Reduced heart-rate variability and increased risk of hypertension-a prospective study of the ELSA-Brasil.

Although autonomic disturbances are known to precede hypertension onset, the risks underlying different ranges of blood pressure and impaired cardiac autonomic modulation are still unknown. This study aimed to identify the risk of hypertension incidence related to low heart-rate variability profile in normotensive blood pressure subcategories: normal (<120/80 mmHg) and prehypertension (120/80-139/89 mmHg) in a 4-year follow-up. 7665 participants free of hypertension at baseline were examined. They were allocated into one of two groups (

Diabetes and subclinical hypothyroidism on heart rate variability.

BACKGROUND: We aimed to analyse if the effects of coexistent diabetes and subclinical hypothyroidism extend to the cardio autonomic nervous system, using heart rate variability baseline data from the Brazilian Longitudinal Study of Adult Health. MATERIALS AND METHODS: Heart rate variability analyses were performed by linear time and frequency domains in 5-minute time series collected in the supine position. The associations of diabetes and subclinical hypothyroidism with the lowest quartile group for heart rate and the highest quartile group for each heart rate variability parameter were analysed using additive and multiplicative terms in logistic models. For the first approach, the subsample was categorized into four groups: subjects without diabetes and normal thyroid function (controls); subjects without diabetes and subclinical hypothyroidism; patients with diabetes and normal thyroid function; and patients with diabetes and subclinical hypothyroidism. For the interaction alnalysis, diabetes and subclinical hypothyroidism diagnoses were included in separate, along with a multiplicative interaction term between them. RESULTS: Point odds ratio estimates for the 4th quartiles of heart rate, and 1st quartiles of all heart rate variability measurements were higher for subjects with combined diabetes and subclinical hypothyroidism than for diabetes only, independently of main sociodemographic and clinical variables (HR: 8.33 vs 2.63; SDNN: 2.59 vs 1.61; RMSSD: 2.37 vs 1.42; LF: 2.83 vs 1.71; HF: 3.06 vs 1.39), but not independently of HbA1c and TSH. Only the interaction term for the association with heart rate, adjusted for sociodemographic and clinical variables, had borderline statistical significance. CONCLUSION: Diabetes and subclinical hypothyroidism exert a potential joint impact on cardiac autonomic control, showed by additive effects between diabetes and subclinical hypothyroidism, as well as a significant interaction term for the association with heart rate.

Relationship between heart rate variability and carotid intima-media thickness in the Brazilian Longitudinal Study of Adult Health - ELSA-Brasil.

BACKGROUND: Both increased carotid intima-media thickness (cIMT) and low heart rate variability (HRV) have been associated with cardiovascular mortality and morbidity. Thus, the aim of this study was to investigate whether cardio autonomic alterations are accompanied or not by subclinical atherosclerosis in participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: cIMT measures and 5-min HRV analyses were performed in apparently healthy adults. Heart rate variability was evaluated by linear time and frequency domain analyses. cIMT was defined as the average between the mean left and mean right cIMT values and was analysed as continuous and categorized variables (P≥75 or P<75). Multiple linear models using continuous variables and multivariate logistic regression with categorized cIMT and HRV quartiles were performed. RESULTS: Out of 7256 participants eligible for analyses, 23·4% presented cIMT ≥ 75th percentile. Heart rate variability variables were reduced in cIMT ≥ P75 in comparison with cIMT < P75: SDNN 33·0 versus 37·0 ms, P<0·001; RMSSD 22·0 versus 26·0 ms, P<0·001; LF 191·0 versus 260·0 ms2 , P<0·001; HF 164·0 versus 238·5 ms2 , P<0·001. In crude analysis, an increased odds ratio for cIMT ≥ P75 was verified within the lowest two quartiles of LF and HF, but significances did not remain after adjustments for anthropometric and clinical variables. CONCLUSIONS: Considering the entire sample, subjects with cIMT ≥ P75 presented lower HRV values, but no independent relationships were detected between cIMT and HRV after multivariate adjustment.

Decreased heart rate variability as a predictor for diabetes-A prospective study of the Brazilian longitudinal study of adult health.

AIM: To investigate whether heart rate variability (HRV) is a predictor for the incidence of diabetes in a 4-year follow-up. MATERIALS AND METHODS: The HRV of 9192 participants free of diabetes was analysed in time and frequency domains and stratified based on the reference values presented in the literature. The participants were then allocated to one of three groups, according to age-specific value distributions for each HRV domain: lower than the 25th percentile, between the 25th and 75th percentiles, and higher than the 75th percentile. The association between HRV and diabetes incidence at 4-year follow-up was analysed using Poisson regression models with robust estimator. RESULTS: Six hundred thirty-four participants (6.90%) developed diabetes within 4 years and five out of six HRV analysed indices showed increased relative risk of developing diabetes associated with low HRV: SDNN (RR = 1.29; 95% CI, 1.09-1.52; .003), pNN50 (RR = 1.33; 95% CI, 1.11-1.58; .001), RMSSD (RR = 1.29; 95% CI, 1.09-1.53; .004), LF (RR = 1.25; 95% CI, 1.05-1.48; .012), and HF (RR = 1.39; 95% CI, 1.16-1.63; .001). CONCLUSIONS: This study suggests that both overall variability and changes in parasympathetic modulation precede the incidence of diabetes. For four HRV indices below the 25th percentile, the risk for incident diabetes was 68% higher than for those participants who presented none. We concluded that HRV is an independent risk predictor of diabetes in a 4-year period.

Linear and nonlinear analyses of heart rate variability following orthostatism in subclinical hypothyroidism.

Subclinical hypothyroidism (SCHypo) is associated with autonomic disturbances that can interfere in physiological responses. This study was designed to evaluate linear and nonlinear variables of heart rate variability (HRV) following postural change, comparing subjects with SCHypo to euthyroid subjects.HRV analyses were performed in 5-minute time series collected in the supine and standing positions from a subsample of 855 participants of the ELSA-Brasil study. The cardiac autonomic nervous function was evaluated by linear time and frequency domain analyses (SDNN, RMSSD, LFms, HFms, and LF/HF ratio) as well as by nonlinear symbolic dynamics (0, 1, and 2 V).After exclusions, 509 (92.0%) euthyroid and 44 (8.0%) SCHypo participants were eligible for analyses. At the baseline supine rest measurement, the 0 V symbolic pattern was higher (27.7 vs 25.4, P = .02) and 2 V was lower (18.0 vs 22.9, P = .02) than in the euthyroid group. Comparing the variation between positions, the 0 V pattern showed a lower delta in SCHypo than in Euthyroid subjects (8.0 vs 10.8%, P = .04).SCHypo presented lower sympathetic and parasympathetic tonus at rest and a blunted sympathetic response to active postural change, marked by reduced variation in the 0 V of symbolic analysis (SA). Additionally, it is suggested that SA of HR dynamics is an alternative and, possibly, a more sensitive method for cardiac autonomic assessment following orthostatism in this population.

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 (Cohen's d = 0.20) and white participants (Cohen's d = 0.31). Brown relative to white participants also displayed a small but significantly higher HRV (Cohen's 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.

Effects of Kefir on the Cardiac Autonomic Tones and Baroreflex Sensitivity in Spontaneously Hypertensive Rats.

AIMS: It has been previously shown that the probiotic kefir (a symbiotic matrix containing acid bacteria and yeasts) attenuated the hypertension and the endothelial dysfunction in spontaneously hypertensive rats (SHR). In the present study, the effect of chronic administration of kefir on the cardiac autonomic control of heart rate (HR) and baroreflex sensitivity (BRS) in SHR was evaluated. METHODS: SHR were treated with kefir (0.3 mL/100 g body weight) for 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Cardiac autonomic vagal (VT) and sympathetic (ST) tones were estimated through the blockade of the cardiac muscarinic receptors (methylatropine) and the blockade of ß1-adrenoceptor (atenolol). The BRS was evaluated by the tachycardia and bradycardia responses to vasoactive drug-induced decreases and increases in arterial blood pressure (BP), respectively. Additionally, spontaneous BRS was estimated by autoregressive spectral analysis. RESULTS: Kefir-treated SHR exhibited significant attenuation of basal BP, HR, and cardiac hypertrophy compared to non-treated SHR (12, 13, and 21%, respectively). Cardiac VT and ST were significantly altered in the SHR (~40 and ~90 bpm) compared with Wistar rats (~120 and ~30 bpm) and were partially recovered in SHR-kefir (~90 and ~25 bpm). SHR exhibited an impaired bradycardic BRS (~50%) compared with Wistar rats, which was reduced to ~40% in the kefir-treated SHR and abolished by methylatropine in all groups. SHR also exhibited a significant impairment of the tachycardic BRS (~23%) compared with Wistar rats and this difference was reduced to 8% in the SHR-kefir. Under the action of atenolol the residual reflex tachycardia was smaller in SHR than in Wistar rats and kefir attenuated this abnormality. Spectral analysis revealed increased low frequency components of BP (~3.5-fold) and pulse interval (~2-fold) compared with Wistar rats and these differences were reduced by kefir-treatment to ~1.6- and ~1.5-fold, respectively. Spectral analysis also showed an impairment of spontaneous BRS in SHR, but kefir-treatment caused only a tendency to reverse this result. CONCLUSIONS: The novelty of this study is that daily chronic consumption of a low dose of kefir reduced the impairment of the cardiac autonomic control of HR and of the impaired BRS in SHR.

Differential Associations of Specific Selective Serotonin Reuptake Inhibitors With Resting-State Heart Rate and Heart Rate Variability: Implications for Health and Well-Being.

OBJECTIVE: Debate has focused on the effects of the selective serotonin reuptake inhibitor (SSRI) antidepressants on heart rate (HR) and HR variability (HRV), both of which are predictors of adverse cardiovascular events. Here, we examine the associations between specific SSRI antidepressants and resting state HR (and HRV) after accounting for a host of potential confounding factors using propensity score techniques. METHODS: Participants included 10,466 not taking antidepressants, 46 participants taking escitalopram, 86 taking citalopram, 66 taking fluoxetine, 103 taking paroxetine, and 139 taking sertraline. HR and HRV (root mean square of successive squared differences, high frequency) were extracted from 10-minute resting-state ECGs. Analyses including propensity score weighting and matching were conducted using R-statistics to control for potentially confounding variables. RESULTS: Major findings indicated that users of all SSRI medications-except fluoxetine-displayed lower HRV relative to nonusers. Users of paroxetine also displayed significantly lower HRV relative to users of citalopram (Cohen's d = 0.42), fluoxetine (Cohen's d = 0.54), and sertraline (Cohen's d = 0.35), but not escitalopram. Although associations were also observed for HR, these were less robust than those for HRV. CONCLUSIONS: Although paroxetine is associated with decreases in HRV relative to nonusers, as well as users of other SSRI medications, fluoxetine was the only medication not to display significant alterations in HR or HRV. These conclusions are limited by the cross-sectional design and nonrandomized nature of medication prescriptions. Findings highlight the importance of focusing on specific medications, rather than more heterogeneous groupings according to antidepressant action, and may have implications for health and well-being for the longer term.

Insulin resistance and carotid intima-media thickness mediate the association between resting-state heart rate variability and executive function: A path modelling study.

BACKGROUND: Research has linked high-frequency heart rate variability (HF-HRV) to cognitive function. The present study adopts a modern path modelling approach to understand potential causal pathways that may underpin this relationship. METHODS: Here we examine the association between resting-state HF-HRV and executive function in a large sample of civil servants from Brazil (N=8114) recruited for the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). HF-HRV was calculated from 10-min resting-state electrocardiograms. Executive function was assessed using the trail-making test (version B). RESULTS AND CONCLUSIONS: Insulin resistance (a marker of type 2 diabetes mellitus) and carotid intima-media thickness (subclinical atherosclerosis) mediated the relationship between HRV and executive function in seriatim. A limitation of the present study is its cross-sectional design; therefore, conclusions must be confirmed in longitudinal study. Nevertheless, findings support that possibility that HRV provides a 'spark' that initiates a cascade of adverse downstream effects that subsequently leads to cognitive impairment.

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 (Cohen's d, 0.72-0.81), followed by serotonin and norepinephrine reuptake inhibitors (Cohen's d, 0.42-0.95) and other antidepressants (Cohen's 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.

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.