Effect of VAChT reduction on lung alterations induced by exposure to iron particles in an asthma model.

INTRODUCTION: Pollution harms the health of people with asthma. The effect of the anti-inflammatory cholinergic pathway in chronic allergic inflammation associated to pollution is poorly understood. METHODS: One hundred eight animals were divided into 18 groups (6 animals). Groups included: wild type mice (WT), genetically modified with reduced VAChT (VAChTKD), and those sensitized with ovalbumin (VAChTKDA), exposed to metal powder due to iron pelletizing in mining company (Local1) or 3.21 miles away from a mining company (Local2) in their locations for 2 weeks during summer and winter seasons. It was analyzed for hyperresponsivity, inflammation, remodeling, oxidative stress responses and the cholinergic system. RESULTS: During summer, animals without changes in the cholinergic system revealed that Local1 exposure increased the hyperresponsiveness (%Rrs, %Raw), and inflammation (IL-17) relative to vivarium animals, while animals exposed to Local2 also exhibited elevated IL-17. During winter, animals without changes in the cholinergic system revealed that Local2 exposure increased the hyperresponsiveness (%Rrs) relative to vivarium animals. Comparing the exposure local of these animals during summer, animals exposed to Local1 showed elevated %Rrs, Raw, and IL-5 compared to Local 2, while in winter, Local2 exposure led to more IL-17 than Local1. Animals with VAChT attenuation displayed increased %Rrs, NFkappaB, IL-5, and IL-13 but reduced alpha-7 compared to animals without changes in the cholinergic system WT. Animals with VAChT attenuation and asthma showed increased the hyperresponsiveness, all inflammatory markers, remodeling and oxidative stress compared to animals without chronic lung inflammation. Exposure to Local1 exacerbated the hyperresponsiveness, oxidative stressand inflammation in animals with VAChT attenuation associated asthma, while Local2 exposure led to increased inflammation, remodeling and oxidative stress. CONCLUSIONS: Reduced cholinergic signaling amplifies lung inflammation in a model of chronic allergic lung inflammation. Furthermore, when associated with pollution, it can aggravate specific responses related to inflammation, oxidative stress, and remodeling.

Does physical activity and inflammation mediate the job stress-headache relationship? A sequential mediation analysis in the ELSA-Brasil study.

BACKGROUND: Evidence indicates that physical activity reduces stress and promote a myriad of health-enhancing effects through anti-inflammatory mechanisms. However, it is unknown whether these mechanisms interfere in the association between psychosocial job stress and headache disorders. OBJECTIVE: To test whether physical activity and its interplay with the systemic inflammation biomarkers high-sensitivity C-reactive protein (hs-CRP) and acute phase glycoproteins (GlycA) would mediate the associations between job stress and headache disorders. METHODS: We cross-sectionally evaluated the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) regarding job stress (higher demand and lower control and support subscales), migraine and tension-type headache (ICHD-2 criteria), self-reported leisure-time physical activity, and plasma hs-CRP and GlycA levels. Conditional process analyses with a sequential mediation approach were employed to compute path coefficients and 95 % confidence intervals (CI) around the indirect effects of physical activity and biomarkers on the job stress-headache relationship. Separate models were adjusted for sex, age, and depression and anxiety. Further adjustments added BMI smoking status, and socioeconomic factors. RESULTS: In total, 7,644 people were included in the study. The 1-year prevalence of migraine and tension-type headache were 13.1 % and 49.4 %, respectively. In models adjusted for sex, age, anxiety, and depression, the association between job stress (lower job control) and migraine was mediated by physical activity [effect = -0.039 (95 %CI: -0.074, -0.010)] but not hs-CRP or GlycA. TTH was associated with higher job control and lower job demand, which was mediated by the inverse associations between physical activity and GlycA [Job Control: effect = 0.0005 (95 %CI: 0.0001, 0.0010); Job Demand: effect = 0.0003 (95 %CI: 0.0001, 0.0007]. Only the mediating effect of physical activity in the job stress-migraine link remained after further adjustments including socioeconomic factors, BMI, smoking, and the exclusion of major chronic diseases. CONCLUSION: In the ELSA-Brasil study, physical activity reversed the link between job stress and migraine independently of systemic inflammation, while the LTPA-mediated downregulation of GlycA was associated with lower job stress-related TTH.

Association between branched-chain amino acids and renal function in the ELSA-Brasil study.

BACKGROUND & AIMS: Epidemiologic studies show high circulating Branched-chain amino acids (BCAA) are associated with excess body weight, impaired fasting glucose, insulin resistance, high blood pressure, and dyslipidemia. There is scarce data on the association between renal function and circulating levels of BCAA. Therefore, we aim to study this association in a sample of the Brazilian Longitudinal Study of Adults (ELSA-Brasil) METHODS: We analyzed participants who had at the baseline BCAA: valine, isoleucine, and leucine measured through nuclear magnetic resonance. The outcomes evaluated were estimated glomerular function (eGFR - CKD-EPI without race) and 12h-albumin-creatinine ratio (ACR). In addition, we built unadjusted and adjusted multivariable linear regression models to investigate the association between the BCAA (total and individual) and eGFR and ACR. RESULTS: We studied 4912 participants (age 51.7(±9.0) years, 53.4% women, 59.5% White (59.5%), 32.7% hypertension, and 18.2% diabetes). The mean BCAA level was 429.15 ± 87.15. The mean eGFR was 84.95 ± 15 ml/min/1.73 m2, and the median ACR was 6.5 (1.8-4920) mg/g. Descriptive analyses comparing eGFR stratified <60 ml/min/1.73 m2 and ACR≥30 mg/g demonstrate that BCAA levels are higher in patients with eGFR<60 and ACR ≥30. Regarding eGFR, an inverse association was detected with BCAA levels when adjusted for demographic variables, and it is not maintained after adjustments for other confounders. Also, a positive association was found for ACR≥30 mg/g, and BCAA levels, and this association is not confirmed after adjustments. CONCLUSIONS: BCAA levels were inversely associated with eGFR and positively associated with ACR. Further studies are necessary to allow the comprehension of those associations.

Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

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 optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis.

BACKGROUND: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT4 based on the risk of cardiovascular disease and mortality. METHODS: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT4, and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT4, thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. FINDINGS: We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 cohorts agreed to participate. We included IPD on 134 346 participants with a median age of 59 years (range 18-106) at baseline. There was a J-shaped association of FT4 with the composite outcome and secondary outcomes, with the 20th (median 13·5 pmol/L [IQR 11·2-13·9]) to 40th percentiles (median 14·8 pmol/L [12·3-15·0]) conveying the lowest risk. Compared with the 20-40th percentiles, the age-adjusted and sex-adjusted hazard ratio (HR) for FT4 in the 80-100th percentiles was 1·20 (95% CI 1·11-1·31) for the composite outcome, 1·34 (1·20-1·49) for all-cause mortality, 1·57 (1·31-1·89) for cardiovascular disease mortality, and 1·22 (1·11-1·33) for cardiovascular disease events. In individuals aged 70 years and older, the 10-year absolute risk of composite outcome increased over 5% for women with FT4 greater than the 85th percentile (median 17·6 pmol/L [IQR 15·0-18·3]), and men with FT4 greater than the 75th percentile (16·7 pmol/L [14·0-17·4]). Non-linear associations were identified for TSH, with the 60th (median 1·90 mIU/L [IQR 1·68-2·25]) to 80th percentiles (2·90 mIU/L [2·41-3·32]) associated with the lowest risk of cardiovascular disease and mortality. Compared with the 60-80th percentiles, the age-adjusted and sex-adjusted HR of TSH in the 0-20th percentiles was 1·07 (95% CI 1·02-1·12) for the composite outcome, 1·09 (1·05-1·14) for all-cause mortality, and 1·07 (0·99-1·16) for cardiovascular disease mortality. INTERPRETATION: There was a J-shaped association of FT4 with cardiovascular disease and mortality. Low concentrations of TSH were associated with a higher risk of all-cause mortality and cardiovascular disease mortality. The 20-40th percentiles of FT4 and the 60-80th percentiles of TSH could represent the optimal healthy ranges of thyroid function based on the risk of cardiovascular disease and mortality, with more than 5% increase of 10-year composite risk identified for FT4 greater than the 85th percentile in women and men older than 70 years. We propose a feasible approach to establish the optimal healthy ranges of thyroid function, allowing for better identification of individuals with a higher risk of thyroid-related outcomes. FUNDING: None.

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

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.

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

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.

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.

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.

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.

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.

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

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.

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.

Association between coffee consumption with serum lipid profile in ELSA-Brasil study: a metabolomic approach.

PURPOSE: This study evaluated the association between coffee consumption and serum lipid profile in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: This is a cross-sectional study on baseline data from participants of the cohort ELSA-Brasil. Only participants of São Paulo Research Center who underwent a nuclear magnetic resonance (NMR) spectroscopy examination of lipid profile were included (N = 4736). Coffee intake was categorized into four categories (cups/day, in reference cup size of 50 mL, which is the household measure adopted in Brazil): never/almost never, ≤ 1, 1-3, and > 3. Serum lipid profile [i.e., Total Cholesterol (TC), Total Triglycerides (TG), Very Low-Density Lipoprotein-cholesterol (VLDL-c), Low-Density Lipoprotein-cholesterol (LDL-c), High-Density Lipoprotein-cholesterol (HDL-c), Triglyceride-rich Lipoprotein Particles (TRLP) and subfractions particles] was analyzed. To estimate the effect of coffee consumption on serum lipid profile, multivariate Generalized Linear Models were performed. RESULTS: Compared to participants who never or almost never drink coffee, individuals who consumed more than 3 cups/day showed an increase in concentrations of TC (ß: 4.13; 95% CI 0.81, 7.45), TG (ß: 9.53; 95% CI 1.65, 17.42), VLDL-c (ß: 1.90; 95% CI 0.38, 3.42), TRLP (ß: 8.42; 95% CI 1.24, 15.60), and Very Small-TRLP and Medium-TRLP subfractions (ß: 7.36; 95% CI 0.21, 14.51; ß: 2.53; 95% CI 0.89, 4.16, respectively), but not with HDL-c and LDL-c. Among individuals with low (≤ 1 cup/day) and moderate (1-3 cups/day) coffee consumption, no significant associations with lipids was observed. CONCLUSION: High coffee consumption (more than 3 cups per day) was associated with an increase in serum lipids, namely TC, TG, VLDL-c, and TRL particles, highlighting the importance of a moderate consumption of this beverage.

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

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.

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

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.

Associations of depression and intake of antioxidants and vitamin B complex: Results of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Optimum functioning of the central nervous system is dependent on a wide range of nutrients, so mental illness can be impacted by diet via several mechanisms. We aimed to investigate the associations of antioxidants (vitamin A, C and E, and selenium and zinc) and vitamin B complex (B6, folate and B12) intake with depression in 14,737 subjects of the Brazilian Longitudinal Study of Adult Health. METHODS: Baseline cross-sectional data was analyzed. Micronutrients intake was measured using the Food Frequency Questionnaire, and depression was assessed using the Clinical Interview Schedule Revised. Logistic regression models were built using daily intake quintiles of micronutrients. RESULTS: A significant inverse relationship was observed between depression and higher intake of selenium, zinc, vitamins B6 and B12 for the total sample. Among women, a similar pattern of associations was observed, in addition to the higher intake of vitamins A and C. Among men, a significant inverse relationship between depression was observed only with the intake of vitamins B12 and B6. Higher total antioxidant intake was significantly associated with lower odds of depression and an inverse dose-response effect between total antioxidant intake and clinical severity of depression was observed among women, in adjusted models. LIMITATIONS: Recall bias in assessing diet. Misclassification bias regarding current depression. CONCLUSIONS: Depression is associated with lower intake of antioxidants and B vitamins. Higher intake of selected micronutrients may contribute to reduce depression occurrence and severity.

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.

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.