Percentiles of predicted 10-year cardiovascular disease risk by sex and age in Brazil and their association with estimated risk of long-term atherosclerotic events.

OBJECTIVE: Expressing the cardiovascular disease (CVD) risk in relation to peers may complement the estimation of absolute CVD risk. We aimed to determine 10-year CVD risk percentiles by sex and age in the Brazilian population and evaluate their association with estimated long-term atherosclerotic CVD (ASCVD) risk. METHODS: A cross-sectional analysis of baseline data from the ELSA-Brasil study was conducted in individuals aged 40-74 years without prior ASCVD. Ten-year CVD risk and long-term ASCVD risk were estimated by the WHO risk score and the Multinational Cardiovascular Risk Consortium tool, respectively. Ten-year risk percentiles were determined by ranking the calculated risks within each sex and age group. RESULTS: Ten-year CVD risk versus percentile plots were constructed for each sex and age group using data from 13,364 participants (55% females; median age, 52 [IQR, 46-59] years). Long-term ASCVD risk was calculated in 12,973 (97.1%) participants. Compared to individuals at the <25th risk percentile, those at the ≥75th percentile had a greater risk of being in the highest quartile of long-term risk (ORs [95% CIs] 6.57 [5.18-8.30] in females and 11.59 [8.42-15.96] in males) in regression models adjusted for age, race, education, and 10-year CVD risk. In both sexes, the association between risk percentile and long-term risk weakened after age 50. A tool for calculating 10-year CVD risk and the corresponding percentile is available at https://bit.ly/3CzPUi6. CONCLUSIONS: We established percentiles of predicted 10-year CVD risk by sex and age in the Brazilian population, which independently reflect the estimated long-term ASCVD risk in younger individuals.

Adiposity, hepatic steatosis, and metabolic health transitions in people with obesity: Influences of age and sex.

BACKGROUND AND AIMS: Metabolically healthy (MHO) and unhealthy obesity (MUO) may be transient conditions. This study aimed to quantify and identify predictive factors of metabolic transitions in obesity, exploring influences of age and sex. METHODS AND RESULTS: We retrospectively evaluated adults with obesity who underwent routine health evaluation. In a cross-sectional analysis of 12,118 individuals (80% male, age 44.3 ± 9.9 years), 16.8% had MHO. In a longitudinal evaluation of 4483 participants, 45.2% of individuals with MHO at baseline had dysmetabolism after a median follow-up of 3.0 (IQR 1.8-5.2) years, whereas 13.3% MUO participants became metabolically healthy (MH). Development of hepatic steatosis (HS, ultrasound) was an independent predictor of MHO conversion to dysmetabolism (OR 2.36; 95% CI 1.43, 3.91; p < 0.001), while HS persistence was inversely associated with transition from MUO to MH status (OR 0.63; 95% CI 0.47, 0.83; p = 0.001). Female sex and older age were associated with a lower chance of MUO regression. A 5% increment in body mass index (BMI) over time increased the likelihood of metabolic deterioration by 33% (p = 0.002) in females and 16% (p = 0.018) in males with MHO. A 5% reduction in BMI was associated with a 39% and 66% higher chance of MUO resolution in females and males, respectively (both p < 0.001). CONCLUSION: The findings support a pathophysiological role of ectopic fat depots in metabolic transitions in obesity and identify female sex as an aggravating factor for adiposity-induced dysmetabolism, which has implications for personalized medicine.

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

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.

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.

The association between triglyceride-rich lipoproteins, circulating leukocytes, and low-grade inflammation: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Experimental studies have linked triglyceride-rich lipoproteins (TRLs) to inflammation, but the extent of this phenomenon in vivo has not been completely elucidated. OBJECTIVE: We investigated the association between TRL subparticles and inflammatory markers (circulating leukocytes, plasma high-sensitivity C-reactive protein [hs-CRP], and GlycA) in the general population. METHODS: This was a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). TRLs (number of particles per unit volume) and GlycA were measured by nuclear magnetic resonance spectroscopy. The association between TRLs and inflammatory markers was determined by multiple linear regression models adjusted for demographic data, metabolic conditions, and lifestyle factors. Standardized regression coefficients (beta) with 95% confidence intervals are reported. RESULTS: The study population comprised 4,001 individuals (54% females, age 50 ± 9 years). TRLs, especially medium and large subparticles, were associated with GlycA (beta 0.202 [0.168, 0.235], p<0.001 for total TRLs). There was no association between TRLs and hs-CRP (beta 0.022 [-0.011, 0.056], p = 0.190). Medium, large, and very large TRLs were associated with leukocytes, with stronger connections with neutrophils and lymphocytes than monocytes. When TRL subclasses were analyzed as the proportion of the total pool of TRL particles, medium and large TRLs were positively related to leukocytes and GlycA, whereas smaller particles were inversely associated. CONCLUSIONS: There are different patterns of association between TRL subparticles and inflammatory markers. The findings support the hypothesis that TRLs (especially medium and larger subparticles) may induce a low-grade inflammatory environment that involves leukocyte activation and is captured by GlycA, but not hs-CRP.

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

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.

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.

Are physical inactivity, sitting time and screen time associated with obstructive sleep apnea in adults? A cross-sectional study.

BACKGROUND: Sitting time, screen time and low physical activity (PA) levels have been associated with several diseases and all-cause mortality. PA is related to better sleep quality and absence of daytime sleepiness, along with lower risks of obstructive syndrome apnea (OSA). However, studies on the relationship between sitting time, screen time and OSA are scarce in the literature. OBJECTIVE: To analyze associations between PA levels, sitting time, screen time and OSA among adults with suspected sleep disorder. DESIGN AND SETTING: Cross-sectional study conducted at Hospital Israelita Albert Einstein. METHODS: Data were collected from 369 adults with suspected sleep disorders who visited the hospital's neurophysiology clinic between August 2015 and January 2017. RESULTS: Correlations between hypopnea and PA indicators were demonstrated for total sitting time (0.123; P = 0.019) and total screen time (0.108; P = 0.038). There was also a correlation between latency for rapid-eye-movement sleep (REM_LAT) and total sitting time (0.103; P = 0.047) and a negative correlation between mean oxyhemoglobin saturation (SaO_Avg) and total PA time (-0.103; P = 0.048). There were no associations between PA parameters and apnea-hypopnea index. After adjusting for confounding factors (body mass index, age and gender), sitting time and screen time were not associated with OSA. CONCLUSION: After adjusting for anthropometric and clinical factors, excessive sitting time or screen time was not associated with OSA in adults suspected of sleep disorders. Age, gender, hypertension, body mass index and waist circumference were associated with OSA.

Prediction of metabolic syndrome: A machine learning approach to help primary prevention.

AIMS: To describe the performance of machine learning (ML) applied to predict future metabolic syndrome (MS), and to estimate lifestyle changes effects in MS predictions. METHODS: We analyzed data from 17,182 adults attending a checkup program sequentially (37,999 visit pairs) over 17 years. Variables on sociodemographic attributes, clinical, laboratory, and lifestyle characteristics were used to develop ML models to predict MS [logistic regression, linear discriminant analysis, k-nearest neighbors, decision trees, Light Gradient Boosting Machine (LGBM), Extreme Gradient Boosting]. We have tested the effects of changes in lifestyle in MS prediction at individual levels. RESULTS: All models showed adequate calibration and good discrimination, but the LGBM showed better performance (Sensitivity = 87.8 %, Specificity = 70.2 %, AUC-ROC = 0.86). Causal inference analysis showed that increasing physical activity level and reducing BMI by at least 2 % had an effect of reducing the predicted probability of MS by 3.8 % (95 % CI = -4.8 %; -2.7 %). CONCLUSION: ML models based on data from a checkup program showed good performance to predict MS and allowed testing for effects of lifestyle changes in this prediction. External validation is recommended to verify models' ability to identify at-risk individuals, and potentially increase their engagement in preventive measures.

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

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).

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).

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

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).

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).

The contribution of the systolic and diastolic components for the diagnosis of arterial hypertension under the 2017 ACC/AHA Guideline and metabolic heterogeneity among individuals with Stage 1 hypertension.

Little is known about the impact of the 2017 ACC/AHA hypertension guideline on the distribution pattern of hypertension modalities (isolated systolic hypertension [ISH], isolated diastolic hypertension [IDH], and systolic-diastolic hypertension [SDH]). This cross-sectional study had the following objectives: to compare the prevalence of hypertension, ISH, IDH, and SDH, according to the definitions of the JNC 7 or the 2017 guideline; to determine the relative contribution of the systolic and the diastolic components for the diagnosis of hypertension; and to compare the metabolic profile of ISH, IDH, or SDH among new hypertensive individuals by the 2017 guideline. The authors retrospectively evaluated 33 594 patients (42 ± 10 years, 67% male) who underwent a routine health evaluation. Hypertensive patients not using antihypertensive medication were classified into ISH, IDH, or SDH using guideline-defined thresholds. The prevalence of hypertension increased from 21.1% by the JNC 7 definition to 54.7% using the 2017 criteria (2.6-fold increase). More profound increases were seen in the prevalence of IDH (8.7-fold) and SDH (3.3-fold), whereas the prevalence of ISH reduced from 1.1% (JNC 7) to 0.5% (2017 definition). Among patients with Stage 1 hypertension by the 2017 document, 85% had IDH and fewer metabolic abnormalities compared to those with SDH or ISH. The authors concluded that the 2017 guideline inflates the role of the diastolic component and diminishes the contribution of the systolic component for the diagnosis of hypertension. Individuals with Stage 1 hypertension by the 2017 guideline are metabolically heterogeneous and may have different long-term prognoses.

Natural antibodies and complement modulate intimal thickening after arterial injury.

Immune factors are involved in modulating neointimal response to arterial wall injury, but the role of individual immune effectors in this response remains unclear. Using a carotid cuff injury model in mice, we tested the role of immunoglobulin isotypes in modulating intimal thickening by using adoptive transfer of splenocytes from WT mice, or the direct administration of IgG or IgM into immune-deficient Rag-1-/- [Rag-1 knockout (Rag-1KO)] mice. The direct role of complement was also tested by depletion of complement. Splenocytes from WT mice were isolated and adoptively transferred to Rag-1KO mice subjected to carotid cuff arterial injury. Transfer of splenocytes to Rag-1KO mice resulted in increased serum IgM and IgG within 48 h and were comparable to WT levels by 21 days after injury. Splenocyte transfer in Rag-1KO decreased intimal area by 40% compared with Rag-1KO mice without cell transfer. To further differentiate the relative contribution of IgM or IgG in reducing intimal thickening, additional groups of Rag-1KO mice were subjected to injury and given intravenous injections of pooled mouse IgG or IgM. Both IgG and IgM treatment significantly reduced intimal thickening compared with untreated Rag-1KO mice. Immunoglobulin treatments modified serum complement C3 profile and decreased C3 presence in injured arteries. Depletion of C3 using cobra venom factor in Rag-1KO mice significantly decreased intimal thickening. Our results identify the direct role of natural IgG and IgM, and complement in the modulation of neointimal response to arterial injury.

Highlights from the I international symposium of thrombosis and anticoagulation in internal medicine, October 23-25, 2008, Sao Paulo, Brazil.

The importance of thrombosis and anticoagulation in clinical practice is rooted firmly in several fundamental constructs that can be applied both broadly and globally. Awareness and the appropriate use of anticoagulant therapy remain the keys to prevention and treatment. However, to assure maximal efficacy and safety, the clinician must, according to the available evidence, choose the right drug, at the right dose, for the right patient, under the right indication, and for the right duration of time. The first International Symposium of Thrombosis and Anticoagulation in Internal Medicine was a scientific program developed by clinicians for clinicians. The primary objective of the meeting was to educate, motivate and inspire internists, cardiologists and hematologists by convening national and international visionaries, thought-leaders and dedicated clinician-scientists in Sao Paulo, Brazil. This article is a focused summary of the symposium proceedings.

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.

Low-density lipoprotein-cholesterol lowering in individuals at intermediate cardiovascular risk: Percent reduction or target level?

BACKGROUND: Recommendations for blood cholesterol management differ across different guidelines. HYPOTHESIS: Lipid-lowering strategies based on low-density lipoprotein-cholesterol (LDL-c) percent reduction or target concentration may have different effects on the expected cardiovascular benefit in intermediate-risk individuals. METHODS: We selected individuals between 40 and 75 years of age with 10-year risk for atherosclerotic cardiovascular disease (ASCVD) between 5.0% and <7.5% who underwent a routine health screening. For every subject, we simulated a strategy based on a 40% LDL-c reduction (S40% ) and another strategy based on achieving LDL-c target ≤100 mg/dL (Starget-100 ). The cardiovascular benefit was estimated assuming a 22% relative risk reduction in major cardiovascular events for each 39 mg/dL of LDL-c lowered. RESULTS: The study comprised 1756 individuals (94% men, 52 ± 5 years old). LDL-c and predicted 10-year ASCVD risk would be slightly lower in S40% compared to Starget-100 . The number needed to treat to prevent 1 major cardiovascular event in 10 years (NNT10 ) would be 56 with S40% and 66 with Starget-100 . S40% would prevent more events in individuals with lower baseline LDL-c, whereas Starget-100 would be more protective in those with higher LDL-c. A dual-target strategy (40% minimum LDL-c reduction and achievement of LDL-c ≤100 mg/dL) would be associated with outcomes similar to those expected with the S40% (NNT10 = 55). CONCLUSIONS: In an intermediate-risk population, cardiovascular benefit from LDL-c lowering may be optimized by tailoring the treatment according to the baseline LDL-c or by setting a dual-target strategy (fixed dose statin plus achievement of target LDL-c concentration).

Association between Thyroid-Stimulating Hormone Levels and Non-Alcoholic Fatty Liver Disease Is Not Independent from Metabolic Syndrome Criteria.

INTRODUCTION: Thyroid hormones are involved in the regulation of body composition, lipid metabolism, and insulin resistance. Thus, it is possible that they might play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of thyroid function on NAFLD is not well defined. In this study, we evaluated the relationship between thyroid-stimulating hormone (TSH) levels, within the reference range, and presence of NAFLD in asymptomatic individuals. STUDY DESIGN: We included all individuals evaluated at a preventive clinic of the Hospital Israelita Albert Einstein, between 2014 and 2015. The prevalence of NAFLD (analyzed by abdominal ultrasound), according to TSH quartiles, within the reference range, was determined. The association between TSH quartiles and NAFLD was analyzed by logistic regression adjusted for possible confounders. RESULTS: We evaluated 10,539 individuals (73% male, age 43.4 ± 9.4 years). The prevalence of NAFLD was 34, 38, 38, and 39% in the first to the fourth TSH quartiles (0.46-1.44, 1.45-1.97, 1.98-2.68, and 2.69-4.68 mUI/L, respectively, p for trend < 0.001). At univariate analysis, higher TSH levels were associated with the diagnosis of NAFLD. When data were adjusted for the metabolic syndrome characteristics (waist circumference, HDL-cholesterol and triglycerides levels, presence of diabetes, and systemic arterial hypertension), the association was no longer significant. CONCLUSIONS: Although the TSH variability within the reference range is associated with NAFLD in univariable models, once adjusted for metabolic syndrome factors no significant association is noted.

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

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.

Statin Eligibility in Primary Prevention: From a Risk-Based Strategy to a Personalized Approach Based on the Predicted Benefit.

Guidelines have recommended statin initiation based on the absolute cardiovascular risk. We tested the hypothesis that a strategy based on the predicted cardiovascular benefit, compared with the risk-based approach, modifies statin eligibility and the estimated benefit in a population in primary cardiovascular prevention. The study included 16,008 subjects (48 ± 6 years, 73% men) with low-density lipoprotein cholesterol levels of 70 to <190 mg/dl, not on lipid-lowering drugs, who underwent a routine health screening in a single center. For the risk-based strategy, criterion for statin eligibility was defined as a 10-year atherosclerotic cardiovascular disease (ASCVD) risk of ≥7.5%. In the benefit-based strategy, subjects were considered for statin according to the predicted absolute cardiovascular risk reduction, so that the number of statin candidates would be the same as in the risk-based strategy. The benefit-based strategy would replace 11% of statin candidates allocated in the risk-based approach with younger, lower risk subjects with higher low-density lipoprotein cholesterol. Using the benefit-based strategy, 13% of subjects with 5.0% to < 7.5% ASCVD risk would shift from a statin-ineligible to a statin-eligible status, whereas 24% of those with 7.5% to <10.0% ASCVD risk would become statin ineligible. These effects would transfer the benefit from higher to lower risk subjects. In the entire population, no clinically meaningful change in the benefit would be expected. In conclusion, switching from a risk-based strategy to a benefit-based approach, while keeping the same rate of statin use in the population, is expected to promote substantial changes in statin eligibility in subjects at intermediate cardiovascular risk, modifying the subpopulation to be benefited by the treatment.