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.

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.

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.

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.

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.

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.

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.

The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension - Study design and challenges during the COVID-19 pandemic

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.

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)

Precision non-implantable neuromodulation therapies: a perspective for the depressed brain

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more "precision-oriented" practice.

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.

Electrocardiographic Findings in Brazilian Adults without Heart Disease: ELSA-Brasil / Medidas Eletrocardiográficas de Adultos Brasileiros sem Cardiopatia Estabelecida: ELSA-Brasil

Abstract Background: The electrocardiogram (ECG) is widely used in population-based studies. However, there are few studies on electrocardiographic findings in Latin America and in Brazil. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) comprised 15,105 participants (35-74 years) from six Brazilian capitals. Objectives: To describe electrocardiographic findings in Brazilian adults without heart disease, stratified by sex, age and race/skin color. Methods: Cross-sectional study with baseline data of 11,094 adults (44.5% men) without heart disease from ELSA-Brasil. The ECGs were recorded with the Burdick Atria 6100 machine and stored at the Pyramis System. ECG analysis was automatically performed using the Glasgow University software. A descriptive analysis of heart rate (HR), P, QRS and T waves' duration, PR and QT intervals, and P, R and T axes was performed. After stratification by sex, race/color and age, the groups were compared by the Wilcoxon and Kruskal-Wallis test at a significance level of 5%. Linear regression models were used to evaluate the behavior of electrocardiographic parameters over age. Major electrocardiographic abnormalities defined by the Minnesota code were manually revised. Results: Medians values of the electrocardiographic parameters were different between men and women: HR 63 vs. 66 bpm, PR 164 vs.158 ms, QT corrected 410 vs. 421 ms, QRS duration 92 vs. 86 ms, P-wave duration 112 vs. 108 ms, P-wave axis 54 vs. 57 degrees, R-wave axis 35 vs. 39 degrees, T-wave axis 39 vs. 45 degrees (p < 0.001 for all). The 2nd and the 98th percentiles of each variable were also obtained, and graphs were constructed to illustrate the behavior of the electrocardiographic findings over age of participants stratified by sex and race/skin color. Conclusions: The values for the electrocardiographic measurements herein described can be used as reference for Brazilian adults free of heart disease, stratified by sex. Our results suggest that self-reported race/skin color have no significant influence on electrocardiographic parameters.

Resumo Fundamento: O eletrocardiograma (ECG) é amplamente utilizado em estudos de base populacional. Porém, poucos desses estudos descrevem achados eletrocardiográficos na América Latina e particularmente no Brasil. O Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) incluiu 15105 participantes (35-74 anos) de seis capitais brasileiras. Objetivos: Descrever as medidas eletrocardiográficas em adultos brasileiros não cardiopatas, estratificados por sexo, raça/cor e idade. Métodos: Estudo transversal com dados da linha de base do ELSA-Brasil (n=11094, 44,5% homens) de participantes sem doença cardiopatia prevalente. Os ECGs foram obtidos no aparelho Burdick Atria 6100 e armazenados pelo Sistema Pyramis. A análise dos ECGs foi realizada automaticamente utilizando-se o software da Universidade de Glasgow. Realizou-se análise descritiva da frequência cardíaca, da duração das ondas P, QRS e T, dos intervalos (i) PR e QT, e dos eixos de P, R e T. A comparação dos grupos estratificados por sexo, raça/cor e idade, foi feita pelos testes de Wilcoxon e Kruskal-Wallis com nível de significância definido em 5%. O comportamento das medidas eletrocardiográficas ao longo da idade foi avaliado por modelos de regressão linear. Alterações eletrocardiográficas definidas como maiores pelo código de Minnesota foram revisadas manualmente. Resultados: As medianas das mensurações foram diferentes entre homens e mulheres: FC 63 vs 66 bpm, iPR 164 vs 158 ms, iQT corrigido 410 vs. 421 ms, QRS 92 vs 86 ms, onda P 112 vs 108 ms, eixo da onda P 54 vs 58, eixo da onda R 35 vs 39 e eixo da onda T 39 vs 45 (p < 0,001 para todas). Os percentis 02 e 98 foram obtidos para cada variável analisada, assim como gráficos demonstrando o comportamento dos parâmetros eletrocardiográficos ao longo da idade dos participantes estratificados por sexo e raça/cor. Conclusões: Os valores descritos para as medidas eletrocardiográficas analisadas poderão ser utilizados como referência para adultos brasileiros sem cardiopatia prevalente, estratificados por sexo. Os resultados sugerem que não existe grande influência da raça/cor autodeclarada nas mensurações eletrocardiográficas realizadas.

Persistent Depressive Symptoms are Independent Predictors of Low-Grade Inflammation Onset Among Healthy Individuals / Sintomas Depressivos Persistentes são Preditores Independentes de Início de Inflamação de Baixo Grau em Indivíduos Saudáveis

Abstract Background: Depressive symptoms are independently associated with an increased risk of cardiovascular disease (CVD) among individuals with non-diagnosed CVD. The mechanisms underlying this association, however, remain unclear. Inflammation has been indicated as a possible mechanistic link between depression and CVD. Objectives: This study evaluated the association between persistent depressive symptoms and the onset of low-grade inflammation. Methods: From a database of 1,508 young (mean age: 41 years) individuals with no CVD diagnosis who underwent at least two routine health evaluations, 134 had persistent depressive symptoms (Beck Depression Inventory - BDI ≥ 10, BDI+) and 1,374 had negative symptoms at both time points (BDI-). All participants had been submitted to repeated clinical and laboratory evaluations at a regular follow-up with an average of 26 months from baseline. Low-grade inflammation was defined as plasma high-sensitivity C-Reactive Protein (CRP) concentrations > 3 mg/L. The outcome was the incidence of low-grade inflammation evaluated by the time of the second clinical evaluation. Results: The incidence of low-grade inflammation was more frequently observed in the BDI+ group compared to the BDI- group (20.9% vs. 11.4%; p = 0.001). After adjusting for sex, age, waist circumference, body mass index, levels of physical activity, smoking, and prevalence of metabolic syndrome, persistent depressive symptoms remained an independent predictor of low-grade inflammation onset (OR = 1.76; 95% CI: 1.03-3.02; p = 0.04). Conclusions: Persistent depressive symptoms were independently associated with low-grade inflammation onset among healthy individuals.

Resumo Fundamento: Sintomas depressivos estão associados de forma independente ao risco aumentado de doença cardiovascular (DCV) em indivíduos com DCV não diagnosticada. Os mecanismos subjacentes a essa associação, entretanto, não estão claros. Inflamação tem sido indicada como um possível elo mecanicista entre depressão e DCV. Objetivos: Este estudo avaliou a associação entre sintomas depressivos persistentes e o início de inflamação de baixo grau. Métodos: De um banco de dados de 1.508 indivíduos jovens (idade média: 41 anos) sem diagnóstico de DCV submetidos a pelo menos duas avaliações de saúde de rotina, 134 tinham sintomas depressivos persistentes (Inventário de Depressão de Beck - BDI ≥10, BDI+) e 1.374 não apresentavam sintomas em nenhuma das ocasiões (BDI-). Todos os participantes foram submetidos a repetidas avaliações clínicas e laboratoriais em seguimento regular, cuja média foi de 26 meses desde a condição basal. Definiu-se inflamação de baixo grau como concentração plasmática de proteína C reativa (PCR) ultrassensível > 3 mg/L. O desfecho foi a incidência de inflamação de baixo grau por ocasião da segunda avaliação clínica. Resultados: A incidência de inflamação de baixo grau foi maior no grupo BDI+ em comparação ao grupo BDI- (20,9% vs. 11,4%; p = 0,001). Após ajuste para sexo, idade, circunferência abdominal, índice de massa corporal, níveis de atividade física, tabagismo e prevalência de síndrome metabólica, os sintomas depressivos persistentes continuaram sendo um preditor independente de início de inflamação de baixo grau (OR = 1,76; IC 95%: 1,03-3,02; p = 0,04). Conclusões: Sintomas depressivos persistentes foram independentemente associados com início de inflamação de baixo grau em indivíduos saudáveis.