Sympathetic Overactivity In Patients Research Articles

Effect of baroreflex activation therapy on renal sodium excretion in patients with resistant hypertension.

Activation of the sympathetic nervous system increases sodium retention in resistant hypertension. Baroreflex activation therapy (BAT) is an interventional method to reduce sympathetic overactivity in patients with resistant hypertension. This study aimed to assess the effect of BAT on urinary sodium excretion. From 2012 to 2015, consecutive patients with resistant hypertension and blood pressure (BP) above target despite polypharmacy strategies were consecutively included in this observational study. BAT was provided with the individual adaption of programmed parameters over the first months. 24-h urinary sodium excretion (UNa) was estimated at baseline and after 6 months using the Kawasaki formula in patients undergoing BAT. Additionally, the fractional sodium excretion, plasma renin activity, and aldosterone levels were assessed. Forty-two patients completed the 6-month follow-up period. Office systolic and ambulatory 24-h systolic BP at baseline were 169 ± 27mmHg and 148 ± 16mmHg despite a median intake of 7(3-9) antihypertensive drugs. After 6 months of BAT, systolic office BP decreased to 150 ± 29mmHg (p < 0.01), 24-h systolic BP to 142 ± 22mmHg (p = 0.04) and 24-h UNa increased by 37% compared to baseline (128 ± 66 vs. 155 ± 83mmol/day, p < 0.01). These findings were accompanied by a significant increase in fractional sodium excretion (0.74% [0.43-1.47] to 0.92% [0.61-1.92]; p = 0.02). However, in contrast to the significant BP reduction, eGFR, plasma sodium, renin activity and aldosterone levels did not change during BAT. The increase in sodium excretion was correlated with the change in eGFR (r = 0.371; p = 0.015). The present study revealed a significant increase of estimated 24-h UNa which may contribute to the long-term BP-lowering effects of this interventional method.

Effect of arousal on sympathetic overactivity in patients with obstructive sleep apnea

ObjectiveObstructive sleep apnea (OSA) is associated with sympathetic overactivity. Intermittent hypoxemia and repetitive arousals are the proposed mechanisms; however, the main contributing factor for sympathetic overactivity remains to be determined. We therefore investigated the independent effect of apnea or arousal on sympathetic activity in a large cohort of OSA patients using heart rate variability analysis. MethodsFrequency domain heart rate variability parameters were measured and compared between 782 patients with OSA (198 mild, 259 moderate, 325 severe) and 119 non-OSA controls. Univariate analysis was performed to identify associations between clinical and polysomnographic variables and heart rate variability measurements. Multivariate analysis was further performed to determine the potential contributing factors for sympathetic overactivity. ResultsPatients with OSA exhibited overall alterations in heart rate variability measures indicating sympathetic overactivity compared to controls, and this tendency was more pronounced in those with severe OSA. Univariate analysis showed that both apnea-hypopnea and arousal indices correlated with increased sympathetic activity and decreased parasympathetic activity. In multivariate analysis, arousal index was found to be more closely associated with sympathetic overactivity than apnea-hypopnea index. ConclusionThe present study showed that arousal may be a more potent contributing factor than apnea for sympathetic overactivity in OSA patients. Our results suggest that arousal index, rather than apnea-hypopnea index, could be considered as a surrogate marker for sympathetic overactivity in OSA. Further longitudinal studies should elucidate causal relationship between arousals and sympathetic overactivity in patients with OSA.

AB0833 The clinical significance sympathetic overactivity in patients with systemic sclerosis: Reverse dipper pattern of blood pressure and ADMA

BackgroundSystemic sclerosis (SSc) is a multisystem disorder characterized by extensive vascular damage, with early generalized microangiopathy and fibrosis of the skin and internal organs. SSc is characterized by parasympathetic impairment...

Baroreflex Sensitivity and Its Response to Deep Breathing Predict Increase in Blood Pressure in Type 1 Diabetes in a 5-Year Follow-Up

OBJECTIVEWe have recently demonstrated that early autonomic dysfunction, defined as low baroreflex sensitivity (BRS), could be functional and reversible. However, potential temporal changes in BRS have not yet been addressed by longitudinal studies in type 1 diabetes. Moreover, it is not known whether low BRS predisposes to hypertension or other nonfatal diabetes complications.RESEARCH DESIGN AND METHODSWe conducted a 5-year prospective study including 80 patients with type 1 diabetes. We measured ambulatory blood pressure and autonomic function tests. BRS was assessed by six different methods during spontaneous, controlled, and slow deep breathing at baseline and follow-up.RESULTSSpontaneous BRS declined over time (BRSaverage 16.2 ± 0.8 vs. 13.2 ± 0.8 ms/mmHg; P < 0.01), but the change was not significant when adjusted for time of follow-up. Low BRS at baseline did not progress to cardiac autonomic neuropathy but predicted an increase in the nighttime systolic blood pressure (BRSaverage r = −0.37; P < 0.05). Additionally, BRS response to deep breathing at baseline predicted an increase in 24-h ambulatory blood pressure (BRS-αLF r = 0.323–0.346; P < 0.05).CONCLUSIONSThe decline in spontaneous BRS over time in patients with type 1 diabetes seems to be due to normal aging, which supports a functional etiology behind early autonomic derangements. Decreased resting BRS and the magnitude of improvement by deep breathing may be due to sympathovagal imbalance, a well-known mechanism in the development of hypertension. Early interventions aiming to reduce sympathetic overactivity in patients with low BRS might delay the development of hypertension.

Sympathetic Overactivity in Patients with Pulmonary Stenosis and Improvement after Percutaneous Balloon Valvuloplasty

Percutaneous balloon valvulotomy (PBV) is the procedure of choice for the treatment of valvular pulmonary stenosis (PS) with similar results comparable to surgical valvotomy but less invasive. Twenty-seven consecutive patients with PS being evaluated for PBV were enrolled in the study. Peak instantaneous transvalvular gradient, right ventricle (RV) diameter, mean atrial pressures, RV systolic pressure (RVSP), pro-brain natriuretic peptide (proBNP) levels significantly decreased immediately after PBV. Regarding heart rate variability (HRV) parameters, mean HR (heart rate), LF (low frequency) day and night, LF/HF day and night significantly decreased and standard deviation of all NN intervals (SDNN), root mean square of successive differences (RMSSD), P number of NN intervals that differed by more than 50 ms from adjacent interval divided by the total number of all NN intervals (PNN50), HF (High frequency) day and night significantly increased 1 day after PBV and these changes were shown to be preserved at the first month. The increase in SDNN was correlated with the decrease in right atrial pressure (RAP) (r =-0.5, P = 0.04); the increase in standard deviation of the 5-minute mean RR intervals (SDANN) was correlated with the decrease in proBNP (r =-0.4, P = 0.03). Sympathetic overactivity and increased proBNP levels were associated with the symptomatic status of patients with PS. Associated with a decrease in atrial pressures and proBNP levels, PBV yielded a decrease in adrenergic overactivity in the patients with PS.

Hypoadiponectinemia in type 2 diabetes mellitus in men is associated with sympathetic overactivity as evaluated by cardiac 123I-metaiodobenzylguanidine scintigraphy

Hypoadiponectinemia is associated with insulin resistance. However, there is very limited information about the relationship between plasma adiponectin and cardiac autonomic nervous function. We tested the hypothesis that hypoadiponectinemia is associated with cardiac sympathetic overactivity in patients with type 2 diabetes mellitus. Thirty-three male type 2 diabetic patients not on insulin treatment were classified into a hypoadiponectinemia group (plasma adiponectin concentration, <4.0 μg/mL; age, 58.6 ± 8.6 years [mean ± SD]; n = 14) and an age-matched normoadiponectinemia group (serum adiponectin concentration, ≥4.0 μg/mL; age, 58.2 ± 8.1 years; n = 19). In each patient, baroreflex sensitivity, heart rate variability, plasma norepinephrine concentration, and cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphic findings were assessed. Compared with the normoadiponectinemia group, the hypoadiponectinemia group had a higher body mass index ( P < .01), higher plasma concentrations of glucose and insulin ( P < .05 and P < .01, respectively), higher homeostasis model assessment of insulin resistance (HOMA-IR) values ( P < .005), higher plasma triglyceride levels ( P < .05), and lower plasma high-density lipoprotein cholesterol levels ( P < .05). In the hypoadiponectinemia group, the autonomic function measurements included a lower baroreflex sensitivity ( P< .05) and a lower delayed myocardial uptake of 123I-MIBG ( P < .01) with a higher washout rate ( P < .05). Multiple regression analysis revealed that the plasma adiponectin level was independently associated with HOMA-IR (F = 9.916) and the percent washout rate of 123I-MIBG (F = 5.985). Our results suggest that in middle-aged men with type 2 diabetes mellitus, hypoadiponectinemia is associated with cardiac sympathetic overactivity as determined by 123I-MIBG scintigraphy.

Sympathetic Overactivity in Patients With Left Ventricular Aneurysm in Early Period After Anterior Myocardial Infarction: Does Sympathetic Activity Predict Aneurysm Formation?

Left ventricular aneurysm (LVA) is an important complication of acute transmural myocardial infarction (MI) that bears great clinical significance because of high mortality. Heart rate variability (HRV) analysis is extensively used to evaluate autonomic modulation of sinus node and to identify patients at risk for an increased cardiac mortality. In this study, the authors evaluated HRV in patients with LVA in the early period after acute anterior wall MI. They compared 18 patients (7 men, 11 women, with an average age of 56.1 +/-8.2 years) with LVA and 46 patients (34 men, 12 women, with an average age of 56.4 +/-5.9 years) without LVA. Mean heart rate, low frequency (LF) and low-frequency/high-frequency (LF/HF) ratio were significantly higher and standard deviation of normal-to-normal RR intervals (SDNN), root mean square of successive differences (RMSSD), number of NN intervals that differed by more than 50 ms from adjacent interval divided by the total number of all NN intervals (PNN50), and HF were lower in the patients with LVA. A SDNN <78 ms separated the patients with aneurysm from those without aneurysm with a sensitivity of 78%, specificity of 83%, positive predictive accuracy of 79%; a LF/HF ratio >2.4 with a sensitivity of 92%, specificity of 88%, and positive predictive accuracy of 92%. Single-vessel disease increased the left ventricular aneurysm formation by 5.1 fold, total left anterior descending artery (LAD) occlusion by 3.1 fold, mean heart rate >75 beats/minute by 2.3 fold, SDNN <78 ms by 7.9 fold, and LF/HF ratio >2.4 by 12.9 fold, but well-developed collaterals decreased the aneurysm formation by 4.4 fold. As a result, HRV analysis supplies parameters with high predictive value for LVA formation in the early period after acute anterior MI. The higher sympathetic activity and reduced heart rate variability may be associated with a higher incidence of complications such as ventricular arrhythmias and increased mortality in patients with LVA.

Mechanisms of sympathetic overactivity in patients with chronic renal failure: a role for chemoreflex activation?

Mechanisms of sympathetic overactivity in patients with chronic renal failure: a role for chemoreflex activation?

Sympathetic Overactivity in Patients with Chronic Renal Failure - The Culprit of Increased Cardiovascular Mortality?

Tonic activation of the sympathetic nervous system is a major factor contributing to hypertension in patients with chronic renal failure. Besides its role in blood pressure regulation, sympathetic overactivity causes structural and functional alterations of the myocardium and large artery walls. Altogether, these factors contribute substantially to the increased cardiovascular morbidity and mortality in patients with chronic renal disease. Moreover, increased sympathetic outflow in conjunction with increased oxidative stress causes progression of renal disease thereby accelerating the course towards the need of renal replacement therapy. The origin of increased sympathetic outflow in patients with renal disease still has not been fully elucidated. There is sound evidence that signals arising from the diseased kidneys - mediated via renal afferent nerves – cause tonic activation of efferent sympathetic nerve fibres. Renal ischemia with release of adenosine and renal chemoreceptor activation, accumulation of angiotensin II and fibroproliferative scarring with renal mechanoreceptor dysfunction may be involved in the activation of renal afferences. Sympathetic overactivity in renal disease can be diminished by blockers of the renin angiotensin aldosterone system, by adrenoreceptor blockers and by substances inhibiting central sympathetic outflow such as imidazolines. These drugs not only reduce sympathetic nerve activity, they attenuate cardiovascular pathology and they slow the progression of renal disease. A combination of these drugs in patients with chronic renal failure seems promising and warrants randomized large-scale studies.

Sympathetic overactivity in patients with rheumatic mitral stenosis.

Mitral stenosis may increase sympathetic nervous activity by increasing left atrial pressure and reducing cardiac output. And elevated sympathetic nerve activity may be a risk factor for the development of clinical manifestations of mitral stenosis. In this study, we assessed the autonomic nervous system activity in patients with mitral stenosis by heart rate variability analysis and defined factors affecting autonomic functions. Fifty-four patients with rheumatic mitral stenosis were compared with an age- and gender-matched control group composed of 42 healthy individuals. SDNN, RMSSD, PNN50, and HF were lower; mean heart rate (HR), LF and LF/HF ratio were higher in the patients with mitral stenosis compared to the control group. SDNN was correlated positively with left ventricle ejection fraction (LVEF), negatively with mitral valve area, left atrial (LA) diameter, and duration of symptoms. RMSSD was correlated positively with mean transmitral gradient, negatively correlated with age; PNN50 was correlated negatively with mitral valve area and positively correlated with transmitral gradient. LF was positively and HF was negatively correlated with LA diameter; LF was correlated positively, and HF was negatively correlated with duration of symptoms. LF/HF ratio was positively correlated with LA diameter and duration of symptoms, negatively with LVEF and mean valve area. As a result, sympathetic nervous system activity is increased in patients with mitral stenosis and sympathetic overactivity worsens their symptoms. Most significant factors that affect autonomic functions in these patients are left atrial dilatation and mitral valve area.

Chronic atrial fibrillation does not influence the magnitude of sympathetic overactivity in patients with heart failure

In this study we sought to assess the influence of atrial fibrillation (AF) on sympathetic nervous system overactivity in congestive heart failure (CHF) patients. We studied 133 consecutive patients with moderate to severe CHF. Subjects underwent haemodynamic assessment (right heart catheterization) and assessment of total systemic and cardiac sympathetic activity by the norepinephrine (NE) spillover method. The study population included 108 patients in sinus rhythm (SR) and 25 in AF. While AF patients had a lower cardiac output (CO) (SR vs AF: 4.2+/-0.1 vs 3.7+/-0.2l/min, P<0.05), the groups were otherwise matched for systemic blood pressure (BP), heart rate and filling pressures. In conjunction, total body NE spillover (SR vs AF: 5.8+/-0.4 vs 4.9+/-0.5 nmol/min, P>0.05) and cardiac NE spillover (SR vs AF: 339+/-21 vs 393+/-49 pmol/min, P>0.05) were not significantly different between the two groups, while the systemic clearance rate for NE was lower in the AF group (SR vs AF: 2.2+/-0.1 vs 1.6+/-0.1l/min, P<0.05). Congestive heart failure patients in AF do not appear to have heightened sympathetic tone compared to CHF patients in SR.

Sympathetic overactivity in patients with chronic renal failure.

Hypertension is a frequent complication of chronic renal failure, but its causes are not fully understood. There is indirect evidence that increased activity of the sympathetic nervous system might contribute to hypertension in patients with end-stage renal disease, but sympathetic-nerve discharge has not been measured directly in patients or animals with chronic renal failure. We recorded the rate of postganglionic sympathetic-nerve discharge to the blood vessels in skeletal muscle by means of microelectrodes inserted into the peroneal nerve in 18 patients with native kidneys who were undergoing long-term treatment with hemodialysis (of whom 14 had hypertension), 5 patients receiving hemodialysis who had undergone bilateral nephrectomy (of whom 1 had hypertension), and 11 normal subjects. RESULTS. The mean (+/- SE) rate of sympathetic-nerve discharge was 2.5 times higher in the patients receiving hemodialysis who had not undergone nephrectomy than in the normal subjects (58 +/- 3 vs. 23 +/- 3 bursts per minute, P < 0.01). In contrast, the rate of sympathetic-nerve discharge was similar in the patients receiving hemodialysis who had undergone bilateral nephrectomy (21 +/- 6 bursts per minute) and the normal subjects. The rate of sympathetic-nerve discharge in the patients receiving hemodialysis who had not undergone nephrectomy was also significantly higher (P < 0.01) than that in the patients with bilateral nephrectomy, and it was accompanied in the former group by higher values for vascular resistance in the calf (45 +/- 4 vs. 22 +/- 4 units, P < 0.05) and mean arterial pressure (106 +/- 4 vs. 76 +/- 14 mm Hg, P < 0.05). The rate of sympathetic-nerve discharge was not correlated with either plasma norepinephrine concentrations or plasma renin activity. Chronic renal failure may be accompanied by reversible sympathetic activation, which appears to be mediated by an afferent signal arising in the failing kidneys.

Renal contribution TC sympathetic overactivity in patients with cirrhosis

The purpose of this study was to estimate the relative contribution of the kidneys to overall sympathetic activity in a large series of cirrhotic patients. In 55 patients with cirrhosis, plasma norepinephrine concentrations (PNCI were measured by HPLC with electrochemical detection in the right renal vein and in the pulmonary artery. Following values were calculated: plasWl norepinrphtine renal outflow = PNC in the right renal vein x renal plasma flow (PAH clearance and extraction method); total plasma norepinephrine flow = PNC in the pulmonary artery Y cardiac output x (1-M.). Results are mean + SE. PNC was significantly higher in the right renal vein than in the pulmonary artery (803 + 54 and 608 f 47 pghl. respectively). Total phsma norepinephrine flow was 3073 +271. Plasma norepinephrine renal outflow was 480 + 50. The ratio between these two values ranged from 3 to 491. Total plasma norepinephrine flow was significantly correlated with renal norepinephrine outflow (r-=0.663; p<O.Ol{'a~~ the slope was elevated (3.59). In cirrhotics, the kidneys participate to overall sympathetic overactivity but their role fs passed by other organs in patients with the highest srpathetic overactivity.