Grant-funded Project Nr. 077/1999/C/1.LF
Final Report

Project title:The influence of hypercortisolism on the becoming and development of atherosclerotic changes of vessels
Research leader:Prof.MUDr. Josef Marek, DrSc.
Co-researcher: MUDr. Michal Kršek, CSc.; MUDr. Markéta Marková; MUDr. Martin Haluzík, CSc.; MUDr. Jana Ježková; MUDr. Martin Práznŭ; MUDr. Josef Šilha; MUDr. Renáta Vacková; MUDr. Zuzana Adamcová; MUDr. Martina Rosická
Period of project:1999-2001
Overall grant:1103 000 CZK

Project Results

Hypercortisolism, both endogenous as well as induced by the treatment with glucocorticoids,  is known to fasten atherosclerotic process. Our task was to discover 1) if this process continues even after the cure of the florid phase of hypercortisolism, 2) which factors participate on this process.
For examination there were used follwing methods: ultrasound examination of carotid vessels, examination of the microcirculation by laser-Doppler flowmetry, routine biochemical examination, densitometric examination of body fat, examination of cytoadhesive molecules, acute phase proteins, effects of free oxigen radicals, some coagulation factors, antiphospholipid, antiendothelial and anti oxidated LDL antibodies and some hormones (IRI, C-peptide, growth hormone, IGF I, IGF BP3). Following groups were examined: 1) patients with Cushing s syndrome, 2) patients with Cushing´s syndrome 6-12 months after the sucessfull surgery, 3) control group matched by gender, age and BMI, 4) patients with cured Cushing´s syndrome before 2-22 (mean 7,7, median) years. 5) Control group to group 4 matched by gender, age and  BMI.
The results: 1) Atherosclerotic process is more advanced even in patients which were attained by hypercortisolism 2-22 years ago. In these patients the incidence of 41,6% sclerotic plaques or stenosis on carotid vessels was found in comparison with 12,5% in the control group, the patients had pathological results of the microcirculation, they were obese, 25% of them were hypertensive, they had increased total and LDL cholesterol, tehy had decreased levels ov VEGF (which contributes to reparation of the endothel) and increased levels of fibrinogen. 2) Patients with florid Cushing´s syndrome had hypertension and hyperlipidemia (increased total and LDL cholesterol, meanwhile absolute levels of TAG were increased but did not differ from the control group. The process of the chronic noninfectious inflammation participate by liberating of cytokines to the atherosclerotic damage. Glucocorticoids are not able to suppress fully these inflammation by its immunosupressive activity: orosomucoid, the positive acuthe phase protein was increased even during the floride phase of hypercortisolism. On the second hand glucocorticoids were effective in suppression of ICAM 1 and in preventing of increase in titres of antiphospholipid, antiendothelial and anti - oxidised LDL antibodies. It can be deduced that the presence of these antibodies is not necessary for the acceleration of atherosclerosis. Glucocorticoids are not able to suppress the production of free oxigen radicals (as given by serum malondialdehyd). Besides, it is possible to speculate that even the lack of growth hormone may participate on the development of atherosclerotic changes in hypercortisolism.
In examination of the atherosclerotic changes the importance of laser-Doppler flowmetry was demonstrated: the pathological changes  outlasted from florid phase over the early operated patients  to previously cured patients.
On the basis of our research results a hypothesis was suggested, that hypercortisolism leaves behind the permanent metabolic changes leading to accelerated atherosclerosis even after cortisol normalisation. This hypothesis will be tested not only in patients with Cushing´s syndrome but even in exogenous hypercortisolism caused by the glucocorticoid treatment.