Introduction Exaggerated blood pressure response to exercise (EEBP = SBP ≥ 190 mmHg for women and ≥210 mmHg for men) during cardiopulmonary exercise test (CPET) is a predictor of cardiovascular risk. Sympathetic hyperactivation and decreased baroreflex sensitivity (BRS) seem to be involved in the progression of metabolic syndrome (MetS) to cardiovascular disease. Objective To test the hypotheses: (1) MetS patients within normal clinical blood pressure (BP) may present EEBP response to maximal exercise and (2) increased muscle sympathetic nerve activity (MSNA) and reduced BRS are associated with this impairment. Methods We selected MetS (ATP III) patients with normal BP (MetS_NT, n = 27, 59.3% males, 46.1 ± 7.2 years) and a control group without MetS (C, n = 19, 48.4 ± 7.4 years). We evaluated BRS for increases (BRS+) and decreases (BRS−) in spontaneous BP and HR fluctuations, MSNA (microneurography), BP from ambulatory blood pressure monitoring (ABPM), and auscultatory BP during CPET. Results Normotensive MetS (MetS_NT) had higher body mass index and impairment in all MetS risk factors when compared to the C group. MetS_NT had higher peak systolic BP (SBP) (195 ± 17 vs. 177 ± 24 mmHg, P = 0.007) and diastolic BP (91 ± 11 vs. 79 ± 10 mmHg, P = 0.001) during CPET than C. Additionally, we found that MetS patients with normal BP had lower spontaneous BRS− (9.6 ± 3.3 vs. 12.2 ± 4.9 ms/mmHg, P = 0.044) and higher levels of MSNA (29 ± 6 vs. 18 ± 4 bursts/min, P < 0.001) compared to C. Interestingly, 10 out of 27 MetS_NT (37%) showed EEBP (MetS_NT+), whereas 2 out of 19 C (10.5%) presented (P = 0.044). The subgroup of MetS_NT with EEBP (MetS_NT+, n = 10) had similar MSNA (P = 0.437), but lower BRS+ (P = 0.039) and BRS− (P = 0.039) compared with the subgroup without EEBP (MetS_NT−, n = 17). Either office BP or BP from ABPM was similar between subgroups MetS_NT+ and MetS_NT−, regardless of EEBP response. In the MetS_NT+ subgroup, there was an association of peak SBP with BRS− (R = −0.70; P = 0.02), triglycerides with peak SBP during CPET (R = 0.66; P = 0.039), and of triglycerides with BRS− (R = 0.71; P = 0.022). Conclusion Normotensive MetS patients already presented higher peak systolic and diastolic BP during maximal exercise, in addition to sympathetic hyperactivation and decreased baroreflex sensitivity. The EEBP in MetS_NT with apparent well-controlled BP may indicate a potential depressed neural baroreflex function, predisposing these patients to increased cardiovascular risk.

Resumo Fundamento: A obesidade afeta a adolescência, podendo levar à síndrome metabólica (SM) e disfunção endotelial, um marcador precoce de risco cardiovascular. Apesar de a obesidade ser fortemente associada à síndrome da apneia obstrutiva do sono (SAOS), ainda não está claro o papel da SAOS na função endotelial em adolescentes obesos. Objetivo: Investigar se a obesidade durante a adolescência leva à SM e/ou SAOS e causa disfunção endotelial nesses indivíduos. Além disso, estudamos a possível associação dos fatores de risco para SM e do índice de apneia e hipopneia (IAH) com disfunção endotelial. Métodos: Estudamos 20 adolescentes obesos sedentários (AO; 14,2±1,6 anos, 100,9±20,3kg), e 10 adolescentes eutróficos (AE, 15,2±1,2 anos, 54,4±5,3kg) pareados por sexo. Avaliamos os fatores de risco para SM (critérios da Federação Internacional de Diabetes), função vascular (dilatação mediada pelo fluxo, DMF), capacidade funcional (VO2pico) e presença de SAOS (IAH > 1 evento/hora, pela polissonografia). Consideramos um p<0,05 como estatisticamente significativo. Resultados: AO apresentaram maior circunferência da cintura (CC), gordura corporal, triglicerídeos, pressão arterial sistólica (PAS) e diastólica (PAD), maiores níveis de LDL e menores HDL e VO2pico em comparação a AE. Não houve diferença no IAH entre os grupos. AO apresentaram menor DMF que AE (6,17±2,72 vs. 9,37±2,20%, p=0,005). Observou-se uma associação entre DMF e CC (R=-0,506, p=0,008) e entre DMF e PAS (R=-0,493, p=0,006). Conclusão: Em adolescentes, a obesidade associou-se à SM e causou disfunção endotelial. CC e PAS aumentadas poderiam estar envolvidas nessa alteração. SAOS foi detectada na maioria dos adolescentes independentemente de obesidade. (Arq Bras Cardiol. 2021; 116(4):795-803)

Cardiovascular disease (CVD) is currently the leading cause of death in Brazil and worldwide. In 2016, CVD accounted for more than 17 million deaths, representing 31% of all deaths globally. Molecular and genetic mechanisms may be involved in vascular protection and should be considered in new therapeutic approaches. In this sense, recent studies have reported that brain-derived neurotrophic factor (BDNF) is reduced in individuals predisposed to develop CVD, and that aerobic physical training increases the amounts of circulating BDNF. BDNF is a neurotrophin found at high concentrations in the hippocampus and cerebral cortex and is considered a key molecule for the maintenance of synaptic plasticity and survival of neuronal cells. In addition to neuronal plasticity, BDNF is also important in vascular function, promoting angiogenesis through the regulation of reactive oxygen species (ROS). However, a variant of the BDNF gene in humans, the Val66Met polymorphism (substitution of the amino acid valine for a methionine at position 66 of the codon), occurring in 20-30% of the Caucasian population, may affect plasma BDNF concentrations and its activity in all peripheral tissues containing tyrosine kinase B receptors (TrkB), such as the endothelium. Thus, we will present a discussion about the role of serum BDNF levels in cardiovascular protection, Val66Met genetic variant in vascular reactivity and the effect of physical exercise.

Obstructive sleep apnea (OSA) increases morbidity and mortality and it is associated with an increased cardiovascular risk. The gold standard treatment for OSA is positive airway pressure therapy (CPAP). However, it is an expensive treatment and several patients do not adapt to CPAP. GOAL:The researchers will verify the effects of low-level laser therapy (LLLT) on OSA, when applied to the soft palate and on the tongue base. METHODS:The researchers will select individuals of both sexes aged 30 to 60 years old who are sedentary and that present a high risk of OSA by the Berlin questionnaire. The evaluations pre and post interventions will be polysomnography; anthropometric and body composition measurements (Bioimpedance); metabolic syndrome risk factors (International Diabetes Federation); physical capacity (VO2 peak at the cardiopulmonary exercise test, CPET); endothelial function (flow-mediated dilatation, FMD); autonomic control (heart rate variability and sympathovagal balance). Those diagnosed with moderate and severe OSA (apnea/hypopnea index, AHI ≥15 events/h) will be invited to participate in the study and they will be randomized into 2 groups: LLLT treatment or placebo (C). The LLLT group will receive applications at 8 points on the soft palate and on the base of the tongue for 8 seconds for each point. The applications of LLLT will occur twice a week, with a minimum interval of 2 days between the applications for 2 months, when using a Therapy Plus NS 13678 Laser. The C group will have similar applications, but with the device turned off. EXPECTED RESULTS:In the individuals with OSA, photobiomodulation through LLLT will decrease the AHI. Additionally, when LLLT is applied in the oral cavity, a highly vascularized region, this may cause improvements in the vascular function and in the autonomic and hemodynamic control. ETHICS AND DISSEMINATION:This protocol was approved by the Research Ethics Committee of the Nove de Julho University, São Paulo, Brazil, on the date of March 11, 2019 (CAAE: 06025618.2.0000.5511 - Acceptance Number: 3.191.077). This trial has been registered with the Brazilian Registry of Clinical Trials (REBEC TRIAL RBR-42v548). This study is not yet recruiting. Issue date: November 4, 2019.

Resumo As doenças cardiovasculares (DCV) são atualmente a maior causa de morte no Brasil e no mundo. Em 2016 as DCV foram responsáveis por mais de 17 milhões de mortes, representando 31% de todas as mortes em nível global. Mecanismos moleculares e genéticos podem estar envolvidos na proteção cardiovascular e devem ser considerados nas novas abordagens terapêuticas. Nesse sentido, recentes estudos têm relatado que o Fator Neurotrófico Derivado do Encéfalo (Brain-Derived Neurotrophic Factor, BDNF) está reduzido em indivíduos predispostos a desenvolverem DCV, e que o treinamento físico aeróbio aumenta as quantidades de BDNF circulante. O BDNF é uma neurotrofina encontrada em altas concentrações no hipocampo e córtex cerebral, sendo considerada molécula-chave na manutenção da plasticidade sináptica e na sobrevivência das células neuronais. Além da plasticidade neuronal, BDNF também é importante na função vascular, promovendo angiogênese por meio da regulação por espécies reativas de oxigênio (ROS). Entretanto, uma variante do gene do BDNF em humanos, o polimorfismo Val66Met (substituição do aminoácido valina por uma metionina na posição 66 do códon), que ocorre em 20-30% da população caucasiana, pode afetar as concentrações de BDNF no plasma e sua atividade em todos os tecidos periféricos contendo receptores tirosina quinase B (TrkB), como o endotélio. De fato, recentemente observamos que o polimorfismo Val66Met prejudica a reatividade vascular e o BDNF circulante em resposta ao treinamento físico. Dessa forma, apresentaremos a seguir uma discussão sobre os níveis séricos de BDNF na proteção cardiovascular, a variante genética Val66Met na reatividade vascular e o efeito do exercício físico.

PurposeLow functional capacity is associated with cardiovascular risk factors. Cardiopulmonary exercise test (CPET) is the gold standard evaluation to determine functional capacity through maximal oxygen uptake (VO2max) measurement. However, the high financial cost, the material and the time spent on this method difficult its use in a large number of clinicals. In this sense, it is possible to determine VO2max via the equivalence formulas. The aim of this study was to verify the agreement between indirect calculation of VO2max using American College of Sports Medicine (ACSM) equation and the directly measure of maximal oxygen uptake in metabolic syndrome (MetS) patients.MethodsSixty non‐diabetic and without medication patients with MetS (ATP‐III) were divided in 2 groups, according to gender: Male (n=32; 46±9 y; 31.2±3.0 kg/m2); and Female (n=28; 49±9 y; 32.7±3.1 kg/m2). VO2max was measured during CPET in a cycle ergometer with ramp protocol and estimated by ACSM’s equation [VO2= 7.0+ (1.8 x work rate)/body mass].ResultsAll patients included achieved respiratory exchange rate (RER=VCO2/VO2) >1.10 at maximal exercise. In Male group, despite correlation between methods (R=0.78; P=0.0001), VO2max estimated by ACSM’s equation was higher than the VO2max of the direct measurement (28.7±3.1 vs. 26.9±6.0 ml/kg/min; P=0.049). Similarly, in Female group there was correlation (R=0.79; P=0.0001), however VO2max estimated by ACSM’s equation was higher than direct measured VO2max (20.3±3.3 vs. 18.8±3.3 ml/kg/min; P=0.0008). In both genders, Bland‐Altman plot analysis suggested a lack of agreement between predicted and direct VO2max.ConclusionIn bout groups, Male and Female, the ACSM’s equation overestimates the VO2max. It seems that ACSM’s equation is not capable of accurately predicting VO2max in men and women with MetS.

BACKGROUND:High-level spinal cord injury (SCI) results in profound spinal and supraspinal deficits, leading to substantial ventilatory limitations during whole-body hybrid functional electrical stimulation (FES)-rowing, a form of exercise that markedly increases the active muscle mass via electrically induced leg contractions. This study tested the effect of noninvasive ventilation (NIV) on ventilatory and aerobic capacities in SCI. METHODS:This blinded, randomized crossover study enrolled 19 patients with SCI (level of injury ranging from C4 to T8). All patients were familiar with FES-rowing and had plateaued in their training-related increases in aerobic capacity. Patients performed two FES-rowing peak exercise tests with NIV or without NIV (sham). RESULTS:NIV increased exercise tidal volume (peak, 1.50 ± 0.31 L vs 1.36 ± 0.34 L; P < .05) and reduced breathing frequency (peak, 35 ± 7 beats/min vs 38 ± 6 beats/min; P < .05) compared with the sham test, leading to no change in alveolar ventilation but a trend toward increased oxygen uptake efficiency (P = .06). In those who reached peak oxygen consumption (Vo2peak) criteria (n = 13), NIV failed to significantly increase Vo2peak (1.73 ± 0.66 L/min vs 1.78 ± 0.59 L/min); however, the range of responses revealed a correlation between changes in peak alveolar ventilation and Vo2peak (r = 0.89; P < .05). Furthermore, those with higher level injuries and shorter time since injury exhibited the greatest increases in Vo2peak. CONCLUSIONS:Acute NIV can successfully improve ventilatory efficiency during FES exercise in SCI but may not improve Vo2peak in all patients. Those who benefit most seem to be patients with cervical SCI within a shorter time since injury. TRIAL REGISTRY:ClinicalTrials.gov; Nos.: NCT02865343 and NCT03267212; URL: www.clinicaltrials.gov.

BACKGROUND:Obstructive sleep apnea (OSA) is a risk factor frequently present in patients with metabolic syndrome (MetS). Additionally, moderate and severe OSA are highly prevalent in patients with cardiac disease, as they increase the riskfor cardiovascular events by 80%. The gold standard diagnostic method for OSA is overnight polysomnography (PSG), which remains unaffordable for the overall population. The aim of the present study was to evaluate whether the Berlin Questionnaire (BQ) is anuseful tool for assessing the risk of OSA in patients with MetS. METHODS:97 patients, previously untreated and recently diagnosed with MetS (National Cholesterol Education Program, Adult Treatment Panel III, ATP-III) underwent a PSG. OSA was characterized by the apnea-hypopnea index (AHI). BQ was administered before PSG and we evaluated sensitivity, specificity, positive and negative predictive values, and accuracy. RESULTS:Of the 97 patients with MetS, 81 patients had OSA, with 47 (48.5%) presenting moderate and severe OSA. For all MetS with OSA (AHI≥5 events/hour), the BQ showed good sensitivity (0.65, 95% CI 0.54 to 0.76) and fair specificity (0.38, 95% CI 0.15-0.65) with a positive predictive value of 0.84, a negative predictive value of 0.18 and an 84% accuracy. Similarly, for moderate-to-severe OSA (AHI≥15 events/hour) we found good sensitivity (0.73, 95% CI 0.58-0.85) and fair specificity (0.40, 95% CI 0.27-0.55). Interestingly, for severe OSA (AHI≥30 events/hour), there was a very good sensitivity (0.91, 95% CI 0.72-0.99) and moderate specificity (0.42, 95% CI 0.31-0.54). CONCLUSION:The BQ is a valid tool for screening the risk of OSA in MetS patients in general, and it is particularly useful in predicting severe OSA.

Obstructive sleep apnea (OSA) has been linked to altered cardiovascular response to exercise. A systematic review and individual patient data (IPD) meta-analysis were conducted to assess whether OSA patients present reduced exercise capacity. PubMed, Embase and Web of Science were searched until September 2018. Studies which performed sleep recording in both OSA patients and controls and measured maximal oxygen consumption (VO2peak) via a maximal exercise test were included. IPD were provided for five trials upon the 18 eligible (N = 289) and a two-stage IPD meta-analysis model was used, allowing to standardize the apnea cutoff and adjust for confounders. IPD meta-analysis demonstrated that moderate to severe OSA patients had similar VO2peak (mean difference: -1.03 mL.kg(-1) min(-1); 95% CI: -3.82 to 1.76; p = 0.47) and cardiovascular response to exercise compared to mild or non-OSA patients. By contrast, aggregate data (AD) meta-analysis including the 13 trials for which IPD were unavailable (N = 605) revealed that VO2peak was reduced in OSA patients compared to controls (mean difference: -2.30 mL.kg(-1) min(-1); 95% CI: -3.96 to -0.63; p < 0.001) with high heterogeneity. In conclusion, IPD meta-analysis suggests that VO2peak and the cardiovascular response to exercise are preserved in moderate to severe OSA patients while AD meta-analysis suggests lower VO2peak in severe OSA. (C) 2019 Elsevier Ltd. All rights reserved.

A previous aggregate data (AD) meta-analysis showed that obstructive sleep apnoea patients had lower exercise capacity compared to controls (Mendelson et al. ERJ 2018). However, these authors reported a high level of heterogeneity, which may be explained by methodological limitations including an OSA definition apnoea-hypopnoea index (AHI) which varied from 5 to 30. The aim of this meta-analysis was to confirm whether exercise capacity is altered in moderate to severe OSA patients using individual patient data (IPD) and AD meta-analysis. A two-stage IPD meta-analysis model was used, allowing to standardize the apnea cutoff (AHI ≥15) and adjust for confounders. Nonrandomized trials performing sleep recording and exercise test with a measured of maximal oxygen consumption (VO2peak) were searched using PubMed, Embase and Web of Science. From the 666 studies identified, 18 met inclusion criteria. IPD were sought for this 18 studies and obtained from 5 trials (28% of all studies, N=289). For the 13 other studies, AD were used in sensitivity analyses (N=605). IPD meta-analysis demonstrated that OSA patients had similar VO2peak (mean difference (MD): -1.0 mL.kg-1.min-1; 95% CI: -3.8 to 1.8; p=0.47) with low heterogeneity compared to mild or non-OSA patients while AD meta-analysis revealed that VO2peak was reduced in OSA patients (MD: -2.3 mL.kg-1.min-1; 95% CI: -4.0 to -0.6; p<0.001) with high heterogeneity (I2=77%; p<0.001). Subgroup AD analysis revealed significant difference in severe OSA. In conclusion, IPD meta-analysis suggests that exercise capacity is preserved in moderate to severe OSA patients while AD meta-analysis suggests lower VO2peak in severe OSA.

Studies have shown that excess of fat in central region is the main substrate for pathophysiological alterations that leads obesity‐associated insulin resistance. Lately, in the medical practice the use of the waist circumference (WC) instead waist‐to‐hip ratio (WHR) is more usual. We hypothesized that WHR is a better tool to infer insulin resistance in young obese women. The aim of this study was to evaluate the insulin‐sensitive/insulin‐resistant in young obese women within central and peripheral body fat distribution. We studied 61 young obese women (BMI 30 to 40 kg/m2) with WC ≥ 88 cm and without comorbidities. They were divided into: with central fat distribution (CF), defined as waist‐to‐hip ratio (WHR) ≥ 0.85 cm (n=30, 33±7 y), and with peripheral fat distribution (PF) with WHR < 0.85 cm (n=31, 33±6 y). All volunteers were submitted to anthropometric, glycemic and insulin measurements and indexes: fasting, HOMA‐IR, QUICKI and area under the curve (AUC) during the Oral Glucose Tolerance Test (OGTT) to assess the insulin sensitivity. Despite the fat distribution, CF and PF shown similar anthropometric measures (weight= 86.8±8.5 vs.87.6±8.3 kg, WC= 109±6 vs.106±8 cm, BMI= 33.2±2.7 vs. 33.7±2.4 kg/m2; respectively, p>0.05). Also, both obese groups, CF and PF, showed normal fasting glucose (84±10 vs. 82±10 mg/dL, p=0.420), based in the IDF criteria (<100mg/dL). However, the group CF compared with PF presented elevated fasting insulin (17.8±8.2 vs. 12.6±6.8 uUI/mL, p=0.008), HOMA‐IR (3.7±1.9 vs. 2.6±1.6 uUI/mL, p=0.011), reduced QUICKI (0.322±0.025 vs. 0.340±0.025, p=0.007). Furthermore, the group CF compared with PF had lower insulin sensitivity as AUCglucose/AUCinsulin ratio from OGTT (1.42±0.67 vs. 2.12±0.86, p=0.001). In conclusion, our data demonstrated that in young obese women with similar WC and fasting glucose, the central body fat distribution increase insulin‐resistant, emphasizing the importance in used the waist‐to‐hip ratio as important tool for identify the additional risk factor in obesity young women.Support or Funding Information#Universidade Nove de Julho (UNINOVE), SP ‐ Brazil.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

We tested the hypothesis that (i) diet associated with exercise would improve arterial baroreflex (ABR) control in metabolic syndrome (MetS) patients with and without obstructive sleep apnea (OSA) and (ii) the effects of this intervention would be more pronounced in patients with OSA.

Background: High-level spinal cord injury (SCI) results in profound pulmonary muscle denervation in addition to motor impairment leading to substantial ventilatory limitation during exercise. This is particularly true when functional electrical stimulation (FES) of the paralyzed legs is added to produce higher exercise capacity. We tested the hypothesis that non-invasive ventilation (NIV) could improve ventilatory capacity and hence aerobic capacity during FES-rowing exercise in SCI. Methods: 13 individuals (40 ± 15 years; BMI = 28 ± 7 kg/m2; forced vital capacity = 62 ± 23 % pred.) with SCI (C4 to T5) were enrolled in a blinded cross-over study. All patients were familiar with FES-rowing exercise. After familiarization, volunteers performed 2 FES-rowing maximal exercise tests with NIV or Sham NIV (IPAP = 22 ± 3 vs. 5 ± 1 mmHg) in a random order. Results: On average, NIV improved peak tidal volume (1.54 ± 0.38 vs.1.30 ± 0.28 L, p = 0.01) and alveolar ventilation (VApeak, 35.0 ± 10.6 vs. 33.4 ± 8.9 L, p = 0.04) compared to sham, with a reduction in breathing frequency (34 ± 8 vs. 38 ± 7 bpm, p = 0.01), but without a significant effect on VO2peak (1.63 ± 1.25 vs.1.69 ± 1.28 L/min). However, there was a range of responses such that half of the subjects had increases in both VApeak and VO2peak while others had decreases in both, resulting a strong relationship between changes in VApeak and VO2peak across all subjects (r = 0.89, p < 0.001). Conclusion: Acute NIV successfully improves ventilation during FES exercise in high-level SCI but may not improve VO2peak in all patients. However, regular training with NIV may have a greater effect than a single acute bout on VO2peak.

PurposePrevious study showed that metabolic syndrome (SMet) subjects have impaired attenuation of heart rate recovery (ΔHRR) after maximal exercise. Autonomic dysfunction is the possible mechanism involved in this alteration. We tested the hypothesis that hypocaloric diet and exercise training (D+ET) improves DHRR, heart rate reserve and autonomic control in MetS subjects.MethodsNever treated patients with MetS (ATP‐III) were assigned into intervention group (MetS/D+ET, n=33) submitted to D (−500 kcal/day) and ET (40 min, 3 times/week of cycle exercise) and control group (MetS/C, n=23) for 4 months. We evaluated pre and post‐intervention or control period, cardiac autonomic control (LF = low frequency, HF = high frequency, LF/HF = sympathovagal balance) by heart rate variability (ECG), muscle sympathetic nervous activity (MSNA ‐ microneurography) and we calculated the ΔHRR (maximal HR minus HR in the 1st, 2nd and 4th min of recovery) and the heart rate reserve (maximal HR minus resting HR) after cardiopulmonary exercise test.ResultsSMet/D+ET improved metabolic profile, functional capacity and reduce body weight. Compared with pre‐intervention, MetS/D+ET increased HF n.u. (33±3 vs. 39±3 bpm, P=0.01) and decreased MSNA (30±1 vs. 25±2 bpm, P<0.001), LF n.u. (67±3 vs. 61±3 bpm, P=0.02) and LF/HF (3.0±0.3 vs. 2.2±0.4 bpm, P=0.02). Furthermore, MetS/D+ET increased ΔHRR at 1st min (16±1 vs. 21±2 bpm, P=0.02), ΔHRR at 2nd min (28±1 vs. 36±2 bpm, P<0.001), ΔHRR at 4th min (46±2 vs. 56±2 bpm, P<0.001) and heart rate reserve (76±3 vs. 86±3 bpm, P <0.001). No significant change was observed in SMet/C.ConclusionThe intervention by hypocaloric diet and exercise training improves the autonomic control, heart rate reserve and heart rate recovery after maximal exercise in subjects with MetS.Support or Funding InformationGrant #2011/17533‐6, #2015/17533‐6 and #2016/16831‐7, São Paulo Research Foundation (FAPESP) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

BackgroundThe increasing prevalence of obesity worldwide impacts childhood and adolescence, and this trend points to a significant growth rate of non‐transmissible chronic diseases in the near future. Endothelial dysfunction is an early marker of cardiovascular risk.ObjectiveTo determine a) whether obese adolescents have endothelial dysfunction and b) whether cardiovascular risk factors and obstructive sleep apnea (OSA) are associated with endothelial dysfunction.MethodsWe studied 20 obese adolescents (OA; median age 14 years, 100.9±20.3 kg), post pubescent, sedentary, not following any special diet or receiving any drug treatment, and compared them with 10 lean adolescents (LA, median age 15 years, 54.4±5.3 kg) paired for sex. Metabolic syndrome risk factors (MetS, International Diabetes Federation), vascular function (flow‐mediated dilation, FMD, and Reactive Hyperemia Index, RHI, by peripheral arterial tonometry, EndoPAT®), functional capacity and OSA using the apnea‐hypopnea index (AHI, polysomnography) were assessed.ResultsThe OA presented higher waist (WC) and cervical circumference, as well as higher proportion of body fat, triglycerides, SBP, DBP, LDL‐c and lower HDL‐c than the LA group. In the OA, 35% presented MetS, which was absent in the LA group. OSA was present in 86.6% of the OA and 50% of LA (AHI>1 event/hour). There was no difference between groups in the AHI, VO2 peak and RHI. The OA presented lower FMD than LA (6.17±2.72 vs. 9.37±2.20%, p=0.005). There was an association between FMD and WC (r=−0.506, p=0.008) and FMD and SBP (r=−0.493, p=0.006).ConclusionOSA was observed in most adolescents, regardless of obesity. OA presented MetS and endothelial dysfunction. Increased WC and SBP seem to be involved in this alteration.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Background: Prior work has found that linear heart rate variability (HRV) indices do not accurately reflect cardiac vagal control, and nonlinear indices of HRV have been proposed as alternative tools that may better capture cardiac vagal effects. We used progressive low dose atropine to induce changes in cardiac vagal tone to test the hypotheses that nonlinear HRV indices accurately reflect cardiac vagal control, and that their changes in response to low dose atropine correlate with those in RR interval. Methods: Changes in RR interval and HRV indices during intravenous injections of saline (control) and 6 cumulative doses of atropine (from 1.4 to 7.2 mu g/kg) during controlled breathing at 15 breaths per minute were assessed in 14 young healthy individuals. Results: As expected, low dose atropine increased average RR interval (vagotonic effect). There was no strong association between vagotonic changes in RR interval and the majority of nonlinear HRV indices, either within or among subjects. Conclusions: These data suggest an inconsistent relationship between responses of nonlinear HRV indices and RR interval to changes in cardiac vagal tone. Therefore, nonlinear HRV indices may not be reliable indices of cardiac vagal control in healthy humans.

Obstructive sleep apnea (OSA) impairs insulin‐glucose metabolism and muscle sympathetic nervous activity (MSNA). Metabolic syndrome (MetS) frequently is common in OSA patients, exacerbating these alterations. In this context, the effect of hypocaloric diet and exercise training (D+ET) in patients with OSA+MetS is not clear. We tested the hypotheses that: 1) D+ET would improve insulin‐glucose metabolism and MSNA; and 2) The reduction in MSNA is associated with the improvement insulin‐glucose metabolism. Never treated OSA patients (apnea‐hypopnea index‐AHI>15 events/h by polysomnography, PSG) and MetS (ATP‐III), were divided into: Control (C, n=10, 46±2y) and D+ET (n=11, 55±3y). D (−500kcal/day) and ET (40min, 3times/week of cycle exercise for 4‐months). We evaluated MSNA (microneurography) and HOMA‐IR and QUICK by fasting insulin/glucose. Both groups were similar in MetS risk factors, PSG parameters, MSNA and fasting insulin/glucose at pre‐intervention. Compared with C, D+ET improved VO 2 peak, body weight, waist circumference, systolic and diastolic blood pressure, AHI (P<0,05). D+ET decreased MSNA (31±2 vs. 25±2 bursts/min, P=0.01), fasting insulin (13±1.3 vs. 9±1.0 μUI/mL, P=0.02), HOMA‐IR (3.4±0.4 vs. 2.2±0.3, P=0.03) and increased QUICK (0.32±0.01 vs. 0.35±0.01, P=0.02). No changes were found in C group. Further analysis showed a significant association between change in fasting insulin (R=0.49, P=0.03), in HOMA‐IR (R=0.54, P=0.02) and in QUICK (R=−0.55, P=0.02) with the change in MSNA. D+ET improved insulin‐glucose metabolism and MSNA in patients with OSA+MetS. The effect of D+ET in insulin‐glucose metabolism, can be a candidate to explain, at least in part, the improvement in sympathetic activity. Support or Funding Information Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) #2011/17533‐6, #2015/17533‐6 and #2016/16831‐7

Introduction Metabolic syndrome (MetS) is associated with structural and functional vascular abnormalities that can lead to increased arterial stiffness, which predicts cardiovascular events and increases mortality. However, little is known regarding the implications of risk factor clustering in the arterial stiffness. Objective In MetS, determine the clustering and the combining pattern of risk factors and its association with arterial stiffness. Methods We selected recently diagnosed patients with MetS (n=47, 51 ± 6 y) according to ATP III criteria. A control group (C, n=17, 50 ± 4 years) was also studied. Arterial stiffness was evaluated by pulse wave velocity (PWV) in carotid‐femoral segment. The patients were categorized and analyzed according MetS risk factors clustering (3, 4 and 5 factors). We performed correlation tests and multiple linear regressions to determine predictor variables with PWV and independent variables of sex, age, body mass index, and MetS risk factors. Results Patients with MetS had increased PWV compared to C (8.8 ± 0.7, 9.8 ± 1.4 m/s, p=0.01). In multivariate analysis, the variables that remained as predictor of PWV were age (β=0.35, p= 0.01) and triglycerides (β=0.29, p= 0.03). There was a progressive increase of PWV to increase the number of risk factors. Furthermore, the PWV compared to C group was similar for cluster of 3 risk factors, whereas were higher for cluster of 4 and 5 risk factors (8.7 m/s [7.8 to 10.0], 9.4 m/s [7.7to 11.7], 9.8 m/s [7.3 to 13.4] and 10 m/s [9.3 to 13.4]). Conclusion The number of risk factors amplifies the arterial stiffness. The presence of alteration in the triglycerides worsening the stiffness of large vessels, emphasizing the importance in addressing this risk factor for MetS patients. Support or Funding Information This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP# 2011/17533‐6 ) and, in part, by Fundação Zerbini. Sara Rodrigues was supported by FAPESP# 2013/15323‐0, Edgar Toschi‐Dias was supported by FAPESP# 2013/07651‐7, Felipe X Cepeda was supported by FAPESP# 2015/ 03274‐0.

Obesity impairs autonomic control with an adverse effect on cardiovascular risk. The association of obesity and autonomic dysfunction seems to be dependent on the distribution of body fat. The evaluation of heart rate (HR) at rest and during exercise may reflect autonomic dysfunction. The aim of this study was to evaluate the modulation of HR at rest and during exercise and its association with the body fat distribution in obese young women. We selected 49 young obese women (BMI 30 to 40 kg/m2) with waist circumference (WC) ≥ 88 cm and without comorbidities. They were divided into: with central fat distribution (CF), defined as waist‐to‐hip ratio (WHR) ≥ 0.85 cm (n=26, 34±1.4 y, 33.2±0,5 kg/m2), and with peripheral fat distribution (PF) with WHR < 0.85 cm (n=23, 33±1.4 y, 33.6±0,5 kg/m2). All volunteers were submitted to anthropometric and clinical assessment and to cardiopulmonary exercise test to assess the HR at rest; and changes from rest to peak exercise and during 6 min of recovery. Despite the fat distribution, CF and PF shown similar functional capacity (VO2 peak, 18.4±0.5 vs. 17.9±0.8 mL/kg/min, respectively; p=0.66). However, CF and PF presented diminished functional capacity compared with the estimate functional capacity for similar age and sex (60±2 and 57±3%; p=0.46). Based in the cut‐off values that designated cardiovascular risk, i. e., rest HR >75 bpm and chronotropic reserve (peak HR – rest HR) <89 beats, both obese groups, CF and PF, presented elevated resting HR (89 [82–98] and 86 [81–97] bpm, respectively) and reduced chronotropic reserve (78±3 and 72±4 beats). Furthermore, the group CF (WHR ≥ 0.85) presented reduced attenuation of HR at 1st min of recovery compared with PF (14±1 vs. 20±2 beats, p=0.044). In conclusion, our data suggest that young obese women had impaired sympatho‐vagal balance, observed by resting HR and chronotropic reserve during maximal progressive exercise test. The central body fat distribution potentiates the vagal dysfunction, characterized by reduced attenuation of HR at 1st min of recovery after maximal exercise test.