Maria Teresa Zanella

Influência da distribuição da gordura corporal sobre a prevalência de hipertensão arterial e outros fatores de risco cardiovascular em indivíduos obesos

INTRODUCTION: Obese people are at higher cardiovascular risk than people with normal body weight. The objective of this study was to establish the relationship between obesity, body fat distribution and cardiovascular risk factors. METHODS: Body mass index (BMI), waist-hip ratio (WHR) systolic (SBP) and diastolic blood pressure (DBP), plasma cholesterol, triglycerides and glucose levels were determined in a population of 499 overweight and obese patients (432F/67M; age 39±12.9y). RESULTS: High prevalence of abnormal glucose tolerance or diabetes (21.8%), hypercholesterolenemia (49.1%), hypertri glyceridemia (21.3%) and hypertension (43.8%) were found in this population. The prevalence of hypertension increased from 23% in patients with BMI 25-29.9 kg/m2 to 67.1% (p 40kg/m2 and also from 35.7% in patients with WHR between 0.73 and 0.88 to 66.6% in those with WHR >0.97 (p 40kg/m2, (p<0.05). CONCLUSION: Our data reinforce the association between obesity and high cardiovascular risk. In addition, our findings suggested a role for body fat distribution in the development of hypertension in obese patients.

Gordura visceral e síndrome metabólica: mais que uma simples associação

ABSTRACT Visceral Fat and Metabolic Syndrome: More Than a Simple Association.Metabolic syndrome (MS) is seen nowadays as a worldwide epidemicevent associated with high cardiovascular morbi-mortality and highsocioeconomic cost. The ponderal gain is an independent predictor forthe development of MS, although not all obese individuals present it. Onthe other hand, some populations with low obesity prevalence presenthigh prevalence of MS and cardiovascular mortality. The distribution ofcorporal fat is relevant and visceral fat (VF), specifically, seems to be thelink between adipose tissue and insulin resistance (IR), a mean featureof MS. Adipose tissue is now considered a complex organ with multiplefunctions. VF presents metabolic properties, which are different from thegluteo-femoral subcutaneous fat and related to IR. Several studies showthe narrow relationship of abdominal adiposity with the glucose tole-rance, hyperinsulinemia, hypertriglyceridemia and arterial hypertension.More than a simple association, recently it is thought that the VF plays acentral part in the physiopathology of MS. Consequently, the quantifi-cation of VF plays an important role to identify individuals with larger risk

Ultrasonography for the Evaluation of Visceral Fat and Cardiovascular Risk

Visceral fat accumulation is associated with increased cardiovascular risk. Clinical evaluation of visceral fat is limited because of the lack of reliable and low-cost methods. To assess the correlation between ultrasonography and computed tomography (CT) for the evaluation of visceral fat, 101 obese women, age 50.5±7.7 years with a body mass index of 39.2±5.4 kg/m2, were submitted to ultrasonograph and CT scans. Visceral fat measured by ultrasonography, 1 cm above the umbilical knot, showed a high correlation with CT-determined visceral fat (r =0.67, P <0.0001). The ultrasonograph method showed good reproducibility with an intra-observer variation coefficient of <2%. Both ultrasonograph and CT visceral fat values were correlated with fasting insulin (r =0.29 and r =0.27, P <0.01) and plasma glucose 2 hours after oral glucose load (r =0.22 and r =0.34, P <0.05), indicating that ultrasonography is a useful method to evaluate cardiovascular risk. A significant correlation was also found between visceral fat by CT and serum sodium (r =0.18, P <0.05). A ultrasonograph-determined visceral-to-subcutaneous fat ratio of 2.50 was established as a cutoff value to define patients with abdominal visceral obesity. This value also identified patients with higher levels of plasma glucose, serum insulin and triglycerides and lower levels of HDL-cholesterol, which are metabolic abnormalities characteristic of the metabolic syndrome. Our data demonstrate that ultrasonography is a precise and reliable method for evaluation of visceral fat and identification of patients with adverse metabolic profile.

Treatment of Obesity Hypertension and Diabetes Syndrome

Obesity has been shown to be an independent risk factor for coronary heart disease. The insulin resistance associated with obesity contributes to the development of other cardiovascular risk factors, including dyslipidemia, hypertension, and type 2 diabetes. The coexistence of hypertension and diabetes increases the risk for macrovascular and microvascular complications, thus predisposing patients to cardiac death, congestive heart failure, coronary heart disease, cerebral and peripheral vascular diseases, nephropathy, and retinopathy. Body weight reduction increases insulin sensitivity and improves both blood glucose and blood pressure control. Metformin therapy also improves insulin sensitivity and has been associated with decreases in cardiovascular events in obese diabetic patients. Antihypertensive treatment in diabetics decreases cardiovascular mortality and slows the decline in glomerular function. However, pharmacological treatment should take into account the effects of the antihypertensive agents on insulin sensitivity and lipid profile. Diuretics and beta-blockers are reported to reduce insulin sensitivity and increase triglyceride levels, whereas calcium channel blockers are metabolically neutral and ACE inhibitors increase insulin sensitivity. For the high-risk hypertensive diabetic patients, ACE inhibition has proven to confer additional renal and vascular protection. Because hypertension and glycemic control are very important determinants of cardiovascular outcome in obese diabetic hypertensive patients, weight reduction, physical exercise, and a combination of antihypertensive and insulin sensitizers agents are strongly recommended to achieve target blood pressure and glucose levels.

Metabolic syndrome, dyslipidemia, hypertension and type 2 diabetes in youth: from diagnosis to treatment

Overweight and obesity in youth is a worldwide public health problem. Overweight and obesity in childhood and adolescents have a substantial effect upon many systems, resulting in clinical conditions such as metabolic syndrome, early atherosclerosis, dyslipidemia, hypertension and type 2 diabetes (T2D). Obesity and the type of body fat distribution are still the core aspects of insulin resistance and seem to be the physiopathologic links common to metabolic syndrome, cardiovascular disease and T2D. The earlier the appearance of the clustering of risk factors and the higher the time of exposure, the greater will be the chance of developing coronary disease with a more severe endpoint. The age when the event may occur seems to be related to the presence and aggregation of risk factors throughout life.The treatment in this age-group is non pharmacological and aims at promoting changes in lifestyle. However, pharmacological treatments are indicated in special situations.The major goals in dietary treatments are not only limited to weight loss, but also to an improvement in the quality of life. Modification of risk factors associated to comorbidities, personal satisfaction of the child or adolescent and trying to establish healthy life habits from an early age are also important. There is a continuous debate on the best possible exercise to do, for children or adolescents, in order to lose weight. The prescription of physical activity to children and adolescents requires extensive integrated work among multidisciplinary teams, patients and their families, in order to reach therapeutic success.The most important conclusion drawn from this symposium was that if the growing prevalence of overweight and obesity continues at this pace, the result will be a population of children and adolescents with metabolic syndrome. This would lead to high mortality rates in young adults, changing the current increasing trend of worldwide longevity. Government actions and a better understanding of the causes of this problem must be implemented worldwide, by aiming at the prevention of obesity in children and adolescents.

Uric acid as a factor in the metabolic syndrome.

Hyperuricemia is a prevalent finding in patients presenting metabolic syndrome, although its clinical meaning is still controversial and often underestimated. Men and women have different serum urate levels at all ages, and the impact of hyperuricemia in cardiovascular and renal outcomes is generally associated with a worse prognosis in women. Recent studies also have called attention to another perspective on hyperuricemia, indicating that it may be not only a consequence of insulin resistance states but also a significant predictor of the development of metabolic syndrome. This review discusses recent evidence related to the clinical significance of hyperuricemia in both sexes and the potential benefits of lowering serum uric acid levels.

Consequences of obstructive sleep apnea on metabolic profile: A Population-Based Survey†

Epidemiologic studies that control for potential confounders are needed to assess the independent associations of obstructive sleep apnea (OSA) with metabolic abnormalities. The aim of our study was to evaluate the associations of OSA with metabolic abnormalities among the adult population of Sao Paulo, Brazil.

Continuous positive airway pressure therapy improves hypoadiponectinemia in severe obese men with obstructive sleep apnea without changes in insulin resistance.

BACKGROUND Obstructive sleep apnea (OSA) is associated with several conditions that could facilitate the onset of cardiovascular and metabolic dysfunctions. Continuous positive airway pressure (CPAP) therapy has been shown to improve cardiovascular morbidity and mortality related to OSA, but the mechanisms underlying this association are not fully understood. OBJECTIVE The aim of the present study was to evaluate whether sleep apnea contributes to insulin resistance and inflammatory marker alterations and to evaluate the benefits of nasal CPAP therapy in severe obese patients with OSA. METHODS Plasma inflammatory cytokines and the homeostasis model assessment of insulin resistance index (HOMA-IR, Insulin Sensitivity Index [ISI]) were measured in severe obese male with OSA (n = 16) and compared with body mass index (BMI)-matched male controls without OSA (n = 13). Seven patients with severe sleep apnea (apnea-hypopnea index >30 events/h) were reevaluated after 3 months of nasal CPAP therapy. RESULTS OSA patients had a significantly lower adiponectin levels than obese controls (8.7 +/- 1.18 ng/mL vs. 15.0 +/- 2.55 ng/mL, P = 0.025). HOMA-IR, ISI, tumor necrosis factor-alpha (TNF-alpha, C-reactive protein (CRP), and interleukin-6 (IL-6) levels were not different between groups. Although insulin resistance index and BMI values did not change after 3 months of nCPAP therapy, adiponectin levels increased (P = 0.036) and the levels of TNF-alpha tended to decrease (P = 0.065). Changes in adiponectin levels during nCPAP therapy were positively correlated with an improvement in minimum oxygen saturation (r = 0.773; P = 0.041) and negatively correlated with changes in TNF-alpha levels (r = -0.885; P = 0.008). CONCLUSIONS nCPAP therapy reverses hypoadiponectinemia levels present in obese men with OSA, probably through reductions in hypoxia and inflammation activity.

Angiotensin converting enzymes from human urine of mild hypertensive untreated patients resemble the N-terminal fragment of human angiotensin I-converting enzyme.

Angiotensin I-converting enzyme (ACE) activity was analyzed in human urine collected from mild hypertensive untreated patients. DEAE-cellulose chromatography using linear gradient elution revealed two forms of angiotensin I-converting enzyme, eluted in the conductivity of 0.75 and 1.25 mS. The fractions of each conductivity were pooled and submitted to direct gel filtration in an AcA-34 column, and the apparent molecular weights of urinary ACEs were estimated as 90 kDa (for ACE eluted in 0.75 mS) and 65 kDa (for ACE eluted in 1.25 mS). Both enzymes have a K(i) of the order of 10(-7) M for the specific inhibitors studied, and are able to hydrolyze luteinizing hormone-releasing hormone and N-acetyl-Ser-Asp-Lys-Pro as described for N-domain ACE. By Western blot analysis, both peaks were recognized by ACE-specific antibody Y4, confirming the molecular weight already described. A plate precipitation assay using monoclonal antibodies to the N-domain of ACE showed that both forms of ACE binds with all monoclonal antibodies to the active N-domain ACE, suggesting that these forms of human urine ACEs resemble the N-fragment of ACE. The HP2 ACE (65 kDa) is similar to low molecular weight (LMW) ACE from normal subjects, and the HP2 ACE (90 kDa) is different from high molecular weight (190 kDa) and LMW (65 kDa) normal ACEs. The 90 kDa ACE could have an important role in development of hypertension. It will be fundamental to elucidate the molecular mechanism responsible for the genesis of this isoform.

Effect of continuous positive airway pressure therapy on hypothalamic-pituitary-adrenal axis function and 24-h blood pressure profile in obese men with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) increases the risk of cardiovascular events. Sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis activation may be the mechanism of this relationship. The aim of this study was to evaluate HPA axis and ambulatory blood pressure monitoring in obese men with and without OSAS and to determine whether nasal continuous positive airway pressure therapy (nCPAP) influenced responses. Twenty-four-hour ambulatory blood pressure monitoring and overnight cortisol suppression test with 0.25 mg of dexamethasone were performed in 16 obese men with OSAS and 13 obese men controls. Nine men with severe apnea were reevaluated 3 mo after nCPAP therapy. Body mass index and blood pressure of OSAS patients and obese controls were similar. In OSAS patients, the percentage of fall in systolic blood pressure at night (P = 0.027) and salivary cortisol suppression postdexamethasone (P = 0.038) were lower, whereas heart rate (P = 0.022) was higher compared with obese controls. After nCPAP therapy, patients showed a reduction in heart rate (P = 0.036) and a greater cortisol suppression after dexamethasone (P = 0.001). No difference in arterial blood pressure (P = 0.183) was observed after 3 mo of nCPAP therapy. Improvement in cortisol suppression was positively correlated with an improvement in apnea-hypopnea index during nCPAP therapy (r = 0.799, P = 0.010). In conclusion, men with OSAS present increased postdexamethasone cortisol levels and heart rate, which were recovered by nCPAP.