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Background: OSA is associated with metabolic syndrome (MS), but it is unclear whether OSA treatment with CPAP can revert MS., Research Question: Does OSA treatment with CPAP per se have effects on the MS reversibility and the associated metabolic, adiposity and vascular parameters?, Study Design and Methods: The TREATOSA-MS trial is a randomized placebo-controlled trial that enrolled adult patients with a recent diagnosis of MS and moderate or severe OSA (apnea-hypopnea index [AHI], ≥ 15 events/h) to undergo therapeutic CPAP or nasal dilator strips (placebo group) for 6 months. Before and after each intervention, we measured anthropometric variables, BP, glucose, and lipid profile. To control potential-related mechanisms and consequences, we also measured adiposity biomarkers (leptin and adiponectin), body composition, food intake, physical activity, subcutaneous and abdominal fat (visceral and hepatic fat), and endothelial function., Results: One hundred patients (79% men; mean age, 48 ± 9 years; BMI, 33 ± 4 kg/m 2 ; AHI, 58 ± 29 events/h) completed the study (n = 50 per group). The mean CPAP adherence was 5.5 ± 1.5 h/night. After 6 months, most patients with OSA randomized to CPAP retained the MS diagnosis, but the rate of MS reversibility was higher than observed in the placebo group (18% vs 4%; OR, 5.27; 95% CI, 1.27-35.86; P = .04). In the secondary analysis, CPAP did not promote significant reductions in the individual components of MS, weight, hepatic steatosis, lipid profile, adiponectin, and leptin, but did promote a very modest reduction in visceral fat and improved endothelial function (all analyses were adjusted for baseline values)., Interpretation: Despite the higher rate of MS reversibility after CPAP therapy as compared with placebo, most patients retained this diagnosis. The lack of significant or relevant effects on adiposity biomarkers and depots supports the modest role of OSA in modulating MS., Trial Registration: ClinicalTrials.gov; No.: NCT02295202; URL: www., Clinicaltrials: gov., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The metabolic syndrome (MetS) is an obesity-associated disorder of pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered neural autonomic regulation, are important components and drivers of pathogenesis. Galantamine, an acetylcholinesterase inhibitor and a cholinergic drug that is clinically-approved (for Alzheimer's disease) has been implicated in neural cholinergic regulation of inflammation in several conditions characterized with immune and metabolic derangements. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS. Trial Design and Methods: The effects of galantamine treatment, 8 mg daily for 4 weeks or placebo, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS ( n = 22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment. Results: Galantamine treatment significantly increased antioxidant enzyme activities, including SOD [+1.65 USOD/mg protein, [95% CI 0.39-2.92], P = 0.004] and CAT [+0.93 nmol/mg, [95% CI 0.34-1.51], P = 0.01], decreased lipid peroxidation [thiobarbituric acid reactive substances [log scale 0.72 pmol/mg, [95% CI 0.46-1.07], P = 0.05], and systemic nitrite levels [log scale 0.83 μmol/mg protein, [95% CI 0.57-1.20], P = 0.04] compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment. Conclusion: Low-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates neural autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with the cholinergic drug galantamine to ameliorate MetS., Competing Interests: VP and KT have published patents (US 8,865,641 B2 and US 8,003,632 B2) broadly relevant to this work and have assigned their rights to the Feinstein Institutes for Medical Research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sangaleti, Katayama, De Angelis, Lemos de Moraes, Araújo, Lopes, Camacho, Bortolotto, Michelini, Irigoyen, Olofsson, Barnaby, Tracey, Pavlov and Consolim Colombo.)

Objectives: The aim of this study was to determine if carvedilol improved structural and functional changes in the left ventricle and reduced mortality in patients with hypertensive heart disease., Methods: Blood pressure, heart rate, echocardiographic parameters, and laboratory variables, were assessed pre and post treatment with carvedilol in 98 eligible patients., Results: Carvedilol at a median dose of 50 mg/day during the treatment period in hypertensive heart disease lowered blood pressure 10/10 mmHg, heart rate 10 beats/min, improved left ventricular ejection fraction from baseline to follow-up (median: 6 years) (36%-47%)) and reduced left ventricular end-diastolic and end-systolic dimensions (62 vs 56 mm; 53 vs 42 mm, respectively, all p-values <0.01). Left ventricular ejection fraction increased in 69% of patients. Patients who did not have improved left ventricular ejection fraction had nearly six-fold higher mortality than those that improved (relative risk; 5.7, 95% confidence interval: 1.3-25, p = 0.022)., Conclusion: Carvedilol reduced cardiac dimensions and improved left ventricular ejection fraction and cardiac remodeling in patients with hypertensive heart disease. These treatment-related changes had a favorable effect on survival., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Untreated obstructive sleep apnea (OSA) is common in patients with hypertension and may impair blood pressure (BP) and target-organ damage responses to antihypertensive therapy. In this study, we recruited hypertensive patients who underwent treatment with a 30-day regimen of hydrochlorothiazide 25 mg plus enalapril (20 mg BID) or losartan (50 mg BID) and were assessed with a baseline clinical evaluation, polysomnography, 24-hour ambulatory BP monitoring, and carotid-femoral pulse wave velocity. All the examinations except for polysomnography were repeated at 6 and 18 months of follow-up. We studied 94 hypertensive patients (mean age, 55±9 years). The frequency of OSA was 55%. Compared with baseline, we did not observe significant differences between groups in 24-hour BP, daytime systolic and diastolic BPs, or night-time systolic BP at 6 and 18 months. The BP control rate at 24 hours (<130/80 mm Hg) was similar between the groups (baseline, 42.3% versus 45.2%; 6 months, 46.9% versus 57.5%; 18 months, 66.7% versus 61.5%). However, patients with OSA had higher night-time diastolic BP decrease than did the non-OSA group (6 months, -4.9±11.8 versus -0.3±10.3 mm Hg; 18 months, -6.7±11.1 versus -1.2±10.6 mm Hg; P =0.027). There were no differences in the number and class of antihypertensive medications prescribed during follow-up. In terms of arterial stiffness, patients with OSA had higher pulse wave velocity than did patients without OSA at baseline (10.3±1.9 versus 9.2±1.7 m/s; P =0.024), but both groups had similar decreases in pulse wave velocity during follow-up. In conclusion, with combined antihypertensive treatment aimed at controlling BP, hypertensive patients with OSA had similar 24-hour BP and arterial stiffness to those without OSA., (© 2018 American Heart Association, Inc.)

Background: Recent evidence suggests that obstructive sleep apnea (OSA) is common in patients with metabolic syndrome (MetS) and may contribute to metabolic deregulation, inflammation, and atherosclerosis in these patients. In clinical practice, however, OSA is frequently underdiagnosed. We sought to investigate the clinical predictors of OSA in patients with MetS., Methods: We studied consecutive patients newly diagnosed with MetS (Adult Treatment Panel-III). All participants underwent clinical evaluation, standard polysomnography, and laboratory measurements. We performed a logistic regression model, including the following variables: gender, age >50 years, neck and waist circumferences, hypertension, diabetes, body mass index (BMI) >30 kg/m 2 , high risk for OSA by Berlin questionnaire, presence of excessive daytime somnolence (Epworth Sleepiness Scale), abnormal serum glucose, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol., Results: We studied 197 patients (60% men; age: 49 ± 10 years; BMI: 32.9 ± 5.1 kg/m 2 ). OSA (defined by an apnea-hypopnea index ≥15 events per hour) was diagnosed in 117 patients [59%; 95% confidence interval (CI): 52-66]. In multivariate analysis, male gender [odds ratio (OR): 3.28; 95% CI: 1.68-6.41; P < 0.01], abnormal glucose levels (OR: 3.01; 95% CI: 1.50-6.03; P < 0.01), excessive daytime sleepiness (OR: 2.38; 95% CI: 1.13-5.04; P = 0.02), and high risk for OSA by Berlin questionnaire (OR: 4.33; 95% CI: 2.06-9.11; P < 0.001) were independently associated with OSA., Conclusions: Simple clinical and metabolic characteristics may help to improve the underdiagnosis of OSA in patients with MetS.

Whether sex influences the association of obstructive sleep apnea (OSA) with markers of cardiovascular risk in patients with hypertension is unknown. In this study, 95 hypertensive participants underwent carotid-femoral pulse wave velocity, 24-hour ambulatory blood pressure monitoring, echocardiogram, and polysomnography after a 30-day standardized treatment with hydrochlorothiazide plus enalapril or losartan. OSA was present in 52 patients. Compared with non-OSA patients, pulse wave velocity values were higher in the OSA group (men: 11.1±2.2 vs 12.7±2.4 m/s, P=.04; women: 11.8±2.4 vs 13.2±2.2 m/s, P=.03). The proportion of diastolic dysfunction was significant in men and women with OSA. Compared with non-OSA patients, nondipping systolic blood pressure in OSA was higher in men (14.3% vs 46.4%) and in women (41.4% vs 65.2%). OSA was independently associated with pulse wave velocity (β=1.050; P=.025) and nondipping systolic blood pressure (odds ratio, 3.03; 95% confidence interval, 1.08-8.55; P=.035) in the regression analysis. In conclusion, OSA is independently associated with arterial stiffness and nondipping blood pressure in patients with hypertension regardless of sex., (©2017 Wiley Periodicals, Inc.)

Background: Metabolic syndrome (MetS) is an obesity-driven condition of pandemic proportions that increases the risk of type 2 diabetes and cardiovascular disease. Pathophysiological mechanisms are poorly understood, though inflammation has been implicated in MetS pathogenesis. The aim of this study was to assess the effects of galantamine, a centrally acting acetylcholinesterase inhibitor with antiinflammatory properties, on markers of inflammation implicated in insulin resistance and cardiovascular risk, and other metabolic and cardiovascular indices in subjects with MetS., Methods: In this randomized, double-blind, placebo-controlled trial, subjects with MetS (30 per group) received oral galantamine 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo. The primary outcome was inflammation assessed through plasma levels of cytokines and adipokines associated with MetS. Secondary endpoints included body weight, fat tissue depots, plasma glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol (total, HDL, LDL), triglycerides, BP, heart rate, and heart rate variability (HRV)., Results: Galantamine resulted in lower plasma levels of proinflammatory molecules TNF (-2.57 pg/ml [95% CI -4.96 to -0.19]; P = 0.035) and leptin (-12.02 ng/ml [95% CI -17.71 to -6.33]; P < 0.0001), and higher levels of the antiinflammatory molecules adiponectin (2.71 μg/ml [95% CI 1.93 to 3.49]; P < 0.0001) and IL-10 (1.32 pg/ml, [95% CI 0.29 to 2.38]; P = 0.002) as compared with placebo. Galantamine also significantly lowered plasma insulin and HOMA-IR values, and altered HRV., Conclusion: Low-dose galantamine alleviates inflammation and insulin resistance in MetS subjects. These findings support further study of galantamine in MetS therapy., Trial Registration: ClinicalTrials.gov, number NCT02283242., Funding: Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, and the NIH.

Young adult offspring of hypertensive parents (pHTN⊕) are a good model for assessing abnormalities of anthropometric, cardiometabolic, and autonomic variables prior to clinical hypertension. The objectives of this study were to determine whether these variables and autonomic responses to oral carbohydrates were altered in offspring of pHTN⊕. Two hundred consecutive patients, including 100 pHTN⊕, were evaluated, with 29 patients, including 14 pHTN⊕, given a 70-gram carbohydrate load. The pHTN⊕ group had higher blood pressure, pulse pressure, abdominal circumference (AC), weight, body mass index, and basal metabolic rate than offspring of normotensive parents (pHTN∅). At baseline, the low-frequency (LF, sympathetic) to high-frequency (HF, parasympathetic) ratio, assessed by spectral analysis of heart rate variability, was similar in both groups. After the carbohydrate load, the LF/HF ratio was greater in offspring of pHTN⊕. pHTN⊕ individuals have abnormalities of anthropometric and hemodynamic variables at baseline and autonomic responses to oral carbohydrates before developing hypertension., (© 2016 Wiley Periodicals, Inc.)

The association of anthropometric (waist circumference) and hemodynamic (blood pressure) changes with abnormalities in glucose and lipid metabolism has been motivation for a lot of discussions in the last 30 years. Nowadays, blood pressure, body mass index/abdominal circumference, glycemia, triglyceridemia, and HDL-cholesterol concentrations are considered in the definition of Metabolic syndrome, referred as Visceral adiposity syndrome (VAS) in the present review. However, more than 250 years ago an association between visceral and mediastinal obesity with hypertension, gout, and obstructive apnea had already been recognized. Expansion of visceral adipose tissue secondary to chronic over-consumption of calories stimulates the recruitment of macrophages, which assume an inflammatory phenotype and produce cytokines that directly interfere with insulin signaling, resulting in insulin resistance. In turn, insulin resistance (IR) manifests itself in various tissues, contributing to the overall phenotype of VAS. For example, in white adipose tissue, IR results in lipolysis, increased free fatty acids release and worsening of inflammation, since fatty acids can bind to Toll-like receptors. In the liver, IR results in increased hepatic glucose production, contributing to hyperglycemia; in the vascular endothelium and kidney, IR results in vasoconstriction, sodium retention and, consequently, arterial hypertension. Other players have been recognized in the development of VAS, such as genetic predisposition, epigenetic factors associated with exposure to an unfavourable intrauterine environment and the gut microbiota. More recently, experimental and clinical studies have shown the autonomic nervous system participates in modulating visceral adipose tissue. The sympathetic nervous system is related to adipose tissue function and differentiation through beta1, beta2, beta3, alpha1, and alpha2 adrenergic receptors. The relation is bidirectional: sympathetic denervation of adipose tissue blocks lipolysis to a variety of lipolytic stimuli and adipose tissue send inputs to the brain. An imbalance of sympathetic/parasympathetic and alpha2 adrenergic/beta3 receptor is related to visceral adipose tissue storage and insulin sensitivity. Thus, in addition to the well-known factors classically associated with VAS, abnormal autonomic activity also emerges as an important factor regulating white adipose tissue, which highlights complex role of adipose tissue in the VAS.

Background: Adipocyte-derived factors and regulators likely contribute to the metabolic syndrome (MetS) in patients with central obesity. This study was undertaken to assess the contribution of leptin, adiponectin, and acylation stimulating protein (ASP-C3ades/ARG) to hemodynamic (blood pressure [BP]) and metabolic (insulin, glucose, lipids) features of MetS., Methods: In this study, leptin, adiponectin, and C3ades/ARG were measured at baseline and in response to an infusion of Intralipid(®) and heparin in 12 lean healthy controls and 12 patients with MetS., Results: Baseline plasma leptin (27.6 ± 6.2 vs. 10.9 ± 3.8 ng/mL, p < 0.01) and plasma C3ades/ARG (273 ± 79 vs 198 ± 57 mg/dL, p < 0.05) were higher in the MetS than control group, whereas baseline plasma adiponectin was higher in the control than MetS group (9.9 ± 1.9 vs. 5.4 ± 0.6 g/mL). Plasma leptin correlated with body mass index (BMI), systolic and diastolic BP (r = 0.53-0.77, p < 0.01). Conversely, adiponectin correlated inversely with insulin, glucose, waist circumference, and insulin sensitivity (r = 0.48-0.51, p ≤ 0.02). Plasma triglycerides increased similarly in MetS and control groups after 4-hours of Intralipid and heparin. C3ades/ARG increased only in lean volunteers. The decrease in triglycerides 1-hour post-infusion was lower in the MetS than control group (-116 ± 33 vs. -282 ± 81 mg/dL, p = 0.01) and correlated inversely with the change in C3ades/ARG., Conclusion: These data suggest that leptin is more closely associated with hemodynamic (BP) aspects of MetS, whereas adiponectin and C3ades/ARG are more closely associated with metabolic components.

Objectives: We explored whether high blood pressure is associated with metabolic, inflammatory and prothrombotic dysregulation in patients with metabolic syndrome., Methods: We evaluated 135 consecutive overweight/obese patients. From this group, we selected 75 patients who were not under the regular use of medications for metabolic syndrome as defined by the current Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults criteria. The patients were divided into metabolic syndrome with and without high blood pressure criteria (≥130/≥85 mmHg)., Results: Compared to the 45 metabolic syndrome patients without high blood pressure, the 30 patients with metabolic syndrome and high blood pressure had significantly higher glucose, insulin, homeostasis model assessment insulin resistance index, total cholesterol, low-density lipoprotein-cholesterol, triglycerides, uric acid and creatinine values; in contrast, these patients had significantly lower high-density lipoprotein-cholesterol values. Metabolic syndrome patients with high blood pressure also had significantly higher levels of retinol-binding protein 4, plasminogen activator inhibitor 1, interleukin 6 and monocyte chemoattractant protein 1 and lower levels of adiponectin. Moreover, patients with metabolic syndrome and high blood pressure had increased surrogate markers of sympathetic activity and decreased baroreflex sensitivity. Logistic regression analysis showed that high-density lipoprotein, retinol-binding protein 4 and plasminogen activator inhibitor-1 levels were independently associated with metabolic syndrome patients with high blood pressure. There is a strong trend for an independent association between metabolic syndrome patients with high blood pressure and glucose levels., Conclusions: High blood pressure, which may be related to the autonomic dysfunction, is associated with metabolic, inflammatory and prothrombotic dysregulation in patients with metabolic syndrome.

Background: Obstructive Sleep Apnea (OSA) is tightly linked to some components of Metabolic Syndrome (MetS). However, most of the evidence evaluated individual components of the MetS or patients with a diagnosis of OSA that were referred for sleep studies due to sleep complaints. Therefore, it is not clear whether OSA exacerbates the metabolic abnormalities in a representative sample of patients with MetS., Methodology/principal Findings: We studied 152 consecutive patients (age 48+/-9 years, body mass index 32.3+/-3.4 Kg/m2) newly diagnosed with MetS (Adult Treatment Panel III). All participants underwent standard polysomnography irrespective of sleep complaints, and laboratory measurements (glucose, lipid profile, uric acid and C-reactive protein). The prevalence of OSA (apnea-hypopnea index>or=15 events per hour of sleep) was 60.5%. Patients with OSA exhibited significantly higher levels of blood pressure, glucose, triglycerides, cholesterol, LDL, cholesterol/HDL ratio, triglycerides/HDL ratio, uric acid and C-reactive protein than patients without OSA. OSA was independently associated with 2 MetS criteria: triglycerides: OR: 3.26 (1.47-7.21) and glucose: OR: 2.31 (1.12-4.80). OSA was also independently associated with increased cholesterol/HDL ratio: OR: 2.38 (1.08-5.24), uric acid: OR: 4.19 (1.70-10.35) and C-reactive protein: OR: 6.10 (2.64-14.11). Indices of sleep apnea severity, apnea-hypopnea index and minimum oxygen saturation, were independently associated with increased levels of triglycerides, glucose as well as cholesterol/HDL ratio, uric acid and C-reactive protein. Excessive daytime sleepiness had no effect on the metabolic and inflammatory parameters., Conclusions/significance: Unrecognized OSA is common in consecutive patients with MetS. OSA may contribute to metabolic dysregulation and systemic inflammation in patients with MetS, regardless of symptoms of daytime sleepiness.

Obstructive sleep apnea (OSA) and the metabolic syndrome (MS) are independently associated with increased cardiovascular risk. The objective of the present study was to determine the prevalence of OSA among consecutive patients with MS and to determine whether OSA is associated with impaired glycemic control. Fifty consecutive patients with a recent diagnosis of MS and no previous diagnosis of OSA underwent a polysomnography and anthropometric and laboratory measurements. The prevalence of OSA (apnea-hypopnea index >or=15 events per hour of sleep) was 68% and in the same range of all other individual components of MS. Moreover, OSA was associated with increased levels of glucose (P=.03) and glycosylated hemoglobin (P=.03) but not with body mass index (P=.30). Glycosylated hemoglobin was independently associated with glucose (P<.001) and apnea-hypopnea index (P=.03). The prevalence of OSA is in the same range as all the individual components of MS and is independently associated with impaired glycemic control.

Endothelium may be damaged, especially at the coronary microcirculation, in animal models of Chagas' disease by several mechanisms. Endothelial dysfunction has been reported in chronic Chagas' heart disease patients with heart failure. Nevertheless, peripheral endothelial function has never been studied in patients with Chagas' heart disease without heart failure and other conditions that could per se alter the endothelial function. Endothelial function was evaluated in 9 patients with Chagas' heart disease (44.8 +/- 1.5 years, 5 females, left ventricular ejection fraction > or = 60%) and 10 healthy matched controls (38.6 +/- 5.5 years, 5 females). Extreme caution was exercised to select patients with no other conditions that could per se alter the endothelial function. Forearm blood flow was measured at baseline and during intra-brachial artery infusion of crescent doses of acetylcholine (0.75, 5, and 15 microg/100 mL tissue/min) and nitroprusside (1, 2, and 4 microg/ 100 mL tissue/min), an endothelium-dependent and an endothelium-independent vasoactive drug, respectively. At baseline, blood pressure and heart rate (continuously recorded with Finapress) and the forearm blood flow were similar in both groups. Acetylcholine (ACh) and sodium nitroprusside (SNP) caused significant and similar dose-dependent increases in forearm blood flow of all subjects: maximum ACh response of 24.8 versus 23.7, and maximum SNP response 24.4 versus 23.7 mL/100 mL tissue/min, respectively, for control and chagasic Groups. No significant systemic hemodynamic changes were observed during the intra-arterial infusion of the drugs. The authors conclude that the peripheral endothelial function is preserved in Chagas' heart disease patients without heart failure.

Oxidative stress emerges as a potential factor in the pathogenesis of hypertension and a common signal transduction mechanism by which various risk factors mediate cardiovascular and renal disease. A greater level of oxidative stress could contribute to higher rates of hypertension and related cardiovascular and renal complications in African Americans than in white Americans. The objective of this study was to compare oxidative stress induced by a standardized episode of acute hyperlipidemia in the two groups. Fifteen African Americans (37 +/- 1 years, 9 women/6 men, body mass index 30 +/- 2 kg/m(2)) and 15 whites (38 +/- 2 years, 9 women/6 men, body mass index 27 +/- 1 kg/m(2)) were evaluated. Acute hyperlipidemia was induced by a 4-h long infusion of Intralipid and heparin. Blood samples were drawn at baseline and after 2 and 4 h of acute hyperlipidemia for nonesterified fatty acids, triglycerides, and F2-isoprostanes, a biomarker of oxidative stress. Plasma nonesterified fatty acids and triglycerides increased significantly and similarly in African Americans and whites after 2 and 4 h of the Intralipid and heparin infusion. Although baseline plasma F2-isoprostanes did not differ between groups, F2-isoprostanes increased more in African Americans than in whites at 2 h (12.2 +/- 2.6 v 5.0 +/- 2.9 pg/mL, P <.05) and 4 h (13.9 +/- 3.1 v 3.0 +/- 3.0 pg/mL, P <.05) of acute hyperlipidemia. The results indicate that acute hyperlipidemia increases F2-isoprostanes more in African Americans than in whites. The findings may have important implications for ethnic differences in the prevalence of hypertension and cardiovascular and renal disease.

Evidence suggests that obesity may raise blood pressure (BP) through oxidative stress-sensitive mechanisms and that the Dietary Approaches to Stop Hypertension combination diet (DASH-CD) may decrease BP by enhancing antioxidant capacity. To address this question, 12 obese patients with high-normal-to-stage 1 hypertension (hypertensives) and 12 lean normotensives were studied on their usual diets and after following the DASH-CD and a low-antioxidant diet in random sequence for 4 weeks each. Acute oxidative stress was induced by a 4-hour infusion of intralipid and heparin. Ferric-reducing activity of plasma (FRAP) and plasma F2-isoprostanes were measured as biomarkers of antioxidant capacity and oxidative stress, respectively. BP was lower in obese hypertensives on the DASH-CD than on the usual and low-antioxidant diets (-8.1+/-1.5/-7.4+/-1.6 mm Hg, P<0.05). BP did not change significantly in lean normotensives after 4 weeks on the DASH-CD but tended to rise on the low-antioxidant diet. FRAP on usual diets was higher in lean subjects than in obese subjects. FRAP increased in obese but not lean volunteers on the DASH-CD compared with usual diet, and the group difference disappeared. F2-isoprostanes increased from baseline during intralipid and heparin in both groups on the low-antioxidant diet but not in obese hypertensives on the DASH-CD. Among free-living obese hypertensives, the DASH-CD raises antioxidant capacity, lowers BP, and reduces oxidative stress induced by acute hyperlipidemia. The findings are consistent with evidence that elevated BP in obese subjects may reflect an imbalance between antioxidant capacity and oxidative stress that is improved by the DASH-CD.

Objective: To determine whether raised concentrations of non-esterified fatty acids (NEFAs) may contribute to the cardiovascular risk factor cluster by increasing oxidative stress in vivo., Design and Methods: Plasma and urine F2-isoprostanes, biomarkers of oxidative stress, were measured after an overnight fast and during a 4 h infusion of Intralipid and heparin to increase NEFAs in 10 obese hypertensive patients with and 12 healthy normotensive individuals without evidence of insulin resistance. A time-control group of nine healthy normotensive individuals received saline and heparin., Results: Plasma F2-isoprostanes increased more in obese hypertensive individuals than in lean normotensive individuals after 2 h (14.9 +/- 2.8 ng/ml compared with 4.6 +/- 2.8 ng/ml; P < 0.05) but not after 4 h (10.3 +/- 2.5 ng/ml compared with 8.1 +/- 4.1 ng/ml; NS) of the Intralipid and heparin infusion. When obese and lean individuals were combined, plasma (+9.1 +/- 2.5 ng/ml; P < 0.05) and urine (+0.7 +/- 0.3 ng/mg creatinine; P < 0.05) F2-isoprostanes increased by about 20% after 4 h of Intralipid and heparin, whereas plasma F2-isoprostanes decreased by approximately 20% (-9.7 +/- 4.5 ng/ml; P < 0.05) after 4 h of saline and heparin. When individuals from both infusions were combined, the correlation between changes in plasma NEFAs and F2-isoprostanes after 4 h persisted after controlling for changes in triglyceride concentrations (partial r = 0.49; P < 0.01), whereas the correlation between changes in triglycerides and F2-isoprostanes did not persist after controlling for changes in NEFA concentrations (partial r = 0.33, NS)., Conclusions: The findings indicate that an acute increase in plasma lipids increases the concentration of F2-isoprostanes, biomarkers of oxidative stress, especially in obese hypertensive individuals. The observations raise the possibility that increased concentrations of NEFAs contribute to the cardiovascular risk factor cluster through oxidative-stress-sensitive mechanisms.