Cerebrovascular risk factors and their time-dependent effects on stroke survival in the EMMA cohort study

To investigate the time-dependent effects of traditional risk factors on functional disability in all-cause mortality post-stroke, we evaluated data from a long-term stroke cohort. Baseline cerebrovascular risk factors (CVRF) and functionality at 1 and 6 months were evaluated in survivors from a prospective stroke cohort using the modified Rankin scale (m-RS), which classifies participants as improvement of disability, unchanged disability (at least moderate), and worsening disability. Cox regression models considering baseline risk factors, medication use, and functionality 6 months after stroke were fitted to identify their time-dependent effects up to 12 years of follow-up. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) are presented. Among 632 survivors (median age 68, 54% male, 71% first-ever episode), age and functional disability (unchanged and worsening) 6 months after ischemic stroke had time-dependent effects on all-cause mortality risk up to 12 years of follow-up. The most impacting risk factors were unchanged (at least moderate) (HR, 2.99; 95%CI: 1.98-4.52) and worsening disability (HR, 2.85; 95%CI: 1.26-6.44), particularly in the first two years after a stroke event (Time 1: ≥6 mo to <2.5 y). Worsening disability also impacted mortality in the period from ≥2.5 to <7.5 years (Time 2) of follow-up (HR, 2.43 (95%CI: 1.03-5.73). Other baseline factors had a fixed high-risk effect on mortality during follow-up. Post-stroke and continuous medication use had a fixed protective effect on mortality. Functional disability was the main contributor with differential risks of mortality up to 12 years of follow-up.

Association of coronary artery calcium with heart rate variability in the Brazilian Longitudinal Study of Adult Health - ELSA-Brasil

Current data shows that the autonomic and vascular systems can influence each other. However, only a few studies have addressed this association in the general population. We aimed to investigate whether heart rate variability (HRV) was associated with coronary artery calcium (CAC) in a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We examined baseline data from 3138 participants (aged 35 to 74 years) without previous cardiovascular disease who underwent CAC score assessment and had validated HRV recordings. Prevalent CAC was defined as a CAC score>0, and HRV analyses were performed over 5-min segments. We detected CAC score>0 in 765 (24.4%) participants. Subgroup analyses in older participants (≥49 years) adjusted for sociodemographic and clinical variables revealed that CAC score>0 was associated with lower values of standard deviation of NN intervals (SDNN) (odds ratio [OR]=1.32; 95%CI: 1.05,1.65), root mean square of successive differences between adjacent NN intervals (RMSSD) (OR=1.28; 95%CI: 1.02,1.61), and low frequency (LF) (OR=1.53, 95%CI: 1.21,1.92). Interaction analysis between HRV indices and sex in age-stratified groups revealed significant effect modification: women showed increased OR for prevalent CAC in the younger group, while for men, the associations were in the older group. In conclusion, participants aged ≥49 years with low SDNN, RMSSD, and LF values were more likely to present prevalent CAC, suggesting a complex interaction between these markers in the pathogenesis of atherosclerosis. Furthermore, our results suggested that the relationship between CAC and HRV might be sex- and age-related.

Eight-year change in carotid intima-media thickness and associated risk factors in adults with and without psoriasis - the ELSA-Brasil cohort study

The longitudinal association between psoriasis and carotid intima-media thickness (CIMT) has not yet been established. This study aimed do compare CIMT and its change (∆CIMT) after an 8-year follow-up according to psoriasis diagnosis and the association with risk factors in the ELSA-Brasil study. Data from 7564 participants were analyzed (median age of 50.0 [44.0-57.0] years, 56.9% women). CIMT was assessed by ultrasound and ∆CIMT was calculated by subtracting baseline values from follow-up values. Psoriasis participants were identified by self-reported medical diagnosis (n=143) and compared with matched participants without disease (n=572) and with the entire sample without psoriasis (n=7421). Baseline CIMT explained the 8-year CIMT increase only in 36.9% among psoriasis participants and in ∼43.0% in participants without disease. CIMT was associated with age (β=0.002, P=0.002) and hypertension (β=0.029, P=0.034) in psoriasis participants. Among participants without psoriasis, CIMT was associated with age, male sex, low educational attainment, past smoking, obesity, diabetes, hypertension, and dyslipidemia (P<0.05). There was an inverse association of CIMT with private health insurance (β=-0.004, P=0.042) and White ethnicity (β=-0.006, P=0.004) in the entire sample without psoriasis but not in matched participants. Psoriasis participants showed an inverse association between ∆CIMT and diabetes (β=-0.214, P=0.011), while the entire sample without psoriasis showed an inverse association between ∆CIMT and age (β=-0.005, P<0.001), past smoking (β=-0.048, P=0.009), and hypertension (β=-0.048, P=0.009). In conclusion, psoriasis was not associated with CIMT after an 8-year follow-up. The inverse association of ∆CIMT with diabetes in psoriasis participants needs further clarification.

Neck and waist circumference values according to sex, age, and body-mass index: Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Body fat distribution predicts cardiovascular events better than body-mass index (BMI). Waist circumference (WC) and neck circumference (NC) are inexpensive anthropometric measurements. We aimed to present the conditional distribution of WC and NC values according to BMI, stratified by age and sex, from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline data. We analyzed 15,085 ELSA-Brasil participants with complete data. We used spline quantile regression models, stratified by sex and age, to estimate the NC and WC quantiles according to BMI. To test a putative association between age and median NC or WC values, we built sex-specific median regression models using both BMI and age as explanatory variables. We present estimated 25th, 50th, 75th, and 90th percentiles for NC and WC values, according to BMI, age, and sex. Predicted interquartile intervals for NC values varied from 1.6 to 3.8 cm and, for WC values, from 5.1 to 10.3 cm. Median NC was not associated with age in men (P=0.11) nor in women (P=0.79). However, median WC increased with advancing age in both sexes (P<0.001 for both). There was significant dispersion in WC and NC values for a given BMI and age strata for both men and women. WC, but not NC values, were associated with increasing age. The smaller influence of advancing age on the relationship between BMI and NC (compared to WC) values may be useful in longitudinal studies.

Reproducibility of carotid ultrasound measurements in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) at baseline

Carotid artery assessment by ultrasound is a non-invasive evaluation of subclinical atherosclerosis and a predictor of cardiovascular events. However, ultrasound examinations are operator-dependent. In the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), ultrasound images have been acquired from more than 10,000 participants. In this article, we describe the reproducibility of carotid intima-media thickness (CIMT), carotid plaque detection, and carotid plaque score (defined as the number of arterial sites with plaques) using ELSA-Brasil protocol, in a subset of 118 participants. Two board-certified radiologists and a trained technician read carotid images. We calculated intra- and inter-observer intraclass correlation (ICC) for CIMT values. We also present kappa coefficients for plaque detection and weighted kappa coefficients for carotid plaque score. Participants were aged 58.2±6.6 years, and 60 (50.8%) were men. For common carotid artery CIMT measurements, intra- and inter-observer ICC values were very good to excellent, ranging from 0.90 (95% confidence interval [95%CI]: 0.72-0.95) to 0.98 (95%CI: 0.97-0.99). For carotid plaque, intra- (0.96 [95%CI: 0.96-0.96]) and inter- (0.99 [95%CI: 0.99-0.99]) observer weighted kappa coefficients were very good. Intra- and inter-observer Kappa coefficients for the presence of plaques by site were good to very good, ranging from 0.69 to 1.00. In conclusion, we found very good reproducibility for carotid plaque score and CIMT measurements in the ELSA-Brasil at baseline. These results are comparable to the best findings from similar large cohorts that analyzed carotid ultrasound data.

Relationship between heart rate variability and subclinical thyroid disorders of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

The association between subclinical thyroid dysfunctions and autonomic modulation changes has been described by many studies with conflicting results. We aimed to analyze the association between subclinical hyperthyroidism (SCHyper), subclinical hypothyroidism (SCHypo), and heart rate variability (HRV) using the baseline from ELSA-Brasil. SCHyper and SCHypo were classified by use of medication to treat thyroid disorders, thyrotropin levels respectively above and under the reference range, and normal free thyroxine levels. For HRV, the participants underwent 10 min in supine position and the R-R intervals of the final 5 min were selected for analysis. We first used linear regression models to report crude data and then, multivariate adjustment for sociodemographic (age, sex, and race) and cardiovascular risk factors (hypertension, dyslipidemia, diabetes, smoking, body mass index, use of alcohol, and leisure physical activity) using the euthyroid group as reference. From 9270 subjects (median age, 50; interquartile range: 44-56), 8623 (93.0%) were classified as euthyroid, 136 (1.5%) as SCHyper, and 511 (5.5%) as SCHypo. Compared to euthyroid subjects, SCHyper participants presented significantly higher heart rate (68.8 vs 66.5 for euthyroidism, P=0.007) and shorter R-R intervals (871.4 vs 901.6, P=0.007). Although SCHyper was associated with lower standard deviation of NN interval (SDNN) (β: -0.070; 95% confidence interval (95%CI): -0.014 to -0.009) and low-frequency (LF) (β: -0.242, 95%CI: -0.426 to -0.058) compared to the euthyroid group, these differences lost significance after multivariate adjustment for confounders. No significant differences were found for HRV in SCHypo. No association was found between HRV and SCHyper or SCHypo compared to euthyroid subjects in this sample of apparently healthy subjects.

Psoriasis severity and hypothalamic-pituitary-adrenal axis function: results from the CALIPSO study

Psoriasis is a chronic inflammatory disease that significantly impacts life quality, being associated with stress and mental disorders. We investigated whether the activity of the hypothalamic-pituitary-adrenal (HPA) axis was associated with psoriasis severity, daily life stress and anxiety, and depressive symptoms. In this ancillary study, which was part of the CALIPSO (coronary artery calcium in psoriasis) study, saliva was collected from 102 patients with psoriasis immediately upon awakening, 30, and 60 min after awakening, at 2:00 pm and at bedtime (five time points) to determine salivary cortisol levels. We used Pearson's correlation coefficient to evaluate the association of clinical and psychopathological variables with HPA activity. We found a direct correlation between bedtime cortisol and psoriasis severity evaluated by the psoriasis area severity index (PASI; r=0.39, P<0.001). No correlations between other clinical and psychopathological variables or with other cortisol assessments were observed. The findings indicated that HPA dysfunction may be present in psoriasis, as bedtime cortisol was correlated with psoriasis severity. Our study is limited by the lack of a control group; therefore, we were not able to explore whether these cortisol values were different compared with a concurrent, healthy sample.