GlycA Levels Independently Predict Coronary Artery Calcium Incidence and Progression in the ELSA-Brasil Cohort (Brazilian Longitudinal Study of Adult Health).

Atherosclerosis is an inflammatory disease. Coronary artery calcium (CAC) is a marker of atherosclerotic disease events and mortality risk. Elevated GlycA, an emerging marker of inflammation, is associated with a higher risk for coronary artery disease (CAD). However, there is conflicting evidence on whether GlycA predicts subclinical CAD progression. We hypothesized that GlycA can predict subclinical CAC incidence/progression in healthy individuals. We included 2,690 ELSA-Brasil cohort participants without cardiovascular/chronic inflammatory disease not receiving statin therapy who had GlycA levels measured and two interval CAC assessments between 2010 through 2018. Multivariable logistic and linear regression models were computed to evaluate GlycA as a predictor of CAC incidence and progression. CAC incidence required a baseline CAC of 0. CAC progression required a baseline CAC > 0. The mean age of participants was 48.6 ± 7.7 years, 56.7% were female, 54.6% and 16.1% (429/2690) were White and Black, respectively. The mean CAC interscan period was 5.1 ± 0.9 years, the mean GlycA level was 414.7 ± 65 µmol/L, and the incidence of CAC was 13.1% (280/2,129). GlycA level odds ratio (OR) for CAC incidence was 1.002 [95% confidence interval (CI) 1.0005-1.005, p=0.016] adjusted for demographics, lifestyle, a family history of early CAD (≤60 years), lipids, and comorbidities. The GlycA (≤p25 vs ≥p75) OR for CAC progression (Berry definition) was 1.77 (95% CI 1.07-2.96, p=0.03) in a similar multivariable-adjusted model. Higher GlycA levels were associated with CAC incidence and progression in a healthy Brazilian cohort.

Thyroid hormone homeostasis in levothyroxine-treated patients: Findings from ELSA-Brasil.

CONTEXT: The effectiveness of levothyroxine (LT4) in restoring thyroid hormone (TH) homeostasis, particularly serum thyroxine (T4) and triiodothyronine (T3) levels, remains debatable. OBJECTIVE: To assess TH homeostasis in LT4-treated individuals using data from the Longitudinal Study of Adult Health in Brazil (ELSA-Brasil) study. METHODS: The ELSA-Brasil study follows 15,105 adult Brazilians (aged 35 to 74 years) over 8.2 years (2008-2019) with 3 observation points assessing health parameters including serum thyroid stimulating hormone (TSH), free T4 (FT4), and free T3 (FT3) levels. We analyzed 186 participants that initiated treatment with LT4 during the study, and 243 individuals continuously treated with LT4 therapy. RESULTS: Initiation of therapy with LT4 resulted in a 11-19% decrease in TSH, a ∼19% increase in FT4, and a 7% reduction in FT3 serum levels (FT3 dropped >10% in ∼40% of the LT4-treated patients). This was associated with an increase in triglyceride levels and utilization of hypolipidemic and anti-diabetic medications. Participants continuously treated with LT4 exhibited a stable elevation in serum FT4 and, a reduction in serum FT3 and TSH levels. While 115 participants (47.3%) had at least one serum FT4 levels above the control reference range (>1.52 ng/dL), 38 participants (15.6%) had at least one serum FT3 below the reference range (<0.23 ng/dL). CONCLUSION: The present results challenge the dogma that treatment with LT4 for hypothyroidism restores TH homeostasis in all patients. A substantial number of LT4-treated patients exhibit repeated FT4 and FT3 levels outside the normal reference range, despite normal TSH levels. Further studies are needed to define the clinical implications of these findings.

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.

Home-Use Transcranial Direct Current Stimulation for the Treatment of a Major Depressive Episode: A Randomized Clinical Trial.

Importance: Transcranial direct current stimulation (tDCS) is moderately effective for depression when applied by trained staff. It is not known whether self-applied tDCS, combined or not with a digital psychological intervention, is also effective. Objective: To determine whether fully unsupervised home-use tDCS, combined with a digital psychological intervention or digital placebo, is effective for a major depressive episode. Design, Setting, and Participants: This was a double-blinded, sham-controlled, randomized clinical trial with 3 arms: (1) home-use tDCS plus a digital psychological intervention (double active); (2) home-use tDCS plus digital placebo (tDCS only), and (3) sham home-use tDCS plus digital placebo (double sham). The study was conducted between April 2021 and October 2022 at participants' homes and at Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. Included participants were aged 18 to 59 years with major depression and a Hamilton Depression Rating Scale, 17-item version (HDRS-17), score above 16, a minimum of 8 years of education, and access to a smartphone and internet at home. Exclusion criteria were other psychiatric disorders, except for anxiety; neurologic or clinical disorders; and tDCS contraindications. Interventions: tDCS was administered in 2-mA, 30-minute prefrontal sessions for 15 consecutive weekdays (1-mA, 90-second duration for sham) and twice-weekly sessions for 3 weeks. The digital intervention consisted of 46 sessions based on behavioral therapy. Digital placebo was internet browsing. Main Outcomes and Measures: Change in HDRS-17 score at week 6. Results: Of 837 volunteers screened, 210 participants were enrolled (180 [86%] female; mean [SD] age, 38.9 [9.3] years) and allocated to double active (n = 64), tDCS only (n = 73), or double sham (n = 73). Of the 210 participants enrolled, 199 finished the trial. Linear mixed-effects models did not reveal statistically significant group differences in treatment by time interactions for HDRS-17 scores, and the estimated effect sizes between groups were as follows: double active vs tDCS only (Cohen d, 0.05; 95% CI, -0.48 to 0.58; P = .86), double active vs double sham (Cohen d, -0.20; 95% CI, -0.73 to 0.34; P = .47), and tDCS only vs double sham (Cohen d, -0.25; 95% CI, -0.76 to 0.27; P = .35). Skin redness and heat or burning sensations were more frequent in the double active and tDCS only groups. One nonfatal suicide attempt occurred in the tDCS only group. Conclusions and Relevance: Unsupervised home-use tDCS combined with a digital psychological intervention or digital placebo was not found to be superior to sham for treatment of a major depressive episode in this trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04889976.

Predictive value of functional disability scales among stroke survivors: A long-term mortality evaluation in a Brazilian stroke cohort.

OBJECTIVE: To assess the influence of two functional scales- Modified Rankin Scale (m-RS) and Modified Katz Index (m-Katz Index) on long-term mortality in a stroke cohort. MATERIAL AND METHODS: Among 760 stroke survivors (median age: 66 (IQR:56-75), 56.4 % women) m-Katz Index and m-RS scales applied at 1 and 6 months after stroke, were investigated in relation to 12-years of all-cause mortality. Kaplan-Meier survival curves were computed, and time-varying covariate Cox regression models were fitted to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs) in all sample and by sex. The prognostic ability of the fitted models was computed for each model by six different measures. RESULTS: After 12 years of follow-up (median survival time: 7.3 years), 311 participants died. Overall survival curves show lower survival rates among those with the highest levels of disability/dependence (all log-rank p-values <0.0001). These findings were confirmed in all regression models for both sexes, particularly in men who had higher levels of dependence on Activities of Daily Living (ADLs) by m-Katz Index and severe disability by m-RS and presented the highest HR of dying (HR: 3.34 (95 %CI: 2.27-4.92) and HR: 4.94 (95 % CI: 3.15-7.75), respectively). CONCLUSIONS: Both the m-Katz Index and the m-RS scale were good predictors of long-term mortality, which is of importance for guiding the functional rehabilitation of stroke patients. Besides, high levels of disability and dependence were implicated with high mortality risks, regardless of sex.

Incident Coronary Calcium Score in Patients With OSA With and Without Excessive Sleepiness: Brazilian Longitudinal Study of Adult Health.

BACKGROUND: Uncertainty exists about the impact of OSA and its phenotypes on cardiovascular disease. RESEARCH QUESTION: Are OSA and clinical features such as daytime sleepiness associated with incident subclinical coronary atherosclerosis? STUDY DESIGN AND METHODS: In this prospective community-based cohort study, we administered a sleepiness questionnaire, actigraphy, and home sleep studies at baseline. Coronary artery calcium (CAC; 64-slice multidetector CT scan imaging) was measured at two different time points throughout the study (baseline, between 2010 and 2014, and follow-up, between 2016 and 2018). Incidence of subclinical atherosclerosis was defined as baseline CAC of 0 followed by CAC of > 0 at a 5-year follow-up visit. The association of incident CAC outcome was assessed using logistic regression. Stratified analyses based on excessive daytime sleepiness (EDS) were performed. RESULTS: We analyzed 1,956 participants with available CAC scores at baseline (mean age, 49 ± 8 years; 57.9% female; 32.4% with OSA). In covariate-adjusted analyses (n = 1,247; mean follow-up, 5.1 ± 0.9 years), we found a significant association between OSA and incidence of subclinical atherosclerosis (OR, 1.26; 95% CI, 1.06-1.48), with stronger effects among those reporting EDS (OR, 1.66; 95% CI, 1.30-2.12; P = .028 for interaction). Interestingly, EDS per se was not associated with any CAC outcome. An exploratory analysis of the square root of CAC progression (baseline CAC > 0 followed by a numerical increase in scores at follow-up; n = 319) showed a positive association for both OSA (ß = 1.084; 95% CI, 0.032-2.136; P = .043) and OSA with EDS (ß = 1.651; 95% CI, 0.208-3.094; P = .025). INTERPRETATION: OSA, particularly with EDS, predicts the incidence and progression of CAC. These results support biological plausibility for the increased cardiovascular risk observed among patients with OSA with excessive sleepiness.

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.

Carotid intima-media thickness and incident hypertension: the Brazilian Longitudinal Study of Adult Health.

BACKGROUND: High blood pressure (BP) increases carotid intima-media thickness (CIMT). On the other hand, it is not clear whether the vascular abnormalities reflected in high CIMT may predict incident hypertension. The present study aims to investigate the association between CIMT and incident hypertension after 4 years of follow-up in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multiethnic sample of middle-aged adults from six Brazilian cities. METHODS: We analyzed data from 6682 ELSA-Brasil participants (aged 35-74) without hypertension and with complete CIMT data at baseline. After 4 years of follow-up, we describe hypertension incidence, stratifying the sample according to age, sex, and race-specific CIMT quartiles. We also built crude and adjusted Poisson regression models to analyze the association between mean and maximal CIMT values and incident hypertension. RESULTS: We found incident hypertension in 987 (14.8%) participants. According to mean CIMT quartile groups, hypertension incidence varied from 10.2% (first quartile group) to 22.4% (fourth quartile group; P for trend <0.001). In fully adjusted models, 0.1 mm increments in mean CIMT values were associated with a 16% [relative risk (RR):1.16; 95% confidence interval (95% CI) 1.10-1.21; P  < 0.001] higher risk of incident hypertension, respectively. Results were similar when maximal CIMT values were considered instead of mean CIMT values. CONCLUSION: CIMT values at baseline strongly predicted incident hypertension after 4 years of follow-up in this large multiethnic cohort. This highlights the relationship between CIMT and BP and may provide important insights into the significance of this ultrasound measurement.

Anaemia and its causes at the Brazilian Longitudinal Study of Adult Health: a cross-sectional analysis of baseline data.

BACKGROUND: Most anaemia studies focus on children and women of childbearing age. We assessed the frequency and main aetiologies of anaemia according to sociodemographic characteristics at the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a cohort of middle-aged adults. METHODS: The primary analyses included 15,051 participants aged 35-74 years with a valid blood cell count. We built logistic models to analyse the association between socioeconomic characteristics and anaemia diagnosis. We also described the main aetiologies in a subset (n = 209) of participants with anaemia. RESULTS: Anaemia was present in 3.0% (95% confidence interval [95%CI]: 2.6-3.4%) of men and 7.4% (95%CI: 6.9-8.0%) of women. The frequency of anaemia diagnosis was higher in women in all subgroups except for the oldest age stratum (65-74 years). The frequency of anaemia was particularly high in Blacks (6.0% and 15.5% in men and women, respectively). The most common causes of anaemia were iron deficiency (in women), chronic kidney disease, and chronic inflammation (in men). The frequency of unexplained anaemia was respectively 33.3% and 34.2% for men and women, and this condition was more frequent among participants of Black or Mixed races. CONCLUSIONS: Anaemia was associated with age, female sex, Black race, and low socioeconomic status. Unexplained anaemia was common and more frequent in individuals of Black and Mixed races. ELSA-Brasil follow-up data may provide further insight into the relevance of unexplained anaemia in this setting.

This study aims to assess the frequency, associated factors, and (in a subsample) the leading causes of anaemia in a large epidemiological study in 6 Brazilian state capitals. Our primary analyses included 15,051 participants aged 35­74 years. Anaemia was present in 3.0% of men and 7.4% of women. The frequency of anaemia diagnosis was higher in women in all subgroups except for the oldest age stratum (65­74 years). The frequency of anaemia was particularly high in Blacks (6.0% and 15.5% in men and women, respectively). The most common causes of anaemia were iron deficiency (in women), chronic kidney disease, and chronic inflammation (in men). Despite an extensive workout to determine the causes of anaemia, this condition remained unexplained in approximately one-third of cases. Unexplained anaemia was more frequent among participants of Black or Mixed races. Besides providing a clear epidemiological description of anaemia in this setting, our work also provides insight into the interpretation of current cutoffs for anaemia diagnosis.

Percentiles of predicted 10-year cardiovascular disease risk by sex and age in Brazil and their association with estimated risk of long-term atherosclerotic events.

OBJECTIVE: Expressing the cardiovascular disease (CVD) risk in relation to peers may complement the estimation of absolute CVD risk. We aimed to determine 10-year CVD risk percentiles by sex and age in the Brazilian population and evaluate their association with estimated long-term atherosclerotic CVD (ASCVD) risk. METHODS: A cross-sectional analysis of baseline data from the ELSA-Brasil study was conducted in individuals aged 40-74 years without prior ASCVD. Ten-year CVD risk and long-term ASCVD risk were estimated by the WHO risk score and the Multinational Cardiovascular Risk Consortium tool, respectively. Ten-year risk percentiles were determined by ranking the calculated risks within each sex and age group. RESULTS: Ten-year CVD risk versus percentile plots were constructed for each sex and age group using data from 13,364 participants (55% females; median age, 52 [IQR, 46-59] years). Long-term ASCVD risk was calculated in 12,973 (97.1%) participants. Compared to individuals at the <25th risk percentile, those at the ≥75th percentile had a greater risk of being in the highest quartile of long-term risk (ORs [95% CIs] 6.57 [5.18-8.30] in females and 11.59 [8.42-15.96] in males) in regression models adjusted for age, race, education, and 10-year CVD risk. In both sexes, the association between risk percentile and long-term risk weakened after age 50. A tool for calculating 10-year CVD risk and the corresponding percentile is available at https://bit.ly/3CzPUi6. CONCLUSIONS: We established percentiles of predicted 10-year CVD risk by sex and age in the Brazilian population, which independently reflect the estimated long-term ASCVD risk in younger individuals.

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

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 ß (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 (ß, 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.

Identifying and understanding the care pathway of patients with atrial fibrillation in Brazil and the impact of the COVID-19 pandemic: A mixed-methods study.

BACKGROUND: Atrial fibrillation (AF) is a major risk factor for stroke. To enable improvements to AF diagnosis and follow-up care, understanding current patient pathways and barriers to optimal care are essential. We investigated the patient care pathways and their drivers, and the impact of the COVID-19 pandemic on patient pathways in a middle-income country setting, Brazil. METHODS: This mixed-methods study in São Paulo, included adults (≥18y) with AF from 13 primary/secondary healthcare facilities. Surveys using baseline, follow-up (administered ≥two months after baseline) and COVID-19 questionnaires (quantitative), and three focus group discussions (FGDs) were conducted. Minimum sample size for the quantitative component was 236 and we aimed to reach saturation with at least three FGDs for the qualitative component. Descriptive statistics were used for quantitative data and a content analysis was used for qualitative data to identify themes related to AF diagnosis and follow-up care. RESULTS: 267 participants completed the baseline questionnaire: 25% were diagnosed in primary care, 65% in an emergency or inpatient department. At follow-up (n = 259), 31% visited more than one facility for AF care, and 7% had no follow-up. Intervals between international normalised ratio (INR) tests were increased during the pandemic, and the number of healthcare visits and availability of medication were reduced. Seventeen patients participated in three FGDs and revealed that AF diagnosis often occurred following a medical emergency and patients often delay care-seeking due to misconceptions about AF symptoms. Long waiting times, doctor/patient interactions and health system factors, such as doctor availability and the referral system, influence where participants visited for follow-up care. CONCLUSIONS: Lack of public awareness and underdeveloped primary healthcare lead to delayed diagnosis, which impacts clinical outcomes and excess patient and healthcare system costs. Health system, care-provider, and pandemic factors disrupt timely and effective continuity of care.

Gender Modulated the Association of Sleep Apnea and Sleep Duration with Arterial Stiffness: The ELSA-Brasil Study.

Increased arterial stiffness is independently associated with cardiovascular risk. Obstructive sleep apnea (OSA) and sleep duration (SDUR) may contribute to increased arterial stiffness, but it is unclear whether this association is modulated by gender. We aimed to evaluate the potential impact of gender in modulating the association of OSA and SDUR with arterial stiffness. Participants from the ELSA-Brasil study performed sleep assessments with portable polygraph to define OSA severity and SDUR by 1-week wrist actigraphy. Pulse wave velocity (PWV) was measured using a standard technique without access to the sleep data. We studied 1863 participants (42.2% male, age: 49±8 years, respiratory disturbance index (RDI): 9.9 (4.5-19.4) events/h, SDUR: 6.5 (5.9-7.1) hours, mean PWV: 7.3 ± 1.2 m/s). We found that men had higher PWV, higher frequency of diabetes, and higher blood pressure when compared to women. The regression analysis showed an independent association between increased RDI and PWV in men (ß: 0.007; 95% CI: 0.001-0.012), but not in women. In contrast, an independent association between SDUR and increased arterial stiffness was observed only in women (ß: 0.068; 95% CI: 0.002-0.134). In conclusion, the association of sleep disorders with arterial stiffness showed a distinct gender pattern depending on the sleep variable studied.

Comorbid association of obstructive sleep apnea (OSA) and thrombotic primary antiphospholipid syndrome (tPAPS): A more severe phenotype?

OBJECTIVE: We aimed to evaluate the frequency of obstructive sleep apnea (OSA) in patients with thrombotic primary antiphospholipid syndrome (tPAPS), to investigate the performance of screening tools for OSA in this scenario and to compare clinical/laboratorial differences in tPAPS patients with and without OSA. METHODS: We consecutively enrolled patients with tPAPS to undergo sleep studies using a portable monitor. OSA was defined as apnea-hypopnea index ≥15 events/h. Frequency of OSA in tPAPS was evaluated and compared with age-, gender-, and BMI-matched controls (1:3 ratio) from the Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Next, we tested the performance of three different screening tools for assessing OSA in patients with tPAPS. Finally, patients with tPAPS were stratified according to OSA status comparing their clinical and laboratory characteristics (including damage burden measured by Damage Index for Antiphospholipid Syndrome [DIAPS] and biomarkers associated with thrombosis) using standard statistical procedures. RESULTS: Fifty-two patients were included for analysis (females: 82.7%; mean age: 48 ± 14 years; body-mass index: 31.1 ± 6.5 Kg/m2; 25% with moderate-severe OSA). When compared to matched controls from ELSA-Brasil (n = 115), there was no significant differences in the frequencies of OSA (tPAPS: 12/42 [28.6%] vs. controls: 35/115 [30.4%], p = 0.821). Among screening tools, NoSAS had the highest area under ROC curve (AUC 0.806, CI 95% 0.672-0.939, p = 0.001), followed by STOP-Bang (AUC 0.772, CI 95% 0.607-0.938, p = 0.004). Patients with comorbid tPAPS and OSA presented higher levels of von Willebrand factor (vWF) (median 38.9 vs. 32.6, p = 0.038) and DIAPS (median 5 vs. 2, p = 0.020), when compared to those without OSA. OSA remained statistically associated with higher DIAPS, even after controlling for age, disease duration and BMI. CONCLUSION: OSA is common in patients with tPAPS, with rates comparable to a non-referred population. Both NoSAS and STOP-Bang scores seems to be useful for screening OSA in these patients. Patients with tPAPS+OSA had higher damage burden and higher levels of vWF, which might suggest a more severe phenotype of tPAPS in this scenario.

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.

GlycA as a Novel Biomarker of Systemic Inflammation in Hypothyroidism.

Background: GlycA is a novel glycoprotein biomarker of systemic inflammation and cardiovascular risk. Our objective was to assess the levels of GlycA in individuals with hypothyroidism. We also explored whether levothyroxine (LT4)-treated patients had different levels of GlycA, with attention to thyrotropin (TSH) levels. Methods: We performed a cross-sectional analysis, using baseline data from the ELSA-Brasil cohort study. We included only participants with serum TSH and GlycA levels measurements, using magnetic resonance spectroscopy (n = 4745). We excluded individuals with endogenous hyperthyroidism and those using drugs impacting thyroid function. Participants not taking LT4 and whose serum TSH was 0.4-4.0 mIU/L were classified as euthyroid (EU) and those with elevated TSH as undiagnosed hypothyroidism (UH). For those on LT4 (n = 345), adequacy of treatment was defined as TSH within the reference range. Those with TSH <0.4 mIU/L were considered over-treated (OT), and those >4.0 mIU/L, under-treated (UT). Both (UT+OT) were considered inadequately treated (IT). Group comparisons were performed by Kruskal-Wallis, adjusted Chi-square, and the post hoc Dunn test. Additional subgroup analysis were performed in patients with circulating thyroperoxidase antibodies (TPO-Ab+). Respective multivariable analyses were performed to evaluate the relationship between thyroid-related variables and GlycA levels (Generalized Linear Model), as well as an abnormal GlycA (>400 µmol/L; Logistic Binary Regression). Results: The prevalence rate of UH was 9.8% (467/4745) and, among those on LT4, only 61.7% (213/345) were adequately treated (AT). GlycA levels were higher in IT in comparison to EU (429 vs. 410 µmol/L, p < 0.01) but did not differ between UH (413 µmol/L) and euthyroidism. However, the subgroup analysis of those TPO-Ab+ showed that not only those with IT, but also those with UH, had higher levels of GlycA in comparison to euthyroidism (423 and 424 vs. 402 µmol/L, p = 0.04). This association between higher levels of GlycA and IT was maintained even in multivariable analysis (odds ratio 1.53, confidence interval 1.03 to 2.31) Lower levels of GlycA were detected in AT (405 µmol/L,) compared with OT (432 µmol/L, 0.04) and UT (423 µmol/L, p = 0.02). Conclusions: Patients with IT, both OT and UT, had higher GlycA levels, which may be associated with low-grade systemic inflammation and, possibly, increased cardiovascular risk.

Combined Association of Novel and Traditional Inflammatory Biomarkers With Carotid Artery Plaque: GlycA Versus C-Reactive Protein (ELSA-Brasil).

Elevated levels of glycoprotein acetylation (GlycA) and C-reactive protein (CRP) have been associated with carotid artery plaque (CAP). However, it is not yet established if elevations in both inflammatory biomarkers provide incremental association with CAP. This study aimed evaluate the cross-sectional association of high CRP and GlycA with CAP at baseline participants from the ELSA-Brasil adult cohort. Participants with information on CRP, GlycA, and CAP with neither previous cardiovascular disease nor CRP >10 mg/L were included. High GlycA and CRP were defined as values within upper quintile and >3 mg/L, respectively. Participants were classified into 4 groups: 1. nonelevated CRP/GlycA (reference group); 2. elevated CRP alone; 3. elevated GlycA alone; and 4. both elevated. The analysis included 4,126 participants with median age of 50 years-old, being 54.2% of women. Prevalence of CAP was 36.1%. Participants with high CRP had the highest frequency of obesity, whereas participants with high GlycA presented higher cardiovascular risk factor burden and were more likely to have CAP than the reference group (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.11 to 1.73), persisting after multivariable adjustment (OR 1.37, 95% CI 1.02 to 1.83). Participants with both elevated CRP and GlycA were more likely to have CAP in crude (OR 1.35, 95% CI 1.10 to 1.65) but not in adjusted models. The findings suggest potential different biologic pathways between inflammation and carotid atherosclerosis: high GlycA was associated with CAP whereas high CRP was more associated with obesity.

Life's Essential 8 is associated with atherosclerotic cardiovascular disease but not venous thromboembolism in men: a prospective cohort study.

Background: Atherosclerotic cardiovascular disease (ASCVD) shares several risk factors with venous thromboembolism (VTE). The American Heart Association's Life's Simple 7 (LS7), which included seven health and behavioural factors for CVD prevention, has recently been upgraded to Life's Essential 8 (LE8) score. We aimed to examine the prospective association between LE8 and the risks of ASCVD and VTE in Finland.Methods: We utilized data based on 1899 men aged 42-61 years in the Kuopio Ischaemic Heart Disease (KIHD) prospective study. The LE8 score was generated from baselines measures of four health behaviours (physical activity, diet, nicotine exposure and sleep health) and four health factors (BMI, blood lipids, blood glucose and blood pressure). Each factor was scored from 0 to 100 and summed into a composite score. Participants were classified into quartiles (Q) based on the total LE8 score - Q1, ≤ 420; Q2, >420 to 485; Q3, >485 to 550; Q4, >550. Multivariable Cox regression models were utilized to determine the hazard ratios (HRs) along with the 95% confidence intervals (CI) for ASCVD and VTE.Results: After median follow-up durations of 24 and 25 years, 889 ASCVD and 127 VTE events were recorded, respectively. The risk of ASCVD was found to be 58% lower in men belonging to the highest LE8 quartile compared to those in the lowest quartile (HR:0.42; 95%CI: 0.34-0.51). There was no significant evidence of an association between LE8 and VTE risk (Q4 vs Q1, HR:1.02; 95%CI: 0.60-1.74).Conclusion: The risk of ASCVD was significantly lower in middle-aged and older Finnish men who had a high LE8 score, but there was no significant association with VTE. Further large-scale prospective studies conducted in women and other population groups are necessary to confirm these findings.

Key MessagesMen who had total Life's Essential 8 (LE8) score more than 550 had lower risk of atherosclerotic cardiovascular disease (ASCVD) compared with those with LE8 score ≤ 420.Increasing LE8 score by 50 can lower the risk of ASCVD, but not venous thromboembolism (VTE).The result supports continuous improvement in combined healthy behaviours and factors in LE8 composite score may lower future risk of heart disease or stroke.

Generalisability of and lessons learned from a mixed-methods study conducted in three low- and middle-income countries to identify care pathways for atrial fibrillation.

BACKGROUND: Identifying existing care pathways is the first step for understanding how services can be improved to enable early diagnosis and effective follow-up care for non-communicable diseases (NCDs); however, evidence on how care pathways can and should be identified in low- and middle-income countries (LMICs) is lacking. OBJECTIVE: To describe generalisability and lessons learned from recruitment and data collection for the quantitative component of a mixed methods study designed to determine the care pathway for atrial fibrillation (AF) in Brazil, China and Sri Lanka. METHODS: Adults (≥18 years) that spoke the local language and with an AF diagnosis were eligible. We excluded anyone with a hearing or cognitive impairment or ineligible address. Eligible participants were identified using electronic records in Brazil and China; in Sri Lanka, researchers attended the outpatient clinics to identify eligible participants. Data were collected using two quantitative questionnaires administered at least 2-months apart. A minimum sample size of 238 was required for each country. RESULTS: The required sample size was met in Brazil (n = 267) and China (n = 298), but a large proportion of AF patients could not be contacted (47% and 27%, respectively) or refused to participate (36% and 38%, respectively). In Sri Lanka, recruitment was challenging, resulting in a reduced sample (n = 151). Mean age of participants from Brazil, China and Sri Lanka was 69 (SD = 11.3), 65 (SD = 12.8) and 58 (SD = 11.7), respectively. Females accounted for 49% of the Brazil sample, 62% in China and 70% in Sri Lanka. CONCLUSIONS: Generalisability was an issue in Brazil and China, as was selection bias. Recruitment bias was highlighted in Sri Lanka. Additional or alternative recruitment methods may be required to ensure generalisability and reduce bias in future studies aimed at identifying NCD care pathways in LMICs.

Suicide risk classification with machine learning techniques in a large Brazilian community sample.

Even though suicide is a relatively preventable poor outcome, its prediction remains an elusive task. The main goal of this study was to develop machine learning classifiers to identify increased suicide risk in Brazilians with common mental disorders. With the use of clinical and sociodemographic baseline data (n = 4039 adult participants) from a large Brazilian community sample, we developed several models (Elastic Net, Random Forests, Naïve Bayes, and ensemble) for the classification of increased suicide risk among individuals with common mental disorders. 1120 participants (27.7%) presented increased suicide risk. The Random Forests model achieved the best AUC ROC (0.814), followed by Naive Bayes (0.798) and Elastic Net (0.773). Sensitivity varied from 0.922 (Naive Bayes) to 0.630 (Random Forests), while specificity varied from 0.792 (Random Forests) to 0.473 (Naive Bayes). The ensemble model presented an AUC ROC of 0.811, sensitivity of 0.899, and specificity of 0.510. Features representing depression symptoms were the most relevant for the classification of increased suicide risk. Some of our models presented good performance metrics in the classification of increased suicide risk in the investigated sample, which can provide the means to early preventive interventions.