Paulo Andrade Lotufo

Rheumatoid arthritis (RA) is associated with mental health disorders, but longitudinal evidence remains limited. To examine the association of RA with depressive episode, generalized anxiety disorder (GAD), and common mental disorders (CMD) in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). This case-cohort analysis included 1,795 participants: 252 in the RA case group and 1,543 in a randomly selected reference sample. For each incident outcome, participants with the condition at baseline or without follow-up information were excluded. Outcomes were assessed over 12 years of follow-up. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for sociodemographic and clinical covariates. At baseline, depressive episode was present in 19 (7.5%) participants in the RA group and 60 (3.9%) in the reference sample, GAD in 45 (18.1%) and 186 (12.2%), and CMD in 92 (36.5%) and 411 (26.6%), respectively. Fully adjusted ORs for the association of RA with depressive episode, GAD, and CMD were 1.52 (95% CI 0.85–2.74), 1.30 (0.89–1.90), and 1.41 (1.04–1.90), respectively. During follow-up, depressive episode occurred in 24 (14.4%) participants in the RA group and 94 (9.4%) in the reference sample, GAD in 37 (25.2%) and 120 (13.3%), and CMD in 43 (36.4%) and 164 (20.9%), respectively. Corresponding fully adjusted ORs were 1.41 (0.84–2.36), 2.04 (1.30–3.18), and 2.06 (1.33–3.18), respectively. RA was associated with baseline CMD and incident GAD and CMD, but not with baseline depressive episode, baseline GAD, or incident depressive episode after adjustment.

Aims: Cross‐national research on mental health trajectories requires harmonised measures that are valid and comparable. However, measurement scales often differ between cohorts in item content and cultural context. This study aimed to develop a framework for harmonising mental health measures across international cohorts, focussing on depression and anxiety symptoms. Methods: We applied a structured, theory‐driven approach to align item content across two longitudinal ageing cohorts that used different self‐report instruments with heterogeneous item codings: ELSA‐UK and ELSA‐Brasil. Data were collected before, during, and after the COVID‐19 pandemic, providing a natural experiment for examining temporal changes in mental health. The harmonisation process involved: (1) mapping items to DSM‐5 symptom domains via expert review; (2) transforming response formats into harmonised ordinal indicators; (3) leveraging the Harmony AI tool to identify semantically equivalent items; and (4) testing measurement invariance across waves and cohorts using multi‐group confirmatory factor analysis (MGCFA). Results: Scalar invariance was achieved for depression in both longitudinal and cross‐cohort models, enabling meaningful latent mean comparisons between cohorts. For anxiety, scalar invariance was supported within but not across cohorts, likely due to the limited number of conceptually matching items. Conclusion: The proposed harmonisation framework demonstrates the feasibility of robust cross‐cultural comparisons of mental health constructs. Its success depends on the conceptual alignment and quality of available items. This approach provides a methodological template for future harmonisation efforts in global health and psychiatric epidemiology.

To investigate the association between hearing loss and postural balance in adults and the elderly participating in the Estudo Longitudinal da Saúde do Adulto (ELSA-Brazil - Longitudinal Study of Adult Health). Cross-sectional study with data from the fourth wave (2020–2025) of ELSA-Brazil, in the center of São Paulo. Sociodemographic, clinical, and audiological variables were analyzed. Hearing loss was defined by the average of the tonal thresholds (> 25 dBHL) in different criteria: PTA (0.5 kHz-2kHz), speech-frequency PTA (0.5 kHz-4kHz), and high-frequency PTA (3 kHz-8kHz), considering the better and the worst hearing ear. Balance was assessed using the modified Romberg test, in four progressive conditions (eyes open on a firm surface, eyes closed on a firm surface, eyes open on a soft surface, and eyes closed on a soft surface), with a binary classification (pass/fail). The outcome was performance in the balance test. A total of 540 participants were assessed, mostly women, self-declared white, mean age of 63.1 years, mean Body Mass Index (BMI) of 28.4 kg/m², with higher education and income between R$ 1,245.00 and R$ 3,319.00. The rate of balance failure was 13.3%. The prevalence of hearing loss ranged from 13.7% to 59.8%, depending on the criteria used. There was an association between hearing loss and worse performance in the balance test, especially for high-frequency PTA. In the logistic regression models, there was a significant association between the explanatory variable age and failure in the balance test. After excluding the age variable, there was an association for hearing loss, BMI, schooling, and income. There was an association between hearing loss and poorer balance performance. The highest proportion of failures was for the hearing loss criterion that included high frequencies. Age was the most relevant explanatory variable in balance test performance, in addition to hearing loss, schooling, income, and BMI, emphasizing the need for a multifactorial view of this function.

Objective: To investigate the association between rheumatoid arthritis (RA) and coronary artery calcium (CAC) prevalence, incidence, and progression over four years in adults without prior cardiovascular disease. Methods: A case‐cohort study within the Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil) included 585 participants (86 patients with RA, 499 controls). Longitudinal analyses were restricted to those with CAC reassessed at four years (58 patients with RA, 352 controls). CAC was quantified by computed tomography (Agatston method). Incidence was defined as new CAC among those with baseline zero CAC; progression used Berry criteria. Multivariable regression models were hierarchically adjusted. Nonparametric bootstrap estimated 95% confidence intervals (CIs) for progression. Results: Mean ± SD age was 51.5 ± 8.9 years; 55.5% were female. RA was not associated with CAC prevalence (odds ratio [OR] 1.34; 95% CI 0.69–2.55) or incidence (OR 0.83; 95% CI 0.05–3.08) after adjustment. Conversely, RA was associated with CAC progression after multivariable adjustment (Model 1 OR 3.11; 95% bootstrap CI 1.52–8.41; Model 2 OR 4.29; 95% bootstrap CI 1.98–14.65). Conclusion: In this cohort, RA was associated with CAC progression despite no association with prevalence or incidence. These findings suggest chronic inflammation may drive calcification progression through nontraditional pathways, supporting longitudinal cardiovascular monitoring in RA.

BACKGROUND: Obesity is an established risk factor for cardiovascular disease (CVD); however, the overall and sex-specific relationships across the full spectrum of body mass index (BMI), particularly severe obesity defined as class 2 (BMI 35 to 2 ) and class 3 (BMI ≥40 kg/m ² ), and long-term CVD outcomes remain incompletely described. METHODS: We included 289 875 participants (mean age, 60.3 years; 79.2% women) from 21 cohorts of the Cross-Cohort Collaboration enrolled between 1948 and 2015 with harmonized BMI data, a BMI ≥18.5 kg/m ² , and at least one of nine adjudicated outcomes: time to first fatal and non-fatal myocardial infarction (MI), fatal and nonfatal stroke, heart failure (HF), atrial fibrillation (AF), total coronary heart disease (CHD), total CVD, CHD mortality, CVD mortality, and all-cause mortality. Multivariable Cox proportional hazard models with restricted cubic splines were used to estimate the hazard ratio (HR) of BMI for each outcome, adjusting for demographic and clinical risk factors. RESULTS: Over 19.2 median years (25th, 11.6; 75th, 23.5 percentile) of follow-up, there were a total of 15 542 incident MI events, 15 467 incident stroke events, 14 172 incident HF events, 9066 diagnosed AF, and 113 918 total deaths, of which 14 647 were CHD-related and 28 879 were CVD-related. Overall, compared with individuals with normal weight, those with class 2 and class 3 obesity had the highest risk of HF (HR, 2.1, 95% CI, 2.0–2.3, and HR, 3.0, 95% CI, 2.7–3.2, respectively) and AF (HR, 1.8, 95% CI 1.7–2.0, and HR, 2.8, 95% CI, 2.5–3.1, respectively). Compared with men, women experienced higher relative increases in the risk associated with severe obesity for outcomes stroke, CVD, and all-cause mortality (P for interaction: <0.001, 0.003, and <0.001, respectively). Furthermore, in men, no increase in stroke risk was observed with higher BMI categories (P trend=0.49), whereas in women, the risk of stroke plateaued across obesity subclasses (compared with normal weight) yet remained significantly increased. CONCLUSIONS: Higher BMI was robustly associated with increased risk for most outcomes, particularly HF and AF, even after adjusting for traditional risk factors. Observed sex differences in the relative hazard of higher BMI categories and stroke, total CVD, and all-cause mortality suggest potential differences in underlying biological mechanisms.

Background: Elevated parathyroid hormone (PTH) levels have been linked to higher cardiovascular (CV) and all-cause mortality in individuals with hyperparathyroidism or high-risk conditions (individuals with a mean age of 75-85 years and patients undergoing coronary angiography). However, it remains uncertain whether sex- and age-related differences influence these associations among normocalcemic and middle-aged adults from the general population. Methods: We analyzed 4736 participants from the ELSA-Brasil study (mean age, 51.7 years; 55% females), followed for a median of 11.2 years. Baseline serum PTH was measured by electrochemiluminescence immunoassay. Associations of PTH with outcomes were assessed using Cox regression for all-cause mortality, reporting hazard ratios (HRs), and Fine-Gray models for CV mortality, accounting for competing risks and reporting subdistribution hazard ratios (sHRs), adjusted for total calcium, and other relevant covariates. Results: A baseline PTH concentration >56 pg/mL was independently associated with higher CV mortality (sHR 1.92; 95% CI 1.22-3.01) and all-cause mortality (HR 1.61; 95% CI 1.25-2.07). Sex- and age-stratified analyses showed that females with elevated PTH had a 179% increased CV mortality risk (sHR 2.79; 95% CI 1.37-5.70), whereas no significant association was seen in males. Elevated PTH was also associated with increased CV mortality in adults ≤64 years (sHR 1.80; 95% CI 1.05-3.09) but not in older individuals. For all-cause mortality, PTH >56 pg/mL conferred a higher risk in both females (HR 1.75; 95% CI 1.15-2.66) and males (HR 1.59; 95% CI 1.16-2.19), with consistent associations across both age groups (≤64 and >64 years). Conclusion: In this large, community-based cohort, PTH levels at the upper end of the reference range were associated with greater CV and all-cause mortality. The excess CV risk was restricted to females and younger adults, suggesting that PTH may serve as an early, sex-sensitive biomarker of cardiometabolic risk.