Obese Normotensives Research Articles

Effect of obesity and hypertension on left ventricular geometry and function among asymptomatic Indian adults.

Hypertension & obesity are important independent predictors of cardiovascular morbidity & mortality specifically left ventricular (LV) functions. With the Objectives to examine the effect of obesity & hypertension on echocardiographic parameters of geometry, systolic, and diastolic functions of left ventricle in asymptomatic adults the cross-sectional study was conducted with 100 individuals (60 male & 40 female). Their Blood Pressure & Body Mass Index was recorded following which they were divided into obese normotensives & non-obese hypertensive. Echocardiographic parameters indicating LV geometry and function were recorded. Data was statistically analysed with Unpaired t test considering p value <0.05 as significant. LV geometry and LV systolic function parameters were significantly altered in non-obese hypertensive. Parameters of LV diastolic functions were affected in obese normotensives. 54% of obese normotensives had LV diastolic dysfunction & 58% of non-obese hypertensive had LV diastolic dysfunction. 2% of obese non-hypertensive individuals had LV systolic dysfunction & 6% of non-obese hypertensive had LV diastolic dysfunction. Hypertension significantly affects LV geometry, LV systolic and diastolic function. Obesity affects LV geometry & diastolic functions of LV even in individuals with preserved systolic function.

High molecular weight adiponectin as a biomarker of hypertension in children and adolescents with obesity.

Lower HMW (high molecular weight) adiponectin levels are associated with obesity, insulin resistance, and metabolic syndrome in children and adolescents. However, data on HMW levels in pediatric population with hypertension are lacking. This study aimed to examine the association and predictive capacity of HMW levels, HMW/HOMA-IR, and HMW/APN ratio with hypertension in obese children and adolescents. The 299 pediatric subjects were grouped in obese hypertensive (OH), obese normotensive (ON), and normal weight normotensive (NN). Plasma concentrations of HMW were investigated by ELISA. ANOVA was used to compare study groups, and a binary logistic regression analysis was used to verify if HMW, HMW/HOMA-IR, HMW/APN, APN, APN/HOMA-IR, and HOMA-IR are associated to hypertension regardless obesity in children and adolescents. To compare the strength and performance of each biomarker to classify individuals with and without hypertension, the receiver-operating characteristic (ROC) curve, area under the curve (AUC), and Youden index (J) were evaluated. Both HMW plasma levels and the HMW/HOMA-IR ratio were significantly lower in the OH group when compared to the ON group (HMW: 2.00 ± 1.33µg/mL vs 2.48 ± 1.48µg/mL; HMW/HOMA-IR ratio: 0.87 ± 0.95 vs 1.27 ± 1.2; P < 0.05) and NN weight groups (HMW: 2.00 ± 1.33µg/mL vs 4.02 ± 1.99µg/mL; HMW/HOMA-IR ratio: 0.87 ± 0.95 vs 2.62 ± 1.86; P < 0.05). Hypertension was associated with lowest HMW (OR = 4.50; 95% CI = 1.41-15.84) and HMW/HOMA-IR (OR = 12.13; 95% CI = 2.51-92.93) regardless of obesity. However, HOMA-IR or the HMW/APN was not significant (P > 0.05). In the ROC curve analyses, the HMW and HMW/HOM-IR were more sensitive to detect hypertension in children and adolescents with obesity. Conclusion: Low levels of HMW oligomer and HMW/HOM-IR are associated with hypertension in childhood obesity. Thus, these biomarkers could be clinically useful in identifying hypertension in childhood obesity. What is Known: • HMW has previously been reported as the most biologically active isoform of adiponectin, and lower HMW concentrations are associated with obesity, insulin resistance, and metabolic syndrome in children and adolescents. • HMW/HOMA-IR ratio is a sensitive predictor for metabolic syndrome in adults. What is New: • HMW levels are associated with hypertension in children and adolescents, independently of presence of obesity. • HMW was more sensitive to detect hypertension in children and adolescents with obesity when compared to HMW/HOMA-IR, HMW/APN, APN, APN/HOMA-IR, or HOMA-IR.

Impact of obesity with or without hypertension on systemic haemodynamic and renal responses to lower body negative pressure

Purpose Sodium and water handling by the kidney and the sympathetic nervous system have been implicated in the development of obesity-related hypertension and kidney disease. They have seldom been studied together during stress conditions. The objective of this study was to compare the systemic, renal and hormonal responses to lower body negative pressure (LBNP) in adult healthy participants (H), obese normotensive (OBN) and obese hypertensive patients (OBH). Materials and methods This was a prospective case-control study. Participants from the three groups were exposed to one hour of LBNP. Systemic and renal haemodynamics, sodium and water excretion and hormones were measured before and after LBNP. Intergroup LBNP responses were tested using a Student t-test or a Wilcoxon rank-sum test. An extension of the Wilcoxon rank-sum test was used to test for a trend across the three groups. Results The study included 54 participants (H: 25, OBN: 16, OBH: 13). LBNP induced a stepwise increase in systolic blood pressure (+2.7 ± 4.7 mmHg (H) vs. +4.7 ± 8.8 mmHg (OBN) vs. +8.0 ± 8.6 mmHg (OBH, p = .028)) and heart rate (−1.3 ± 4.9 bpm (H) vs. 2.2 ± 6.1 bpm (OBN) vs. 1.9 ± 4.1 bpm (OBH, p = .041). Urinary output (−2.8 ± 2.1 ml/min vs. −1.4 ± 1.7 ml/min, p = .028) and free water clearance (−1.9 ± 1.7 mOsm/kg vs. −0.7 ± 1.3 mOsm/kg, p = .016) responses were more marked in OBN compared to H. Conclusions These results show that the systemic and the renal response to LBNP differ according to weight and to BP categories. Systolic BP and heart show a progressive increased response form healthy volunteers to OBN and then to obese hypertensive participants while urinary output and free water clearance responses are increased in OBN only, suggesting that the occurrence of hypertension in obese individuals modifies the early kidney responses to stress. ClinicalTrial.gov Identifier NCT01734096

PP.34.01] NECK CIRCUMFERENCE AND WAIST-HIP RATIO, INDEPENDENTLY OF BODY MASS INDEX, ARE MORE RELATED WITH MASKED HYPERTENSION IN OBESE NORMOTENSIVE INDIVIDUALS WITH OBSTRUCTIVE SLEEP APNEA

Objective: Obesity has been associated to development of sleep obstructive apnea (SOA). At same token, SOA is recognized as secondary cause of arterial hypertension (AH). The aim of this study was to evaluate antropometric parameters and ambulatory blood pressure associated to SOA in obese normotensive subjects. Design and method: Obese normotensive (ON) subjects were enrolled in a cross-sectional study. Based on apnea-hypopnea index (AHI) obtained with Watch-PAT200, a home device for sleep study, patients were divided into the group with absent/mild OSA (Group 1, AHI = 15). All patients were submitted to clinical evaluation and 24-h ambulatory blood pressure monitoring with SpaceLabs 90207. Results: We studied 81 ON, 21 men and 61 women, mean age 42 ± 6 yo. ON were divided in 2 groups (G) by apnea-hypopnea index (AHI), G1 = 15/h (n = 26). Anthropometrics data: body mass index (BMI) (G1 = 33.9 ± 3.2 vs G2 = 33.8 ± 2.9 Kg/m2 p = 0.855), neck circumference (NC) (G1 = 38.0 cm ± 3.3 vs 40.5 ± 3.2 cm p = 0.001) and waist-hip ratio (WHR) (G1 = 0.89 ± 0.01 vs G2 = 0.94 ± 0.01 p = 0.003). Office Systolic (SBP) and Diastolic (DBP) blood pressure were similar (G1 = 121 ± 8 vs G2 = 123 ± 8 mmHg and G1 = 79 ± 8 vs G2 = 77 ± 8 mmHg, p = 0.32). Daytime SBP (G1 = 120 ± 8 vs G2 = 126 ± 6 mmHg, p = 0.037), nighttime SBP (110 ± 10 vs 115 ± 7 mmHg, p = 0.036), daytime DBP (76 ± 7.6 vs 81 ± 8. 5 mmHg p = 0.025) nighttime DBP (66 ± 8 vs 70 ± 7 mmHg p = 0.02) and G2 presented greater nocturne DBP load (45 vs 31%, p = 0.041). In this Obese Normotensive population, AHI presented positive correlation with NC (r = 0.42, p Conclusions: In this group of obese normotensive individuals, neck circumference and waist-hip ratio were the factors more associated with the presence of sleep obstructive apnea and masked hypertension, independently of body mass index. These findings suggest that obese normotensive subjects with increased neck circumference should be evaluated with ABPM and sleep study.

Effects of Dietary l-Arginine on Nitric Oxide Bioavailability in Obese Normotensive and Obese Hypertensive Subjects.

Obesity related hypertension is a major risk factor for resistant hypertension. We do not completely understand the mechanism(s) underlying the development of obesity related hypertension which hinders the development of novel treatment strategies for this condition. Data from experimental studies and small clinical trials indicate that transport of l-arginine, the substrate for nitric oxide (NO), and subsequent NO production are reduced in obesity induced hypertension. Reduced NO bioavailability can induce hypertension via multiple mechanisms. Mirmiran et al. recently analyzed data from a large population study and found that the association between dietary l-arginine and serum nitrate and nitrite was weakened in obese hypertensive subjects compared to obese normotensives. These data suggest that l-arginine dependent NO production is impaired in the former group compared to the latter which may represent a novel mechanism contributing to hypertension in the setting of obesity.

Effect of plasma NOx values on cardiac function in obese hypertensive and normotensive pediatric patients.

Hypertension (HT) is a major comorbidity of obesity that is associated with an increased risk of cardiovascular disease and higher mortality. The aim of our study was to evaluate cardiac function in obese hypertensive (OHT) and obese normotensive (ONT) pediatric patients and determine the effects of plasma nitric oxide (NOx) values on cardiac function, while demonstrating the role of plasma NOx in HT in obese pediatric patients. The study population consisted of 62 patients (27 boys, 35 girls), aged 13-18years and 21 age-matched healthy controls. All subjects enrolled in the study underwent echocardiography (Echo) evaluation and ambulatory blood pressure monitoring for HT. Plasma NOx and biochemical values were studied in both patient groups separately. Plasma NOx levels were found to be lower in the OHT group than in the ONT and control groups (p < 0.001) and to be negatively correlated with left ventricular mass index values (p < 0.05). Both the OHT and ONT groups had concentric hypertrophy of the heart. Plasma NOx plays an essential role in obesity-induced HT. Concentric hypertrophy of the left ventricle was found in both the OHT and ONT groups, indicating structural deformation of the heart.

Augmented endothelial-specific L-arginine transport prevents obesity-induced hypertension.

Hypertension is a major clinical complication of obesity. Our previous studies show that abnormal uptake of the nitric oxide precursor L-arginine, via the cationic amino acid transporter-1 (CAT1), contributes to endothelial dysfunction in cardiovascular disease. In this study, we tested the hypothesis that abnormal L-arginine transport may be a key mediator of obesity-induced hypertension. Mean arterial pressure (MAP) was monitored by telemetry in conscious wild-type (WT; n=13) mice, and transgenic mice with endothelial-specific overexpression of CAT1 (CAT+; n=14) fed a normal or a high fat diet for 20weeks. Renal angiotensin II (Ang II), CAT1 mRNA and plasma nitrate/nitrite levels were then quantified. In conjunction, plasma nitrate/nitrite levels were assessed in obese normotensive (n=15) and obese hypertensive subjects (n=15). Both genotypes of mice developed obesity when fed a high fat diet (P≤0.002). Fat fed WT mice had 13% greater MAP and 78% greater renal Ang II content, 42% lesser renal CAT1 mRNA levels and 42% lesser plasma nitrate/nitrite levels, than WT mice fed a normal fat diet (P≤0.02). In contrast, none of these variables were significantly altered by high fat feeding in CAT+ mice (P≥0.36). Plasma nitrate/nitrite levels were 17% less in obese hypertensives compared with obese normotensives (P=0.02). Collectively, these data indicate that obesity-induced down-regulation of CAT1 expression and subsequent reduced bioavailability of nitric oxide may contribute to the development of obesity-induced hypertension.

Community collaboration improves blood pressure control by 13.5% in a medium-sized metropolitan area

The purpose of this study was to compare CPP (a surrogate for aortic elasticity) in a population of 59 obese pts whose BMI was >30kg/sqm. These pts were divided into hypertensive obese (HTNO) 35 pts and normotensive obese (NTO) 24 pts. Both groups were also divided according to age to the following groups: 30-39, 40-49, 50-59, and over 60 years of age. We also compared both groups, to a group of 100 volunteers (Control group, CTRL) that were normotensive and nonobese. CPP was determined using the Sphygmocor System. The mean CPP for HTNO pts was 48.8 15 mmHg. Mean CPP for NTO pts was 45.5 13 mmHg. Mean CPP for CTRL pts was 44.0 7.7 mmHg. The mean CPP difference between HTNO pts and CTRL pts was significant with a p 1⁄4 0.03; the mean CPP difference between NTO pts and CTRL pts was nonsignificant with a p 1⁄4 0.198. These results are shown graphically in figure #1. We conclude that even in a small population of HTNO and NTO pts, CPP was able to show a significant difference between HTNO compared to CTRL. This finding may suggest that hypertensive obese pts may have a higher vascular risk than NTO because of impaired aortic elasticity. Our preliminary finding should be confirmed by studying a larger population of obese pts and including pulse wave velocity.

Central pulse pressure (CPP) in obese hypertensive and obese normotensive patients

The purpose of this study was to compare CPP (a surrogate for aortic elasticity) in a population of 59 obese pts whose BMI was >30kg/sqm. These pts were divided into hypertensive obese (HTNO) 35 pts and normotensive obese (NTO) 24 pts. Both groups were also divided according to age to the following groups: 30-39, 40-49, 50-59, and over 60 years of age. We also compared both groups, to a group of 100 volunteers (Control group, CTRL) that were normotensive and nonobese. CPP was determined using the Sphygmocor System. The mean CPP for HTNO pts was 48.8 15 mmHg. Mean CPP for NTO pts was 45.5 13 mmHg. Mean CPP for CTRL pts was 44.0 7.7 mmHg. The mean CPP difference between HTNO pts and CTRL pts was significant with a p 1⁄4 0.03; the mean CPP difference between NTO pts and CTRL pts was nonsignificant with a p 1⁄4 0.198. These results are shown graphically in figure #1. We conclude that even in a small population of HTNO and NTO pts, CPP was able to show a significant difference between HTNO compared to CTRL. This finding may suggest that hypertensive obese pts may have a higher vascular risk than NTO because of impaired aortic elasticity. Our preliminary finding should be confirmed by studying a larger population of obese pts and including pulse wave velocity.

Abstract P209: Which Comes First, Type 2 Diabetes (T2DM) or Hypertension?

Objectives: It is well demonstrated that there is a higher prevalence of hypertension (HT) in patients with type 2 diabetes (T2DM) than non-DM individuals as well as higher prevalence of DM in HT than normotensives (NT). However, it has not been clarified which of DM or HT leads to other, and what mechanisms may play a major role. Methods: In the present study, we compared neurohormonal parameters in the following 4 groups in weight loss (WL) program with a mild calorie restriction and exercise over 12 weeks; 53 obese NT without DM, 44 NT with T2DM, 68 HT without DM, and 43 HT with T2DM. HT and T2DM were all diagnosed in the last 3 months and none had medications. At entry period, the 4 groups were strictly matched in BMI and in BP. They were measured BMI, total body fat-mass, waist/hip ratio (W/H), BP, PR, HbA 1c , fasting glucose, insulin (HOMA-IR), norepinephrine (NE) and leptin (LEP) at entry, 4 and 12 weeks. Results: At entry, fat-mass was greater in subjects with T2DM than non-DM in both NT and HT and HT had slightly greater fat-mass than NT, although BMI were strictly matched in the 4 study groups. HbA 1c in T2DM was greater than non-DM, and slightly greater in HT than NT. Fasting insulin was greater in HT and T2DM than NT or non-DM, and HOMA-IR was slightly greater in HT than NT and significantly greater in T2DM than non-DM. LEP was similar between NT and HT, but it was greater in T2DM than non-DM. (HbA 1c , HT with T2DM&gt;NT with T2DM&gt;&gt;HT without DM&gt;NT without DM; Insulin, HT with T2DM&gt;NT with T2DM&gt;&gt;HT without DM&gt;NT without DM; NE, HT with T2DM&gt;&gt;HT without DM≥NT with T2DM&gt;&gt;NT without DM; LEP, HT with T2DM≈NT with T2DM&gt;&gt;HT without DM&gt;NT without DM). WL over 12 wks in HT and T2DM were smaller than those in NT or non-DM. At 12 weeks, in HT groups regardless of T2DM, percent (%) decreases in plasma NE and BP, and reductions in HbA 1c were smaller than those in NT groups, although reductions in fat-mass and leptin were similar. In T2DM groups regardless of BP levels at entry, reductions in BMI, BP, HbA 1c , HOMA-IR and NE were smaller than those in non-DM group. In the 4 groups, reductions in plasma NE was observed at first followed by reductions in HOMA-IR, HbA 1c, BMI and BP over 12 weeks. Conclusions: These findings demonstrate that insulin resistance (IR) may play an important role on the onset of T2DM and high plasma NE appears to cause HT. HT had resistance to normalized high plasma NE and %reductions in NE, and T2DM had resistance to normalize IR and sympathetic overactivity. We previously reported that high plasma NE could predict future weight gain and BP elevation, and high NE preceded IR in non-obese subjects. Taken together, sympathetic overactivity observed in high NE may cause obesity and HT, and then IR seems to start with weight gain leading T2DM, suggesting that HT may lead to T2DM with this mechanisms.

Obese Hypertensive Men Have Plasma Concentrations of C-Reactive Protein Similar to That of Obese Normotensive Men

Low-grade chronic inflammation is a characteristic feature of obesity, the most important lifestyle risk factor for hypertension. Elevated plasma concentrations of the inflammatory biomarker C-reactive protein (CRP) are associated with an increased risk of hypertension, but elevated plasma CRP concentrations are also closely associated with obesity. It is uncertain whether CRP is directly involved in the pathogenesis of hypertension or is only a marker of other pathogenic processes closely related to obesity. We studied 103 obese men (body mass index (BMI) ≥ 30.0 kg/m(2)); 63 of these men had 24-hour ambulatory blood pressure (ABP) ≥ 130/80 mm Hg and comprised the obese hypertensive (OHT) group. The 40 remaining obese men had 24-hour ABP < 130/80 mm Hg and comprised the obese normotensive (ONT) group. Our control group comprised 27 lean normotensive (LNT) men. All participants were medication-free. We measured plasma CRP concentrations with a high-sensitivity assay and determined body composition by dual energy x-ray absorptiometry scanning. There were no differences in anthropometric measures (BMI, waist circumference, or total fat mass percentage) between OHT and ONT groups (P ≥ 0.08). The obese groups had higher CRP concentrations than the LNT group (OHT: median = 2.30, interquartile range (IQR) = 1.10-4.10mg/L; ONT: median = 2.55, IQR = 1.25-4.80 mg/L; LNT: median = 0.60, IQR = 0.30-1.00 mg/L; P < 0.001), but there was no difference in CRP concentrations between OHT and ONT groups (P = 1.00). In the obese men, CRP was not correlated with either 24-hour systolic (r = 0.04; P = 0.71) or 24-hour diastolic ABP (r = -0.03; P = 0.78). Obese hypertensive men, matched for anthropometric measurements, have plasma CRP concentrations similar to those of obese normotensive men.

The Relationship between Serum Leptin and Blood Pressure in Obese and Non Obese Male Subjects

Objectives: To clarify the relationship between serum leptin level and arterial bloodpressure (ABP) and lipid profile in obese and non-obese male subjects. Methods: Thepresent study was performed in Beni Suef University, Faculty of medicine betweenDecember 2007 and December 2008. Fasting serum leptin level, arterial bloodpressure, lipid profile, waist circumference (WC) and body mass index (BMI) weremeasured in 10 lean normotensive (LN), 10 obese normotensive (ON), 10 leanhypertensive (LH) and 10 obese hypertensive males (OH). Results: In the presentstudy, serum leptin, BMI, and WC were significantly elevated in obese subjects thanin lean subjects whether normotensive or hypertensive (P < 0.001). In lean groups,serum leptin level was significantly higher in hypertensive than in normotensivepersons (P < 0.001). In all studied subjects, mean ABP was significantly related toserum leptin. In obese groups, and in lean groups, serum leptin was positivelycorrelated with mean ABP and all measured lipid profile parameters except highdensity lipoprotein (HDL) to which it was negatively correlated. Serum leptin waspositively correlated with WC in obese normotensive group, (r =0.657) ( p= 0.039 ),but it was positively correlated with BMI in obese hypertensive group (r =0.675) (p=.032). Conclusion: This study suggested that hyperleptinemia may play a role inthe pathophysiology of hypertension independently of adiposity and the mostcorrelated parameter to mean ABP among the measured parameters was serumleptin.

Impaired autonomic function in normotensive obese children

To evaluate baroreflex sensitivity and autonomic control in a cohort of normotensive obese (OB) children. A cross-sectional investigation, in which, baroreflex sensitivity and autonomic control were evaluated using transfer function and power spectral density analysis (PSDA) of the electrocardiogram and beat-to-beat blood pressures in normotensive OB children and normal weight normotensive controls. All methods used were noninvasive and data were captured while seated and at rest. The OB and control subjects non-obese (NO) were of similar age (OB 9.1±1.9 years vs. NO 9.2±1.4 years). The OB group was classified as having a BMI greater than the 95th percentile adjusted for age and gender, and a NO group with a BMI at or less than the 95th percentile (BMI percentile OB. 97.5±1.3 vs. NO 58.5±24.1). Both groups had similar normotensive blood pressures. T tests revealed that baroreflex sensitivity and HFRR were significantly reduced in the OB 9.2±2.7 vs. 15.2±4.7 (ms/mmHg) and 6.7±1.1 vs. 8.2±1.1 ms2, respectively, while LFSBP and LF/HF ratio were significantly increased in the OB 11.9±5.6 vs. 8.2±4.7 mmHg2 and 1.2±0.7 vs. 0.54±0.3, respectively. Normotensive OB children exhibited significantly reduced baroreflex sensitivity, parasympathetic control as well as increased sympathetic control when compared with healthy, NO controls. Findings in this investigation raise the awareness that autonomic dysfunction is present in young OB normotensive children.

NORMAL BLOOD PRESSURE IN OBESITY IS ASSOCIATED WITH REDUCED PERIPHERAL VASCULAR RESISTANCE: 8B.05

Objective: The link between obesity and elevated blood pressure is firmly established. However, not all obese individuals are hypertensive, suggesting that adaptive mechanisms are present in at least some obese individuals which allow them to maintain normal levels of blood pressure (BP). The aim of the current study was to examine the mechanisms underlying different levels of BP in obese individuals. Design and Method: Data from 2511 individuals (1262 males) were available from The Enigma Study for the current analyses. All individuals were aged between 18–40 years, and were free of cardiovascular disease and medication. Detailed demographic, biochemical and haemodynamic data, including BP, cardiac output (CO) and peripheral resistance (PVR) were obtained in all individuals. They were then stratified according to BMI (normal weight, overweight and obese) using WHO criteria, and seated brachial BP (optimal, normal, high-normal and hypertensive) using JNC 6 criteria. For the current analyses, comparisons were made between 3 groups: normal-weight normotensives (controls, optimal and normal BP, n = 1360), obese normotensives (optimal and normal BP, n = 61) and obese hypertensives (n = 79). Results: Compared with controls, obese individuals were older, had an increased family history of hypertension and an adverse biochemical profile (P < 0.01 for all). In addition, heart rate, CO and stroke volume were all significantly elevated in obese individuals (P < 0.001 for all). However, the elevation in CO was more marked in obese individuals who were hypertensive (P < 0.05 versus obese normotensives). In contrast, PVR was significantly lower in obese individuals with normal BP (P < 0.05 versus controls and obese hypertensives). Conclusions: These data suggest that a reduction in peripheral resistance is an important mechanism by which some obese individuals maintain normal blood pressure despite having a significantly elevated cardiac output. Although the factors underlying the reduction in PVR in these individuals remain to be elucidated, they are likely to provide an intriguing insight into the pathophysiology of obesity-related hypertension.

Adrenergic Overdrive as the Link Among Hypertension, Obesity, and Impaired Thermogenesis

The sympathetic nervous system plays a pivotal role in both blood pressure and metabolic homeostatic control by regulating cardiac output, peripheral vascular resistance, heat production, and resting metabolic rate, which accounts for a large fraction of adult energy expenditure. Throughout the years, the attractive hypothesis based on this evidence has been advanced that an alteration in blood pressure regulation, as well as in thermogenesis control exerted by the sympathetic nervous system, represents the pathogenetic background for 2 diseases of common detection in current clinical practice, that is, hypertension and obesity, respectively. As far as high blood pressure is concerned, a number of studies based on indirect or direct methodologic approaches to assess neuroadrenergic function have unequivocally demonstrated that a hyperactivity of the sympathetic nervous system contributes at the development, maintenance, and progression of the hypertensive state.1–4 They have also shown that neurogenic mechanisms favor the genesis of hypertension-related end organ damage, that is, left ventricular hypertrophy, arterial and arteriolar hypertrophy, and vascular remodelling.5,6 Even when blood pressure is normal, an adrenergic overdrive has also been reported in the obese state,7,8 and independent but additive increases in sympathetic activity have been described when obesity is coupled with hypertension.9 Traditionally, obesity-related hypertension has been regarded, at least in part, as the result of a hyperactivity of the sympathetic nervous system, related to some extent to the weight-associated increase in sympathetic cardiovascular drive.9,10 …

Mechanisms of Sympathetic Activation in Obesity-Related Hypertension

Obesity prevalence is soaring in industrialized countries and progressively increasing in the developing world. Altered patterns of nutrition and reduction in work-related energy expenditure have led to obesity becoming a truly global health issue. The central thermodynamic formulation for the origins of obesity, a mismatched energy balance equation, with an excess of dietary calorie intake over body energy expenditure, is a first step in the understanding of this phenomenon but leaves the diverse causal issues unexplored. Dietary calorie intake is modified by multiple social, economic, and cultural issues. Similarly, the reduction in energy expenditure in recent decades has complex origins, deriving from demographic and social change, which includes third-world transition from a labor-intensive agricultural economy to an industrial base, the introduction of household labor-saving devices, the popularity of transportation modes not reliant on physical effort, and from changed recreational habits, particularly in childhood (computer games instead of physical games). The prevalence of childhood obesity is escalating, having whimsically but not entirely unrealistically been attributed to “potato chips and computer chips.” Obesity and hypertension are intimately associated, and both very commonly coexist in individual patients with insulin resistance, hyperinsulinemia, and hyperlipidemia, this clustering of adverse health factors1 being designated the metabolic syndrome. The pathophysiological mechanisms by which obesity leads to hypertension remain uncertain. Understanding these processes might, perhaps, provide a more rational basis for drug treatment of obesity-related hypertension. Attempts at reduction in body weight, although pivotal in the treatment of obesity-related hypertension, more often than not fail, so that antihypertensive drug therapy is often needed. This review analyses the proposition that obesity is characterized by activation of the sympathetic nervous system and that obesity-related hypertension is, in fact, neurogenic, being initiated and sustained by neural mechanisms. At one time, this idea would have been held to fly in the …

Plasma Leptin and its Relationship with Lipid Peroxidation and Nitric Oxide in Obese Female Patients with or without Hypertension

Recent evidence suggested that leptin-induced oxidative stress in human endothelial cells in vivo and increased oxidative stress in human essential hypertension may further contribute to both the development of atherosclerosis and other cardiovascular diseases. We investigated the association of plasma leptin levels with plasma lipid peroxidation and nitric oxide metabolites (NOx) in obese hypertensive atherosclerosis model. Plasma leptin, lipid peroxidation and NOx levels were determined in age-matched non-obese normotensive female subjects (n = 30), obese normotensive female subjects (n = 45), and obese hypertensive female subjects (n = 50). Plasma leptin levels were determined by immunoradiometric method. Lipid peroxidation was determined as thiobarbituric acid reactive substances (TBARS) using spectrophotometric method. NOx levels were determined using enzymatic method. We found that plasma leptin and TBARS levels were increased in obesity, and obese hypertensives have significantly higher plasma leptin and TBARS levels than obese normotensives (p <0.001 and p <0.001). Obese hypertensives have significantly lower plasma NOx levels than obese normotensives (p <0.001). In univariate and multivariate regression analysis, plasma leptin levels were significantly correlated with TBARS (p <0.01 and p <0.01) in obese subjects. Plasma TBARS were also inversely correlated with NOx in hypertensive obese subjects (r = -0.412, p <0.01). Our results have shown that elevated leptin levels may be associated with increased oxidative stress and free-radical-induced decreased NOx levels. Therefore, hyperleptinemia may be an important contributor to the generation of hypertension in obesity.

The impact of body mass index on pulse pressure in obesity

Pulse pressure, a marker of arterial vascular properties, has been linked to cardiovascular diseases and complications. This study examined the impact of excess body mass and cardiovascular disease risk factors on pulse pressure (PP). Cross-sectional and prospective study. Baseline data consist of 219 obese African Americans, with mean +/- SD age of 46.8 +/- 10.9 years enrolled in a diet and exercise program of weight reduction. A non-invasive monitoring device was used to acquire 24 hourly ambulatory blood pressures. Pulse pressure was calculated as the difference between the average 24-h systolic and diastolic blood pressure and studied as a continuous variable and according to quartiles. The cross-sectional association of pulse pressure with body mass index (BMI) was examined using multivariate linear regression and proportional odds models that controlled for cardiovascular disease risk factors. In addition, we examined prospectively, in 36 participants, the effect of weight loss on pulse pressure, using the Wilcoxon signed ranked test. At baseline, a 5 kg/m2 increase in BMI was independently associated with a 35% risk [relative risk (RR) = 1.35, confidence interval (CI) = 1.10-1.65, P < 0.01] in the general study population and 19% (RR = 1.19, CI = 1.07-1.56, P = 0.04) in obese normotensives for increasing PP by one quartile after adjustment for other significant variables. After 3 months of diet and exercise intervention, BMI decreased by an average of 10.6% (P < 0.01) and resulted in an 8.8% (P < 0.01) reduction in PP. In the context of obesity, increasing BMI is independently associated with decreasing arterial compliance, as reflected in PP. This association highlights the potential value to cardiovascular health of any reduction in body weight in obese individuals.

Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives

Previous studies have shown that obesity is characterized by a sympathetic overactivity coupled with an insulin resistance state and a baroreflex impairment. The present study was set out to compare the effects of peripheral versus central obesity on sympathetic, metabolic and reflex function. In 36 lean subjects (age 35.8 +/- 1.4 years, mean +/- SEM), 20 subjects with peripheral obesity (PO) and 26 subjects with central obesity (CO), all age-matched and with normal blood pressure values, we measured beat-to-beat arterial blood pressure (Finapres), heart rate (HR, ECG), homeostasis model assessment (HOMA) index, plasma norepinephrine (NE, high-performance liquid chromatography) and postganglionic muscle sympathetic nerve traffic (MSNA, microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Both HOMA index, NE and MSNA values were significantly increased (P < 0.01) in obese as compared with lean individuals. Subjects with CO displayed MSNA and HOMA values significantly greater than those found in individuals with PO (65.4 +/- 2.0 versus 47.9 +/- 1.9 bs/100hb and 2.85 +/- 0.10 versus 2.43 +/- 0.11 a.u., respectively, P < 0.05 for both). Both in male and female subjects with CO or PO, MSNA, HOMA index and waist-to-hip ratio were significantly related to each other. Baroreceptor-HR and -MSNA control was significantly (P < 0.01) impaired in obese as compared with lean subjects, the degree of impairment being similar in CO and PO. These data suggest that CO is characterized by a sympathetic activation greater for magnitude than that detectable in PO. This appears not to be related to gender or to baroreflex mechanisms but rather to metabolic factors, i.e. to the greater insulin resistance characterizing CO.

Natriuretic peptides as markers of preclinical cardiac disease in obesity.

Aim of the study was to evaluate the role of atrial (ANP) and brain natriuretic peptides (BNP) as markers of preclinical cardiac disease in obesity. We selected 26 obese (BMI > 29 kg m(-2)) never-treated hypertensives (24-h BP > 140 and/or 90 mmHg), 26 obese normotensives (24-h BP < 130/80 mmHg) and 25 lean (BMI < or = 25 kg m(-2)) never-treated hypertensives. Each subject underwent measurements of ANP and BNP plasma levels, 24-h ambulatory blood pressure (BP) monitoring, digitized M-mode and Doppler echocardiography. Mean values of ANP and BNP were similar among the three groups. All the subjects had normal left ventricular (LV) systolic function. Within each group ANP levels were higher in patients with LV diastolic dysfunction than in patients with normal diastolic function, and BNP levels were higher in patients with LV hypertrophy and in patients with LV diastolic dysfunction. Within each group, ANP levels were inversely correlated with LV diastolic indices, whereas BNP levels were directly correlated with LV mass index and inversely correlated with LV diastolic indices. ANP and BNP levels were not correlated with other echocardiographic parameters, age, BMI or 24-h BP values. In normotensive and hypertensive obese subjects the relationships of ANP and BNP levels with LV morpho-functional characteristics follow the same trend as in lean hypertensives, with ANP mainly influenced by diastolic dysfunction and BNP influenced by both LV hypertrophy and LV diastolic dysfunction. Therefore ANP and BNP can be considered useful markers of preclinical cardiac disease in obesity.