Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study.
ABSTRACT Hypertension is associated with impaired glucose metabolism and insulin resistance. Chronic activation of the sympathetic nervous system may contribute to either condition. We investigated the effect of catheter-based renal sympathetic denervation on glucose metabolism and blood pressure control in patients with resistant hypertension.
We enrolled 50 patients with therapy-resistant hypertension. Thirty-seven patients underwent bilateral catheter-based renal denervation, and 13 patients were assigned to a control group. Systolic and diastolic blood pressures, fasting glucose, insulin, C peptide, hemoglobin A(1c), calculated insulin sensitivity (homeostasis model assessment-insulin resistance), and glucose levels during oral glucose tolerance test were measured before and 1 and 3 months after treatment. Mean office blood pressure at baseline was 178/96±3/2 mm Hg. At 1 and 3 months, office blood pressure was reduced by -28/-10 mm Hg (P<0.001) and -32/-12 mm Hg (P<0.001), respectively, in the treatment group, without changes in concurrent antihypertensive treatment. Three months after renal denervation, fasting glucose was reduced from 118±3.4 to 108±3.8 mg/dL (P=0.039). Insulin levels were decreased from 20.8±3.0 to 9.3±2.5 μIU/mL (P=0.006) and C-peptide levels from 5.3±0.6 to 3.0±0.9 ng/mL (P=0.002). After 3 months, homeostasis model assessment-insulin resistance decreased from 6.0±0.9 to 2.4±0.8 (P=0.001). Additionally, mean 2-hour glucose levels during oral glucose tolerance test were reduced significantly by 27 mg/dL (P=0.012). There were no significant changes in blood pressure or metabolic markers in the control group.
Renal denervation improves glucose metabolism and insulin sensitivity in addition to a significantly reducing blood pressure. However, this improvement appeared to be unrelated to changes in drug treatment. This novel procedure may therefore provide protection in patients with resistant hypertension and metabolic disorders at high cardiovascular risk.
URL: http://www.ClinicalTrials.gov. Unique identifiers: NCT00664638 and NCT00888433.
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ABSTRACT: Ventricular arrhythmias (VAs) remain the major cause of mortality and sudden cardiac death (SCD) in almost all forms of heart disease. Despite so many therapeutic advances, such as pharmacological therapies, catheter ablation, and arrhythmia surgery, management of VAs remains a great challenge for cardiologists. Evidence from histological studies and from direct nerve activity recordings have suggested that increased sympathetic nerve density and activity contribute to the generation of VAs and SCD. It is well known that renal sympathetic nerve (RSN), either afferent component or efferent component, plays an important role in modulation of central sympathetic activity. We have recently shown that RSN activation by electrical stimulation significantly increases cardiac and systemic sympathetic activity and promotes the incidence of acute ischemia-induced VAs, suggesting RSN has a role in the development of VAs. Initial experience of RSN denervation (RDN) in patients with resistant hypertension showed that this novel and minimally invasive device-based approach significantly reduced not only kidney but also whole-body norepinephrine spillover. In addition, experimental studies find that left stellate ganglion nerve activity is significantly decreased after RDN. Based on these observations, it is reasonable to conclude that RDN may be an effective therapy for the management of VAs. Indeed, RDN has provided a protection against VAs in both animal models and patients. In this article, we review the role of the RSN in the generation of VAs and SCD and the role of RDN as a potential treatment strategy for VAs and SCD.Clinical research in cardiology : official journal of the German Cardiac Society. 01/2015;
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ABSTRACT: Renal sympathetic denervation (RSD) opens new perspectives and possibilities not only in the treatment of resistant hypertension but also of other cardiometabolic diseases. In patients with hypertension, it has been demonstrated that activity of the sympathetic nervous system correlates with grade of hypertension. Decreasing sympathetic activity using RSD significantly reduces blood pressure in resistant hypertension. It is too early to say a definite opinion about appropriateness of this method in the treatment of resistant hypertension, because there are not great studies with huge number of the patients. After we get and evaluate these results through a longer span of time, only than we shall know what is the role of RSD in the treatment of resistant hypertension and other cardiometabolic conditions related to increased function of the sympathetic nervous system, such as heart failure, diabetes mellitus, obstructive sleep apnea, renal disease with microalbuminuria and macroalbuminuria.Medical archives (Sarajevo, Bosnia and Herzegovina). 12/2013; 67(6):454-9.
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ABSTRACT: Arterial hypertension (HTN) is a major health problem worldwide. Treatment-resistant hypertension (trHTN) is defined as the failure to achieve target blood pressure despite the concomitant use of maximally tolerated doses of three different antihypertensive medications, including a diuretic. trHTN is associated with considerable morbidity and mortality. Renal sympathetic denervation (RDn) is available and implemented abroad as a strategy for the treatment of trHTN and is currently under clinical investigation in the United States. Selective renal sympathectomy via an endovascular approach effectively decreases renal sympathetic nerve hyperactivity leading to a decrease in blood pressure. The Symplicity catheter, currently under investigation in the United States, is a 6-French compatible system advanced under fluoroscopic guidance via percutaneous access of the common femoral artery to the distal lumen of each of the main renal arteries. Radiofrequency (RF) energy is then applied to the endoluminal surface of the renal arteries via an electrode located at the tip of the catheter. Two clinical trials (Symplicity HTN 1 and Symplicity HTN 2) have shown the efficacy of RDn with a post-procedure decline of 27/17mmHg at 12 months and 32/12 mmHg at 6 months, respectively, with few minor adverse events. Symplicity HTN-3 study is a, multi-center, prospective, single-blind, randomized, controlled study currently under way and will provide further insights about the safety and efficacy of renal denervation in patients with trHTN.The Yale journal of biology and medicine 12/2014; 87(4):527-535.