The impact of diabetes and subclinical hypothyroidism association with coronary artery calcium: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: We aimed to analyze the association of diabetes and subclinical hypothyroidism with subclinical atherosclerosis measured by coronary artery calcium (CAC) in the baseline of the ELSA-Brasil study. Materials and methods: CAC was measured using a 64-detector computed tomographic scanner. The association of CAC > 0 was presented as an odds ratio (OR) and 95% confidence intervals (95%CI) in logistic models and as β (95%CI) in linear models after multivariable adjustment for confounders. Results: We analyzed 3,809 participants (mean-age (SD) 50.5 (8.8); 51.7% women). In the main analysis, we did not find an association of diabetes and subclinical hypothyroidism with CAC. However, in stratified analysis according to age strata, we found no significative interaction terms, an important heterogeneity between the groups, with the younger age strata showing an association of the group with both diseases and CAC > 0 (OR 7.16; 95%CI, 1.14; 44.89) with a wide but significative 95%CI, suggesting that the smaller number of participants in the younger group may influence the results. Our findings also showed an association of CAC > 0 and log (CAC+1) with diabetes in logistic (OR, 1.31; 95%CI, 1.05-1.63) and linear models (β, 0.24, 0.16, 0.40), respectively. Diabetes was independently associated with CAC > 0 in linear models. Discussion: In conclusion, our results showed a great heterogeneity in stratified analysis based on age in the younger age strata. Although we found no significant interaction factors, the smaller sample size for the analysis may influence the negative findings.

Prognóstico Relacionado à Terapia de Reperfusão Pós-Síndrome Coronariana Aguda na Atenção Secundária: Análise de Sobrevida em Longo Prazo na Estratégia ERICO / Prognosis Related to Reperfusion Therapy Post-Acute Coronary Syndrome in Secondary Care: Long-Term Survival Analysis in the ERICO Study

Resumo Fundamento A relação entre terapia de reperfusão após a síndrome coronariana aguda (SCA) e mortalidade na atenção secundária não é bem conhecida. Objetivos Avaliar o impacto de três estratégias terapêuticas: (1) terapia medicamentosa exclusiva, (2) Angioplastia Transluminal percutânea coronaria (ATPC) e (3) revascularização do miocárdio (RM) na sobrevida em longo prazo de participantes da Estratégia de Registro de Insuficiência Coronariana Aguda (ERICO). Métodos Análises de sobrevida para mortalidade por todas as causas, mortalidade por doença cardiovascular (DCV) e mortalidade por doença arterial coronariana (DAC) foram realizadas de acordo com três estratégias terapêuticas (tratamento clínico exclusivo, ATPC ou RM). Modelos de regressão de Cox foram usados para estimar o hazard ratio (HR) com intervalo de confiança de 95% (IC95%) de 180 dias a quatro anos de acompanhamento após a SCA. Os modelos são apresentados como modelo sem ajuste ou ajustado quanto à idade, sexo e DAC prévia, tipo de SCA, tabagismo, hipertensão, dislipidemia, fração de ejeção do ventrículo esquerdo e de acordo com o número de artérias coronárias principais obstruídas (≥50%). Resultados Entre os 800 participantes, as piores taxas de sobrevida (mortalidade por todas as causas e DCV) foram detectadas entre os indivíduos que se submeteram a RM. Houve correlação entre RM e DAC [HR: 2,19 (IC95% 1,05-4,55)], mas o risco perdeu significância no modelo multivariado. A ATPC foi associada a uma menor probabilidade de eventos fatais durante os quatro anos de acompanhamento: mortalidade por todas as causas [HR, análise multivariada: 0,42 (IC95% 0,26-0,70)], por DCV [HR: 0,39 (95% CI: 0,20-0,73)] e DAC [HR, análise multivariada: 0,24 (IC95% 0,09-0,63)] em comparação aos submetidos ao tratamento clínico exclusivo. Conclusão No ERICO, a ATPC após a SCA foi associada a um melhor prognóstico, principalmente sobrevida por DAC.

Abstract Background Relationship between reperfusion therapy post-acute coronary syndrome (ACS) and mortality in secondary care is not well-known. Objectives To evaluate the impact of three therapeutic strategies: (1) exclusive medical therapy, (2) percutaneous coronary intervention (PCI) and (3) coronary artery bypass grafting (CABG) on long-term survival of participants in the Strategy of Registry of Acute Coronary Syndrome (ERICO) study. Methods Survival analyses for all-cause, cardiovascular (CVD) and coronary artery disease (CAD) mortality were performed according to three therapeutic strategies (exclusive medical therapy, PCI or CABG). Cox regression models were used to estimate the hazard ratio (HR) with respective 95% confidence interval (95%CI) from 180 days to four years of follow-up after ACS. Models are presented as crude, age-sex adjusted and further adjusted for previous CAD, ACS subtype, smoking, hypertension, dyslipidemia, left ventricular ejection fraction and according to the number of obstructed (≥ 50%) major coronary arteries. Results Among 800 participants, the lowest crude survival rates were detected among individuals who underwent CABG (all-cause and CVD). CABG was correlated to CAD (HR: 2.19 [95% CI: 1.05-4.55]). However, this risk lost significance in the full model. PCI was associated to lower probability of fatal events during four-year follow-up: all-cause [multivariate HR: 0.42 (95% CI: 0.26-0.70)], CVD [HR: 0.39 (95% CI: 0.20-0.73)] and CAD [multivariate HR: 0.24 (95% CI: 0.09-0.63)] compared to those submitted to exclusive medical therapy. Conclusion In the ERICO study, PCI after ACS was associated to better prognosis, particularly CAD survival.

The association of diabetes, subclinical hypothyroidism and carotid intima-media thickness: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brazil)

Abstract Introduction: The association of diabetes with subclinical thyroid diseases may increase the risk of cardiovascular diseases. We analyzed the association of subclinical hypothyroidism, diabetes, and both diseases with carotid Intima-Media Thickness (cIMT) as a surrogate maker for early cardiovascular disease in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: Cross-sectional analysis with data from the 3rd visit (2017‒2019). Linear regression models were used to evaluate the association of subclinical hypothyroidism, diabetes and of both diseases with a cIMT presented as Beta (95% Confidence Interval - 95% CI) without adjustment, with adjustment for sociodemographic variables (Model 1) and multivariable adjustment (Model 1 more cardiovascular risk factors). We also used logistic regression models to analyze the Odds Ratio (OR) and 95% CI for the association of both diseases using cIMT > P75%. Results: After the exclusion of patients with previous cardiovascular disease, 5,077 participants with no diseases, 1578 with diabetes, 662 with subclinical hypothyroidism, and 234 with both diseases were included in the analysis. Linear regression models showed an association of cIMT with only diabetes (β = 0.019; 95% CI 0.012 to 0.027; p < 0.0001) and subclinical hypothyroidism more diabetes (β = 0.03; 95% CI 0.010‒0.047, p < 0.0001). The logistic regression model reported an association between diabetes and CIMT higher than P75% (OR = 1.49, 95% CI 1.30‒1.71). No interaction between diabetes and subclinical hypothyroidism was detected using cIMT respectively as a continuous (p = 0.29) or as a categorical variable (p = 0.92). Discussion: Diabetes was associated with higher cIMT values. However, no additive effect of subclinical hypothyroidism associated with diabetes over cIMT was detected.

Association between psoriasis and thyroid function: results from the Brazilian Longitudinal Study of Adults Health (ELSA-Brasil)

ABSTRACT Objective: To determine the relationship between psoriasis, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triodothyronine (FT3), thyroid peroxidase antibodies (TPOAb), and subclinical thyroid dysfunctions in middle-aged and older adults. Materials and methods: Cross-sectional analyses included a self-reported medical diagnosis of psoriasis and thyroid function from the 3rd visit (2017-2019) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). TSH, FT4, and FT3 levels were analyzed as continuous variables and quintiles, and TPOAb positivity and subclinical hypothyroidism as a yes/no variable. Logistic regression models were built as crude and adjusted by main confounders (age, sex, education level, race/ethnicity, and smoking). Results: From 9,649 participants (52.3% women; 59.2 ± 8.7 years old), the prevalence of psoriasis was 2.8% (n = 270). TSH, FT4, TPOAb positivity, and subclinical hypothyroidism were not associated with psoriasis in the main analyses. In the stratified analysis, our findings showed positive associations of the lowest (OR = 2.01; 95% CI 1.05-3.84; p = 0.036) and the highest (OR = 2.13; 95% CI 1.12-4.05; p = 0.022) quintiles of FT4 and a protective association of TPOAb positivity (OR = 0.43; 95% CI 0.19-0.98; p = 0.046) with prevalent psoriasis in women. In the logistic regression for FT3, participants in the 1st quintile showed a statistically significant association with psoriasis for the whole sample (OR = 1.66; 95% CI 1.11-2.46; p = 0.013) and for men (OR = 2.25; 95% CI 1.25-4.04; p = 0.007) in the sex-stratified analysis. Conclusions: The present study showed that the association of FT4 levels with psoriasis are different according to sex, with a possible U-shaped curve in women but not in men. Although there were some associations of FT3 with psoriasis, they may be a consequence of non-thyroidal illness syndrome. Further prospective data may clarify the association of thyroid function and psoriasis.

Saúde Cardiovascular e Fibrilação ou Flutter Atrial: Um Estudo Transversal do ELSA-Brasil / Cardiovascular Health and Atrial Fibrillation or Flutter: A Cross-Sectional Study from ELSA-Brasil

Resumo Fundamento A associação entre o status de saúde cardiovascular ideal ( ideal cardiovascular health ( ICVH) e diagnóstico de fibrilação ou flutter atrial (FFA) foi menos estudado em comparação a outras doenças cardiovasculares. Objetivos Analisar a associação entre o diagnóstico de FFA e métricas e escores de ICVH no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Métodos Este estudo analisou dados de 13141 participantes com dados completos. Os traçados eletrocardiográficos foram codificados de acordo com o Sistema de Minnesota, em um centro de leitura centralizado. As métricas do ICVH (dieta, atividade física, índice de massa corporal, tabagismo, glicemia de jeju, e colesterol total) e escores do ICVH foram calculados conforme proposto pela American Heart Association . Modelos de regressão logística bruta e ajustada foram construídos para analisar associações de métricas e escores do ICVH com diagnóstico de FFA. O nível de significância foi estabelecido em 0,05. Resultados A idade mediana da amostra foi de 55 anos, e 54,4% eram mulheres. Nos modelos ajustados, os escores de ICVH não apresentaram associação significativa com diagnóstico de FFA prevalente [odds ratio (OR):0,96; intervalo de confiança de 95% (IC95%):0,80-1,16; p=0,70). Perfis de pressão arterial ideal (OR:0,33; IC95%:0,1-0,74; p=0,007) e colesterol total ideal (OR:1,88; IC95%:1,19-2,98; p=0,007) foram significativamente associados com o diagnóstico de FFA. Conclusões Não foram identificadas associações significativas entre escores de ICVH global e diagnóstico de FFA após ajuste multivariado em nossas análises, devido, ao menos em parte, às associações antagônicas da FFA com métricas de pressão arterial e de colesterol total do ICVH. Nossos resultados sugerem que estimar a prevenção da FFA por meio de escore de ICVH global pode não ser adequado, e as métricas do ICVH devem ser consideradas separadamente.

Abstract Background The association between ideal cardiovascular health (ICVH) status and atrial fibrillation or flutter (AFF) diagnosis has been less studied compared to other cardiovascular diseases. Objective To analyze the association between AFF diagnosis and ICVH metrics and scores in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods This study analyzed data from 13,141 participants with complete data. Electrocardiographic tracings were coded according to the Minnesota Coding System, in a centralized reading center. ICVH metrics (diet, physical activity, body mass index, smoking, blood pressure, fasting plasma glucose, and total cholesterol) and scores were calculated as proposed by the American Heart Association. Crude and adjusted binary logistic regression models were built to analyze the association of ICVH metrics and scores with AFF diagnosis. Significance level was set at 0.05. Results The sample had a median age of 55 years and 54.4% were women. In adjusted models, ICVH scores were not significantly associated with prevalent AFF diagnosis (odds ratio [OR]:0.96; 95% confidence interval [95% CI]:0.80-1.16; p=0.70). Ideal blood pressure (OR:0.33; 95% CI:0.15-0.74; p=0.007) and total cholesterol (OR:1.88; 95% CI:1.19-2.98; p=0.007) profiles were significantly associated with AFF diagnosis. Conclusions No significant associations were identified between global ICVH scores and AFF diagnosis after multivariable adjustment in our analyses, at least partially due to the antagonistic associations of AFF with blood pressure and total cholesterol ICVH metrics. Our results suggest that estimating the prevention of AFF burden using global ICVH scores may not be adequate, and ICVH metrics should be considered in separate.

ELSA-Brasil: a 4-year incidence of hearing loss in adults with and without hypertension

ABSTRACT OBJECTIVE To compare the incidence of hearing loss among adults stratified by the occurrence of hypertension, and to investigate the association between hypertension and hearing loss. METHODS Longitudinal observational study, part of the Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil, Longitudinal Study on Adult's Health). Data from the first and second waves were analyzed, including information from audiological assessment and general health of the subjects. As outcome, we considered the presence of hearing loss (hearing thresholds above 25 dBHL at frequencies from 500 Hz to 8 kHz) and, as exposure variable, hypertension (report of medical diagnosis of hypertension; and/or use of drugs to treat hypertension; and/or pressure systolic blood pressure ≥ 140 mmHg; or diastolic blood pressure ≥ 90 mmHg). As covariables for adjustment were considered: sex, age, education, race / ethnicity, income, smoking, diabetes, and occupational exposure to noise. Poisson regression analysis was conducted, estimating the crude and adjusted relative risks, with 95% confidence intervals, in order to assess the factors associated with hearing loss. RESULTS In crude analyses, the incidence of hearing loss was higher for subjects with hypertension (9.7% versus 5.4%). The crude relative risks for hearing loss was almost double (1.93; 95%CI: 1.10-3.39) for subjects with hypertension in the right ear. In the adjusted analyses, the relative risks was not significant for the hypertension variable (1.42; 95%CI: 0.75-2.67). Being 60 years or older (RR: 5.41; 95%CI: 2.79-10.50) showed a statistically significant association with hearing loss, indicating that older adults have higher relative risks for hearing loss. CONCLUSION In the adjusted analyses controlled for multiple risk factors there was no association between hypertension and hearing loss. The dichotomous variable age (being 60 years or older), on the other hand, has shown a significant association with hearing loss.

Reference range of serum uric acid and prevalence of hyperuricemia: a cross-sectional study from baseline data of ELSA-Brasil cohort

Abstract Background: Most of the few studies that have established reference ranges for serum uric acid (SUA) have not taken into account factors which may interfere with its levels and followed rigorous laboratory quality standards. The aim of this study was to establish reference ranges for SUA and determine the prevalence of hyperuricemia. Method: Cross-sectional study including 15,100 participants (all sample) aged 35 to 74 years from baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicentric cohort of volunteer civil servants from five universities and one research institute located in different regions of Brazil. It was established a reference sample excluding participants with factors that directly influence SUA levels: glomerular filtration rate lower than 60 ml/min, excessive alcohol intake, use of diuretics, aspirin, estrogen or urate-lowering therapy. SUA was measured using the uricase method and following rigorous international quality standards. Reference ranges were defined as values between percentiles 2.5 (P2.5) and 97.5 (P97.5) of SUA distribution in the reference sample, stratified by sex. Hyperuricemia was defined as SUA ≥ 7 mg/100 ml in the all sample. Results: The reference sample was composed of 10,340 individuals (55.3% women, median age 50 years). Reference ranges (P2.5 to P97.5) for SUA were: 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Sex was a major determinant for SUA levels (median [IQR], mg/100 ml: 6.1 [5.3-7.0] for men versus 4.5 [3.9-5.3] for women, p < 0.001). Higher levels of SUA were found in patients with higher BMI. Higher age had (a modest) influence only for women. The prevalence of hyperuricemia for all sample (N = 15,100) was 31.9% (95% confidence interval [CI] 30.8- 33.0%) in men and 4.8% (95% CI 4.3-5.3%) in women. Conclusion: SUA reference ranges were 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Prevalence of hyperuricemia was 31.9% in men and 4.8% in women. Updated SUA reference ranges and prevalence of hyperuricemia are higher nowadays and might be used to guide laboratories and the screening for diseases related to SUA.

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.

Incidence of TPOAb over a 4-year follow-up period: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: Although some previous data have suggested a high iodine intake in Brazil, the prevalence of antithyroperoxidase antibodies (TPOAb) in the country is compatible with rates from countries with adequate iodine intake. This observation emphasizes the importance of knowing the incidence of TPOAb in Brazil. Materials and methods: This prospective analysis included euthyroid participants with negative TPOAb at baseline and a thyroid function assessment at a 4-year follow-up. TPOAb was measured by electrochemiluminescence and considered positive when titers were ≥34 IU/mL. TSH and free T4 (FT4) levels were determined by a third-generation immunoenzymatic assay. The incidence of TPOAb is expressed in percentage per year or as a cumulative incidence within the 4-year follow-up period. Results: Of 8,922 euthyroid participants (mean age 51.1 years; 50.9% women) with a negative TPOAb test at baseline, 130 presented incident TPOAb at the 4-year follow-up, yielding an annual incidence of TPOAb of 0.38%/year (95% confidence interval [95% CI], 0.37-0.39%/year) and a cumulative incidence over 4 years of 1.46% (95% CI, 1.21-1.71%). In men, the annual incidence was 0.32% (95% CI, 0.31-0.33%), and the cumulative incidence over 4 years was 1.23% (95% CI, 0.90-1.56%). In women, the annual incidence was 0.43%/year (95% CI, 0.42-0.44%/year) and the cumulative incidence over 4 years was 1.67% (95% CI, 1.30-2.04%). The only factor associated with incident TPOAb was the occurrence of thyroid diseases at follow-up. No differences in TPOAb incidence were detected across ELSA-Brasil research centers. Conclusion: Based on the results of this study, the incidence of TPOAb per year and at a 4-year follow-up period are compatible with those of a country with adequate iodine intake.

Diagnóstico de Fibrilação Atrial na Comunidade Utilizando Eletrocardiograma e Autorrelato: Análise Transversal do ELSA-Brasil / Atrial Fibrillation Diagnosis using ECG Records and Self-Report in the Community: Cross-Sectional Analysis from ELSA-Brasil

Resumo Fundamento: A fibrilação ou flutter atrial (FFA) é a arritmia cardíaca sustentada mais comum. Existem poucos dados sobre a epidemiologia da FFA na América do Sul. Objetivo: O presente estudo procurou descrever a epidemiologia clínica da FFA e o uso de anticoagulantes na avaliação da linha de base do Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil). Métodos: Foram analisados dados de 13.260 participantes do ELSA-Brasil. A FFA foi definida pelo eletrocardiograma ou por autorrelato. Modelos de regressão logística foram construídos para analisar fatores associados à FFA. Este estudo também analisou se idade e sexo estavam associados ao uso de anticoagulantes para evitar acidente vascular cerebral. O nível de significância foi de 5%. Resultados: A idade mediana foi de 51 anos, e 7.213 (54,4%) participantes eram mulheres. A FFA foi detectada em 333 (2,5%) participantes. O aumento da idade (razão de chances [RC]:1,05; intervalo de confiança de 95% [IC95%]: 1,04-1,07), hipertensão (RC:1,44; IC95%:1,14-1,81) coronariopatia (RC: 5,11; IC95%:3,85-6,79), insuficiência cardíaca (RC:7,37; IC95%:5,00-10,87) e febre reumática (RC:3,38; IC95%:2,28-5,02) foram associadas à FFA. Dos 185 participantes com FFA e pontuação no CHA2DS2-VASc≥2, apenas 20 (10,8%) usavam anticoagulantes (50,0% entre aqueles com FFA no eletrocardiograma de linha de base). O uso de anticoagulantes nesse grupo foi associado a maior idade (1,8% vs 17,7% naqueles com idade ≤ 54 e ≥ 65 anos, respectivamente; p=0,013). Observou-se uma tendência ao menor uso de anticoagulantes em mulheres (7,1% vs. 16,4% em mulheres e homens, respectivamente; p=0,055). Conclusões: No recrutamento do ELSA-Brasil, 2,5% dos participantes tinham FFA. O baixo uso de anticoagulantes era comum, o que representa um desafio para os cuidados de saúde nesse cenário.

Abstract Background: Atrial fibrillation or flutter (AFF) is the most common sustained cardiac arrhythmia. Limited data can be found on AFF epidemiology in South America. Objective: The present study sought to describe the clinical epidemiology of AFF and the use of stroke prevention medication in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline assessment. Methods: This study analyzed data from 13,260 ELSA-Brasil participants. AFF was defined according to ECG recording or by self-report. Logistic regression models were built to analyze factors associated with AFF. This study also analyzed if age and sex were associated with anticoagulant use for stroke prevention. Significance level was set at 5%. Results: Median age was 51 years and 7,213 (54.4%) participants were women. AFF was present in 333 (2.5%) participants. Increasing age (odds ratio [OR]:1.05; 95% confidence interval [95%CI]: 1.04-1.07), hypertension (OR:1.44; 95%CI: 1.14-1.81), coronary heart disease (OR: 5.11; 95%CI: 3.85-6.79), heart failure (OR:7.37; 95%CI: 5.00-10.87), and rheumatic fever (OR:3.38; 95%CI: 2.28-5.02) were associated with AFF. From 185 participants with AFF and a CHA2DS2-VASc score ≥2, only 20 (10.8%) used anticoagulants (50.0% among those with AFF in the baseline ECG). Stroke prevention in this group was associated with a higher age (1.8% vs 17.7% in those aged ≤ 54 and ≥ 65 years, respectively; p=0.013). A trend towards a reduced anticoagulant use was observed in women (7.1% vs. 16.4% in women and men, respectively; p=0.055). Conclusions: At the ELSA-Brasil baseline, 2.5% of the participants had AFF. The lack of stroke prevention was common, which is an especially challenging point for healthcare in this setting.

Incidence of thyroid diseases: Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: To evaluate incidence of subclinical and overt hyperthyroidism and hypothyroidism. Subjects and methods: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a prospective cohort study of 15,105 civil servants, examined at baseline and over a 4-year follow-up. This analysis included 9,705 participants with normal thyroid function at baseline, follow-up information about thyroid function and with no report of using drugs that may interfere in the thyroid function. Thyroid function was defined by TSH/FT4 levels or routine use of thyroid hormones/anti-thyroid medications. Annual and cumulative (over 4-year) incidence rates were presented as percentages (95% Confidence Intervals). Results: The incidence of all overt and subclinical thyroid disease was 6.7% (1.73%/year): 0.19% for overt hyperthyroidism (0.048%/year), 0.54% for subclinical hyperthyroidism (0.14%/year), 1.98% for overt hypothyroidism (0.51%/year), and 3.99% for subclinical hypothyroidism (1.03%/year). The incidence of all thyroid diseases was higher in women, when compared to men, with a low women:men ratio (1.36). For Blacks the highest incidence was for overt hyperthyroidism, while for Whites, the highest incidence was for overt hypothyroidism. However, the highest incidence of overt hyperthyroidism was detected in Asian descendants. The presence of antithyroperoxidase antibodies at baseline was associated with higher incidence of overt thyroid diseases. Conclusion: These results showed a high incidence of hypothyroidism, which is compatible with a country with a more-than-adequate iodine intake. The low women:men ratio of the incidence of thyroid dysfunction highlights the importance of the diagnosis of thyroid diseases among men in Brazil.

Longitudinal measurement invariance of neuropsychological tests in a diverse sample from the ELSA-Brasil study

Objective: Longitudinal measurement invariance analyses are an important way to assess a test's ability to estimate the underlying construct over time, ensuring that cognitive scores across visits represent a similar underlying construct, and that changes in test performance are attributable to individual change in cognitive abilities. We aimed to evaluate longitudinal measurement invariance in a large, social and culturally diverse sample over time. Methods: A total of 5,949 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were included, whose cognition was reassessed after four years. Longitudinal measurement invariance analysis was performed by comparing a nested series of multiple-group confirmatory factor analysis models (for memory and executive function factors). Results: Configural, metric, scalar and strict invariance were tested and supported over time. Conclusion: Cognitive temporal changes in this sample are more likely to be due to normal and/or pathological aging. Testing longitudinal measurement invariance is essential for diverse samples at high risk of dementia, such as in low- and middle-income countries.

Hearing loss, tinnitus, and hypertension: analysis of the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

OBJECTIVES: To investigate the association among hypertension, tinnitus, and sensorineural hearing loss and evaluate the influence of other covariates on this association. METHODS: Baseline data (2008-2010) from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were analyzed. Altogether, 900 participants were evaluated. The baseline assessment consisted of a 7-hour examination to obtain clinical and laboratory variables. Hearing was measured using pure-tone audiometry. RESULTS: Overall, 33.3% of the participants had hypertension. Participants with hypertension were more likely to be older, male, and diabetic compared to those without hypertension. The prevalence of tinnitus was higher among hypertensive participants and the odds ratio for tinnitus was higher in participants with hypertension than in those without hypertension. However, the difference was not significant after adjusting for age. Audiometric results at 250-8,000 Hz were worse in participants with hypertension than in those without hypertension in the crude analysis; however, the differences were not significant after adjustment for age, sex, diagnosis of diabetes, and exposure to noise. No significant difference was observed in hearing thresholds among participants having hypertension for <6 years, those having hypertension for ≥6 years, and individuals without hypertension. CONCLUSION: Hearing thresholds were worse in participants with hypertension. However, after adjusting for age, sex, diagnosis of diabetes, and exposure to noise, no significant differences were observed between participants with and without hypertension. A higher prevalence of tinnitus was observed in participants with hypertension compared to those without hypertension, but without significance after adjusting for age.

Frequência e Motivos para a não Administração e Suspensão de Medicamentos durante um Evento de Síndrome Coronariana Aguda. Estudo ERICO / Frequency and Reasons for Non-Administration and Suspension of Drugs During an Acute Coronary Syndrome Event. The ERICO Study

Resumo Fundamentos: Poucos estudos discutiram causas para o subtratamento medicamentoso na SCA. Objetivos: Avaliar a não-administração e suspensão de medicamentos durante o tratamento intra-hospitalar da SCA na Estratégia de Registro de Síndrome Coronariana Aguda (estudo ERICO). Métodos: Analisamos prontuários de 563 participantes ERICO para avaliar a frequência e motivos da não administração e/ou suspensão de medicamentos. Construímos modelos de regressão logística para avaliar se sexo, idade ≥65 anos, nível educacional ou subtipo de SCA estavam associados com (a) não administração de ≥1 medicamentos; e (b) não administração ou suspensão de ≥1 medicamentos. O nível de significância foi 5%. Resultados: A amostra é composta por 58,1% de homens e com idade mediana de 62 anos. Em 183 (32,5%) participantes ≥1 medicamentos não foram administrados e 288 (51,2%) apresentaram ≥1 medicamentos não administrados ou suspensos. As causas mais frequentes foram risco de sangramento (aspirina, clopidogrel e heparina), insuficiência cardíaca (betabloqueadores) e hipotensão (inibidores da enzima conversora da angiotensina e bloqueadores dos receptores da angiotensina). Indivíduos com idade ≥65 anos (razão de chances [RC]:1,51; intervalo de confiança de 95% [IC95%]:1,05-2,19) e com angina instável (RC:1,72; IC95%:1,07-2,75) tiveram maior chance de não-administração. Considerando apenas pacientes com infarto do miocárdio, idade ≥65 anos foi associada tanto à não administração quanto à não administração ou suspensão. Conclusões: A não administração ou suspensão de ≥1 medicamento não foi rara no estudo ERICO. Indivíduos com idade ≥65 anos ou com angina instável tiveram maior chance de não administração e podem ser subtratados nesse cenário.

Abstract Background: Few studies have discussed the reasons for pharmacological undertreatment of Acute Coronary Syndrome (ACS). Objectives: To determine the frequency and reasons for the non-administration and suspension of medications during in-hospital treatments of ACS in the Strategy of Registry of Acute Coronary Syndrome (ERICO) study. Methods: The present study analyzed the medical charts of the 563 participants in the ERICO study to evaluate the frequency and reasons for the non-administration and/or suspension of medications. Logistic regression models were built to analyze if sex, age ≥65 years of age, educational level, or ACS subtype were associated with (a) the non-administration of ≥1 medications; and (b) the non-administration or suspension of ≥1 medications. The significance level was set at 5%. Results: This study's sample included 58.1% males, with a median of 62 years of age. In 183 (32.5%) participants, ≥1 medications were not administered, while in 288 (51.2%), ≥1 medications were not administered or were suspended. The most common reasons were the risk of bleeding (aspirin, clopidogrel, and heparin), heart failure (beta blockers), and hypotension (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers). Individuals aged ≥65 (odds ratio [OR]:1.51; 95% confidence interval [95% CI]:1.05-2.19) and those with unstable angina (OR:1.72; 95% CI:1.07-2.75) showed a higher probability for the non-administration of ≥1 medication. Considering only patients with myocardial infarction, being ≥65 years of age was associated with both the non-administration and the non-administration or suspension of ≥1 medication. Conclusions: Non-administration or suspension of ≥1 medication proved to be common in this ERICO study. Individuals of ≥65 years of age or with unstable angina showed a higher probability of the non-administration of ≥1 medication and may be undertreated in this scenario. (Arq Bras Cardiol. 2020; 115(5):830-839)

Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT polymorphisms with tDCS and escitalopram efficacy: ancillary analysis of a double-blind, placebo-controlled trial

Objective: We investigated whether single nucleotide polymorphisms (SNPs) associated with neuroplasticity and activity of monoamine neurotransmitters, such as the brain-derived neurotrophic factor (BDNF, rs6265), the serotonin transporter (SLC6A4, rs25531), the tryptophan hydroxylase 1 (TPH1, rs1800532), the 5-hydroxytryptamine receptor 2A (HTR2A, rs6311, rs6313, rs7997012), and the catechol-O-methyltransferase (COMT, rs4680) genes, are associated with efficacy of transcranial direct current stimulation (tDCS) in major depression. Methods: Data from the Escitalopram vs. Electrical Current Therapy for Treating Depression Clinical Study (ELECT-TDCS) were used. Participants were antidepressant-free at baseline and presented with an acute, moderate-to-severe unipolar depressive episode. They were randomized to receive escitalopram/tDCS-sham (n=75), tDCS/placebo-pill (n=75), or placebo-pill/sham-tDCS (n=45). General linear models assessed the interaction between treatment group and allele-wise carriers. Additional analyses were performed for each group and each genotype separately. Results: Pairwise group comparisons (tDCS vs. placebo, tDCS vs. escitalopram, and escitalopram vs. placebo) did not identify alleles associated with depression improvement. In addition, exploratory analyses also did not identify any SNP unequivocally associated with improvement of depression in any treatment group. Conclusion: Larger, combined datasets are necessary to identify candidate genes for tDCS response.

Homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic syndrome at baseline of a multicentric Brazilian cohort: ELSA-Brasil study / Modelo de avaliação da homeostase de resistência à insulina (HOMA-IR) e síndrome metabólica na linha de base de uma coorte brasileira multicêntrica: estudo ELSA-Brasil / Modelo homeostático para evaluar la resistencia a la insulina (HOMA-IR) y síndrome metabólico en la línea de base de una cohorte brasileña multicéntrica: estudio ELSA-Brasil

Abstract: Homeostasis model assessment of insulin resistance (HOMA-IR) is a method to measure insulin resistance. HOMA-IR cut-offs for identifying metabolic syndrome might vary across populations and body mass index (BMI) levels. We aimed to investigate HOMA-insulin resistance cut-offs that best discriminate individuals with insulin resistance and with metabolic syndrome for each BMI category in a large sample of adults without diabetes in the baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Among the 12,313 participants with mean age of 51.2 (SD 8.9) years, the prevalence of metabolic syndrome was 34.6%, and 60.1% had overweight or obesity. The prevalence of metabolic syndrome among normal weight, overweight and obesity categories were, respectively, 13%, 43.2% and 60.7%. The point of maximum combined sensitivity and specificity of HOMA-IR to discriminate the metabolic syndrome was 2.35 in the whole sample, with increasing values at higher BMI categories. This investigation contributes to better understanding HOMA-IR values associated with insulin resistance and metabolic syndrome in a large Brazilian adult sample, and that use of cut-off points according to ROC curve may be the better strategy. It also suggests that different values might be appropriate across BMI categories.

Resumo: O modelo de avaliação da homeostase da resistência à insulina (HOMA-IR) é um método para medir a resistência à insulina. Os pontos de corte do HOMA-IR para identificar a síndrome metabólica podem variar entre as populações e os níveis de índice de massa corporal (IMC). Nosso objetivo foi investigar os pontos de corte do HOMA-IR que melhor discriminam indivíduos com resistência à insulina e com síndrome metabólica para cada categoria de IMC em uma grande amostra de adultos sem diabetes na linha de base do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Entre os 12.313 participantes com média de idade de 51,2 (DP 8,9) anos, a prevalência de síndrome metabólica foi de 34,6%, e 60,1% apresentavam sobrepeso ou obesidade. As prevalências de síndrome metabólica nas categorias de peso normal, sobrepeso e obesidade foram, respectivamente, 13%, 43,2% e 60,7%. O ponto de máxima sensibilidade e especificidade combinadas do HOMA-IR para discriminar a síndrome metabólica foi de 2,35 em toda a amostra, com valores crescentes nas categorias de IMC mais elevadas. Esta investigação contribui para o melhor entendimento dos valores de HOMA-IR associados à resistência à insulina e síndrome metabólica em uma grande amostra de adultos brasileiros, e que o uso de pontos de corte de acordo com a curva ROC pode ser a melhor estratégia. Também sugere que valores diferentes podem ser apropriados nas categorias de IMC.

Resumen: El modelo homeostático para evaluar la resistencia a la insulina (HOMA-IR) es un método para medir la resistencia a la insulina. Los cortes HOMA-IR para identificar el síndrome metabólico pueden variar entre las poblaciones y los niveles del índice de masa corporal (IMC). El objetivo fue investigar los cortes de HOMA-IR que mejor discriminaban individuos con resistencia a la insulina y con síndrome metabólico para cada categoría de IMC, en una extensa muestra de adultos sin diabetes en la base de referencia del Estudio Longitudinal de Salud del Adulto (ELSA-Brasil). Entre los 12.313 participantes con una media de edad de 51,2 años (DE 8,9), la prevalencia de síndrome metabólico fue 34,6%, y un 60,1% sufría sobrepeso u obesidad. La prevalencia de síndrome metabólico entre las categorías: peso normal, sobrepeso y obesidad fueron respectivamente, 13%, 43,2% y 60,7%. El punto de máxima sensibilidad combinada y especificidad de HOMA-IR para discriminar el síndrome metabólico fue 2,35 en toda la muestra, con valores crecientes en las categorías de IMC más altas. Esta investigación contribuye a entender mejor los valores HOMA-IR, asociados con resistencia a la insulina y síndrome metabólico en una gran muestra de adultos brasileños, además del planteamiento de que el uso de puntos de corte según la curva ROC es quizás la mejor estrategia a seguir. También sugiere que valores diferentes pueden ser apropiados a través de las categorías de IMC.

Prevalence of antithyroperoxidase antibodies in a multiethnic Brazilian population: The ELSA-Brasil Study

ABSTRACT Objective In this study, we aimed to describe the prevalence and distribution of positive antithyroperoxidase antibodies (TPOAb) according to sex, age strata, and presence of thyroid dysfunction using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Materials and methods Thyroid hormone tests were obtained from each study participant at baseline. Levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured using a third-generation immunoenzymatic assay. Antithyroperoxidase antibodies were measured by electrochemiluminescence and were considered to be positive when ≥ 34 IU/mL. Results The prevalence of TPOAb among 13,503 study participants was 12%. Of participants with positive TPOAb, 69% were women. Almost 60% of the individuals with positive TPOAb were white. The presence of positive TPOAb was associated with the entire spectrum of thyroid diseases among women, but only with overt hyperthyroidism and overt hypothyroidism in men. Conclusion The distribution of positive TPOAb across sex, race, age, and thyroid function in the ELSA-Brasil study is aligned with the worldwide prevalence of positive TPOAb reported in iodine-sufficient areas. In women, the presence of TPOAb was related to the entire spectrum of thyroid dysfunction, while in men, it was only related to the occurrence of overt thyroid disease.

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.

Impact of High Risk for Obstructive Sleep Apnea on Survival after Acute Coronary Syndrome: Insights from the ERICO Registry / Impacto do Alto Risco para Apneia Obstrutiva do Sono na Sobrevida após Síndrome Coronariana Aguda: Achados do Registro ERICO

Abstract Background: Obstructive sleep apnea (OSA) is a very often clinical condition that can be associated with high mortality risk, particularly in coronary heart disease (CHD). The diagnosis of OSA is not always accessible via the gold-standard method polysomnography. Objective: To evaluate long-term influence of the high risk for OSA on fatal and non-fatal outcomes after acute coronary syndrome (ACS) in the Acute Coronary Syndrome Registry Strategy (ERICO) Study using the Berlin questionnaire as a surrogate. Methods: Berlin questionnaire, a screening questionnaire for OSA, was applied in 639 cases of ACS 30 days after the index event. Cox regression proportional-hazards model was used to calculate the hazard ratio (HR) of all-cause, cardiovascular and CHD (myocardial infarction) mortality, as well as, the combined endpoint of fatal or recurrent non-fatal CHD. Results: The high-risk group for OSA had higher frequencies of previous personal/family history of CHD and diabetes, in addition to a poorer event-free survival, as compared to the low-risk group (p-log-rank=0.03). The HR for fatal or recurrent non-fatal CHD was 4.26 (95% confidence interval, 1.18 - 15.36) in patients at high risk for OSA compared to those at low risk for OSA after a 2.6-year mean follow-up. Conclusions: Using Berlin questionnaire, we were able to identify high risk for OSA as an independent predictor of non-fatal reinfarction or CHD mortality in post-ACS individuals in a long-term follow-up.

Resumo Fundamento: Apneia obstrutiva do sono (AOS) é uma condição clínica muito frequente, que pode estar associada a alto risco de mortalidade, particularmente em doença arterial coronariana (DAC). Nem sempre o diagnóstico de AOS acha-se disponível por polissonografia, o método padrão-ouro. Objetivo: Avaliar, usando o Questionário de Berlim como substituto, a influência a longo prazo do alto risco para AOS nos desfechos fatal e não fatal após síndrome coronariana aguda (SCA) na Estratégia de Registro de Insuficiência Coronariana (estudo ERICO). Métodos: O Questionário de Berlim, para triagem de AOS, foi aplicado a 639 casos de SCA 30 dias após o evento índice. Usou-se o modelo de riscos proporcionais de Cox para calcular a razão de risco (HR) para mortalidade por todas as causas, por doença cardiovascular e por IAM (infarto agudo do miocárdio), assim como os desfecho combinado infarto do miocárdio fatal e recorrente não fatal. Resultados: O grupo de alto risco para AOS apresentou maior frequência de história pessoal/familiar de DAC e diabetes, assim como pior sobrevida livre de evento, quando comparado ao de baixo risco (p-log-rank = 0,03). A HR para IAM fatal e recorrente não fatal foi 4,26 (intervalo de confiança 95%: 1,18-15,36) para os pacientes de alto risco para AOS em comparação àqueles de baixo risco após seguimento médio de 2,6 anos. Conclusões: Usando o Questionário de Berlim, conseguimos identificar alto risco para AOS como fator preditivo independente de reinfarto não fatal ou mortalidade por IAM após SCA em seguimento em longo prazo.

Circulating early biomarkers of atherogenesis in participants of the Longitudinal Study of Adult Health (ELSA-Brasil) without diabetes or cardiovascular disease

ABSTRACT Objective Our aim was to describe the distribution of selected biomarkers according to age and sex, adjusted for HOMA-IR and adiposity, in a subset of middle-aged individuals of Brazilian Longitudinal Study of Adult Health-ELSA without diabetes mellitus or CVD. Subjects and methods This cross-sectional study was conducted in 998 participants of the ELSA-Brasil without diabetes and/or cardiovascular disease. In addition to the traditional risk factors, several biomarkers concentrations were compared according to sex, age groups (35-44; 45-54 yrs) and HOMA-IR tertiles. Linear regression was used to examine independent associations of sex and age with selected novel biomarkers, adjusted for body adiposity and HOMA-IR. Results Fifty-five percent were women. Men had higher mean values of body mass index, waist circumference, blood pressure, plasma glucose, HOMA-IR, worse lipid profile and higher E-selectin and lower leptin concentrations than women; while women had higher levels of HDL-cholesterol and leptin than men. Mean values of waist circumference, systolic BP, plasma glucose and apolipoprotein B (Apo B) increased with age in both sexes. Leptin and E-selectin concentrations increased across HOMA-IR tertiles. Independent associations of Apo B with age were found only in male sex, while of leptin with body mass index and HOMA-IR, and of E-selectin with HOMA-IR in both sexes. Conclusions In conclusion, our data indicate age, sex, adiposity and, consequently, insulin resistance, influence circulating levels of Apo B, leptin and E-selectin, suggesting that those aspects should be taken into consideration when assessing these parameters for research or clinical purposes in individuals at relatively low cardiometabolic risk.