Our mission is to become a worldwide reference for education in the field for all professionals involved in the process to dissemintate knowledge & skills of Acute Cardiovascular Care
Our mission is to promote excellence in clinical diagnosis, research, technical development, and education in cardiovascular imaging in Europe.
Our mission: To promote excellence in research, practice, education and policy in cardiovascular health, primary and secondary prevention.
Our goal is to reduce the burden in cardiovascular disease in Europe through percutaneous cardiovascular interventions.
Our Mission is "to improve the quality of life of the population by reducing the impact of cardiac rhythm disturbances and reduce sudden cardiac death"
To improve quality of life and logevity, through better prevention, diagnosis and treatment of heart failure, including the establishment of networks for its management, education and research.
Working Groups goals is to stimulate and disseminate scientific knowledge in different fields of cardiology.
ESC Councils goal is to share knowledge among medical professionals practising in specific cardiology domains.
OUR MISSION: TO REDUCE THE BURDEN OF CARDIOVASCULAR DISEASE
Ms M.K Jezovnik
Endothelial dysfunction is an early marker of atherosclerosis and levels of vascular relaxation are an indicator of endothelial health. Measured response to pharmacological agents or hemodynamic provocation tests is the means to assess it. To this end, flow mediated dilatory capability of brachial artery testing, peripheral arterial tonometry, venous occlusion pletismography and study of circulatory markers are non-invasive alternatives to intra-arterial and or intravacular testing.
Assessment of the pathophysiology of the endothelium and its ability to act as a potential therapeutic target is a growing area of research. Over the past two decades, its role in the initiation, progression, and clinical sequelae of atherosclerosis has been both increasingly studied and recognised (1). Moreover, endothelial dysfunction has been shown in varied populations to be a predictor of cardiovascular events. Concomitantly, disturbances in vascular biology provide a pathophysiological basis for identifying individuals at increased risk of future acute cardiovascular events. Together, these findings might lead to widespread prevention of atherosclerosis - in its preclinical stage, which would have a major global health impact. Nevertheless, endothelial function has, for the time being, been demonstrated to be a marker for risk of cardiovascular events in high risk groups only. Additionally, there is considerable debate regarding what is the most appropriate method for assessing endothelial function. Here we explore methods available. Whether in coronary or peripheral arteries, response to pharmacological agents and/or to hemodynamic provocation tests is assessed as a measure of endothelial function (2). There are invasive and non-invasive techniques exploring various aspects of pathobiology (3).
The invasive technique involves delivery of vasoactive agents via intra-arterial infusion. Response is measured either with high resolution ultrasound or strain gauge pletismography. Intra-arterial examination can be combined with intravascular examination through intravascular infusion of vasoactive stimulus. Response is then measured through intravascular ultrasound. Acetyl-choline is the vasodilatory agent that is usually used. It activates endothelial cells and stimulates nitric oxide release. Physiologically, in patients with a normal endothelial response, acetyl-choline will cause released access to the vasodilators, and result in dilation of blood vessels and hyperaemia. In patients with endothelial dysfunction, this process is disturbed and results in decreased vasodilation, thus demonstrating the dysfunction. However, in certain patients, a paradoxical vasoconstriction event ensues (4) such that this technique actually carries a risk of coronary ischemia. Moreoever, this technique is invasive and costly, therefore, wide spread use and clinical utility is limited.
Atherosclerosis and endothelial dysfunction are diffuse disease processes affecting coronary and peripheral arteries, hence, the physiological basis in assessing endothelium-dependent vasomotion in peripheral vessels. Peripheral vessels are accessible for non-invasive testing and may be considered a “window to the circulatory system”. Numerous methods for evaluating the peripheral arterial system have emerged as alternatives to coronary endothelial function testing.
Exploration of the brachial artery's flow mediated dilatory capability is the most commonly used technique. High-resolution vascular ultra-sound investigation of the brachial artery before and during reactive hyperaemia (1) shows vasodilatation from the release of nitric oxide as a response to stress induced during increased blood flow. A lack of vasodilation would suggest decreased release of endogenous vasodilators and therefore, endothelial dysfunction, thus indicating future cardiovascular risk: increased risk for future cardiovascular events and a potential need for revascularisation (5). Impaired peripheral endothelial function has also independently predicted adverse outcomes in specific patient cohorts, such as heart failure cohorts (6). Further studies indicated that FMD can reveal the effects of treatment of cardiovascular diseases, and an association between improvement of brachial artery FMD with reduction of cardiovascular event was shown (7). Flow mediated dilatory capability of brachial artery is widely used, however there are technical and interpretational limitations to this method. Further studies are needed to determine whether this methodology is sufficiently reproducible and whether biological variability is low enough to make of assessment of FMD a clinically useful measure of cardiovascular risk.
Peripheral arterial tonometry (PAT) evaluates pulse wave amplitude and is linked to endothelial dysfunction: abnormalities in pulse wave amplitude have long been described in peripheral circulation in patients with atherosclerosis (8). Furthermore, peripheral arterial tonometry hyperaemia has been shown to be an adequate surrogate marker to assess changes in vascular function over time and in the Framingham cohort, it was closely linked with cardiovascular risk factor (9). Lastly, studies showed that results correlate with brachial artery as well as coronary artery endothelial function testing (10). How FMD and PAT differ Flow mediated dilatory capability of brachial artery and PAT have been shown to be reduced 1) in a dose-dependent fashion in the presence of cardiovascular risk factors, as well as 2) in the presence of atherosclerosis. However, studies have also shown that FMD is not correlated with PAT findings (11). This is not suprising since FMD of brachial artery and PAT are very different methods for identification of vascular reactivity of different arterial territories: FMD of brachial artery directly registers the dilation capability of the large-conduit artery whereas PAT measures flow response on reactive hyperaemia which is itself related to endothelial function of small (digital) arteries and to the endothelial function of microcirculation.
Venous occlusion pletismography measures volume changes induced 1) by mercury strain gauge during hyperaemia in the forearm provoked by vasoactive agents, - including drugs to release nitric oxide or inhibitors of endothelial nitric oxide synthesis or 2) by reactive hyperaemia following forearm occlusion (12). Measuring the vasoactive response to brachial artery infusion of acetylcholine in patients with known coronary artery disease has been shown to be a prognostic marker for future cardiovascular events (12). Fore-arm endothelial dysfunction as confirmed by occlusion pletismography is also a marker for long-term cardiovascular complications in patients with hypertension (8). How FMD and Venous occlusion pletismography differ In contrast to FMD, which measures changes in the brachial artery, occlusion pletismography registers changes in blood flow. These changes are pre-regulated by peripheral resistance from endothelial function of resistance arteries and microcirculation.
In addition to vascular imaging techniques and measures of blood flow, other testing may provide information regarding endothelial health.
Knowledge regarding the health of endothelium in a given patient would be useful to identify subjects at risk for cardiovascular events according to the estimated risk they have for atherosclerosis and even irrespective of these risks. It would then be possible to know in which cases to administer intensive medical therapy and elimination of risk factors very early on.
Non-invasive assessment of endothelial function might be a welcome addition to the physician’s diagnostic armamentarium, allowing for detection of subjects who have a higher than expected cardiovascular risk, and should be considered for intensification of therapy (16). Nevertheless which is the ideal technique, -i.e most reliable, producible, affordable, and easy to perform- has yet to be confirmed.
1. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R. 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(2):257-265. 2. Poredos P. Endothelial dysfunction and cardiovascular disease. Pathophysiol Haemost Thromb 2002; 32(5-6):274-277. 3. Agewall S, Doughty RN, Bagg W, Whalley GA, Braatvedt G, Sharpe N. Comparison of ultrasound assessment of flow-mediated dilatation in the radial and brachial artery with upper and forearm cuff positions. Clin Physiol 2001; 21(1):9-14. 4. Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 1986; 315(17):1046-1051. 5. Neunteufl T, Heher S, Katzenschlager R, Wolfl G, Kostner K, Maurer G, Weidinger F. Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol 2000; 86(2):207-210. 6. Heitzer T, Baldus S, von Kodolitsch Y, Rudolph V, Meinertz T. Systemic endothelial dysfunction as an early predictor of adverse outcome in heart failure. Arterioscler Thromb Vasc Biol 2005; 25(6):1174-1179. 7. Suessenbacher A, Frick M, Alber HF, Barbieri V, Pachinger O, Weidinger F. Association of improvement of brachial artery flow-mediated vasodilation with cardiovascular events. Vasc Med 2006; 11(4):239-244. 8. Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A, Ferraro A, Chello M, Mastroroberto P, Verdecchia P, Schillaci G. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 2001; 104(2):191-196. 9. Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, Heckbert SR, Johnson KC, Manson JE, Sidney S, Trevisan M.Calcium/vitamin D supplementation and cardiovascular events. Circulation 2007; 115(7):846-854. 10. Kuvin JT, Patel AR, Sliney KA, Pandian NG, Sheffy J, Schnall RP, Karas RH, Udelson JE. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J 2003; 146(1):168-174. 11. Aizer J, Karlson EW, Chibnik LB, Costenbader KH, Post D, Liang MH, Gall V, Gerhard-Herman MD. A controlled comparison of brachial artery flow mediated dilation (FMD) and digital pulse amplitude tonometry (PAT) in the assessment of endothelial function in systemic lupus erythematosus. Lupus 2009; 18(3):235-242. 12. Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001; 104(22):2673-2678. 13. Parker Iii C, Vita JA, Freedman JE. Soluble adhesion molecules and unstable coronary artery disease. Atherosclerosis 2001; 156(2):417-424. 14. Jansson JH, Nilsson TK, Johnson O. von Willebrand factor in plasma: a novel risk factor for recurrent myocardial infarction and death. Br Heart J 1991; 66(5):351-355. 15. Lerman A, Edwards BS, Hallett JW, Heublein DM, Sandberg SM, Burnett JC, Jr. Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis. N Engl J Med 1991; 325(14):997-1001. 16. Ramcharan AS, Van Stralen KJ, Snoep JD, Mantel-Teeuwisse AK, Rosendaal FR, Doggen CJM. HMG-CoA reductase inhibitors, other lipid-lowering medication, antiplatelet therapy, and the risk of venous thrombosis. Journal of Thrombosis and Haemostasis 2009; 7(4):514-520.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
© 2016 European Society of Cardiology. All rights reserved