Aktuelle Kardiologie 2014; 3(5): 314-318
DOI: 10.1055/s-0034-1383228
Übersichtsarbeit
Georg Thieme Verlag KG Stuttgart · New York

Prognostische Bedeutung der endothelialen Dysfunktion

The Prognostic Meaning of Endothelial Dysfunction
M. Vosseler
II. Medizinische Klinik und Poliklinik, Kardiologie und Angiologie, Universitätsmedizin Mainz, Mainz
,
P. Wild
II. Medizinische Klinik und Poliklinik, Kardiologie und Angiologie, Universitätsmedizin Mainz, Mainz
,
T. Gori
II. Medizinische Klinik und Poliklinik, Kardiologie und Angiologie, Universitätsmedizin Mainz, Mainz
› Author Affiliations
Further Information

Publication History

Publication Date:
05 November 2014 (online)

Zusammenfassung

Eine Reihe von Biomarkern und Risikoscores wurde entwickelt, um eine Risikostratifizierung bei gesunden und kranken Menschen, die ein kardiovaskuläres Risiko haben, durchzuführen. Obwohl sie auf Populationsebene wirken und in Guidelines implementiert wurden, wird trotzdem ein Teil der Population falsch klassifiziert. Wichtiger ist jedoch, dass die Aussagekraft auf dem Level einzelner Patienten niedrig ist und spezifische klinische Entscheidungen nicht allein dadurch getroffen werden können. Des Weiteren liefern diese Risikoscores keine Informationen über den Einfluss auf das Outcome der Patienten unter medikamentöser Therapie. Sie liefern ebenfalls keine Information, ob sich das individuelle Risiko über die Zeit verändert. Die Messung der endothelialen Funktion liefert Informationen über den gesamten Einfluss aller Risikofaktoren, bekannte und unbekannte, auf die gesamte Gefäßfunktion. Somit kann diese Messung theoretisch Informationen über den Einfluss der Risikofaktoren und den Einfluss einer Therapie eines einzelnen Patienten liefern. Während diese biologische Sichtweise solide erscheint, gibt es jedoch eine Reihe von Limitationen, die, technisch wie auch theoretisch, den Einsatz der Endothelfunktionsmessung in der täglichen Routine einschränken.

Abstract

A number of biomarkers or risk scores have been developed to allow risk stratification in patients and healthy subjects at risk for cardiovascular events. Although these scores work at a population level and are suited to design guidelines, yet a significant portion of the population is still misclassified. More importantly, the performance of these tools at the level of individual patients is relatively poor, and specific clinical decisions can hardly be made based on general risk scores. Further, risk scores do not provide information on the impact of medical treatments on patientsʼ outcome, and they do not provide information on whether the individual risk changes over time. The assessment of endothelial function is thought to provide information on the combined effect of all risk factors – known and unknown – on vascular function. Therefore, in theory, endothelial function assessment can theoretically provide information on the impact of these risk factors, and on the responsiveness to therapies, in individual patients. While this biological rationale appears to be solid, a number of limitations, both technical and theoretical, limit the impact of endothelial function assessment in daily clinical practice. These limitations are discussed in the present review.

 
  • Literatur

  • 1 Khot UN, Khot MB, Bajzer CT et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA 2003; 290: 898-904
  • 2 Forconi S, Gori T. Endothelium and hemorheology. Clin Hemorheol Microcirc 2013; 53: 3-10
  • 3 Flammer AJ, Anderson T, Celermajer DS et al. The assessment of endothelial function: from research into clinical practice. Circulation 2012; 126: 753-767
  • 4 Gori T, Damaske A, Muxel S et al. Endothelial function and hemorheological parameters modulate coronary blood flow in patients without significant coronary artery disease. Clin Hemorheol Microcirc 2012; 52: 255-266
  • 5 Munzel T, Sinning C, Post F et al. Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction. Ann Med 2008; 40: 180-196
  • 6 Lekakis J, Abraham P, Balbarini A et al. Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation. Eur J Cardiovasc Prev Rehabil 2011; 18: 775-789
  • 7 Ludmer PL, Selwyn AP, Shook TL et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 1986; 315: 1046-1051
  • 8 Ong P, Athanasiadis A, Borgulya G et al. Clinical usefulness, angiographic characteristics, and safety evaluation of intracoronary acetylcholine provocation testing among 921 consecutive white patients with unobstructed coronary arteries. Circulation 2014; 129: 1723-1730
  • 9 Anderson TJ, Uehata A, Gerhard MD et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 1995; 26: 1235-1241
  • 10 Gori T, Di Stolfo G, Sicuro S et al. Correlation analysis between different parameters of conduit artery and microvascular vasodilation. Clin Hemorheol Microcirc 2006; 35: 509-515
  • 11 Ostad MA, Wild PS, Schnorbus B et al. Predictive value of brachial reactive hyperemia and flow-mediated dilation in stable coronary artery disease. Clin Hemorheol Microcirc 2014; 56: 247-257
  • 12 Celermajer DS, Sorensen KE, Gooch VM et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111-1115
  • 13 Corretti MC, Anderson TJ, Benjamin EJ et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002; 39: 257-265
  • 14 Gori T, Muxel S, Damaske A et al. Endothelial function assessment: flow-mediated dilation and constriction provide different and complementary information on the presence of coronary artery disease. Eur Heart J 2012; 33: 363-371
  • 15 Ghiadoni L, Salvetti M, Muiesan ML et al. Evaluation of Endothelial Function by Flow Mediated Dilation: Methodological Issues and Clinical Importance. High Blood Press Cardiovasc Prev 2014; [Epub ahead of print]
  • 16 Shimbo D, Grahame-Clarke C, Miyake Y et al. The association between endothelial dysfunction and cardiovascular outcomes in a population-based multi-ethnic cohort. Atherosclerosis 2007; 192: 197-203
  • 17 Yeboah J, Folsom AR, Burke GL et al. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation 2009; 120: 502-509
  • 18 Karatzis EN, Ikonomidis I, Vamvakou GD et al. Long-term prognostic role of flow-mediated dilatation of the brachial artery after acute coronary syndromes without ST elevation. Am J Cardiol 2006; 98: 1424-1428
  • 19 Inaba Y, Chen JA, Bergmann SR. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. Int J Cardiovasc Imaging 2010; 26: 631-640
  • 20 Ras RT, Streppel MT, Draijer R et al. Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis. Int J Cardiol 2013; 168: 344-351
  • 21 Chan SY, Mancini GB, Kuramoto L et al. The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease. J Am Coll Cardiol 2003; 42: 1037-1043
  • 22 Ulriksen LS, Malmqvist BB, Hansen A et al. Flow-mediated dilatation has no independent prognostic effect in patients with chest pain with or without ischaemic heart disease. Scand J Clin Lab Invest 2009; 69: 475-480
  • 23 Nakamura T, Kitta Y, Uematsu M et al. Ultrasound assessment of brachial endothelial vasomotor function in addition to carotid plaque echolucency for predicting cardiovascular events in patients with coronary artery disease. Int J Cardiol 2013; 167: 555-560
  • 24 Schaefer S, Muxel S, Fasola F et al. Evidence of a weak correlation between peripheral endothelial function measures and carotid intima-media thickness. Clin Hemorheol Microcirc 2012; 52: 235-243
  • 25 Takishima I, Nakamura T, Hirano M et al. Predictive value of serial assessment of endothelial function in chronic heart failure. Int J Cardiol 2012; 158: 417-422
  • 26 Kitta Y, Obata JE, Nakamura T et al. Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease. J Am Coll Cardiol 2009; 53: 323-330
  • 27 Modena MG, Bonetti L, Coppi F et al. Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol 2002; 40: 505-510
  • 28 Kim DH, Braam B. Assessment of arterial stiffness using applanation tonometry. Can J Physiol Pharmacol 2013; 91: 999-1008
  • 29 Nohria A, Gerhard-Herman M, Creager MA et al. Role of nitric oxide in the regulation of digital pulse volume amplitude in humans. J Appl Physiol (1985) 2006; 101: 545-548
  • 30 Green DJ, Dawson EA, Groenewoud HM et al. Is flow-mediated dilation nitric oxide mediated?: A meta-analysis. Hypertension 2014; 63: 376-382
  • 31 Patvardhan EA, Heffernan KS, Ruan JM et al. Assessment of vascular endothelial function with peripheral arterial tonometry: information at your fingertips?. Cardiol Rev 2010; 18: 20-28
  • 32 Matsue Y, Suzuki M, Nagahori W et al. Endothelial dysfunction measured by peripheral arterial tonometry predicts prognosis in patients with heart failure with preserved ejection fraction. Int J Cardiol 2013; 168: 36-40
  • 33 Schnabel RB, Schulz A, Wild PS et al. Noninvasive vascular function measurement in the community: cross-sectional relations and comparison of methods. Circ Cardiovasc Imaging 2011; 4: 371-380
  • 34 Suessenbacher A, Dorler J, Wunder J et al. Comparison of brachial artery wall thickness versus endothelial function to predict late cardiovascular events in patients undergoing elective coronary angiography. Am J Cardiol 2013; 111: 671-675
  • 35 Careri G, Nerla R, Di Monaco A et al. Clinical correlates and prognostic value of flow mediated dilation in patients with non-ST segment elevation acute coronary syndromes. Am J Cardiol 2013; 111: 51-57
  • 36 Fathi R, Haluska B, Isbel N et al. The relative importance of vascular structure and function in predicting cardiovascular events. J Am Coll Cardiol 2004; 43: 616-623
  • 37 Frick M, Suessenbacher A, Alber HF et al. Prognostic value of brachial artery endothelial function and wall thickness. J Am Coll Cardiol 2005; 46: 1006-1010
  • 38 Gokce N, Keaney jr. JF, Hunter LM et al. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol 2003; 41: 1769-1775
  • 39 Patti G, Pasceri V, Melfi R et al. Impaired flow-mediated dilation and risk of restenosis in patients undergoing coronary stent implantation. Circulation 2005; 111: 70-75
  • 40 Kitta Y, Nakamura T, Kodama Y et al. Endothelial vasomotor dysfunction in the brachial artery is associated with late in-stent coronary restenosis. J Am Coll Cardiol 2005; 46: 648-655
  • 41 Tarro Genta F, Eleuteri E, Temporelli PL et al. Flow-mediated dilation normalization predicts outcome in chronic heart failure patients. J Card Fail 2013; 19: 260-267
  • 42 Fischer D, Rossa S, Landmesser U et al. Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death. Eur Heart J 2005; 26: 65-69
  • 43 Neunteufl T, Heher S, Katzenschlager R et al. Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol 2000; 86: 207-210
  • 44 Brevetti G, Silvestro A, Schiano V et al. Endothelial dysfunction and cardiovascular risk prediction in peripheral arterial disease: additive value of flow-mediated dilation to ankle-brachial pressure index. Circulation 2003; 108: 2093-2098