The detrimental effects of stress on the cardiovascular system have been documented through research in animal models and humans. The INTERHEART Study has shown in a very large population that psychosocial stress is associated with increased risk of acute myocardial infarction independent of other cardiovascular risk factors. Stress cardiomyopathy, also referred to as Takotsubo cardiomyopathy, is an increasingly recognized clinical syndrome characterized by acute reversible apical ventricular dysfunction. Even if stress is indicated as possible trigger for this syndrome the specific mechanisms underlying the development of a Takotsubo syndrome remain poorly understood. Stress acutely induces endothelial dysfunction and activation of the sympathetic nervous system and leads to increased plasma levels of many substances such as cortisol, catecholamines, and endothelin. These mechanisms may play a role in the chain leading from psychological/physical stress to the apical ballooning syndrome.

In a research project founded by the Swiss National Foundation our group plan to improve our knowledge about the mechanisms underlying the effect of stress on cardiovascular surrogate parameters such as endothelial function, platelet function and sympathetic nervous activity. Specifically we plan to evaluate the sympathetic nervous activity in baseline conditions and during different mental stress tests in patients with Takotsubo syndrome and age-matched patients with similar cardiovascular risk profile. We also plan to compare endothelial function, vascular compliance, carotid atherosclerosis, oxidative stress and inflammation parameters and platelet adhesion in those two groups.


Methods:
Sympathetic nervous activity will be directly evaluated with microneurography at rest and after stress test (mental stress, cold face test and cold pressor test) will be evaluated in patients with apical ballooning and in age-matched controls.
Endothelial function will be evaluated non invasively by flow-mediated dilation of the brachial artery.
Vascular compliance will be evaluated by measurement of pulse wave analysis and pulse wave velocity using the SfygmoCor® device.
Carotid media intima-thickness and total plaque area will be measured by ultrasound.
Platelet adhesion will be evaluated using a shear stress-dependent platelet function method.
Oxidative stress will be evaluated as total antioxidative capacity, plasma levels of 8-isoprostanes and of oxidized-LDL; CRP will be evaluated as parameter of inflammation.


Expected value of the proposed project:
A better understanding of the mechanisms underlying the cardiovascular effect of acute stress in patients with apical ballooning syndrome and in age-matched controls may help us to identify preventive and therapeutical strategy leading to a further reduction in cardiovascular risk.



Contact:
Prof. Dr. med. Georg Noll, Dr. med. Isabella Sudano, Susanne Roas, Priska Kaiser and Astrid Hirt
Cardiovascular Center Cardiology, University Hospital of Zurich
Rämistrasse 100
8091 Zürich
Switzerland

Tel: +41 44 255 22 80
Fax: +41 44 255 48 59