Abstract-Excess weight is established as a major risk factor for cardiovascular diseases, particularly in young individuals.To get a better understanding of the pathophysiology underlying increased cardiovascular disease risk, we evaluated early signs of organ damage and their possible relationship to sympathetic nervous activity. Eighteen lean (body mass index Ͻ25 kg/m 2 ) and 25 overweight or obese (body mass index Ͼ25 kg/m 2 ) healthy university students were included in the study. We comprehensively assessed subclinical target organ damage, including the following: (1) assessment of renal function; (2) left ventricular structure and systolic and diastolic function; and (3) O besity is an established risk factor for cardiovascular disease (CVD) development. 1 Although excess adiposity is frequently linked with metabolic abnormalities such as elevated triglycerides, low levels of high-density lipoprotein (HDL), elevated glucose, elevated blood pressure (BP), insulin resistance, and a proinflammatory state, most likely contributing to excess CVD, 2 large scale epidemiological studies have shown that the CVD risk associated with obesity remains appreciable even after correction for these factors. 1,3 Perhaps surprising is the finding that the obesity-related relative risk of death from stroke and all of the CVDs combined is higher in younger than in older subjects, 4,5 indicating that excess adiposity is likely to have deleterious effects on the cardiovascular system already at an early age, well before clinical manifestations of CVD become apparent. In agreement with this view, recent studies have demonstrated that the presence of obesity since childhood was the only consistent and significant determinant of adverse cardiac remodeling 6 and that being overweight at age 20 years or obese at any time in life was linked with a 3-fold increased risk of developing chronic renal failure. 7 Moreover, functional and structural abnormalities of the endothelium are already evident in obese children aged 9 to 12 years. 8 Given that the sympathetic nervous system (SNS) is an important regulatory mechanism of both metabolic and cardiovascular functions, altered SNS may likely play a role in the etiology and complications of obesity. 9 It is now well established that obesity is associated with elevated SNS Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz.

OBJECTIVESympathetic nervous system (SNS) overactivity contributes to the pathogenesis and target organ complications of obesity. This study was conducted to examine the effects of lifestyle interventions (weight loss alone or together with exercise) on SNS function.RESEARCH DESIGN AND METHODSUntreated men and women (mean age 55 ± 1 year; BMI 32.3 ± 0.5 kg/m2) who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated to either dietary weight loss (WL, n = 20), dietary weight loss and moderate-intensity aerobic exercise (WL+EX, n = 20), or no treatment (control, n = 19). Whole-body norepinephrine kinetics, muscle sympathetic nerve activity by microneurography, baroreflex sensitivity, fitness (maximal oxygen consumption), metabolic, and anthropometric measurements were made at baseline and 12 weeks.RESULTSBody weight decreased by −7.1 ± 0.6 and −8.4 ± 1.0 kg in the WL and WL+EX groups, respectively (both P < 0.001). Fitness increased by 19 ± 4% (P < 0.001) in the WL+EX group only. Resting SNS activity decreased similarly in the WL and WL+EX groups: norepinephrine spillover by −96 ± 30 and −101 ± 34 ng/min (both P < 0.01) and muscle sympathetic nerve activity by −12 ± 6 and −19 ± 4 bursts/100 heart beats, respectively (both P < 0.01), but remained unchanged in control subjects. Blood pressure, baroreflex sensitivity, and metabolic parameters improved significantly and similarly in the two lifestyle intervention groups.CONCLUSIONSThe addition of moderate-intensity aerobic exercise training to a weight loss program does not confer additional benefits on resting SNS activity. This suggests that weight loss is the prime mover in sympathetic neural adaptation to a hypocaloric diet.

Moderate weight loss in obese MetS patients is associated with a reduction in albuminuria and an improvement in eGFR which is augmented by exercise co-intervention.

The Postural Orthostatic Tachycardia Syndrome (POTS) is a condition in which heart rate increases abnormally when the individual assumes an upright position. In addition to the marked tachycardia, presyncope, and syncope, patients with POTS often complain of light-headedness, fatigue, and difficulty in concentrating. The present study assessed individuals with POTS for psychiatric comorbidity, anxiety sensitivity and health related quality of life and examined general cognitive ability. Data was obtained from patients with POTS (n = 15, 12 female, aged 30 ± 3 years) and age matched healthy subjects (n = 30, 21 female, aged 32 ± 2 years). Patients with POTS commonly presented with symptoms of depression, elevated anxiety and increased anxiety sensitivity, particularly with regards to cardiac symptoms, and had a poorer health related quality of life in both the physical and mental health domains. While patients with POTS performed worse in tests of current intellectual functioning (verbal and non-verbal IQ) and in measures of focused attention (digits forward) and short term memory (digits back), test results were influenced largely by years of education and the underlying level of depression and anxiety. Acute changes in cognitive performance in response to head up tilt were evident in the POTS patients. From results obtained, it was concluded that participants with POTS have an increased prevalence of depression and higher levels of anxiety. These underlying symptoms impact on cognition in patients with POTS, particularly in the cognitive domains of attention and short-term memory. Our results indicate that psychological interventions may aid in recovery and facilitate uptake and adherence of other treatment modalities in patients with POTS.

Divergent effects of successful weight loss maintenance on whole-body norepinephrine spillover rate and MSNA suggest organ-specific differentiation in SNS adaptation to weight loss under conditions of negative vs. stable energy balance.