A proposed simplified definition of metabolic syndrome in children and adolescents: a global perspective.

Metabolic syndrome (MetS) is becoming prevalent in the pediatric population. The existing pediatric MetS definitions (e.g., the International Diabetes Federation (IDF) definition and the modified National Cholesterol Education Program (NCEP) definition) involve complex cut-offs, precluding fast risk assessment in clinical practice.We proposed a simplified definition for assessing MetS risk in youths aged 6-17 years, and compared its performance with two existing widely used pediatric definitions (the IDF definition, and the NCEP definition) in 10 pediatric populations from 9 countries globally (n = 19,426) using the receiver operating characteristic (ROC) curve analyses. In general, the total MetS prevalence of 6.2% based on the simplified definition was roughly halfway between that of 4.2% and 7.7% estimated from the IDF and NCEP definitions, respectively. The ROC curve analyses showed a good agreement between the simplified definition and two existing definitions: the total area under the curve (95% confidence interval) of the proposed simplified definition for identifying MetS risk achieved 0.91 (0.89-0.92) and 0.79 (0.78-0.81) when using the IDF or NCEP definition as the gold standard, respectively.The proposed simplified definition may be useful for pediatricians to quickly identify MetS risk and cardiometabolic risk factors (CMRFs) clustering in clinical practice, and allow direct comparison of pediatric MetS prevalence across different populations, facilitating consistent pediatric MetS risk monitoring and the development of evidence-based pediatric MetS prevention strategies globally.

Salt Intake in Adults with Diabetes and Hypertension: The Longitudinal Study of Adult Health-Brasil Study.

Background and Objective: Hypertension and type-2 diabetes are strong risk factors for cardiovascular diseases, and their management requires lifestyle changes, including a shift in dietary habits. The consumption of salt has increased in the last decades in some countries, but its association with type-2 diabetes remains unknown. Thus, we aimed to estimate the amount of salt intake among adults with and without diabetes and to assess whether concomitant hypertension and diabetes are associated with higher salt intake. Methods: Data from 11,982 adults 35-74 years of age enrolled in the baseline of the Longitudinal Study of Adult Health-Brasil study (2008-2010) were studied. A clinical and anthropometric evaluation was performed, and their daily salt intake was estimated by the overnight 12-hr urine sodium excretion. Results: Salt intake (gram per day) was higher in participants with diabetes as compared with those without diabetes, regardless of sex (men: 14.2 ± 6.4 vs. 12.4 ± 5.6, P < 0.05; women: 10.5 ± 4.8 vs. 9.1 ± 4.1, P < 0.05). However, salt intake is high in participants with fasting glucose ≥126 mg/dL or HbA1c ≥6.5%, but not in participants with blood glucose 2 hr after the glucose tolerance test ≥200 mg/dL. When hypertension and diabetes coexisted, salt consumption was higher than among people without these conditions. The prevalence of hypertension increased with increasing salt intake in women with diabetes, but not in men with this condition. Conclusions: Our findings highlight the high consumption of salt in individuals with diabetes and/or hypertension, and the need for effective strategies to reduce salt consumption in these groups of increased risk for major cardiovascular events, especially in women.

Fast screening using attenuated total reflectance- fourier transform infrared (ATR-FTIR) spectroscopy of patients based on D-dimer threshold value.

Attenuated Total Reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy is an emerging technology in the medical field. Blood D-dimer was initially studied as a marker of the activation of coagulation and fibrinolysis. It is mainly used as a potential diagnosis screening test for pulmonary embolism or deep vein thrombosis but was recently associated with COVID-19 severity. This study aimed to evaluate the use of ATR-FTIR spectroscopy with machine learning to classify plasma D-dimer concentrations. The plasma ATR-FTIR spectra from 100 patients were studied through principal component analysis (PCA) and two supervised approaches: genetic algorithm with linear discriminant analysis (GA-LDA) and partial least squares with linear discriminant (PLS-DA). The spectra were truncated to the fingerprint region (1800-1000 cm-1). The GA-LDA method effectively classified patients according to D-dimer cutoff (≤0.5 µg/mL and >0.5 µg/mL) with 87.5 % specificity and 100 % sensitivity on the training set, and 85.7 % specificity, and 95.6 % sensitivity on the test set. Thus, we demonstrate that ATR-FTIR spectroscopy might be an important additional tool for classifying patients according to D-dimer values. ATR-FTIR spectral analyses associated with clinical evidence can contribute to a faster and more accurate medical diagnosis, reduce patient morbidity, and save resources and demand for professionals.

Establishing international optimal cut-offs of waist-to-height ratio for predicting cardiometabolic risk in children and adolescents aged 6-18 years.

BACKGROUND: Waist-to-height ratio (WHtR) has been proposed as a simple and effective screening tool for assessing central obesity and cardiometabolic risk in both adult and pediatric populations. However, evidence suggests that the use of a uniform WHtR cut-off of 0.50 may not be universally optimal for pediatric populations globally. We aimed to determine the optimal cut-offs of WHtR in children and adolescents with increased cardiometabolic risk across different countries worldwide. METHODS: We used ten population-based cross-sectional data on 24,605 children and adolescents aged 6-18 years from Brazil, China, Greece, Iran, Italy, Korea, South Africa, Spain, the UK, and the USA for establishing optimal WHtR cut-offs. We performed an external independent test (9,619 children and adolescents aged 6-18 years who came from other six countries) to validate the optimal WHtR cut-offs based on the predicting performance for at least two or three cardiometabolic risk factors. RESULTS: Based on receiver operator characteristic curve analyses of various WHtR cut-offs to discriminate those with ≥ 2 cardiometabolic risk factors, the relatively optimal percentile cut-offs of WHtR in the normal weight subsample population in each country did not always coincide with a single fixed percentile, but varied from the 75th to 95th percentiles across the ten countries. However, these relatively optimal percentile values tended to cluster irrespective of sex, metabolic syndrome (MetS) criteria used, and WC measurement position. In general, using ≥ 2 cardiometabolic risk factors as the predictive outcome, the relatively optimal WHtR cut-off was around 0.50 in European and the US youths but was lower, around 0.46, in Asian, African, and South American youths. Secondary analyses that directly tested WHtR values ranging from 0.42 to 0.56 at 0.01 increments largely confirmed the results of the main analyses. In addition, the proposed cut-offs of 0.50 and 0.46 for two specific pediatric populations, respectively, showed a good performance in predicting ≥ 2 or ≥ 3 cardiometabolic risk factors in external independent test populations from six countries (Brazil, China, Germany, Italy, Korea, and the USA). CONCLUSIONS: The proposed international WHtR cut-offs are easy and useful to identify central obesity and cardiometabolic risk in children and adolescents globally, thus allowing international comparison across populations.

The high salt intake in adults with metabolic syndrome is related to increased waist circumference and blood pressure: the Brazilian Longitudinal Study of Adult Health study (ELSA-Brasil).

OBJECTIVES: The association between metabolic syndrome (MetS), a cluster of cardiometabolic risk factors, and salt consumption has fed intense debate in recent years, although it is yet to be fully elucidated. We aimed to evaluate whether individuals with MetS have a high salt consumption and to identify which components of the MetS diagnosis could be independently related to high salt consumption. METHODS: We analyzed data from 11 982 adults, ages 35 to 74 y, from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort study, from which clinical and anthropometric data were assessed, and a validated 12-h overnight urine collection was used to estimate salt intake. MetS was defined according to the Adult Treatment Panel III criteria. RESULTS: Salt intake was increased in individuals with MetS compared with individuals without MetS, regardless of sex (men: 14.3 ± 6.4 g/d versus 12.2 ± 5.5 g/d, P < 0.001; women: 10.6 ± 4.9 g/d versus 8.9 ± 4.0 g/d, P < 0.001) and increased progressively as the MetS criteria accumulated. The high salt intake in MetS participants, however, was observed only in the presence of elevated waist circumference and/or blood pressure and not with the other MetS criteria (reduced high-density lipoprotein, increased triglycerides, and impaired fasting blood glucose), regardless of the presence of MetS. When diabetes was incorporated as a MetS criterion, increased salt intake was observed in men but not in women. CONCLUSIONS: Salt intake should be reduced worldwide, but strategies must be more intense in people with elevated blood pressure and waist circumference, regardless of MetS diagnosis, to avoid the associated morbidity and mortality.

MALDI(+) FT-ICR Mass Spectrometry (MS) Combined with Machine Learning toward Saliva-Based Diagnostic Screening for COVID-19.

Rapid identification of existing respiratory viruses in biological samples is of utmost importance in strategies to combat pandemics. Inputting MALDI FT-ICR MS (matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry) data output into machine learning algorithms could hold promise in classifying positive samples for SARS-CoV-2. This study aimed to develop a fast and effective methodology to perform saliva-based screening of patients with suspected COVID-19, using the MALDI FT-ICR MS technique with a support vector machine (SVM). In the method optimization, the best sample preparation was obtained with the digestion of saliva in 10 µL of trypsin for 2 h and the MALDI analysis, which presented a satisfactory resolution for the analysis with 1 M. SVM models were created with data from the analysis of 97 samples that were designated as SARS-CoV-2 positives versus 52 negatives, confirmed by RT-PCR tests. SVM1 and SVM2 models showed the best results. The calibration group obtained 100% accuracy, and the test group 95.6% (SVM1) and 86.7% (SVM2). SVM1 selected 780 variables and has a false negative rate (FNR) of 0%, while SVM2 selected only two variables with a FNR of 3%. The proposed methodology suggests a promising tool to aid screening for COVID-19.

Effects of moderate-continuous and high-intensity interval aerobic training on cardiac function of spontaneously hypertensive rats.

The aim of this study was to verify the effects of moderate-intensity continuous (MICT) and high-intensity interval (HIIT) aerobic training on cardiac morphology and function and the mechanical properties of single cardiomyocytes in spontaneously hypertensive rats (SHR) in the compensated phase of hypertension. Sixteen-week-old male SHR and normotensive Wistar (WIS) rats were allocated to six groups of six animals each: SHR CONT or WIS CONT (control); SHR MICT or WIS MICT (underwent MICT, 30 min/day, five days per week for eight weeks); and SHR HIIT or WIS HIIT (underwent HIIT, 30 min/day, five days per week for eight weeks). Total exercise time until fatigue and maximum running speed were determined using a maximal running test before and after the experimental period. Systolic (SAP), diastolic (DAP), and mean (MAP) blood pressures were measured using tail plethysmography before and after the experimental period. Echocardiographic evaluations were performed at the end of the experimental period. The rats were euthanized after in vivo assessments, and left ventricular myocytes were isolated to evaluate global intracellular Ca2+ transient ([Ca2+]i) and contractile function. Cellular measurements were performed at basal temperature (~37°C) at 3, 5, and 7 Hz. The results showed that both training programs increased total exercise time until fatigue and, consequently, maximum running speed. In hypertensive rats, MICT decreased SAP, DAP, MAP, interventricular septal thickness during systole and diastole, and the contraction amplitude at 5 Hz. HIIT increased heart weight and left ventricular wall thickness during systole and diastole and reduced SAP, MAP, and the time to peak [Ca2+]i at all pacing frequencies. In conclusion, both aerobic training protocols promoted beneficial adaptations to cardiac morphology, function, and mechanical properties of single cardiomyocytes in SHR.

Noninvasive Diagnostic for COVID-19 from Saliva Biofluid via FTIR Spectroscopy and Multivariate Analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the worst global health crisis in living memory. The reverse transcription polymerase chain reaction (RT-qPCR) is considered the gold standard diagnostic method, but it exhibits limitations in the face of enormous demands. We evaluated a mid-infrared (MIR) data set of 237 saliva samples obtained from symptomatic patients (138 COVID-19 infections diagnosed via RT-qPCR). MIR spectra were evaluated via unsupervised random forest (URF) and classification models. Linear discriminant analysis (LDA) was applied following the genetic algorithm (GA-LDA), successive projection algorithm (SPA-LDA), partial least squares (PLS-DA), and a combination of dimension reduction and variable selection methods by particle swarm optimization (PSO-PLS-DA). Additionally, a consensus class was used. URF models can identify structures even in highly complex data. Individual models performed well, but the consensus class improved the validation performance to 85% accuracy, 93% sensitivity, 83% specificity, and a Matthew's correlation coefficient value of 0.69, with information at different spectral regions. Therefore, through this unsupervised and supervised framework methodology, it is possible to better highlight the spectral regions associated with positive samples, including lipid (∼1700 cm-1), protein (∼1400 cm-1), and nucleic acid (∼1200-950 cm-1) regions. This methodology presents an important tool for a fast, noninvasive diagnostic technique, reducing costs and allowing for risk reduction strategies.

Genome-Wide Association of Proprotein Convertase Subtilisin/Kexin Type 9 Plasma Levels in the ELSA-Brasil Study.

Pharmacological inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is an established therapeutic option to treat hypercholesterolemia, and plasma PCSK9 levels have been implicated in cardiovascular disease incidence. A number of genetic variants within the PCSK9 gene locus have been shown to modulate PCSK9 levels, but these only explain a very small percentage of the overall PCSK9 interindividual variation. Here we present data on the genetic association structure between PCSK9 levels and genom-wide genetic variation in a healthy sample from the general population. We performed a genome-wide association study of plasma PCSK9 levels in a sample of Brazilian individuals enrolled in the Estudo Longitudinal de Saude do Adulto cohort (n=810). Enrolled individuals were free from cardiovascular disease, diabetes and were not under lipid-lowering medication. Genome-wide genotyping was conducted using the Axiom_PMRA.r3 array, and imputation was performed using the TOPMED multi-ancestry sample panel as reference. Total PCSK9 plasma concentrations were determined using the Quantikine SPC900 ELISA kit. We observed two genome-wide significant loci and seven loci that reached the pre-defined value of p threshold of 1×10-6. Significant variants were near KCNA5 and KCNA1, and LINC00353. Genetic variation at the PCSK9 locus was able to explain approximately 4% of the overall interindividual variations in PCSK9 levels. Colocalization analysis using eQTL data suggested RWDD3, ATXN7L1, KCNA1, and FAM177A1 to be potential mediators of some of the observed associations. Our results suggest that PCSK9 levels may be modulated by trans genetic variation outside of the PCSK9 gene and this may have clinical implications. Understanding both environmental and genetic predictors of PCSK9 levels may help identify new targets for cardiovascular disease treatment and contribute to a better assessment of the benefits of long-term PCSK9 inhibition.

A sex-related mediating effect of uric acid in the association between body composition and blood pressure in children and adolescents.

The increase in blood pressure (BP) during somatic growth might have direct determinants but also mediating factors. We investigated whether uric acid (UA) and other metabolic factors would mediate the association between body composition components and BP. A cross-sectional study was conducted in 928 children and adolescents (aged 6-18 years), in which body composition and blood biochemistry were evaluated. Structural equation modeling was performed to test the direct and indirect pathways between systolic blood pressure (SBP) and body composition parameters. Muscle mass (MM) showed a strong direct effect on BP, regardless of sex. In girls, a mediating pathway through UA was not significant, but the association between fat mass (FM) and MM with SBP was mediated by the cluster of metabolic factors. In boys, both MM and FM were associated with SBP through a mediating pathway via UA, but not via the cluster of metabolic factors. The association between body composition and BP in children and adolescents has a complex design and also has a sex-specific mediating component. The increase in the UA levels may affect BP levels early in boys. Also, metabolic changes elicited by FM contribute to the increase in BP at an early age in girls. Novelty: MM showed a strong direct effect on BP, regardless of sex. In girls, the association between FM and MM with SBP was mediated by the cluster of metabolic factors. In boys, both MM and FM were associated with SBP through a mediating pathway via UA.

Alcoholic beverage consumption, changes in blood pressure, and incidence of hypertension in the Longitudinal Adult Health Study (ELSA-Brasil).

OBJECTIVES: Alcohol consumption is generally associated with increased risk of hypertension. We aimed to investigate, prospectively, the effect of alcoholic-beverage consumption on blood pressure (BP) and incidence of hypertension, after a 4-y follow-up, in participants of the Longitudinal Adult Health Study (ELSA-Brasil). METHODS: We analyzed information from 3,990 participants (ages 35-74 y), men and women, from educational and research institutions, at baseline (2008-2010) and follow-up (2012-2014). Socioeconomic, hemodynamic, anthropometric, and health data were collected. Hypertension was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg and/or use of antihypertensive medication. Change in alcohol consumption (g/d) was estimated by subtracting total consumed at follow-up from total consumed at baseline, and was categorized in tertiles. RESULTS: The consumption of alcoholic beverages was associated with changes in BP and hypertension only in men. Individuals who reduced total consumption of alcohol showed a smaller increase in systolic BP (1.1 versus 2.3 mm Hg; P = 0.03) and diastolic BP (1.3 versus 2.2 mm Hg; P = 0.008) compared to individuals who increased consumption. In addition, individuals in the highest tertiles of total consumption of alcohol (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.14-2.29) and consumption of beer (OR, 1.51; 95% CI, 1.07-12.13), wine (OR, 1.71; 95% CI, 1.01-2.86), and spirits (OR, 2.01; 95% CI, 1.21-3.32) showed higher odds ratios for hypertension compared to the lowest tertile. CONCLUSIONS: Increased consumption of alcoholic beverages was positively associated with increased BP levels and higher chances of developing hypertension in men.

Sugar-sweetened soft drinks consumption and risk of hyperuricemia: Results of the ELSA-Brasil study.

BACKGROUND AND AIMS: The prospective association between sugar-sweetened beverages consumption and hyperuricemia is controversial. The aim was to investigate the association of the consumption of sugar-sweetened soft drinks and unsweetened fruit juices with the incidence of hyperuricemia and the levels of serum uric acid in the participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS AND RESULTS: Longitudinal analysis in ELSA-Brasil participants (baseline 2008-2010 and follow-up 2012-2014). The sample consisted of 10,072 civil servants (35-74 years, both sexes). The consumption of beverages estimated by a food frequency questionnaire (baseline) was divided into five categories: nonconsumption and quartiles (≥0.1 mL/day). Hyperuricemia was defined as uric acid ≥7.0 mg/dL (men) and ≥5.7 mg/dL (women). Poisson regression with robust variance and multiple linear regression were tested. The average consumption of soft drinks was 84 ± 191 mL/day in men and 42 ± 128 mL/day in women. After 4 years of follow-up, the higher consumption of soft drinks (men: 401 ± 303 mL/day; women: 390 ± 290 mL/day) increased the relative risk of hyperuricemia by 30% (men) and 40% (women), and was associated with increased mean uric acid (men: ß = 0.14 mg/dL; 95% CI 0.41-0.24; women: ß = 0.11 mg/dL; 95% CI 0.00-0.21). The consumption of unsweetened juice was not associated with hyperuricemia. CONCLUSION: High consumption of sugar-sweetened soft drinks is associated with an increased relative risk of hyperuricemia and elevated serum uric acid levels in Brazilian adults.

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 (

Uric acid reference values: report on 1750 healthy Brazilian children and adolescents.

BACKGROUND: Our purpose was to determine reference values and determinants of serum uric acid (SUA) in children and adolescents. METHODS: A fasting blood sample was collected from 1750 schoolchildren and adolescents (6-17 years). Puberty was defined according to the Tanner scale. Bodyweight, muscle mass, and body fat percentage were determined by bioimpedance. Data are given as cut-offs and mean ± standard deviation. RESULTS: SUA level was higher in children that had already entered puberty (4.2 ± 1.1 mg/dL) than among prepubescent (3.6 ± 0.8 mg/dL; p < 0.01). Considering the 90 percentile (p90) as the upper reference value, the following values are proposed for boys and girls, respectively: <10 years or prepubescent: ≤4.5 mg/dL and ≤4.8 mg/dL; from 10 to 13 years: ≤5.7 mg/dL and ≤5.2 mg/dL; from 14 to 17 years: ≤6.4 mg/dL and ≤5.3 mg/dL. Muscle mass explained part of the variability in SUA after pubescence, acting as an independent variable for higher levels of SUA. CONCLUSIONS: The sex, age, and phase of puberty influence SUA reference levels, and part of this influence could be explained by the higher muscle mass, mainly after the adolescence onset. IMPACT: The key message of this study is that high levels of uric acid in the blood are associated with metabolic syndrome and cardiovascular risk factors. These diseases should be prevented since the infancy However, it is necessary to establish reference values of uric acid (SUA) for children and adolescents. The Brazilian population is highly admixed and these values were not determined so far. We studied a robust sample of Brazilian schoolchildren and adolescents (6-17 years) and defined the 90th percentile of uric acid as the upper limit of normality for sex, age, and pubertal stage. These values can be used as a reference for other populations with similar characteristics.

Association of uric acid with cardiovascular risk in Brazilian children and adolescents.

BACKGROUND AND AIM: Hyperuricemia in adults is associated with cardiovascular risk factors. However, there is less data regarding this association in children and adolescents. Our purpose was to determine association between serum uric acid (SUA) and cardiovascular risk. METHODS AND RESULTS: A fasting blood sample was collected from 1750 participants aged 6-17 years enrolled in a social project and public schools in Espírito Santo, Brazil. Internal cut-offs were generated to define high SUA (≥90th percentile of SUA concentration for sex and age group). Body mass index percentile (pBMI), body fat percentage (BFP) and muscle mass were determined by bioimpedance. Data are given as mean ± standard deviation. High SUA was associated with overweight/obesity (OR 3.7 CI 95% 2.7-5.0), high waist circumference (WC) (OR 3.9 CI 95% 2.9-5.4), low HDL (OR 2.0 CI 95% 1.5-2.8), high blood pressure (BP) (OR 1.8 CI 95% 1.1-3.2), high BFP (OR 4.1 CI 95% 2.7-6.4), metabolic syndrome (MetS) (OR 3.6 CI 95% 1.8-7.1) and insulin resistance (OR 1.7 CI 95% 1.1-2.7). Individuals in the fourth quartile of SUA, compared to those in the first quartile, showed higher age, pBMI, WC, BFP and muscle mass. Using a reference value of 5.5 mg/dL, the prevalence of hyperuricemia in the sample was 10.3% (CI 95% 8.9-11.7%). CONCLUSION: Higher SUA values are associated with higher cardiovascular risk in childhood and adolescence. The main cardiovascular risk factors associated with hyperuricemia were overweight/obesity, high WC, dyslipidemia, high BFP, high BP, insulin resistance and MetS.

Identifying patterns of diurnal blood pressure variation among ELSA-Brasil participants.

Ambulatory blood pressure monitoring (ABPM) is the gold standard method for the diagnosis of hypertension. ABPM provides a set of repeated measurements for blood pressure (BP), usually over 24 h. Traditional approaches characterize diurnal BP variation by single ABPM parameters such as average and standard deviation, regardless of the temporal nature of the data. In this way, information about the pattern of diurnal BP variation and relationship between parameters is lost. The objective of this study was to identify and characterize daily BP patterns considering the set of repeated measures from 24-h ABPM. A total of 859 adult participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) performed a 24-h ABPM record. Hypertension, sex, age, race/color, education, marital status, smoking, alcohol, physical activity, and BMI were the covariables analyzed. Techniques for longitudinal clustering, multinomial models, and models with mixed effects were used. Three daily BP patterns were identified. Daily BP patterns with high BP presented higher standard deviation and morning surge and lower nocturnal dipping. They showed greater systolic BP variability and faster rise than fall in diastolic BP during sleep. Hypertensive, "pardos," and men had greater odds to present these patterns. Daily BP patterns with high BP presented the worst profile concerning ABPM parameters associated with cardiovascular risk. The daily BP patterns identified contribute to the characterization of diurnal BP variation.

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.

Four-year adiposity change and remission of hypertension: an observational evaluation from the Longitudinal Study of Adult Health (ELSA-Brasil).

The degree to which weight reduction leads to the remission of hypertension in population studies is not clear. We investigated whether the changes in adiposity measures predicted the remission of hypertension in a racially admixed population over a mean 4-year follow-up. All 4847 hypertensive individuals at baseline (2008-2010) from the multicenter Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were included. Changes in weight, waist circumference (WC), or body mass index (BMI) (reduction or increase ≥5% from baseline values, vs stability) and remission of hypertension (SBP < 140 and DBP < 90 mmHg and no use of antihypertensive medication at follow-up visit, in 2012-2014) were investigated using mixed effects logistic regression models. Proportional attributable benefit was additionally calculated. Analyses were stratified by sex and antihypertensive medication use at baseline. Remission of hypertension was 11.3% (n = 546). Among men, after adjustments, the reduction of weight (OR = 1.52 95% CI 1.10-2.10), WC (OR = 1.56 95% CI 1.04-2.35) or BMI (OR = 1.60 95% CI 1.13-2.27) was associated with the remission of hypertension. Among those not taking antihypertensive medication at baseline, after adjustments, the reduction of weight (OR = 1.64 95% CI 1.18-2.27), WC (OR = 1.76 95% CI 1.18-2.61) or BMI (OR = 1.57 95% CI 1.10-2.25) was associated with the remission of hypertension. Proportional attributable benefit among those with adiposity reduction was about 30%, indicating its potential for prevention. In conclusion, our study reinforces the role of adiposity-reducing strategies (e.g., healthy diet and regular physical activity) for the treatment and prevention of hypertension, which might have potential applications for clinical practice.

Influence of muscle mass on the serum uric acid levels in children and adolescents.

BACKGROUND AND AIM: Uric acid (UA) is an end-product of purine catabolism and its increase in blood is a risk factor for several diseases. UA levels in men are usually higher than in women. This difference is partially due to sex hormones. We sought to investigate the onset of sexual difference in UA levels during pubertal development and the determinants of UA levels in children and adolescents. METHODS AND RESULTS: The muscle mass and fat mass were measured by multi-frequency bioelectrical impedance in a cross-sectional study involving 823 children and adolescents (both sexes; 6-18 years). Serum UA was determined using a commercially available kit. UA levels started to become higher in boys (5.0 ± 1.0 mg/dL) than in girls (4.1 ± 0.9 mg/dL) around 13 years. Boys in the highest quartile of muscle mass presented higher UA levels (5.2 ± 0.7 mg/dL) when compared with the third (4.2 ± 0.7 mg/dL), second (3.7 ± 0.9 mg/dL) and first (3.4 ± 0.9 mg/dL). Similarly, girls in the highest quartile of muscle mass presented higher UA levels (4.2 ± 0.7 mg/dL) when compared with the second (3.8 ± 0.9 mg/dL) and first (3.3 ± 0.9 mg/dL). Muscle mass explained 43.0% and 7.7% of the variability of UA in boys and girls, respectively. CONCLUSION: Sexual differences in serum UA levels begin at puberty and partially result from a direct influence of muscle mass.