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Erschienen in: Lung 2/2014

01.04.2014

Increased Sympathetic Nerve Activity in COPD is Associated with Morbidity and Mortality

verfasst von: Stefan Andreas, Helge Haarmann, Stephan Klarner, Gerd Hasenfuß, Tobias Raupach

Erschienen in: Lung | Ausgabe 2/2014

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Abstract

Background

Chronic obstructive lung disease (COPD) is a major cause of comorbidity and mortality. Systemic effects, such as sympathetic activation, might contribute to progression and severity of the disease.

Objectives

This study investigated whether increased sympathetic activity is associated with increased long-term morbidity and mortality with COPD.

Methods

Following a baseline registration of muscle sympathetic nerve activity (MSNA), 21 COPD patients and 21 matched healthy control subjects were contacted after a mean follow-up period of 7 years. Information about the number of hospitalizations during follow-up was obtained from patients who were still alive. Information about the time of death was collected from relatives of the deceased and local registration offices. The primary endpoint was the comparison of MSNA in living patients without hospitalizations versus MSNA in the patients who died or had at least one hospitalization due to exacerbation of COPD.

Results

At baseline, MSNA was significantly increased, whereas forced expiratory volume in 1 s and arterial oxygen tension (PaO2) were significantly decreased in patients compared with controls. MSNA was significantly higher in COPD patients who had reached the combined endpoint of hospitalization or death during follow-up (n = 12) compared with patients who were still alive at follow-up and had not been hospitalized (n = 8): 60.3 ± 15.8 (SD) bursts/min versus 40.5 ± 17.5 bursts/min; p = 0.022.

Conclusions

Our data suggest that sympathetic activation is related to adverse outcome in COPD. Although this finding has to be replicated in larger studies, it implies that neurohumoral activation could be a potential therapeutic target in COPD.
Literatur
1.
Zurück zum Zitat Decramer M, Janssens W, Miravitlles M (2012) Chronic obstructive pulmonary disease. Lancet 379:1341–1351CrossRefPubMed Decramer M, Janssens W, Miravitlles M (2012) Chronic obstructive pulmonary disease. Lancet 379:1341–1351CrossRefPubMed
2.
Zurück zum Zitat Sin DD, MacNee W (2013) Chronic obstructive pulmonary disease and cardiovascular diseases: a “vulnerable” relationship. Am J Respir Crit Care Med 187:2–4CrossRefPubMed Sin DD, MacNee W (2013) Chronic obstructive pulmonary disease and cardiovascular diseases: a “vulnerable” relationship. Am J Respir Crit Care Med 187:2–4CrossRefPubMed
3.
Zurück zum Zitat Stone IS, Barnes NC, Petersen SE (2012) Chronic obstructive pulmonary disease: a modifiable risk factor for cardiovascular disease? Heart 98:1055–1062CrossRefPubMed Stone IS, Barnes NC, Petersen SE (2012) Chronic obstructive pulmonary disease: a modifiable risk factor for cardiovascular disease? Heart 98:1055–1062CrossRefPubMed
4.
Zurück zum Zitat Fabbri LM, Luppi F, Beghe B et al (2008) Complex chronic comorbidities of COPD. Eur Respir J 31:204–212CrossRefPubMed Fabbri LM, Luppi F, Beghe B et al (2008) Complex chronic comorbidities of COPD. Eur Respir J 31:204–212CrossRefPubMed
5.
Zurück zum Zitat Raupach T, Bahr F, Herrmann P et al (2008) Slow breathing reduces sympathoexcitation in COPD. Eur Respir J 32:387–392CrossRefPubMed Raupach T, Bahr F, Herrmann P et al (2008) Slow breathing reduces sympathoexcitation in COPD. Eur Respir J 32:387–392CrossRefPubMed
6.
Zurück zum Zitat Andreas S, Anker SD, Scanlon PD et al (2005) Neurohumoral activation as a link to systemic manifestation of chronic lung disease. Chest 128:3618–3624CrossRefPubMed Andreas S, Anker SD, Scanlon PD et al (2005) Neurohumoral activation as a link to systemic manifestation of chronic lung disease. Chest 128:3618–3624CrossRefPubMed
7.
Zurück zum Zitat Macnee W, Maclay J, McAllister D (2008) Cardiovascular injury and repair in chronic obstructive pulmonary disease. Proc Am Thorac Soc 5:824–833PubMedCentralCrossRefPubMed Macnee W, Maclay J, McAllister D (2008) Cardiovascular injury and repair in chronic obstructive pulmonary disease. Proc Am Thorac Soc 5:824–833PubMedCentralCrossRefPubMed
8.
Zurück zum Zitat Fatouleh R, Macefield VG (2011) Respiratory modulation of muscle sympathetic nerve activity is not increased in essential hypertension or chronic obstructive pulmonary disease. J Physiol 589:4997–5006PubMedCentralCrossRefPubMed Fatouleh R, Macefield VG (2011) Respiratory modulation of muscle sympathetic nerve activity is not increased in essential hypertension or chronic obstructive pulmonary disease. J Physiol 589:4997–5006PubMedCentralCrossRefPubMed
9.
Zurück zum Zitat Floras JS (2009) Sympathetic nervous system activation in human heart failure: clinical implications of an updated model. J Am Coll Cardiol 54:375–385CrossRefPubMed Floras JS (2009) Sympathetic nervous system activation in human heart failure: clinical implications of an updated model. J Am Coll Cardiol 54:375–385CrossRefPubMed
10.
Zurück zum Zitat McMurray JJ, Adamopoulos S, Anker SD et al (2012) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 33:1787–1847CrossRefPubMed McMurray JJ, Adamopoulos S, Anker SD et al (2012) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 33:1787–1847CrossRefPubMed
11.
Zurück zum Zitat Swedberg K, Eneroth P, Kjekshus J et al (1990) Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. Circulation 82:1730–1736CrossRefPubMed Swedberg K, Eneroth P, Kjekshus J et al (1990) Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. Circulation 82:1730–1736CrossRefPubMed
13.
Zurück zum Zitat Heindl S, Lehnert M, Criée CP et al (2001) Marked sympathetic activation in patients with chronic respiratory failure. Am J Respir Crit Care Med 164:597–601CrossRefPubMed Heindl S, Lehnert M, Criée CP et al (2001) Marked sympathetic activation in patients with chronic respiratory failure. Am J Respir Crit Care Med 164:597–601CrossRefPubMed
14.
Zurück zum Zitat Pauwels RA, Buist AS, Ma P et al (2001) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: National Heart, Lung, and Blood Institute and World Health Organization global initiative for chronic obstructive lung disease (GOLD): executive summary. Respir Care 46:798–825PubMed Pauwels RA, Buist AS, Ma P et al (2001) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: National Heart, Lung, and Blood Institute and World Health Organization global initiative for chronic obstructive lung disease (GOLD): executive summary. Respir Care 46:798–825PubMed
15.
Zurück zum Zitat Ferguson DW, Berg WJ, Sanders JS (1990) Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings. J Am Coll Cardiol 16:1125–1134CrossRefPubMed Ferguson DW, Berg WJ, Sanders JS (1990) Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings. J Am Coll Cardiol 16:1125–1134CrossRefPubMed
16.
Zurück zum Zitat Wallin BG, Esler M, Dorward P et al (1992) Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans. J Physiol Lond 453:45–58PubMedCentralCrossRefPubMed Wallin BG, Esler M, Dorward P et al (1992) Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans. J Physiol Lond 453:45–58PubMedCentralCrossRefPubMed
17.
Zurück zum Zitat Heindl S, Dodt C, Krahwinkel M et al (2001) Short term effect of continuous positive airway pressure on muscle sympathetic nerve activity in patients with chronic heart failure. Heart 85:185–190PubMedCentralCrossRefPubMed Heindl S, Dodt C, Krahwinkel M et al (2001) Short term effect of continuous positive airway pressure on muscle sympathetic nerve activity in patients with chronic heart failure. Heart 85:185–190PubMedCentralCrossRefPubMed
18.
Zurück zum Zitat Andreas S, Reiter H, Luthje L et al (2004) Differential effects of theophylline on sympathetic excitation, hemodynamics, and breathing in congestive heart failure. Circulation 110:2157–2162CrossRefPubMed Andreas S, Reiter H, Luthje L et al (2004) Differential effects of theophylline on sympathetic excitation, hemodynamics, and breathing in congestive heart failure. Circulation 110:2157–2162CrossRefPubMed
19.
Zurück zum Zitat Shih HT, Webb CR, Conway WA et al (1988) Frequency and significance of cardiac arrhythmias in chronic obstructive lung disease. Chest 94:44–48CrossRefPubMed Shih HT, Webb CR, Conway WA et al (1988) Frequency and significance of cardiac arrhythmias in chronic obstructive lung disease. Chest 94:44–48CrossRefPubMed
20.
Zurück zum Zitat Jensen MT, Marott JL, Lange P et al (2012) Resting heart rate is a predictor of mortality in chronic obstructive pulmonary disease. Eur Respir J 42(2):341–349CrossRefPubMed Jensen MT, Marott JL, Lange P et al (2012) Resting heart rate is a predictor of mortality in chronic obstructive pulmonary disease. Eur Respir J 42(2):341–349CrossRefPubMed
21.
Zurück zum Zitat Schrier RW, Abraham WT (1999) Hormones and hemodynamics in heart failure. N Engl J Med 341:577–585CrossRefPubMed Schrier RW, Abraham WT (1999) Hormones and hemodynamics in heart failure. N Engl J Med 341:577–585CrossRefPubMed
22.
Zurück zum Zitat Jouven X, Empana JP, Escolano S et al (2009) Relation of heart rate at rest and long-term (>20 years) death rate in initially healthy middle-aged men. Am J Cardiol 103:279–283CrossRefPubMed Jouven X, Empana JP, Escolano S et al (2009) Relation of heart rate at rest and long-term (>20 years) death rate in initially healthy middle-aged men. Am J Cardiol 103:279–283CrossRefPubMed
23.
Zurück zum Zitat Calverley PM, Anderson JA, Celli B et al (2007) Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 356:775–789CrossRefPubMed Calverley PM, Anderson JA, Celli B et al (2007) Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 356:775–789CrossRefPubMed
24.
Zurück zum Zitat Tashkin DP, Celli B, Senn S et al (2008) A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 359:1543–1554CrossRefPubMed Tashkin DP, Celli B, Senn S et al (2008) A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 359:1543–1554CrossRefPubMed
25.
Zurück zum Zitat Rutten FH, Hoes AW (2012) Chronic obstructive pulmonary disease: a slowly progressive cardiovascular disease masked by its pulmonary effects? Eur J Heart Fail 14:348–350CrossRefPubMed Rutten FH, Hoes AW (2012) Chronic obstructive pulmonary disease: a slowly progressive cardiovascular disease masked by its pulmonary effects? Eur J Heart Fail 14:348–350CrossRefPubMed
26.
Zurück zum Zitat Van Eeden S, Leipsic J, Paul Man SF et al (2012) The relationship between lung inflammation and cardiovascular disease. Am J Respir Crit Care Med 186:11–16CrossRefPubMed Van Eeden S, Leipsic J, Paul Man SF et al (2012) The relationship between lung inflammation and cardiovascular disease. Am J Respir Crit Care Med 186:11–16CrossRefPubMed
27.
Zurück zum Zitat Borovikova LV, Ivanova S, Zhang M et al (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458–462CrossRefPubMed Borovikova LV, Ivanova S, Zhang M et al (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458–462CrossRefPubMed
28.
Zurück zum Zitat Barretto AC, Santos AC, Munhoz R et al (2009) Increased muscle sympathetic nerve activity predicts mortality in heart failure patients. Int J Cardiol 135:302–307CrossRefPubMed Barretto AC, Santos AC, Munhoz R et al (2009) Increased muscle sympathetic nerve activity predicts mortality in heart failure patients. Int J Cardiol 135:302–307CrossRefPubMed
29.
Zurück zum Zitat Munhoz RT, Negrao CE, Barretto AC et al (2009) Microneurography and venous occlusion plethysmography in heart failure: correlation with prognosis. Arq Bras Cardiol 92:46–53CrossRefPubMed Munhoz RT, Negrao CE, Barretto AC et al (2009) Microneurography and venous occlusion plethysmography in heart failure: correlation with prognosis. Arq Bras Cardiol 92:46–53CrossRefPubMed
30.
Zurück zum Zitat Heistad DD, Wheeler RC, Mark AL et al (1956) Effects of adrenergic stimulation on ventilation in man. Clin Invest 51(6):1469–1475CrossRef Heistad DD, Wheeler RC, Mark AL et al (1956) Effects of adrenergic stimulation on ventilation in man. Clin Invest 51(6):1469–1475CrossRef
31.
Zurück zum Zitat Coats AJ, Adamopoulos S, Radaelli A et al (1992) Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation, and autonomic function. Circulation 85:2119–2131CrossRefPubMed Coats AJ, Adamopoulos S, Radaelli A et al (1992) Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation, and autonomic function. Circulation 85:2119–2131CrossRefPubMed
32.
Zurück zum Zitat Anker SD, Coats AJ (1999) Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine activation. Chest 115:836–847CrossRefPubMed Anker SD, Coats AJ (1999) Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine activation. Chest 115:836–847CrossRefPubMed
33.
Zurück zum Zitat Packer M (1992) The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol 20:248–254CrossRefPubMed Packer M (1992) The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol 20:248–254CrossRefPubMed
34.
Zurück zum Zitat Somers VK, Anderson EA, Mark AL (1993) Sympathetic neural mechanisms in human hypertension. Curr Opin Nephrol Hypertens 2:96–105CrossRefPubMed Somers VK, Anderson EA, Mark AL (1993) Sympathetic neural mechanisms in human hypertension. Curr Opin Nephrol Hypertens 2:96–105CrossRefPubMed
35.
Zurück zum Zitat Hofford JM, Milakofsky L, Vogel WH et al (1990) The nutritional status in advanced emphysema associated with chronic bronchitis. A study of amino acid and catecholamine levels. Am Rev Respir Dis 141:902–908CrossRefPubMed Hofford JM, Milakofsky L, Vogel WH et al (1990) The nutritional status in advanced emphysema associated with chronic bronchitis. A study of amino acid and catecholamine levels. Am Rev Respir Dis 141:902–908CrossRefPubMed
36.
Zurück zum Zitat Francis GS, McDonald KM, Cohn JN (1993) Neurohumoral activation in preclinical heart failure. Remodeling and the potential for intervention. Circulation 87:IV90–IV96PubMed Francis GS, McDonald KM, Cohn JN (1993) Neurohumoral activation in preclinical heart failure. Remodeling and the potential for intervention. Circulation 87:IV90–IV96PubMed
37.
Zurück zum Zitat Dinenno FA, Jones PP, Seals DR et al (2000) Age-associated arterial wall thickening is related to elevations in sympathetic activity in healthy humans. Am J Physiol Heart Circ Physiol 278:H1205–H1210PubMed Dinenno FA, Jones PP, Seals DR et al (2000) Age-associated arterial wall thickening is related to elevations in sympathetic activity in healthy humans. Am J Physiol Heart Circ Physiol 278:H1205–H1210PubMed
38.
Zurück zum Zitat Swierblewska E, Hering D, Kara T et al (2010) An independent relationship between muscle sympathetic nerve activity and pulse wave velocity in normal humans. J Hypertens 28:979–984CrossRefPubMed Swierblewska E, Hering D, Kara T et al (2010) An independent relationship between muscle sympathetic nerve activity and pulse wave velocity in normal humans. J Hypertens 28:979–984CrossRefPubMed
39.
Zurück zum Zitat Laurent S, Cockcroft J, Van Bortel L et al (2006) Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 27:2588–2605CrossRefPubMed Laurent S, Cockcroft J, Van Bortel L et al (2006) Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 27:2588–2605CrossRefPubMed
40.
Zurück zum Zitat Vlachopoulos C, Aznaouridis K, Stefanadis C (2010) Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 55:1318–1327CrossRefPubMed Vlachopoulos C, Aznaouridis K, Stefanadis C (2010) Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 55:1318–1327CrossRefPubMed
41.
Zurück zum Zitat McAllister DA, Maclay JD, Mills NL et al (2007) Arterial stiffness is independently associated with emphysema severity in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 176:1208–1214PubMedCentralCrossRefPubMed McAllister DA, Maclay JD, Mills NL et al (2007) Arterial stiffness is independently associated with emphysema severity in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 176:1208–1214PubMedCentralCrossRefPubMed
42.
Zurück zum Zitat Maclay JD, McAllister DA, Mills NL et al (2009) Vascular dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 180:513–520CrossRefPubMed Maclay JD, McAllister DA, Mills NL et al (2009) Vascular dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 180:513–520CrossRefPubMed
43.
Zurück zum Zitat Sabit R, Bolton CE, Edwards PH et al (2007) Arterial stiffness and osteoporosis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 175:1259–1265CrossRefPubMed Sabit R, Bolton CE, Edwards PH et al (2007) Arterial stiffness and osteoporosis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 175:1259–1265CrossRefPubMed
44.
45.
Zurück zum Zitat Yucha CB (2000) Use of microneurography to evaluate sympathetic activity in hypertension: a brief review. Appl Psychophysiol Biofeedback 25:55–63CrossRefPubMed Yucha CB (2000) Use of microneurography to evaluate sympathetic activity in hypertension: a brief review. Appl Psychophysiol Biofeedback 25:55–63CrossRefPubMed
46.
Zurück zum Zitat Jennings GL (1998) Noradrenaline spillover and microneurography measurements in patients with primary hypertension. J Hypertens Suppl 16:S35–S38PubMed Jennings GL (1998) Noradrenaline spillover and microneurography measurements in patients with primary hypertension. J Hypertens Suppl 16:S35–S38PubMed
47.
Zurück zum Zitat Hagbarth KE (2002) Microelectrode recordings from human peripheral nerves (microneurography). Muscle Nerve Suppl 11:S28–S35CrossRefPubMed Hagbarth KE (2002) Microelectrode recordings from human peripheral nerves (microneurography). Muscle Nerve Suppl 11:S28–S35CrossRefPubMed
Metadaten
Titel
Increased Sympathetic Nerve Activity in COPD is Associated with Morbidity and Mortality
verfasst von
Stefan Andreas
Helge Haarmann
Stephan Klarner
Gerd Hasenfuß
Tobias Raupach
Publikationsdatum
01.04.2014
Verlag
Springer US
Erschienen in
Lung / Ausgabe 2/2014
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-013-9544-7

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