Excessive Sympathetic Activation in Heart Failure With Obesity and Metabolic Syndrome

Abstract

Abstract-Congestive heart failure is characterized by sympathetic activation, which has also been described in the metabolic syndrome. No information exists, however, as to whether the sympathostimulating effects of these 2 conditions summate when heart failure is complicated by the metabolic syndrome, leading to an exceedingly high adrenergic drive. This is clinically relevant, because in heart failure sympathetic activation is closely related to mortality. We studied 48 control subjects (age: 58.4Ϯ1.6 years, meanϮSEM) and 89 age-matched heart failure patients (New York Heart Association class II), of whom 47 were without and 42 were with metabolic syndrome. Measurements included blood pressure (Finapres), heart rate (ECG), and sympathetic nerve traffic (microneurography) at rest and during baroreceptor manipulation. Waist circumference, blood pressure, and metabolic variables were greater in heart failure with metabolic syndrome than in heart failure without metabolic syndrome and in control subjects. Left ventricular ejection fraction and end-diastolic diameter were similarly altered in the 2 heart failure groups. Compared with control subjects, sympathetic nerve activity was greater in heart failure patients without metabolic syndrome (64.7Ϯ3.2 versus 45.8Ϯ2.9 bursts/100 heartbeats; PϽ0.01), a further pronounced increase being detected in those with metabolic syndrome (80.9Ϯ3.2 bursts/100 heartbeats; PϽ0.01). In the multivariate analysis, waist circumference and body mass index were the variables most closely related to sympathetic activation. Compared with control subjects, baroreflex responses were significantly attenuated in the 2 heart failure groups, the impairment being more marked in the group with than without metabolic syndrome. Thus, obesity and metabolic syndrome potentiate the sympathetic activation characterizing heart failure. This potentiation is likely to mainly depend on metabolic and baroreflex mechanisms. Key Words: baroreflex Ⅲ metabolic syndrome Ⅲ heart failure Ⅲ sympathetic nervous system I ndirect and direct indices of sympathetic activity, such as venous plasma norepinephrine, plasma norepinephrine spillover from adrenergic nerve terminals, and muscle sympathetic nerve firing rate, have shown that sympathetic cardiovascular influences are increased in a high-risk condition such as congestive heart failure (CHF). [1][2][3][4] They have also shown that this neuroadrenergic alteration is directly related to the severity of the CHF state 1,4 and similar in magnitude in CHF of ischemic or idiopathic dilated etiology. 1,5 Evidence has also been provided that a hyperadrenergic state characterizes the clustering of risk factors known as metabolic syndrome (MS), 6-8 which also represents a high-risk condition for the development of CHF. 9 Several studies have shown that some components of MS (eg, obesity and hypertension) have sympathostimulating effects, 10 -13 which can, to some extent, also be seen in CHF patients. 14 Whether and to what extent the clustering of blood pressure, body weight,...

Metabolic Syndrome Increases Mortality in Heart Failure

“…This theory is supported by the recent publication by Grassi et al that showed MetS potentiates the sympathetic activation in HF. 28 In some studies, which included patients after a MI delayed onset of the mortality effects (after 2 years), it has been observed, 13,21,22 while other studies report mortality effects before 2 years. 12,16 Similar to our results, de Simone et al found a higher risk of death according to diabetic status.…”

Sympathetic activation in congestive heart failure: Reproducibility of neuroadrenergic markers

“…Multiunit recording of MSNA was obtained from a microelectrode inserted in a peroneal nerve posterior to the fibular head, as reported previously [6][7][8]12,13,17,18]. Integrated nerve activity was monitored by a loud-speaker, displayed on a storage oscilloscope (model 511A, Tektronix), and continuously recorded with BP and heart rate on an ink polygraph.…”

“…© 2008 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.Keywords: Heart failure; Sympathetic activity; Plasma norepinephrine; Muscle sympathetic nerve traffic; Muscle sympathetic nerve activity Congestive heart failure (CHF) is characterized by a marked sympathetic activation which is 1) directly proportional to the severity of the CHF state [1][2][3][4][5][6], 2) of similar magnitude in CHF of ischaemic and idiopathic dilated aetiology [7], 3) affects several vascular circulations such as the cerebral, the coronary, the muscle and the renal ones [6,7-11], 4) potentiated when other clinical conditions also characterized by adrenergic overdrive, such as hypertension, obesity and metabolic syndrome, are concomitantly present [12,13], and 5) relevant for patient's prognosis because it is inversely related to survival rate [2,[14][15][16]. The adrenergic overdrive characterizing the CHF syndrome is detectable by both indirect and direct approaches to assess sympathetic tone, such as plasma norepinephrine (NE) assay, NE spillover technique as well as microneurographic recording of efferent postganglionic muscle sympathetic nerve activity (MSNA) [1][2][3][4][5][6][7][8][9][10][11].…”

“…In several studies, however, and particularly in those carried out in mild to severe CHF, NE has frequently failed to European Journal of Heart Failure 10 (2008) 1186 -1191 www.elsevier.com/locate/ejheart detect the increase in adrenergic cardiovascular drive documented by approaches directly assessing human sympathetic function [7,12,13]. This is also the case for some of the studies aimed at investigating the effects of non-pharmacological or pharmacological interventions on adrenergic function [17,18].…”

Study on autonomic dysfunction and metabolic syndrome in Chinese patients

“…Therefore, more researchers are paying attention to MetS, and more studies on its mechanism are being carried out. MetS is associated with sympathetic activation4, 5, 6. A previous study found that MetS is a state of peripheral sympathetic nerve hyperactivity7.…”