Eduardo Miranda Dantas

Effects of Depression, Anxiety, Comorbidity, and Antidepressants on Resting-State Heart Rate and Its Variability: An ELSA-Brasil Cohort Baseline Study

OBJECTIVE Increases in resting-state heart rate and decreases in its variability are associated with substantial morbidity and mortality, yet contradictory findings have been reported for the effects of the mood and anxiety disorders and of antidepressants. The authors investigated heart rate and heart rate variability in a large cohort from Brazil, using propensity score weighting, a relatively novel method, to control for numerous potential confounders. METHOD A total of 15,105 participants were recruited in the Brazilian Longitudinal Study of Adult Health. Mood and anxiety disorders were ascertained using the Portuguese version of the Clinical Interview Schedule-Revised. Heart rate and its variability were extracted from 10-minute resting-state electrocardiograms. Regressions weighted by propensity scores were carried out to compare participants with and without depressive or anxiety disorders, as well as users and non-users of antidepressants, on heart rate and heart rate variability. RESULTS Use of antidepressants was associated with increases in heart rate and decreases in its variability. Effects were most pronounced for the tricyclic antidepressants (Cohens d, 0.72-0.81), followed by serotonin and norepinephrine reuptake inhibitors (Cohens d, 0.42-0.95) and other antidepressants (Cohens d, 0.37-0.40), relative to participants not on antidepressants. Only participants with generalized anxiety disorder showed robust, though small, increases in heart rate and decreases in its variability after propensity score weighting. CONCLUSIONS The findings may, in part, underpin epidemiological findings of increased risk for cardiovascular morbidity and mortality. Many factors that have an adverse impact on cardiac activity were controlled for in this study, highlighting the importance of cardiovascular risk reduction strategies. Further study is needed to examine whether, how, and when such effects contribute to morbidity and mortality.

Afericoes e exames clinicos realizados nos participantes do ELSA-Brasil

The article describes assessments and measurements performed in the Brazilian Longitudinal Study for Adult Health (ELSA-Brasil). Some assessments including anthropometric assessment, casual blood pressure measurement, and ankle-brachial index have an established clinical application while others including pulse wave velocity, heart rate variability, and carotid intima-media thickness have no established application and do not have reference values for healthy Brazilian population but may be important predictors of cardiovascular outcomes. Blood pressure measurement following postural change maneuver was included in the ELSA-Brasil because it has not been much tested in epidemiological studies. Innovative approaches were developed for assessing the ankle-brachial index using an automatic device instead of the mercury column to measure blood pressure and for assessing the anterior-posterior diameter of the right lobe of the liver by ultrasound for quantitative assessment of nonalcoholic fatty liver disease. All ELSA-Brasil subjects were younger (35 years or more) than those included in other cohorts studying subclinical atherosclerosis. The inclusion of younger individuals and a variety of assessments make the ELSA-Brasil a relevant epidemiology study nationwide and worldwide.

Heart rate variability is a trait marker of major depressive disorder: evidence from the sertraline vs. electric current therapy to treat depression clinical study

Decreased heart rate variability (HRV) is a cardiovascular predictor of mortality. Recent debate has focused on whether reductions in HRV in major depressive disorder (MDD) are a consequence of the disorder or a consequence of pharmacotherapy. Here we report on the impact of transcranial direct current stimulation (tDCS), a non-pharmacological intervention, vs. sertraline to further investigate this issue. The employed design was a double-blind, randomized, factorial, placebo-controlled trial. One hundred and eighteen moderate-to-severe, medication-free, low-cardiovascular risk depressed patients were recruited for this study and allocated to either active/sham tDCS (10 consecutive sessions plus two extra sessions every other week) or placebo/sertraline (50 mg/d) for 6 wk. Patients were age and gender-matched to healthy controls from a concurrent cohort study [the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)]. The impact of disorder, treatment and clinical response on HRV (root mean square of successive differences and high frequency) was examined. Our findings confirmed that patients displayed decreased HRV relative to controls. Furthermore, HRV scores did not change following treatment with either a non-pharmacological (tDCS) or pharmacological (sertraline) intervention, nor did HRV increase with clinical response to treatment. Based on these findings, we discuss whether reduced HRV is a trait-marker for MDD, which may predispose patients to a host of conditions and disease even after response to treatment. Our findings have important implications for our understanding of depression pathophysiology and the relationship between MDD, cardiovascular disorders and mortality.

Polarity- and valence-dependent effects of prefrontal transcranial direct current stimulation on heart rate variability and salivary cortisol

Recent evidence has supported the notion that the hypothalamic-pituitary-adrenal (HPA) and the sympatho-adreno-medullary (SAM) systems are modulated by cortical structures such as the prefrontal cortex. This top-down modulation may play a major role in the neuroendocrine changes associated with stressful events. We aimed to investigate further this hypothesis by modulating directly prefrontal cortex excitability using transcranial direct current stimulation (tDCS) - a non-invasive, neuromodulatory tool that induces polarity-dependent changes in cortical excitability - and measuring effects on salivary cortisol and heart rate variability as proxies of the HPA and SAM systems. Twenty healthy participants with no clinical and neuropsychiatric conditions were randomized to receive bifrontal tDCS (left anodal/right cathodal or left cathodal/right anodal) or sham stimulation, in a within-subject design. During each stimulation session, after a resting period, subjects were shown images with neutral or negative valence. Our findings showed that excitability enhancing left anodal tDCS induced a decrease in cortisol levels. This effect is more pronounced during emotional negative stimuli. Moreover, vagal activity was higher during left anodal tDCS and emotional negative stimuli, as compared to sham stimulation and neutral images. We also observed an association between higher mood scores, higher vagal activation and lower cortisol levels for anodal stimulation. Subjective mood and anxiety evaluation revealed no specific changes after stimulation. Our findings suggest that tDCS induced transient, polarity specific modulatory top-down effects with anodal tDCS leading to a down-regulation of HPA and SAM systems. Further research using tDCS and neuroendocrine markers should explore the mechanisms of stress regulation in healthy and clinical samples.

Spectral analysis of heart rate variability with the autoregressive method

This work assessed the influence of the autoregressive model order (ARMO) on the spectral analysis of the heart rate variability (HRV). A sample of 68 R-R series obtained from digital ECG records of young healthy adults in the supine position was used. Normalized spectral indexes for each ARMO were compared by Friedman test followed by the Dunns procedure and statistical significance was set at P<0.05. The results showed that the AR method using orders from 9 to 25 produces normalized spectral parameters statistically similar and, hence, the algorithms commonly employed to estimate optimum order are not mandatory in this case.

Distribuição por gênero de ácido úrico sérico e fatores de risco cardiovascular: estudo populacional

FUNDAMENTO: Nao ha dados relativos a epidemiologia da hiperuricemia em estudos brasileiros de base populacional. OBJETIVO: Investigar a distribuicao de acido urico serico e sua relacao com variaveis demograficas e cardiovasculares. METODOS: Estudamos 1.346 individuos. A hiperuricemia foi definida como > 6,8 e > 5,4 mg/dL para homens e mulheres, respectivamente. A sindrome metabolica (SM) foi definida utilizando-se os criterios NCEP ATP III. RESULTADOS: A prevalencia de hiperuricemia foi de 13,2%. A associacao de acido urico serico (AUS) com fatores de risco cardiovasculares foi especifica para o genero: em mulheres, maiores niveis de AUS estiveram associados com IMC elevado, mesmo apos ajustes da pressao arterial sistolica para idade (PAS). Em homens, a relacao do AUS com o colesterol HDL esteve mediada pelo IMC, enquanto em mulheres, o AUS mostrou-se semelhante e dependente do IMC, independentemente dos niveis glicose e presenca de hipertensao. Nos homens, os triglicerideos, a circunferencia abdominal (CA) e a PAS explicaram 11%, 4% e 1% da variabilidade do AUS, respectivamente. Nas mulheres, a circunferencia abdominal e os triglicerideos explicaram 9% e 1% da variabilidade de AUS, respectivamente. Em comparacao com o primeiro quartil, homens e mulheres no quarto quartil apresentavam 3,29 e 4,18 vezes mais de aumento de risco de SM, respectivamente. As mulheres apresentaram uma prevalencia quase tres vezes maior de diabetes melito. Homens normotensos com MS apresentaram maiores niveis de AUS, independente do IMC. CONCLUSAO: Nossos resultados parecem justificar a necessidade de uma avaliacao baseada no genero em relacao a associacao do AUS com fatores de risco cardiovasculares, que se mostraram mais acentuados em mulheres. A SM esteve positivamente associada com AUS elevado, independentemente do genero. A obesidade abdominal e a hipertrigliceridemia foram os principais fatores associados com a hiperuricemia mesmo em individuos normotensos, o que pode adicionar maior risco para a hipertensao.BACKGROUND There is no data concerning the epidemiology of hyperuricemia in Brazilian population-based studies. OBJECTIVE To investigate the distribution of serum uric acid and its relationship with demographics and cardiovascular variables. METHODS We studied 1,346 individuals. Hyperuricemia was defined as ≥ 6.8 and ≥ 5.4 mg/dL for men and women, respectively. Metabolic syndrome (MS) was defined with NCEP ATP III criteria. RESULTS The prevalence of hyperuricemia was 13.2%. The association of serum uric acid (SUA) with cardiovascular risk factors was gender-specific: in women, higher SUA was associated with increasing BMI, even after adjustments for age-systolic blood pressure (SBP). In men, the relationship of SUA with HDLc was mediated by BMI, whereas in women, SUA was similar and dependent on BMI, regardless of glucose levels and presence of hypertension. In men, triglycerides, waist circumference (WC) and SBP explained 11%, 4% and 1% of SUA variability, respectively. In women, WC and triglycerides explained 9% and 1% of SUA variability, respectively. Compared to the first quartile, men and women in the fourth quartile had a 3.29 fold and 4.18 fold increase of MS risk, respectively. Women had almost three fold higher prevalence of diabetes mellitus. Normotensive men with MS presented higher SUA, regardless of BMI. CONCLUSION Our results seem to justify the need for gender-based evaluation regarding the association of SUA with cardiovascular risk factors, which was more pronounced in women. MS was positively associated with increasing SUA, regardless of gender. Abdominal obesity and hypertriglyceridemia were the main factors associated with hyperuricemia even in normotensive individuals, which may add a higher risk for hypertension.

Reproducibility of heart rate variability parameters measured in healthy subjects at rest and after a postural change maneuver

Heart rate variability (HRV) provides important information about cardiac autonomic modulation. Since it is a noninvasive and inexpensive method, HRV has been used to evaluate several parameters of cardiovascular health. However, the internal reproducibility of this method has been challenged in some studies. Our aim was to determine the intra-individual reproducibility of HRV parameters in short-term recordings obtained in supine and orthostatic positions. Electrocardiographic (ECG) recordings were obtained from 30 healthy subjects (20-49 years, 14 men) using a digital apparatus (sampling ratio = 250 Hz). ECG was recorded for 10 min in the supine position and for 10 min in the orthostatic position. The procedure was repeated 2-3 h later. Time and frequency domain analyses were performed. Frequency domain included low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) bands. Power spectral analysis was performed by the autoregressive method and model order was set at 16. Intra-subject agreement was assessed by linear regression analysis, test of difference in variances and limits of agreement. Most HRV measures (pNN50, RMSSD, LF, HF, and LF/HF ratio) were reproducible independent of body position. Better correlation indexes (r > 0.6) were obtained in the orthostatic position. Bland-Altman plots revealed that most values were inside the agreement limits, indicating concordance between measures. Only SDNN and NNv in the supine position were not reproducible. Our results showed reproducibility of HRV parameters when recorded in the same individual with a short time between two exams. The increased sympathetic activity occurring in the orthostatic position probably facilitates reproducibility of the HRV indexes.

Salt excretion in normotensive individuals with metabolic syndrome: a population-based study

The objective of this study was to investigate the association between sodium intake and metabolic syndrome (MS) in individuals free from the confounding effects of increased blood pressure (BP). In all, a total of 1655 individuals (45.8% men) who participated in the MONICA-WHO/Vitoria Project, mean age 45±11 years were investigated. According to NCEP-ATP lll criteria, MS prevalence was 32.9 and 85% of these individuals had BP >130/85 mm Hg. Thus, high BP represents the main MS risk factor. Twelve-hour nocturnal urine (1900 to 0700 hours) was used to measure urinary sodium and potassium excretion. Sodium excretion was associated with BP. From the optimal BP level up to stage lll hypertension, the mean (median) sodium excretion increased from 99 (89) to 128 (134) mEq and from 81 (69) to 112 (103) mEq in men and women, respectively (P<0.001 for trend; median). However, when 781 individuals with BP <130/85 mm Hg (including 80 drug-free normotensive individuals with MS) were stratified according to the gender and number of MS components, no significant differences were observed either in the urinary volume or in the sodium or potassium excretion. For each of the four MS components, sodium excretion was 96±48, 97±53, 108±65 and 97±49 mEq for men, and 83±51, 83±58, 80±49 and 93±45 mEq for women, respectively. No differences were found in urinary sodium excretion in normotensive individuals, regardless of the presence of MS. Therefore, it seems that high sodium intake is not an MS predictor per se as suggested earlier.

Effects of chronic treadmill training on body mass gain and visceral fat accumulation in overfed rats

This study evaluated the effects of chronic treadmill training on body mass gain and visceral fat accumulation in overfed rats. Overfeeding was induced by reducing the litter size to 3 male pups per mother during the suckling period. The litter size of control rats was adjusted to 10 male pups per mother. Seven weeks after birth overfed and normally fed rats were selected and assigned to a sedentary protocol or to a low-intensity treadmill training protocol (60 min, 5 times/week, for 9 weeks). Four groups (overfed sedentary, N = 23; normally fed sedentary, N = 32; overfed exercised, N = 18, and normally fed exercised, N = 18) were evaluated at 18 weeks. Data are reported as means +/- SEM. Initial body weight was similar in control and overfed rats [8.0 +/- 0.2 g (N = 42) vs 8.0 +/- 0.1 g (N = 50); P > 0.05] and body weight gain during the suckling period was higher in the overfed rats (30.6 +/- 0.9 vs 23.1 +/- 0.3 g; P < 0.05). Exercise attenuated the body weight gain of overfed compared to sedentary rats (505 +/- 14 vs 537 +/- 12 g; P < 0.05). The sedentary overfed rats showed higher visceral fat weight compared to normally fed animals (31.22 +/- 2.08 vs 21.94 +/- 1.76 g; P < 0.05). Exercise reduced visceral fat by 36.5% in normally fed rats and by 35.7% in overfed rats. Exercise attenuated obesity in overfed rats and induced an important reduction of visceral fat.

Race and Resting-State Heart Rate Variability in Brazilian Civil Servants and the Mediating Effects of Discrimination: An ELSA-Brasil Cohort Study.

Objectives African Americans are characterized by higher heart rate variability (HRV), a finding ostensibly associated with beneficial health outcomes. However, these findings are at odds with other evidence that blacks have worse cardiovascular outcomes. Here, we examine associations in a large cohort from the ELSA-Brasil study and determined whether these effects are mediated by discrimination. Methods Three groups were compared on the basis of self-declared race: “black” (n = 2,020), “brown” (n = 3,502), and “white” (n = 6,467). Perceived discrimination was measured using a modified version of the Everyday Discrimination Scale. Resting-state HRV was extracted from 10-minute resting-state electrocardiograms. Racial differences in HRV were determined by regression analyses weighted by propensity scores, which controlled for potentially confounding variables including age, sex, education, and other health-related information. Nonlinear mediation analysis quantified the average total effect, comprising direct (race–HRV) and indirect (race–discrimination–HRV) pathways. Results Black participants displayed higher HRV relative to brown (Cohens d = 0.20) and white participants (Cohens d = 0.31). Brown relative to white participants also displayed a small but significantly higher HRV (Cohens d = 0.14). Discrimination indirectly contributed to the effects of race on HRV. Conclusions This large cohort from the Brazilian population shows that HRV is greatest in black, followed by brown, relative to white participants. The presence of higher HRV in these groups may reflect a sustained compensatory psychophysiological response to the adverse effects of discrimination. Additional research is needed to determine the health consequences of these differences in HRV across racial and ethnic groups.