Relationship of blood pressure measured in the calf with arm blood pressure and arterial stiffness: a general population study.

AIM: Leg blood pressure (BP) measurement is needed when arm BP evaluation is not feasible, and calf BP, especially when measured in standing position, may have greater association with cardiovascular remodeling than arm BP. This study evaluated the relationship between calf and arm BP, and investigated whether calf BP would be superior to arm BP in predicting increased arterial stiffness [pulse wave velocity (PWV) > 10 m/s]. METHODS: We evaluated clinical and laboratory characteristics, BP measurements, and PWV in 1397 individuals resident in Baependi, Brazil, between 2017 and 2019. Arm BP was measured in the seated and supine positions while calf BP was measured in supine and standing positions using digital oscillometric devices. Carotid-femoral PWV was measured using a noninvasive mechanotransducer. RESULTS: The sample had 62.7% females, age = 48.1 ±â€Š15.4 years and 8.4% with PWV >10 m/s. Results of linear regression analysis showed that BP values of 140/90 mmHg measured in the arm in supine and seated position were equivalent to calf supine BP values of 164/81 mmHg and 166/78 mmHg and calf standing BP values of 217/137 mmHg and 221/137 mmHg, respectively. Calf-arm BP differences were associated with age, glomerular filtration rate, body mass index, smoking, low-density lipoprotein-cholesterol, diabetes and height. Furthermore, stepwise logistic regression analysis revealed that arm supine systolic BP, but not calf BP measurements, was independently associated with increased arterial stiffness. CONCLUSION: Thresholds of ≈165/80 mmHg and ≈220/135 mmHg could be used for diagnosing hypertension when only calf measurements in supine and standing positions, respectively, are available. Conversely, calf BP was not superior to arm BP in predicting increased arterial stiffness.

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.

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.

Longitudinal study of the sympathovagal balance in women submitted to bariatric surgery.

Studies have shown improvement of the cardiac autonomic balance in post-bariatric patients. Most of these studies included patients using drugs interfering in the autonomic nervous system. This study assessed the time course of changes in the sympathovagal balance after bariatric surgery (Roux-en-Y gastric bypass) in 26 women free from drugs. A 10-min electrocardiographic recording was obtained at baseline and at 3 and 6 months after surgery. Temporal and spectral domains of heart rate variability were analysed. The time domain components of cardiac vagal modulation increased progressively after surgery. In the frequency domain, high frequency power increased from 24.9 at baseline (18.0 to 46.3) to 44.5 at 3 months (23.4 to 65.6), and 54.1 at 6 months after surgery (37.6 to 64.0) (median and IQR in normalized units). Low frequency spectral power decreased from 56.2 at baseline (39.6 to 74.4) to 36.8 at 6 months after surgery (24.9 to 53.9) (P= 0.036). Low frequency/high frequency ratio decreased from 2.3 at baseline (1.0 to 4.2) to 0.8 at 6 months after surgery (0.4 to 1.3) (P= 0.038). Progressive shift towards predominance of vagal tonus was detected in the follow-up. Most of the patients recovered low frequency/high frequency at 6 months after surgery.

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.

Heritability and Sex-Specific Genetic Effects of Self-Reported Physical Activity in a Brazilian Highly Admixed Population.

INTRODUCTION: The engagement in sports or habitual physical activity (PA) has shown an extensive protective role against multiple diseases such as cancer, obesity, and many others. Additionally, PA has also a significant impact on life quality, since it aids with managing stress, preserving cognitive function and memory, and preventing fractures in the elderly. OBJECTIVE: Considering there has been multiple evidence showing that genetic variation underpins variation of PA-related traits, we aimed to estimate the heritability (h2) of these phenotypes in a sample from the Brazilian population and assess whether males and females differ in relation to those estimates. METHODS: 2,027 participants from a highly admixed population from Baependi, MG, Brazil, had information regarding their PA and sedentary behavior (SB) phenotypes collected through a questionnaire (IPAQ-SF). After data cleaning and transformation procedures, we obtained four variables to be evaluated: total PA (TPA MET), walking time, (WK MET), moderate-vigorous PA (MVPA MET), and SB. A model selection procedure was performed using a single-step covariate inclusion approach. We tested for BMI, waist, hip and neck circumferences, smoking, and depression separately, and performed correlation tests among covariates. Linear mixed models, selection procedure, and the variance components approach to estimate h2 were implemented using SOLAR-Eclipse 8.3.1. RESULTS: We obtained estimates of 0.221, 0.109, 0.226, and 0 for TPA MET, WK MET, MVPA MET, and SB, respectively. We found evidence for gene-sex interactions, with males having higher sex-specific heritabilities than females for TPA MET and MVPA MET. In addition, we found higher estimates of the genetic variance component in males than females for most phenotypes. DISCUSSION/CONCLUSION: The heritability estimates presented in this work show a moderate heritable set of genetic factors affecting PA in a sample from the Brazilian population. The evaluation of the genetic variance component suggests segregating genetic factors in male individuals are more heterogeneous, which can explain why men globally tend to need to practice more intense PA than women to achieve similar health benefits. Hence, these findings have significant implications for the understanding of the genetic architecture of PA and might aid to promote health in the future.

Excess weight in children and adolescents is associated with altered subendocardial blood supply among girls but not boys.

Subendocardial viability ratio (SEVR) is a reliable index of myocardial supply-workload balance. This study sought to investigate whether overweight/obese children and adolescents have altered SEVR and to identify which are the associated factors. This cross-sectional study involved 789 individuals. Central haemodynamic was measured by radial applanation tonometry. Diastolic time was shorter (496 ± 122 vs 537 ± 140 ms, P = .014) and diastolic pressure-time index was lower (2681 ± 412 vs 2814 ± 423 mm Hg seconds, P = .024) in overweight/obese compared with eutrophic girls. SEVR was lower in girls than in boys (1.34 ± 0.39 vs 1.48 ± 0.41, P = .018) but only among overweight/obese. SEVR may be affected by small variations in the temporal determinants of cardiac cycle.

Ethnicity and arterial stiffness in children and adolescents from a Brazilian population.

BACKGROUND: Increased stiffness of large arteries is an important determinant of cardiovascular disease risk. Higher values of arterial stiffness measured by carotid-femoral pulse wave velocity (cf-PWV) have been measured in adult African-Americans compared with whites. Studies assessing ethnic differences in cf-PWV among children and adolescents are scarce. This study sought to evaluate the association between ethnicity and cf-PWV in Brazilian children and adolescents. METHODS: Seven hundred and seventy-one children and adolescents (211 blacks and 560 nonblacks, 11.3 ±â€Š2.7 years) were included. Arterial stiffness was evaluated by cf-PWV. The ethnic classification was obtained by a single interviewer according to general phenotypes such as skin color, hair shape and facial traces. RESULTS: Blood pressure was similar in blacks and nonblacks across all pubertal stages. Differently, cf-PWV was higher in blacks than nonblacks pubescent (5.9 ±â€Š0.7 vs. 5.6 ±â€Š0.8 m/s, P = 0.001) and postpubescent (6.1 ±â€Š0.7 vs. 5.7 ±â€Š0.7 m/s, P = 0.042), whereas no difference was detected between blacks and nonblacks prepubescent. These analyses were adjusted for sex, age, height, BMI, SBP and heart rate. CONCLUSION: Our study showed that higher cf-PWV values in blacks appear in adolescence and are independent of blood pressure values. Therefore, our data suggest adolescence as the key phase for the appearance of the vascular profile found in adults black individuals.

Heritability of arterial stiffness in a Brazilian population: Baependi Heart Study.

BACKGROUND: Increased arterial stiffness is an important determinant of cardiovascular disease risk. In addition, it has been recognized that arterial stiffness has familial aggregation; however, there are no studies involving Brazilian families. Thus, the aim of this study was to evaluate the heritability of arterial stiffness in a Brazilian population. METHODS: In this study, 1675 eligible individuals (both sexes and aged 18-102 years) were distributed in 125 families resident in the municipality of Baependi, a city located in the southeast of Brazil. Carotid-femoral pulse wave velocity (PWV) was measured with a noninvasive automatic device (Complior; Artech Medical, Pantin, France). Variance component approaches, implemented in the SOLAR computer package (San Antonio, Texas, USA), were applied to estimate the heritability of the studied phenotype under different statistical models. RESULTS: Heritability estimates for carotid-femoral PWV stratified by age ranging from 11 to 35% (higher in individuals aged ≤45 years and lower in individuals aged 18-102 years). Age and hypertension showed significant effects on the PWV trait and significantly affect heritability estimates in all models. CONCLUSION: We conclude that the heritability of carotid-femoral PWV in a Brazilian population is intermediate, and therefore genetic studies evolving arterial stiffness phenotypes should be encouraged.

Cohort profile: the Baependi Heart Study-a family-based, highly admixed cohort study in a rural Brazilian town.

PURPOSE: Cardiovascular disease (CVD) is a major challenge to global health. The same epidemiological transition scenario is replayed as countries develop, but with variations based on environment, culture and ethnic mixture. The Baependi Heart Study was set up in 2005 to develop a longitudinal family-based cohort study that reflects on some of the genetic and lifestyle-related peculiarities of the Brazilian populations, in order to evaluate genetic and environmental influences on CVD risk factor traits. PARTICIPANTS: Probands were recruited in Baependi, a small rural town in the state of Minas Gerais, Brazil, following by first-degree and then increasingly more distant relatives. The first follow-up wave took place in 2010, and the second in 2016. At baseline, the study evaluated 1691 individuals across 95 families. Cross-sectional data have been collected for 2239 participants. FINDINGS TO DATE: Environmental and lifestyle factors and measures relevant to cardiovascular health have been reported. Having expanded beyond cardiovascular health outcomes, the phenotype datasets now include genetics, biochemistry, anthropometry, mental health, sleep and circadian rhythms. Many of these have yielded heritability estimates, and a shared genetic background of anxiety and depression has recently been published. In spite of universal access to electricity, the population has been found to be strongly shifted towards morningness compared with metropolitan areas. FUTURE PLANS: A new follow-up, marking 10 years of the study, is ongoing in 2016, in which data are collected as in 2010 (with the exception of the neuropsychiatric protocol). In addition to this, a novel questionnaire package collecting information about intelligence, personality and spirituality is being planned. The data set on circadian rhythms and sleep will be amended through additional questionnaires, actimetry, home sleep EEG recording and dim light melatonin onset (DLMO) analysis. Finally, the anthropometric measures will be expanded by adding three-dimensional facial photography, voice recording and anatomical brain MRI.

Heritability of OSA in a Rural Population.

BACKGROUND: OSA has a familial aggregation pattern indicating that it can be partially caused by a genetic component. However, the heritability of OSA has been estimated based on the study of families of obese probands of urban populations with established OSA diagnosis. The objective of this genetic-epidemiologic study is to study families ascertained from a general rural population to determine an unbiased estimate of OSA heritability. METHODS: We studied a sample of families living in Baependi, a small rural southeastern Brazilian city. Participants were assessed for anthropometric measurements, physical examination, Epworth Sleepiness Scale, blood samples for glucose and cholesterol determination, and overnight home portable monitoring. RESULTS: We studied 587 participants (399 women) from 91 families, with a median (interquartile range [IQR]) of 4 (2-8) participants per family. The median age of the population was 44 years (IQR, 29-55 years) and median BMI was 25.0 kg/m(2) (IQR, 22.1-28.6 kg/m(2)). OSA, defined by apnea-hypopnea index (AHI) > 5/h, was diagnosed in 18.6% of the sample. Two polygenic models, model I (no covariate effects) and model II (with covariate effects), were fitted to the data in all analyses. Heritability estimates for AHI were 0.23 and 0.25 for model I and II, respectively. Covariates (age, sex, and BMI) showed no significant effects on the heritability estimate for AHI. CONCLUSIONS: The heritability of AHI in a rural population with low levels of obesity is intermediate (25%).

Shared Genetic Factors of Anxiety and Depression Symptoms in a Brazilian Family-Based Cohort, the Baependi Heart Study.

To investigate the phenotypic and genetic overlap between anxiety and depression symptoms in an admixed population from extended family pedigrees. Participants (n = 1,375) were recruited from a cohort of 93 families (mean age±SD 42±16.3, 57% female) in the rural town of Baependi, Brazil. The Hospital Anxiety and Depression Scale (HADS) was used to assess depression and anxiety symptoms. Heritability estimates were obtained by an adjusted variance component model. Bivariate analyses were performed to obtain the partition of the covariance of anxiety and depression into genetic and environmental components, and to calculate the genetic contribution modulating both sets of symptoms. Anxiety and depression scores were 7.49±4.01 and 5.70±3.82, respectively. Mean scores were affected by age and were significantly higher in women. Heritability for depression and anxiety, corrected for age and sex, were 0.30 and 0.32, respectively. Significant genetic correlations (ρg = 0.81) were found between anxiety and depression scores; thus, nearly 66% of the total genetic variance in one set of symptoms was shared with the other set. Our results provided strong evidence for a genetic overlap between anxiety and depression symptoms, which has relevance for our understanding of the biological basis of these constructs and could be exploited in genome-wide association studies.

General aspects of muscle glucose uptake.

Glucose uptake in peripheral tissues is dependent on the translocation of GLUT4 glucose transporters to the plasma membrane. Studies have shown the existence of two major signaling pathways that lead to the translocation of GLUT4. The first, and widely investigated, is the insulin activated signaling pathway through insulin receptor substrate-1 and phosphatidylinositol 3-kinase. The second is the insulin-independent signaling pathway, which is activated by contractions. Individuals with type 2 diabetes mellitus have reduced insulin-stimulated glucose uptake in skeletal muscle due to the phenomenon of insulin resistance. However, those individuals have normal glucose uptake during exercise. In this context, physical exercise is one of the most important interventions that stimulates glucose uptake by insulin-independent pathways, and the main molecules involved are adenosine monophosphate-activated protein kinase, nitric oxide, bradykinin, AKT, reactive oxygen species and calcium. In this review, our main aims were to highlight the different glucose uptake pathways and to report the effects of physical exercise, diet and drugs on their functioning. Lastly, with the better understanding of these pathways, it would be possible to assess, exactly and molecularly, the importance of physical exercise and diet on glucose homeostasis. Furthermore, it would be possible to assess the action of drugs that might optimize glucose uptake and consequently be an important step in controlling the blood glucose levels in diabetic patients, in addition to being important to clarify some pathways that justify the development of drugs capable of mimicking the contraction pathway.

Heritability of physical activity traits in Brazilian families: the Baependi Heart Study.

BACKGROUND: It is commonly recognized that physical activity has familial aggregation; however, the genetic influences on physical activity phenotypes are not well characterized. This study aimed to (1) estimate the heritability of physical activity traits in Brazilian families; and (2) investigate whether genetic and environmental variance components contribute differently to the expression of these phenotypes in males and females. METHODS: The sample that constitutes the Baependi Heart Study is comprised of 1,693 individuals in 95 Brazilian families. The phenotypes were self-reported in a questionnaire based on the WHO-MONICA instrument. Variance component approaches, implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package, were applied to estimate the heritability and to evaluate the heterogeneity of variance components by gender on the studied phenotypes. RESULTS: The heritability estimates were intermediate (35%) for weekly physical activity among non-sedentary subjects (weekly PA_NS), and low (9-14%) for sedentarism, weekly physical activity (weekly PA), and level of daily physical activity (daily PA). Significant evidence for heterogeneity in variance components by gender was observed for the sedentarism and weekly PA phenotypes. No significant gender differences in genetic or environmental variance components were observed for the weekly PA_NS trait. The daily PA phenotype was predominantly influenced by environmental factors, with larger effects in males than in females. CONCLUSIONS: Heritability estimates for physical activity phenotypes in this sample of the Brazilian population were significant in both males and females, and varied from low to intermediate magnitude. Significant evidence for heterogeneity in variance components by gender was observed. These data add to the knowledge of the physical activity traits in the Brazilian study population, and are concordant with the notion of significant biological determination in active behavior.

APOE polymorphism is associated with lipid profile, but not with arterial stiffness in the general population.

BACKGROUND: Cardiovascular diseases (CVD) are the main cause of death and disability in developed countries. In most cases, the progress of CVD is influenced by environmental factors and multifactorial inheritance. The purpose of this study was to investigate the association between APOE genotypes, cardiovascular risk factors, and a non-invasive measure of arterial stiffness in the Brazilian population. METHODS: A total of 1493 urban Brazilian individuals were randomly selected from the general population of the Vitoria City Metropolitan area. Genetic analysis of the APOE polymorphism was conducted by PCR-RFLP and pulse wave velocity analyzed with a noninvasive automatic device. RESULTS: Age, gender, body mass index, triglycerides, creatinine, uric acid, blood glucose, blood pressure phenotypes were no different between ε2, ε3 and ε4 alleles. The ε4 allele was associated with higher total-cholesterol (p < 0.001), LDL-C (p < 0.001), total-cholesterol/HDL-C ratio (p < 0.001), LDL/HDL-C ratio (p < 0.001), lower HDL-C values (p < 0.001) and higher risk to obesity (OR = 1.358, 95% CI = 1.019-1.811) and hyperuricemia (OR = 1.748, 95% CI = 1.170-2.611). Nevertheless, pulse wave velocity (p = 0.66) measures were no different between genotypes. The significant association between APOE genotypes and lipid levels persisted after a 5-year follow-up interval, but no interaction between time and genotype was observed for lipids longitudinal behavior. CONCLUSION: The ε4 allele of the APOE gene is associated with a worse lipid profile in the Brazilian urban population. In our relatively young sample, the observed effect of APOE genotype on lipid levels was not translated into significant effects in arterial wall stiffness.