,67 familiares por caso índice, o qual é significativamente melhor (p < 0,0001) do que a taxa geral do HipercolBrasil (1,59). Identificamos 36 CIs com variante patogênica ou provavelmente patogênica para HF e 240 familiares de primeiro grau afetados. Conclusão: Nossos dados sugerem que, uma vez detectadas, regiões geográficas específicas justificam uma abordagem direcionada para a identificação de aglomerações de indivíduos com HF.

Abstract Background Familial hypercholesterolemia (FH) is a genetic disease characterized by elevated serum levels of low-density lipoprotein cholesterol (LDL-C), and it is associated with the occurrence of early cardiovascular disease. In Brazil, HipercolBrasil, which is currently the largest FH cascade screening program, has already identified more than 2000 individuals with causal genetic variants for FH. The standard approach is based on cascade screening of referred index cases, individuals with hypercholesterolemia and clinical suspicion of FH. Objectives To perform targeted screening of 11 small Brazilian cities with a suspected high prevalence of people with FH. Methods The selection of cities occurred in 3 ways: 1) cities in which a founder effect was suspected (4 cities); 2) cities in a region with high rates of early myocardial infarction as described by the National Health System database (2 cities); and 3) cities that are geographically close to other cities with a high prevalence of individuals with FH (5 cities). Statistical significance was considered as p value < 0.05. Results One hundred and five index cases and 409 first-degree relatives were enrolled. The yield of such approach of 4.67 relatives per index case was significantly better (p < 0.0001) than the general HipercolBrasil rate (1.59). We identified 36 IC with a pathogenic or likely pathogenic variant for FH and 240 affected first-degree relatives. Conclusion Our data suggest that, once detected, specific geographical regions warrant a target approach for identification of clusters of individuals with FH.

Razão Neutrófilo-Linfócito e Aterosclerose da Aorta Abdominal entre Indivíduos Assintomáticos / Neutrophil-To-Lymphocyte Ratio and Abdominal Aortic Atherosclerosis among Asymptomatic Individuals

Resumo Fundamento A razão neutrófilo-linfócito (RNL) tem sido proposta como um marcador inflamatório possivelmente associado a aterosclerose coronariana, embora a maioria dos dados atuais seja restrita à fase aguda. Além disso, a associação entre a RNL e a aterosclerose extracoronariana ainda não está clara. Objetivo Analisar a associação entre a RNL e aterosclerose da aorta abdominal (AtAA). Métodos Foram incluídos pacientes assintomáticos submetidos a um programa de rastreamento. A AtAA foi avaliada através de ultrassom. Os números absolutos de leucócitos e linfócitos foram utilizados para calcular a RNL. Foi estabelecido um nível de significância estatística de 0,05. Resultados De 36.985 indivíduos (idade: 42±10 anos, 72% homens), foi identificada a presença de AtAA em 7%. Aqueles com AtAA eram mais velhos e tinham maior propensão a serem homens e diabéticos. A presença de AtAA foi associada a RNL aumentada (odds ratio [OR] 1,17; intervalo de confiança de 95% [IC95%] 1,13-1,21). No entanto, a associação deixou de ser significativa quando a análise foi ajustada para os fatores de risco (OR 1,02; IC95% 0,97-1,06), principalmente devido à inclusão da idade no modelo. Quando os neutrófilos e linfócitos foram analisados separadamente, a associação negativa entre os linfócitos e a RNL foi invertida com a inclusão da idade, o que sugere um forte efeito confundidor da idade na relação entre linfócitos e aterosclerose. Por fim, a associação entre os neutrófilos e a AtAA deixou de ser significativa após o ajuste adicional para os fatores de risco tradicionais, mas não apenas para a idade. Conclusão Embora a RNL tenha se associado a AtAA, foi principalmente devido ao efeito confundidor da idade. No geral, os resultados sugerem um papel limitado da contagem de leucócitos como biomarcador de AtAA.

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has been proposed as an inflammatory marker that might be associated with coronary atherosclerosis, although most of the current data is restricted to the acute setting. Additionally, the association of NLR with extracoronary atherosclerosis and stable disease remains unclear. Objective To analyze the association between NLR and abdominal aortic atherosclerosis (AAAt). Methods We included asymptomatic individuals who underwent a health screening program. AAAt was measured by ultrasound. Absolute leukocyte and lymphocyte counts were used to calculate the NLR. The level of significance for statistical analysis was 0.05. Results Among 36,985 individuals (age: 42±10 years, 72% male), AAAt was identified in 7%. Those with AAAt were older and more likely to be male and diabetic. Presence of AAAt was associated with increased NLR (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.13-1.21). However, this association was no longer significant when the analysis was adjusted for risk factors (OR 1.02; 95% CI 0.97-1.06), mostly due to the inclusion of age in the model. When neutrophils and lymphocytes were analyzed separately, the negative association between lymphocytes and AAAt was inverted once age was accounted for, suggesting a strong confounding effect of age on the relationship between lymphocytes and atherosclerosis. Finally, the association of neutrophils and AAAt lost significance after an additional adjustment for traditional risk factors, but not age alone. Conclusion Although the NLR was associated with AAAt, this was largely due to the confounding effect of age. Overall, the results suggest a limited role of leukocyte measurements as biomarkers of AAAt.

Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil

Abstract Objectives This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.

Percepção Inadequada do Risco Cardiovascular e Baixo Conhecimento sobre Hipercolesterolemia Familiar em Indivíduos com Hipercolesterolemia Grave / Cardiovascular Risk Misperception and Low Awareness of Familial Hypercholesterolemia in Individuals with Severe Hypercholesterolemia

Resumo Fundamento Indivíduos com hipercolesterolemia grave apresentam alto risco de desenvolver doença cardiovascular aterosclerótica (DCVA). Muitos deles apresentam hipercolesterolemia familiar (HF). Objetivos Avaliar, a partir da perspectiva dos pacientes, o nível de conhecimento sobre a hipercolesterolemia grave, especialmente em relação a HF, DCVA, percepção de risco, desempenho do rastreamento em cascata e tratamento de indivíduos participantes de um programa de avaliação periódica de saúde. Métodos De um banco de dados de 70.000 brasileiros avaliados entre 2006 e 2016, 1.987 (2,8%) atenderam aos critérios de inclusão (idade ≥ 18 anos e LDL-C ≥ 190 mg/dL ou ≥ 160 mg/dL se sem uso de estatinas ou em terapia com estatinas, respectivamente). Desses, 200 foram aleatoriamente convidados a preencher um questionário extenso. A HF foi diagnosticada em caso de suspeita pelo médico responsável. Resultados Embora 97% da amostra (48±9 anos; 16% do sexo feminino; 95% com ensino superior; 88% em prevenção primária; LDL-C 209±47 mg/dL) tenha apresentado hipercolesterolemia grave, apenas 18% e 29,5% se consideravam de alto risco para desenvolver DCVA e relataram saber sua meta recomendada de LDL-C, respectivamente. Em relação à possibilidade de o colesterol alto ser uma doença hereditária, 58% relataram conhecimento sobre o fato; 24,5% (n = 49) já tinham ouvido falar em HF; e apenas 14% (n = 20) foram previamente identificados com suspeita de HF (idade ao diagnóstico de HF: 35±12 anos; 79% e 31% foram diagnosticados com > 30 e > 40 anos, respectivamente). Apenas 2,5% foram submetidos a testes genéticos; 17%, à rastreamento em cascata; e 17% não faziam uso de tratamento farmacológico. Conclusões Identificou-se uma importante lacuna na percepção de risco, no controle do colesterol e em aspectos relacionados à HF em indivíduos com hipercolesterolemia grave. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

Abstract Background Individuals with severe hypercholesterolemia are at a high risk of developing atherosclerotic cardiovascular disease (ASCVD). Many of them have familial hypercholesterolemia (FH). Objectives To assess from a patient perspective the degree of awareness about severe hypercholesterolemia, especially FH, ASCVD risk perception, cascade screening performance, and treatment of individuals participating in a routine health evaluation program. Methods From a database of 70,000 Brazilian individuals evaluated between 2006 and 2016, 1,987 (2.8%) met the inclusion criteria (age ≥ 18 years and LDL-C ≥ 190 mg/dL or ≥ 160 mg/dL, respectively, if not in use of statins or on statin therapy). Two-hundred individuals were randomly invited to complete an extensive questionnaire. FH was diagnosed if suspected by the attending physician. Results Although 97% of the sample (age 48±9 years; 16% women; 95% college/university education; 88% primary prevention; LDL-C 209±47 mg/dL) had severe hypercholesterolemia, only 18% and 29.5% believed to be at high ASCVD risk and reported knowledge of their recommended LDL-C goal, respectively. Fifty-eight percent reported being informed that high cholesterol could be a family disease, 24.5% (n = 49) had ever heard about FH, and merely 14% (n = 29) had been previously identified as suspected of having FH (age at FH diagnosis 35±12 years; 79% and 31% diagnosed, respectively, > 30 and > 40 years old). Only 2.5% underwent genetic tests, 17% underwent cascade screening, and 17% were not in use of pharmacological treatment. Conclusions An important gap in risk perception, cholesterol management, and aspects related to FH was encountered in individuals with severe hypercholesterolemia. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

COVID-19 and Thromboinflammation: Is There a Role for Statins?

The novel coronavirus disease (COVID-19) showed increased morbidity and mortality rates and worse prognosis in individuals with underlying chronic diseases, especially cardiovascular disease and its risk factors, such as hypertension, diabetes, and obesity. There is also evidence of possible links among COVID-19, myocardial infarction, and stroke. Emerging evidence suggests a pro-inflammatory milieu and hypercoagulable state in patients with this infection. Despite anticoagulation, a large proportion of patients requiring intensive care may develop life-threatening thrombotic complications. Indeed, the levels of some markers of hemostatic activation, such as D-dimer, are commonly elevated in COVID-19, indicating potential risk of deep vein thrombosis and pulmonary thromboembolism. In this review, we critically examine and discuss aspects of hypercoagulability and inflammation in COVID-19 and the possible benefits of statins in this scenario, with emphasis on their underlying molecular mechanisms. Moreover, we present recommendations on the use of antiviral drugs in combination with statins.

Incidence and associated factors of type 2 diabetes mellitus onset in the Brazilian HIV/AIDS cohort study

ABSTRACT Background: People living with HIV (PLH) under combined antiretroviral therapy (cART) are at risk of developing type 2 diabetes mellitus (T2DM). Objective: We examined the incidence of T2DM, associated factors and mean time to outcome in PLH under cART. Method: Data for this multicenter cohort study were obtained from PLH aged over 18, who started cART in 13 Brazilian sites from 2003 to 2013. Factors associated with incident T2DM were evaluated by Cox multiple regression models. Results: A total of 6724 patients (30,997.93 person-years) were followed from January 2003 to December 2016. A T2DM incidence rate of 17.3/1000 person-years (95%CI 15.8-18.8) was observed. Incidence of isolated hypertriglyceridemia and impaired fasting glucose (IFG) were 84.3 (95%CI 81.1-87.6) and 14.5/1000 person-years (95%CI 13.2-15.9), respectively. Mean time to T2DM onset was 10.5 years (95%CI 10.3-10.6). Variables associated with incident T2DM were age 40-50 [Hazard Ratio (HR) 1.7, 95%CI 1.4-2.1] and ≥ 50 years (HR 2.4, 95%CI 1.9-3.1); obesity (HR 2.1, 95%CI 1.6-2.8); abnormal triglyceride/HDL-cholesterol ratio (HR 1.8, 95%CI 1.51-2.2). IFG predicted T2DM (HR 2.6, 95%CI 1.7-2.5) and occurred on average 3.3 years before diabetes onset. Exposure to stavudine for ≥ 2 years was independently associated with incident T2DM [HR 1.6, 95%CI 1.0-2.2). Conclusion: Brazilian PLH under cART are at significant risk of developing T2DM and share risk factors for diabetes onset with the general population, such as older age, obesity, and having metabolic abnormalities at baseline. Moreover, stavudine use was independently associated with incident T2DM. Identifying PLH at a higher risk of T2DM can help caretakers trigger health promotion and establish specific targets for implementation of preventive measures.

Risco Cardiovascular e Elegibilidade Para Estatina na Prevenção Primária: Comparação Entre a Diretriz Brasileira e a Diretriz da AHA/ACC / Cardiovascular Risk and Statin Eligibility in Primary Prevention: A Comparison between the Brazilian and the AHA/ACC Guidelines

Resumo Fundamento Diferenças entre as versões atualizadas da Diretriz Brasileira de Dislipidemias e da Diretriz de Colesterol da American Heart Association (AHA)/American College of Cardiology (ACC) quanto à estratificação de risco cardiovascular e à elegibilidade para a terapia com estatina não são conhecidas. Objetivos Comparar a categorização de risco cardiovascular e a elegibilidade à terapia com estatina estabelecidas segundo a diretriz brasileira ou a diretriz da AHA/ACC em pacientes em prevenção primária. Métodos Nós avaliamos retrospectivamente indivíduos com idade entre 40 e 74 anos sem condições de alto risco, com LDL-c 70 -< 190 mg/dL, sem tratamento com agentes hipolipemiantes, e que passaram por avaliação clínica de rotina. O risco cardiovascular foi estratificado de acordo com a diretriz brasileira e a da AHA/ACC. Os indivíduos foram considerados elegíveis para estatina se os níveis de LDL-c estivessem no mínimo 30 mg/dL acima da meta para o risco cardiovascular (diretriz brasileira) ou se o risco em 10 anos para doença cardiovascular aterosclerótica fosse ≥ 7,5% (diretriz da AHA/ACC). Um valor de p < 0,05 foi considerado estatisticamente significativo. Resultados A amostra do estudo consistiu 18525 indivíduos (69% homens, idade 48 ± 6 anos). Entre os indivíduos considerados de risco intermediário ou alto segundo a diretriz brasileira, mais de 80% seriam classificados em uma categoria de risco mais baixo segundo a diretriz da AHA/ACC. Entre os homens, 45% e 16% seriam considerados elegíveis para a terapia com estatina segundo as diretrizes brasileira e da AHA/ACC, respectivamente (p < 0,001). Entre as mulheres, as respectivas proporções seriam 16% e 1% (p < 0,001). Oitenta e dois porcento das mulheres e 57% dos homens elegíveis para estatina com base no critério da diretriz brasileira não seriam considerados elegíveis para estatina segundo o critério da AHA/ACC. Conclusões Em comparação à diretriz da AHA/ACC, a diretriz brasileira classifica uma maior proporção dos pacientes em prevenção primária em categorias de risco mais alto e aumenta substancialmente a elegibilidade para estatina. (Arq Bras Cardiol. 2020; 115(3):440-449)

Abstract Background Differences between the updated versions of the Brazilian Guideline on Dyslipidemias and the American Heart Association (AHA)/American College of Cardiology (ACC) Cholesterol Guideline regarding cardiovascular risk stratification and statin eligibility are unknown. Objectives To compare cardiovascular risk categorization and statin eligibility based on the Brazilian guideline with those based on the AHA/ACC guideline in primary prevention patients. Methods We retrospectively analyzed individuals aged 40-74 years without high-risk conditions, with LDL-c 70 to < 190 mg/dL, not on lipid-lowering drugs, who underwent routine clinical assessment. Cardiovascular risk was stratified according to the Brazilian and the AHA/ACC guidelines. Subjects were considered eligible for statin therapy if LDL-c was at least 30 mg/dL above the target for the cardiovascular risk (Brazilian guideline) or the 10-year atherosclerotic cardiovascular disease risk was ≥7.5% (AHA/ACC guideline). A p-value < 0.05 was considered statistically significant. Results The study sample consisted of 18,525 subjects (69% male, age 48 ± 6 years). Among subjects considered at intermediate or high risk by the Brazilian guideline, over 80% would be in a lower risk category by the AHA/ACC guideline. Among men, 45% and 16% would be statin eligible by the Brazilian and the AHA/ACC guidelines criteria, respectively (p < 0.001). Among women, the respective proportions would be 16% and 1% (p < 0.001). Eighty-two percent of women and 57% of men eligible for statins based on the Brazilian guideline criterion would not be eligible according to the AHA/ACC guideline criterion. Conclusions Compared with the AHA/ACC guideline, the Brazilian guideline classifies a larger proportion of primary prevention patients into higher-risk categories and substantially increases statin eligibility. (Arq Bras Cardiol. 2020; 115(3):440-449)

Predictors of Family Enrollment in a Genetic Cascade Screening Program for Familial Hypercholesterolemia / Preditores de Recrutamento Familiar em um Programa de Rastreamento Genético em Cascata para Hipercolesterolemia Familiar

Abstract Background: Genetic cascade screening is the most cost-effective method for the identification of individuals with familial hypercholesterolemia (FH), but the best strategies for the enrollment of at-risk individuals in a FH screening program are not fully known. Objective: The aim of this study is to identify the best predictors of familial enrollment into genetic screening, using features derived from tested probands. Methods: One hundred and eighty-three index-cases (ICs) with a positive genetic result that had relatives screened from 01/2011 to 07/2015 were included. The response variable was the number of relatives for each enrolled IC. All variables in the study were based on ICs' derived clinical and socioeconomical features. The effect size of predictor variables were obtained through a general linear model using a negative binomial regression link function. Significance was considered with a p < 0.05. Results: Mean IC age when enrolling into the program was 50 years old; 78.1% of individuals reported knowledge of relatives with dyslipidemia. Mean baseline LDL-cholesterol level was 316 ± 90 mg/dL. Referral origin through the cascade program website vs. tertiary care, IC LDL-cholesterol and familial history of high LDL-cholesterol levels were independent predictors associated with a higher number of enrolled relatives. Conclusions: Our data suggest that FH cascade screening programs can predict family enrollment based on IC features. This information may be useful for devising better and more effective screening approaches for at-risk individuals.

Resumo Fundamento: O rastreamento genético em cascata é o método mais economicamente viável para a identificação de indivíduos com hipercolesterolemia familiar, mas as melhores estratégias para o recrutamento de indivíduos em risco em um programa de rastreamento deste tipo não são inteiramente conhecidas. Objetivo: Identificar os melhores preditores de recrutamento familiar em rastreamento genético, usando características derivadas de probandos testados. Métodos: Foram inscritos 183 casos índices com resultado genético positivo, que tiveram familiares rastreados de janeiro de 2011 a julho de 2015. A variável de resposta foi o número de familiares para cada caso índice inscrito. Todas as variáveis do estudo foram baseadas em características clínicas e socioeconômicas derivadas dos casos índices. O tamanho do efeito das variáveis preditoras foi obtido de modelo linear geral utilizando função de associação de regressão binomial negativa. A significância foi considerada com p < 0,05. Resultados: A média de idade dos casos índices ao ingressar no programa foi de 50 anos; 78,1% dos indivíduos relataram conhecimento de familiares com dislipidemia. O nível médio de LDL-colesterol inicial foi de 316 ± 90 mg/dL. Origem de referência por meio do site do programa em cascata vs. cuidados terciários, LDL-colesterol do caso índice e história familiar de níveis elevados de LDL-colesterol foram preditores independentes associados a um maior número de familiares inscritos. Conclusões: Programas de rastreamento genético em cascata da hipercolesterolemia familiar podem prever o recrutamento da família com base nas características do caso índice. Esta informação pode ser útil para criar abordagens de rastreamento melhores e mais eficazes para indivíduos em risco.

Estimated costs of hospitalization due to coronary artery disease attributable to familial hypercholesterolemia in the Brazilian public health system

ABSTRACT Objective: Cardiovascular diseases are the leading cause of death in Brazil, imposing substantial economic burden on the health care system. Familial hypercholesterolemia (FH) is known to greatly increase the risk of premature coronary artery disease (CAD). This study aimed to estimate the economic impact of hospitalizations due to CAD attributable to FH in the Brazilian Unified Health Care System (SUS). Subjects and methods: Retrospective, cross-sectional study of data obtained from the Hospital Information System of the SUS (SIHSUS). We selected all adults (≥ 20 years of age) hospitalized from 2012­-2014 with primary diagnoses related to CAD (ICD-10 I20 to I25). Attributable risk methodology estimated the contribution of FH in the outcomes of interest, using international data for prevalence (0.4% and 0.73%) and relative risk for events (RR = 8.56). Results: Assuming an international prevalence of FH of 0.4% and 0.73%, of the 245,981 CAD admissions/year in Brazil, approximately 7,249 and 12,915, respectively, would be attributable to an underlying diagnosis ­­of FH. The total cost due to CAD per year, considering both sexes and all adults, was R$ 985,919,064, of which R$ 29,053,500 and R$ 51,764,175, respectively, were estimated to be attributable to FH. The average cost per FH-related CAD event was R$ 4,008. Conclusion: Based on estimated costs of hospitalization for CAD, we estimated that 2.9-5.3% are directed to FH patients. FH can require early specific therapies to lower risk in families. It is mandatory to determine the prevalence of FH and institute appropriate treatment to minimize the clinical and economic impact of this disease in Brazil.

Impact of self-reported fasting duration on lipid profile variability, cardiovascular risk stratification and metabolic syndrome diagnosis

ABSTRACT Objective We sought to investigate the impact of self-reported fasting duration times on the lipid profile results and its impact on the cardiovascular risk stratification and metabolic syndrome diagnosis. Subjects and methods We analyzed data from all consecutive individuals evaluated in a comprehensive health examination at the Hospital Israelita Albert Einstein from January to December 2015. We divided these patients in three groups, according to the fasting duration recalled (< 8h, 8-12h and > 12h). We calculated the global cardiovascular risk and diagnosed metabolic syndrome according to the current criteria and estimated their change according to fasting duration. Results A total of 12,196 (42.3 ± 9.2 years-old, 30.2% females) patients were evaluated. The distribution of cardiovascular risk was not different among groups defined by fasting duration in both men and women (p = 0.547 for women and p = 0.329 for men). Similarly, the prevalence of metabolic syndrome was not influenced by the fasting duration (p = 0.431 for women and p = 0.166 for men). Conclusion Self-reported fasting duration had no significant impact on the lipid profile results, including triglyceride levels. Consequently, no changes on the cardiovascular risk stratification using the Framingham risk score nor changes on the prevalence of metabolic syndrome were noted.

Association of subclinical inflammation, glycated hemoglobin and risk for obstructive sleep apnea syndrome / Associação entre inflamação subclínica, hemoglobina glicada e risco de apneia obstrutiva do sono

ABSTRACT Objective To investigate the inter-relation between high sensitivity C-reactive protein and glycated hemoglobin in prediction of risk of obstructive sleep apnea. Methods We included all individuals participating in a check-up program at the Preventive Medicine Center of Hospital Israelita Albert Einstein in 2014. The Berlin questionnaire for risk of obstructive sleep apnea was used, and the high sensitivity C-reactive protein and glycated hemoglobin levels were evaluated. Results The sample included 7,115 participants (age 43.4±9.6 years, 24.4% women). The Berlin questionnaire showed changes in 434 (6.1%) individuals. This finding was associated with high sensitivity C-reactive protein and glycated hemoglobin levels (p<0.001). However, only the association between the Berlin questionnaire result and glycated hemoglobin remained significant in the adjusted multivariate analysis, for the traditional risk factors and for an additional model, including high-density lipoprotein cholesterol and triglycerides. Conclusion The glycated hemoglobin, even below the threshold for diagnosis of diabetes, is independently associated with obstructive sleep apnea syndrome, even after adjustment for obesity and C-reactive protein. These findings suggest a possible pathophysiological link between changes in insulin resistance and obstructive sleep apnea syndrome, independently from obesity or low-grade inflammation.

RESUMO Objetivo Investigar a inter-relação entre proteína C-reativa de alta sensibilidade e hemoglobina glicada na predição do risco de apneia obstrutiva do sono. Métodos Foram incluídos todos os indivíduos participantes do programa de check-up do Centro de Medicina Preventiva Hospital Israelita Albert Einstein em 2014. Foi aplicado o questionário de Berlin sobre risco de apneia do sono, e avaliadas as dosagens de hemoglobina glicada e proteína C-reativa de alta sensibilidade. Resultados Foram incluídos 7.115 participantes (idade 43,4±9,6 anos, 24,4% mulheres). A prevalência de alteração no questionário de Berlin foi de 434 (6,1%). A alteração do questionário de Berlin associou-se positivamente aos resultados da proteína C-reativa de alta sensibilidade e da hemoglobina glicada (p<0,001). No entanto, apenas a associação entre o resultado do questionário de Berlin e a hemoglobina glicada permaneceu significativa na análise multivariada ajustada tanto para fatores de risco tradicionais quanto para um modelo adicional, que incluiu também lipoproteína de alta densidade-colesterol (HDL-c) e triglicérides. Conclusão A hemoglobina glicada, mesmo em valores abaixo do critério diagnóstico para diabetes mellitus, está associada de forma independente ao risco para síndrome da apneia obstrutiva do sono, mesmo após ajuste para obesidade e proteína C-reativa. Estes achados sugerem possível ligação fisiopatológica entre alterações na resistência insulínica e a síndrome da apneia obstrutiva do sono, que independe da obesidade ou inflamação de baixo grau.

Cardiovascular Risk Stratification and Statin Eligibility Based on the Brazilian vs. North American Guidelines on Blood Cholesterol Management / Estratificação de Risco Cardiovascular e Elegibilidade para Estatina com Base na Diretriz Brasileira vs. Norte-Americana para Manejo do Colesterol

Abstract Background: The best way to select individuals for lipid-lowering treatment in the population is controversial. Objective: In healthy individuals in primary prevention: to assess the relationship between cardiovascular risk categorized according to the V Brazilian Guideline on Dyslipidemia and the risk calculated by the pooled cohort equations (PCE); to compare the proportion of individuals eligible for statins, according to different criteria. Methods: In individuals aged 40-75 years consecutively submitted to routine health assessment at one single center, four criteria of eligibility for statin were defined: BR-1, BR-2 (LDL-c above or at least 30 mg/dL above the goal recommended by the Brazilian Guideline, respectively), USA-1 and USA-2 (10-year risk estimated by the PCE ≥ 5.0% or ≥ 7.5%, respectively). Results: The final sample consisted of 13,947 individuals (48 ± 6 years, 71% men). Most individuals at intermediate or high risk based on the V Brazilian Guideline had a low risk calculated by the PCE, and more than 70% of those who were considered at high risk had this categorization because of the presence of aggravating factors. Among women, 24%, 17%, 4% and 2% were eligible for statin use according to the BR-1, BR-2, USA-1 and USA-2 criteria, respectively (p < 0.01). The respective figures for men were 75%, 58%, 31% and 17% (p < 0.01). Eighty-five percent of women and 60% of men who were eligible for statin based on the BR-1 criterion would not be candidates for statin based on the USA-1 criterion. Conclusions: As compared to the North American Guideline, the V Brazilian Guideline considers a substantially higher proportion of the population as eligible for statin use in primary prevention. This results from discrepancies between the risk stratified by the Brazilian Guideline and that calculated by the PCE, particularly because of the risk reclassification based on aggravating factors.

Resumo Fundamento: Existe controvérsia sobre a melhor forma de selecionar indivíduos para tratamento hipolipemiante na população. Objetivos: Em indivíduos saudáveis em prevenção primária: avaliar a relação entre o risco cardiovascular segundo a V Diretriz Brasileira de Dislipidemias e o risco calculado pelas pooled cohort equations (PCE); comparar a proporção de indivíduos elegíveis para estatinas, de acordo com diferentes critérios. Métodos: Em indivíduos de 40 a 75 anos submetidos consecutivamente a avaliação rotineira de saúde em um único centro, quatro critérios de elegibilidade para estatina foram definidos: BR-1, BR-2 (LDL-c acima ou pelo menos 30 mg/dL acima da meta preconizada pela diretriz brasileira, respectivamente), EUA-1 e EUA-2 (risco estimado pelas PCE em 10 anos ≥ 5,0% ou ≥ 7,5%, respectivamente). Resultados: Foram estudados 13.947 indivíduos (48 ± 6 anos, 71% homens). A maioria dos indivíduos de risco intermediário ou alto pela V Diretriz apresentou risco calculado pelas PCE baixo e mais de 70% daqueles considerados de alto risco o foram devido à presença de fator agravante. Foram elegíveis para estatina 24%, 17%, 4% e 2% das mulheres pelos critérios BR-1, BR-2, EUA-1 e EUA-2, respectivamente (p < 0,01). Os respectivos valores para os homens foram 75%, 58%, 31% e 17% (p < 0,01). Oitenta e cinco por cento das mulheres e 60% dos homens elegíveis para estatina pelo critério BR-1 não seriam candidatos pelo critério EUA-1. Conclusões: Comparada à diretriz norte-americana, a V Diretriz Brasileira considera uma proporção substancialmente maior da população como elegível para estatina em prevenção primária. Isso se relaciona com discrepâncias entre o risco estratificado pela diretriz brasileira e o calculado pelas PCE, particularmente devido à reclassificação de risco baseada em fatores agravantes.

The Expected Cardiovascular Benefit of Plasma Cholesterol Lowering with or Without LDL-C Targets in Healthy Individuals at Higher Cardiovascular Risk / Benefício Cardiovascular Esperado pela Redução do Colesterol Plasmático com ou sem Metas de LDL-C em Indivíduos Saudáveis de Risco Cardiovascular mais Elevado

Abstract Background: There is controversy whether management of blood cholesterol should be based or not on LDL-cholesterol (LDL-c) target concentrations. Objectives: To compare the estimated impact of different lipid-lowering strategies, based or not on LDL-c targets, on the risk of major cardiovascular events in a population with higher cardiovascular risk. Methods: We included consecutive individuals undergoing a routine health screening in a single center who had a 10-year risk for atherosclerotic cardiovascular disease (ASCVD) ≥ 7.5% (pooled cohort equations, ACC/AHA, 2013). For each individual, we simulated two strategies based on LDL-c target (≤ 100 mg/dL [Starget-100] or ≤ 70 mg/dL [Starget-70]) and two strategies based on percent LDL-c reduction (30% [S30%] or 50% [S50%]). Results: In 1,897 subjects (57 ± 7 years, 96% men, 10-year ASCVD risk 13.7 ± 7.1%), LDL-c would be lowered from 141 ± 33 mg/dL to 99 ± 23 mg/dL in S30%, 71 ± 16 mg/dL in S50%, 98 ± 9 mg/dL in Starget-100, and 70 ± 2 mg/dL in Starget-70. Ten-year ASCVD risk would be reduced to 8.8 ± 4.8% in S50% and 8.9 ± 5.2 in Starget-70. The number of major cardiovascular events prevented in 10 years per 1,000 individuals would be 32 in S30%, 31 in Starget-100, 49 in S50%, and 48 in Starget-70. Compared with Starget-70, S50% would prevent more events in the lower LDL-c tertile and fewer events in the higher LDL-c tertile. Conclusions: The more aggressive lipid-lowering approaches simulated in this study, based on LDL-c target or percent reduction, may potentially prevent approximately 50% more hard cardiovascular events in the population compared with the less intensive treatments. Baseline LDL-c determines which strategy (based or not on LDL-c target) is more appropriate at the individual level.

Resumo Fundamentos: Há controvérsias sobre se o controle do colesterol plasmático deve ou não se basear em metas de concentração de colesterol LDL (LDL-c). Objetivos: Comparar o impacto estimado de diferentes estratégias hipolipemiantes, baseadas ou não em metas de LDL-c, sobre o risco de eventos cardiovasculares maiores em uma população de risco cardiovascular mais elevado. Métodos: Foram incluídos indivíduos consecutivamente submetidos a uma avaliação rotineira de saúde em um único centro e que apresentavam um risco em 10 anos de doença cardiovascular aterosclerótica (DCVAS) ≥ 7,5% ("pooled cohort equations", ACC/AHA, 2013). Para cada indivíduo, foram simuladas duas estratégias baseadas em meta de LDL-c (≤ 100 mg/dL [Emeta-100] ou ≤ 70 mg/dL [Emeta-70]) e duas estratégias baseadas em redução percentual do LDL-c (30% [E30%] ou 50% [E50%]). Resultados: Em 1.897 indivíduos (57 ± 7 anos, 96% homens, risco em 10 anos de DCVAS 13,7 ± 7,1%), o LDL-c seria reduzido de 141 ± 33 mg/dL para 99 ± 23 mg/dL na E30%, 71 ± 16 mg/dL na E50%, 98 ± 9 mg/dL na Emeta-100 e 70 ± 2 mg/dL na Emeta-70. O risco em 10 anos de DCVAS seria reduzido para 8,8 ± 4,8% na E50% e para 8,9 ± 5,2 na Emeta-70. O número de eventos cardiovasculares maiores prevenidos em 10 anos por 1.000 indivíduos seria de 32 na E30%, 31 na Emeta-100, 49 na E50% e 48 na Emeta-70. Em comparação com a Emeta-70, a E50% evitaria mais eventos no tercil inferior de LDL-c e menos eventos no tercil superior de LDL-c. Conclusões: As abordagens hipolipemiantes mais agressivas simuladas neste estudo, com base em meta de LDL-c ou redução percentual, podem potencialmente prevenir cerca de 50% mais eventos cardiovasculares graves na população em comparação com os tratamentos menos intensivos. Os níveis basais de LDL-c determinam qual estratégia (baseada ou não em meta de LDL-c) é mais apropriada para cada indivíduo.

Self-Reported High-Cholesterol Prevalence in the Brazilian Population: Analysis of the 2013 National Health Survey / Prevalência de Diagnóstico Médico de Colesterol Alto Autorreferido na População Brasileira: Análise da Pesquisa Nacional de Saúde, 2013

Abstract Background: Data on the prevalence of dyslipidemia in Brazil are scarce, with surveys available only for some towns. Objective: To evaluate the prevalence of the self-reported medical diagnosis of high cholesterol in the Brazilian adult population by use of the 2013 National Health Survey data. Methods: Descriptive study assessing the 2013 National Health Survey data, a household-based epidemiological survey with a nationally representative sample and self-reported information. The sample consisted of 60,202 individuals who reported a medical diagnosis of dyslipidemia. The point prevalence and 95% confidence interval (95%CI) for the medical diagnosis of high cholesterol/triglyceride by gender, age, race/ethnicity, geographic region and educational level were calculated. Adjusted odds ratio was calculated. Results: Of the 60,202 participants, 14.3% (95%CI=13.7-14.8) never had their cholesterol or triglyceride levels tested, but a higher frequency of women, white individuals, elderly and those with higher educational level had their cholesterol levels tested within the last year. The prevalence of the medical diagnosis of high cholesterol was 12.5% (9.7% in men and 15.1% in women), and women had 60% higher probability of a diagnosis of high cholesterol than men. The frequency of the medical diagnosis of high cholesterol increased up to the age of 59 years, being higher in white individuals or those of Asian heritage, in those with higher educational level and in residents of the Southern and Southeastern regions. Conclusion: The importance of dyslipidemia awareness in the present Brazilian epidemiological context must be emphasized to guide actions to control and prevent coronary heart disease, the leading cause of death in Brazil and worldwide.

Resumo Fundamento: A prevalência de hipercolesterolemia no Brasil não é conhecida para todo o país, havendo somente inquéritos em algumas cidades. Objetivo: Avaliar a prevalência de diagnóstico médico de colesterol alto autorreferido na população adulta brasileira, utilizando-se dos dados da Pesquisa Nacional de Saúde (PNS) de 2013. Métodos: Estudo descritivo que avaliou os dados da PNS de 2013, um inquérito epidemiológico de base domiciliar, representativo para o Brasil, com informações autorreferidas. A amostra compreendeu 60.202 indivíduos entrevistados com autorrelato de diagnóstico médico de colesterol. Calculou-se a prevalência de ponto e o intervalo de confiança de 95% (IC95%) para diagnóstico médico de colesterol/triglicerídeos alto(s) por sexo, idade, cor da pele, região geográfica, escolaridade. Foram calculadas as razões de chance ajustadas. Resultados: Dos 60.202 participantes adultos, 14,3% (IC95%=13,7-14,8) nunca tiveram colesterol ou triglicerídeos dosados, sendo que um maior número de mulheres, idosos, indivíduos com instrução superior completa e de raça branca relatou aferição há menos de um ano. A prevalência de diagnóstico médico de colesterol alto foi de 12,5%, maior nas mulheres (15,1%) do que nos homens (9,7%). A frequência de diagnóstico médico de colesterol alto foi maior naqueles com idade até 59 anos, em brancos ou aqueles de origem asiática, em pessoas com maior escolaridade e entre os moradores das macrorregiões Sul e Sudeste do país. Conclusão: A importância do conhecimento da dislipidemia no atual contexto epidemiológico brasileiro deve ser ressaltada para orientar as ações de prevenção das doenças coronarianas, que representam a primeira causa de óbito no Brasil e no mundo.