Effects of environmental exposure to iron powder on healthy and elastase-exposed mice.

Prolonged exposure to iron powder and other mineral dusts can threaten the health of individuals, especially those with COPD. The goal of this study was to determine how environmental exposure to metal dust from two different mining centers in Brazil affects lung mechanics, inflammation, remodeling and oxidative stress responses in healthy and elastase-exposed mice. This study divided 72 male C57Bl/6 mice into two groups, the summer group and the winter group. These groups were further divided into six groups: control, nonexposed (SAL); nonexposed, given elastase (ELA); exposed to metal powder at a mining company (SAL-L1 and ELA-L1); and exposed to a location three miles away from the mining company (SAL-L2 and ELA-L2) for four weeks. On the 29th day of the protocol, the researchers assessed lung mechanics, bronchoalveolar lavage fluid (BALF), inflammation, remodeling, oxidative stress, macrophage iron and alveolar wall alterations (mean linear intercept-Lm). The Lm was increased in the ELA, ELA-L1 and ELA-L2 groups compared to the SAL group (p < 0.05). There was an increase in the total number of cells and macrophages in the ELA-L1 and ELA-L2 groups compared to the other groups (p < 0.05). Compared to the ELA and SAL groups, the exposed groups (ELA-L1, ELA-L2, SAL-L1, and SAL-L2) exhibited increased expression of IL-1ß, IL-6, IL-10, IL-17, TNF-α, neutrophil elastase, TIMP-1, MMP-9, MMP-12, TGF-ß, collagen fibers, MUC5AC, iNOS, Gp91phox, NFkB and iron positive macrophages (p < 0.05). Although we did not find differences in lung mechanics across all groups, there were low to moderate correlations between inflammation remodeling, oxidative stress and NFkB with elastance, resistance of lung tissue and iron positive macrophages (p < 0.05). Environmental exposure to iron, confirmed by evaluation of iron in alveolar macrophages and in air, exacerbated inflammation, initiated remodeling, and induced oxidative stress responses in exposed mice with and without emphysema. Activation of the iNOS, Gp91phox and NFkB pathways play a role in these changes.

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.

Triglyceride-glucose index demonstrates reasonable performance as a screening tool but exhibits limited diagnostic utility for insulin resistance: Data from the ELSA-Brasil cohort.

Insulin resistance (IR) is a key risk factor for chronic metabolic diseases, but its laboratory diagnosis is still costly; thus, the triglyceride-glucose (TyG) index has been proposed as a surrogate method. Our aim was to provide a detailed analysis of cutoffs and test the hypothesis that the TyG index would present reasonable performance parameters for IR screening. This is a cross-sectional study with baseline data from 12,367 eligible participants of both sexes (aged 35-74 years) from the Brazilian Longitudinal Study of Adult Health. TyG correlation and agreement with the Homeostasis Model Assessment for Insulin Resistance were analyzed. Positive and negative predictive values (PV+, PV-) and likelihood ratio (LR+, LR-) were calculated. A moderate positive correlation between TyG and Homeostasis Model Assessment for Insulin Resistance was observed (Pearson r = 0.419). The area under the receiver operating characteristic curve of TyG for IR diagnosis was 0.742 and the optimal cutoff was 4.665, reaching a kappa agreement value of 0.354. For this cutoff, a PV+ of 59.3% and PV- of 76.0%, as well as an LR+ of 2.07 and LR- of 0.45 were obtained. Alternatively, because high sensitivity is desired for screening tests, selecting a lower cutoff, such as 4.505, increases the PV- to 82.1%, despite decreasing the PV+ to 50.8%. We conclude that TyG has important performance limitations for detecting IR, but that it may still be reasonably useful to help screening for IR in adults because it can be calculated from low-cost routine blood tests.

Potential Determinants of Thyroid Peroxidase Antibodies and Mortality Risk: Results From the ELSA-Brasil Study.

CONTEXT: The presence of thyroid peroxidase antibodies (TPOAbs) may be considered as an indicator of adverse health outcomes. OBJECTIVE: We aimed to investigate the potential determinants of TPOAb levels and to analyze the association between TPOAb titers and the risk of all- and specific-cause mortality. METHODS: Baseline and longitudinal data of 13 187 participants from the ELSA-Brasil Study were analyzed. We investigated the association of TPOAb, detectability, positivity, and persistent positivity with sociodemographic and lifestyle factors using logistic regressions. Cox proportional hazards and Fine-Gray subdistribution hazard regression analyses were used to verify the association of TPOAbs with mortality. RESULTS: The determinants of TPOAb detectability and positivity were younger age, higher body mass index, female sex, and former and current smoking status. Black, mixed, and other self-reported races, intermediate and higher education, and heavy drinking were determinants of detectable and positive TPOAb levels. Female sex, White race, and former smoking were determinants of persistent TPOAb positivity at 2 visits, although only the female sex maintained its association at 3 visits. Moreover, after multivariate adjustment, there were associations between higher levels of TPOAbs and higher risk of cancer-related mortality among men, and TPOAb detectability and mortality by other causes among women. CONCLUSION: Sociodemographic and lifestyle-related factors were determinants of multiple TPOAb categories. TPOAb levels were associated with mortality risk; however, the low mortality rate in this sample might have compromised this finding. We suggest further studies to explore the clinical importance of detectable TPOAb levels, not only its positivity, as a potential marker of inflammation.

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.

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.

Urinary levels of 30 metal/metalloids in the Brazilian southeast population: Findings from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

The assessment of risks associated with environmental exposure to metals/metalloids requires well-established reference values for each population since it varies considerably according to distinct local/regional characteristics. However, very few studies establish baseline values for these elements (essential and toxic) in large population groups, especially in Latin American countries. This study was aimed at establishing urinary reference levels of 30 metals/metalloids: aluminum (Al), antimony (Sb), arsenic (As), barium (Ba), beryllium (Be), cadmium (Cd), cerium (Ce), cesium (Cs), chromium (Cr), cobalt (Co), copper (Cu), lanthanum (La), lead (Pb), lithium (Li), strontium (Sr), manganese (Mn), mercury (Hg), molybdenum (Mo), nickel (Ni), platinum (Pt), rubidium (Rb), selenium (Se), silver (Ag), tin (Sn), tellurium (Te), thallium (Tl), thorium (Th), tungsten (W), uranium (U) and zinc (Zn) in a Brazilian southeast adult population. This pilot study is a cross-sectional analysis conducted with the first wave of the ELSA-Brasil cohort (baseline examination). A total of 996 adults (45.5% men, N = 453, mean age: 50.5, and 54.5% women, N = 543, mean age: 50.6) were included in the study. Sample analyses were performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Percentiles (2.5, 10, 25, 50, 75, 95 (CI95%), and 97.5) of each element (µg/g of creatinine) in the study are presented according to sex. Moreover, differences in the mean metal/metalloid urinary levels according to age, education, smoking, and alcohol intake are also presented. Finally, median found values were compared to established values of large human biomonitoring surveys previously conducted in North America and France. This is the first comprehensive and systematic human biomonitoring study that established population reference ranges for 30 (essential and/or toxic elements) in a Brazilian population group.

Associations of prematurity and low birth weight with blood pressure and kidney function in middle-aged participants of the Brazilian Longitudinal Study of Adult Health: ELSA-Brasil.

BACKGROUND: An adverse intrauterine environment reflected by low birth weight (LBW) and prematurity may induce fetal programming that favors kidney dysfunction in adulthood. We examined the association of LBW and prematurity with blood pressure (BP) and kidney function markers in non-diabetic, middle-aged adults without kidney disease from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: A cross-sectional analysis of 768 subjects aged 35-54 years was conducted. Comparisons were performed according to self-reported birth weight: LBW (< 2.5 kg) or normal birth weight (2.5-4.0 kg). Associations of LBW and prematurity with BP levels and kidney function markers "(estimated glomerular filtration rate [eGFR], albumin-creatinine ratio [ACR] and serum cystatin-C) were tested by multiple linear regression using adjustments based on Directed Acyclic Graphs. Propensity score matching was applied to control imbalances. RESULTS: Mean age of participants was 45.5 ± 4.6 years and 56.8% were female; 64 (8.3%) participants reported LBW and 39 (5.0%) prematurity. The LBW group had higher systolic (p = 0.015) and diastolic BP (p = 0.014) and ACR values (p = 0.031) and lower eGFR (p = 0.015) than the normal birth weight group, but no group difference for cystatin-C was found. The preterm group had higher mean levels of systolic and diastolic BP, but no difference in kidney function markers was evident. In a regression model adjusted for sex, skin color and family history of hypertension, both systolic and diastolic BP levels were associated with LBW, but this association disappeared after adding for prematurity, which remained associated with BP (p = 0.017). Having applied a propensity score matching, LBW was associated with ACR values (p = 0.003), but not with eGFR or BP levels. CONCLUSION: The study findings of independent associations of prematurity with higher BP levels, and of LBW with markers of kidney function in adulthood, support that early life events may predict risk for hypertension and kidney dysfunction in adulthood. The study design precluded the inferring of causality, and prospective studies are needed to further investigate this hypothesis.

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.

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.

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.

Variabilidade da Pressão Arterial em Única Visita e Risco Cardiovascular em Participantes do ELSA-Brasil / Within-Visit Blood Pressure Variability and Cardiovascular Risk in ELSA-Brasil Study Participants

Resumo Fundamento A variabilidade da pressão arterial (VPA) tem valor prognóstico para desfechos cardiovasculares fatais e não fatais. Objetivos Este estudo teve como objetivo avaliar a associação entre a VPA em uma única visita e o risco cardiovascular em participantes do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Métodos O presente estudo transversal foi conduzido com dados basais (2008-2010) de 14.357 participantes do ELSA-Brasil, sem história de doença cardiovascular. A VPA foi quantificada pelo coeficiente de variação de três medidas padronizadas da pressão arterial sistólica (PAS) realizadas com um oscilômetro. Medidas antropométricas e exames laboratoriais também foram realizados. O risco cardiovascular foi avaliado pelo estimador de risco de doença cardiovascular aterosclerótica (ASCVD), e se empregou a análise de regressão logística multivariada com nível de significância de 5%. Resultados Um risco cardiovascular significativamente maior foi determinado por uma VPA elevada para ambos os sexos. Uma prevalência significativamente maior de alto risco foi observada mais em homens que em mulheres em todos os quartis, com a maior diferença observada no quarto quartil de variabilidade (48,3% vs. 17,1%). Comparações entre quartis por sexo revelaram um risco significativamente mais alto para homens no terceiro (OR=1,20; IC95%: 1,02 - 1,40) e no quarto quartis OR=1,46; IC95%: 1,25 -1,71), e para mulheres no quarto quartil (OR=1,27; IC95%: 1,03 - 1,57). Conclusão Análises de dados basais de participantes do ELSA-Brasil revelaram que a variabilidade da pressão arterial se associou com risco cardiovascular aumentado, especialmente nos homens.

Abstract Background Blood pressure variability (BPV) is of prognostic value for fatal and non-fatal cardiovascular outcomes. Objective This study aimed to evaluate the association between within-visit BPV and cardiovascular risk among participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods The present cross-sectional study was carried out using baseline data (2008-2010) of 14,357 ELSA-Brasil participants with no prior history of cardiovascular disease. Within-visit BPV was quantified by the coefficient of variation of three standardized systolic blood pressure (SBP) measurements using an oscillometer. Anthropometric measurements and laboratory tests were also performed. Cardiovascular risk was assessed using the atherosclerotic cardiovascular disease risk estimator (ASCVD) and multivariate logistic regression analysis was employed with a significance level of 5%. Results Significantly higher cardiovascular risk was determined by increased BPV for both sexes. A significantly higher prevalence of high risk was found in men than women across all quartiles, with the highest difference observed in the fourth quartile of variability (48.3% vs. 17.1%). Comparisons among quartiles in each sex revealed a significantly higher cardiovascular risk for men in the third (OR=1.20; 95%CI: 1.02 - 1.40) and fourth quartiles (OR=1.46; 95%CI: 1.25 -1.71), and for women in the fourth quartile (OR=1.27; 95%CI: 1.03 - 1.57). Conclusion Analysis of baseline data of the ELSA-Brasil participants revealed that blood pressure variability was associated with increased cardiovascular risk, especially in men.

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.

Molecular and pro-inflammatory aspects of COVID-19: The impact on cardiometabolic health.

Obesity, type 2 diabetes (T2DM), hypertension (HTN), and Cardiovascular Disease (CVD) often cluster together as "Cardiometabolic Disease" (CMD). Just under 50% of patients with CMD increased the risk of morbidity and mortality right from the beginning of the COVID-19 pandemic as it has been reported in most countries affected by the SARS-CoV2 virus. One of the pathophysiological hallmarks of COVID-19 is the overactivation of the immune system with a prominent IL-6 response, resulting in severe and systemic damage involving also cytokines such as IL2, IL4, IL8, IL10, and interferon-gamma were considered strong predictors of COVID-19 severity. Thus, in this mini-review, we try to describe the inflammatory state, the alteration of the adipokine profile, and cytokine production in the obese state of infected and not infected patients by SARS-CoV2 with the final aim to find possible influences of COVID-19 on CMD and CVD. The immunological-based discussion of the molecular processes could inspire the study of promising targets for managing CMD patients and its complications during COVID-19.

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.

Retest effects in a diverse sample: sociodemographic predictors and possible correction approaches / Efeito de reteste em uma amostra diversa: preditores sociodemográficos e possíveis abordagens para a correção

ABSTRACT. Repeated cognitive assessment in longitudinal studies favors the occurrence of retest effects, usually increasing the scores obtained at the follow-up assessments when compared to baseline. Therefore, retest effects can compromise the evaluation of cognitive decline in older adults. Objectives: We aimed to verify the occurrence of the retest effect and the impact of sociodemographic characteristics on the follow-up scores in a sample of 5,592 participants with a diverse sociodemographic profile, who were assessed twice during 4 years of follow-up. Methods: We tested two possible approaches to correct the retest effect and calculated the Reliable Change Index. Results: We observed increased scores at the follow-up assessment after 4 years, but the results indicate a modest occurrence of retest effects. The regression difference correction successfully generated follow-up corrected scores, while the mean difference did not provide effective corrections. Sociodemographic characteristics had a minor impact on the retest. Conclusions: We recommend the regression difference correction for retest effects. The absence of this methodological approach might lead to biased results using longitudinal cognitive scores.

RESUMO. Avaliações cognitivas repetidas em estudos longitudinais favorecem a ocorrência de efeitos de retestagem ou de prática, geralmente aumentando os escores obtidos nas avaliações de acompanhamento quando comparados aos da primeira avaliação. Sendo assim, os efeitos do retestagem podem comprometer a verificação do declínio cognitivo em idosos. Objetivos: Objetivamos verificar a ocorrência do efeito de prática e o impacto das características sociodemográficas nos escores de seguimento em uma amostra de 5.592 participantes com perfil sociodemográfico diverso, avaliada duas vezes durante quatro anos de seguimento. Métodos: Testamos duas abordagens possíveis para corrigir o efeito de prática e calculamos o índice de mudança confiável. Resultados: Observamos escores sutilmente maiores na avaliação de seguimento após quatro anos, o que sugere a ocorrência de efeitos de retestagem. A correção pela diferença da regressão gerou escores corrigidos de acompanhamento satisfatórios, enquanto a correção pela diferença média não forneceu correções eficazes. As características sociodemográficas tiveram impacto mínimo no efeito de prática. Conclusões: Recomendamos a forma de correção pela diferença da regressão para efeitos de retestagem. A ausência dessa abordagem metodológica, quando utilizamos escores cognitivos longitudinais, pode levar a resultados enviesados.

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.