Explore the vast range of titles available.

Renal denervation (RDN) with radiofrequency ablation substantially reduces blood pressure in patients with treatment-resistant hypertension. We assessed the long-term antihypertensive effects and safety. Symplicity HTN-1 is an open-label study that enrolled 153 patients, of whom 111 consented to follow-up for 36 months. Eligible patients had a systolic blood pressure of at least 160 mm Hg and were taking at least three antihypertensive drugs, including a diuretic, at the optimum doses. Changes in office systolic blood pressure and safety were assessed every 6 months and reported every 12 months. This study is registered with ClinicalTrials.gov, numbers NCT00483808, NCT00664638, and NCT00753285. 88 patients had complete data at 36 months. At baseline the mean age was 57 (SD 11) years, 37 (42%) patients were women, 25 (28%) had type 2 diabetes mellitus, the mean estimated glomerular filtration rate was 85 (SD 19) mL/min per 1·73 m2, and mean blood pressure was 175/98 (SD 16/14) mm Hg. At 36 months significant changes were seen in systolic (−32·0 mm Hg, 95% CI −35·7 to −28·2) and diastolic blood pressure (−14·4 mm Hg, −16·9 to −11·9). Drops of 10 mm Hg or more in systolic blood pressure were seen in 69% of patients at 1 month, 81% at 6 months, 85% at 12 months, 83% at 24 months, and 93% at 36 months. One new renal artery stenosis requiring stenting and three deaths unrelated to RDN occurred during follow-up. Changes in blood pressure after RDN persist long term in patients with treatment-resistant hypertension, with good safety. Ardian LLC/Medtronic Inc.

To the Editor: The renal sympathetic nerves have been identified as a major contributor to the complex pathophysiology of hypertension in both experimental models and in humans. 1 Patients with essential hypertension generally have increased efferent sympathetic drive to the kidneys, as evidenced by elevated rates of renal norepinephrine spillover, defined as the amount of transmitter that escapes neuronal uptake and local metabolism and thus “spills over” into the circulation. Hypertension is also characterized by an increased rate of sympathetic-nerve firing, possibly modulated by afferent signaling from renal sensory nerves. 2 – 4 A 59-year-old male patient with long-standing essential hypertension that was . . .

Multiple sham-controlled clinical trials have demonstrated significant reductions in both office and 24-h blood pressure (BP) following radiofrequency renal denervation (RDN) in the uncontrolled hypertension population. Notably, the blood pressure response varies widely within individual participants, thus showing a clinical need to identify potential RDN “responders” prior to the procedure. Despite multiple analytic efforts, no single parameter, aside from baseline blood pressure, has been consistently associated with BP reduction following RDN. However, this failure may be due to limitations in empiric definitions of responders. Indeed, commonly applied responder definitions based on the difference between two point-in-time BP measurements are fraught due to visit-to-visit variability in office and 24-h blood pressure endpoints. Several factors should be considered to develop a more clinically useful operational definition of procedural response including relative changes in office and 24-h BP, consideration of the temporal response to RDN, as well as adjustment for baseline BP. The current evidence may provide incentives for future expert consensus to precisely define responders to hypertension treatments.

Renal denervation (RDN) is an adjunct therapy for resistant hypertension, reducing blood pressure (BP) by inhibiting both afferent sensory and efferent sympathetic renal nerve activity. The resulting reduction in central sympathetic outflow including that directed toward the heart may beneficially impact cardiac remodeling, left ventricular hypertrophy (LVH) and atrial fibrillation (AF). RDN has been shown to reduce left ventricular mass and AF burden but long‐term data is sparse. Forty patients (72.5% male, 69.2 ± 9.6 years) underwent 12‐lead ECG at baseline prior to RDN and at a mean long‐term follow‐up (LTFU) of 8.3 ± 0.9 years post‐intervention. A 24‐h ambulatory blood pressure monitor (ABPM) was obtained at both time points. Cornell voltage indices were calculated at baseline and LTFU, then converted to left ventricular mass based on validated formulae accounting for sex. ECGs underwent cardiologist review for determination of AF at both time‐points. There was no difference in Cornell voltages or left ventricular mass index (LVMI) between baseline and long‐term follow‐up in neither males ( p  = 0.89) nor females ( p  = 0.91). BP lowering at LTFU was correlated with a more pronounced reduction in LVMI ( r  = 0.50, p  = 0.0011) No change was observed in the incidence of atrial fibrillation between baseline or long‐term follow‐up ( p  = 0.99). There was no reduction in mean Cornell voltage or LVMI across the cohort between baseline and long‐term follow‐up. However, changes in ambulatory systolic BP correlated with reduction in LVMI suggestive of an RDN‐induced BP dependent long‐term reduction in LVMI out to eight years post‐RDN.

Amongst other immune cells, neutrophils play a key role in systemic inflammation leading to cardiovascular disease and can release inflammatory factors, including lipocalin-2 (LCN2). LCN2 drives cardiac hypertrophy and plays a role in maladaptive remodelling of the heart and has been associated with renal injury. While lifestyle factors such as diet and exercise are known to attenuate low-grade inflammation, their ability to modulate plasma LCN2 levels is unknown. Forty-eight endurance athletes and 52 controls (18–55 years) underwent measurement for various cardiovascular health indicators, along with plasma LCN2 concentration. No significant difference in LCN2 concentration was seen between the two groups. LCN2 was a very weak predictor or absent from models describing blood pressures or predicting athlete status. In another cohort, 57 non-diabetic overweight or obese men and post-menopausal women who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated into either a control, modified Dietary Approaches to Stop Hypertension (DASH) diet, or DASH and exercise group. Pre- and post-intervention demographic, cardiovascular health indicators, and plasma LCN2 expression were measured in each individual. While BMI fell in intervention groups, LCN2 levels remained unchanged within and between all groups, as illustrated by strong correlations between LCN2 concentrations pre- and 12 weeks post-intervention ( r  = 0.743, P  < 0.0001). This suggests that circulating LCN2 expression are stable over a period of at least 12 weeks and is not modifiable by diet and exercise.

Measures obtained from the full blood count have been shown to vary around a set point, are stable over years, and provide an indication of disease risk and mortality. In this study, we examined the association between sympathetic nerve activity and components of the full blood count. We performed a retrospective analysis of data drawn from our clinical database. Subjects were included if available data comprised full blood count and muscle sympathetic nerve activity (MSNA). Data were obtained from 160 individuals, comprising healthy volunteers, subjects who were overweight or with clinical obesity, and patients with high blood pressure. MSNA was correlated to the red cell distribution width (RDW, Spearman's rho 0.49 for MSNA b/min and 0.48 for MSNA b/100hb, p < 0.001 for both), but bore no association with any of the other blood variables. Regression analysis indicated that the RDW could be predicted by a combination of MSNA and BMI and to the number of components and diagnosis of the metabolic syndrome, measures of insulin resistance, and markers of inflammation. Our observations may provide insight into the possible mechanisms linking the RDW with mortality.

BackgroundCardiovascular disease (CVD) is a major cause of morbidity and mortality in adults with type 2 diabetes mellitus (T2DM). Cardiac dysfunction and decreased exercise capacity are common in people with T2DM, even in those without overt heart failure. Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, reduces major cardiovascular events and mortality in people with T2DM and established CVD, though the underlying mechanisms are not fully elucidated. This study aimed to assess changes in cardiac function and cardiorespiratory fitness (CRF) at rest and during exercise with empagliflozin treatment in people with T2DM.MethodsThis double-masked, single-centre, randomised, placebo-controlled analysis combined two studies involving adults (≥ 18 years) with T2DM comparing empagliflozin 25 mg daily vs. placebo, each over three months. VO₂ peak was measured using a ramp protocol peak exercise test on a bicycle ergometer, and echocardiography assessed changes in cardiac structure and function.ResultsOf 65 recruited participants, 57 completed the study (70.2% male, age 64.9 ± 7.8 year, baseline HbA1c 7.8% (7.5–8.4). Thirty-one participants (67.7% male, age 65.6 ± 6.6 year) were randomised to the placebo group, and 26 participants (73.1% male, age 64.2 ± 9.0 year) were randomised to empagliflozin. No significant between-group difference in the primary outcome of change in VO2 peak was observed. Empagliflozin reduced left ventricular end-diastolic volume (LVEDV) at rest by 9.508 ± 14.54 mL compared with placebo, which increased by 2.13 ± 20.73 mL (p = 0.0232).ConclusionsIn adults with T2D, 12 weeks of empagliflozin significantly reduced LVEDV without changing VO2 peak. Empagliflozin may enhance cardiovascular efficiency without directly improving functional capacity.Trial registrationACTRN12617000490370p & ACTRN12619000887178.Graphical Abstract

Sympathetic Neural Adaptation to Hypocaloric Diet With or Without Exercise Training in Obese Metabolic Syndrome Subjects Nora E. Straznicky 1 , Elisabeth A. Lambert 1 , Paul J. Nestel 2 , Mariee T. McGrane 1 , Tye Dawood 1 , Markus P. Schlaich 3 , Kazuko Masuo 1 , Nina Eikelis 1 , Barbora de Courten 4 , Justin A. Mariani 5 , Murray D. Esler 1 , Florentia Socratous 3 , Reena Chopra 1 , Carolina I. Sari 1 , Eldho Paul 6 and Gavin W. Lambert 1 1 Human Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; 2 Cardiovascular Nutrition Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; 3 Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; 4 Clinical Physiology Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; 5 Heart Failure Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; 6 Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. Corresponding author: Nora E. Straznicky, nora.straznicky{at}bakeridi.edu.au . Abstract OBJECTIVE Sympathetic 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 METHODS Untreated men and women (mean age 55 ± 1 year; BMI 32.3 ± 0.5 kg/m 2 ) 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. RESULTS Body 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. CONCLUSIONS The 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. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received June 28, 2009. Accepted October 4, 2009. © 2010 American Diabetes Association

Conclusive evidence demonstrates that the sympathetic nervous system activation is a hallmark of congestive heart failure. This has been shown via a variety of biochemical, neurophysiological, and neuroimaging approaches for studying human sympathetic neural function. The sympathetic activation appears to be an early phenomenon in the clinical course of the disease, closely related to its severity and potentiated by the concomitant presence of other comorbidities, such as obesity, diabetes mellitus, metabolic syndrome, hypertension, and renal failure. The adrenergic overdrive in heart failure is associated with other sympathetic abnormalities, such as the downregulation of beta-adrenergic adrenoreceptors at cardiac level, and exerts unfavorable consequences on the cardiovascular system. These include the endothelial dysfunction, the development of left ventricular hypertrophy, the atherosclerosis development, as well as the generation of atrial and ventricular arrhythmias, and, at very extreme levels of sympathetic activation, the occurrence of microscopic myocardial necrosis. Given the close direct independent relationships detected in heart failure between sympathetic activation and mortality, the adrenergic overdrive has become a target of neuromodulatory therapeutic interventions, which include non-pharmacological, pharmacological, and device-based interventions. For some of these approaches (specifically bilateral renal nerves ablation and carotid baroreceptor stimulation), additional studies are needed to better define their impact on the clinical course of the disease.