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The biological significance of changes in the vascular wall and atherosclerotic plaque for the development of atherosclerotic disease of the coronary arteries
Horváth, Martin ; Hájek, Petr (advisor) ; Poledne, Rudolf (referee) ; Kovárník, Tomáš (referee)
Acute complications of atherosclerosis are typically caused by arterial occlusion due to acute thrombosis forming over a ruptured vulnerable atherosclerotic plaque (VP). Early identification of such VP prior to their rupture could help prevent these events. At the same time, methods for assessing cardiovascular risk are focused on measures at the population level and are not sensitive and specific enough to assess the risk of individual patients. We therefore focused on the possibilities of in vivo detection of VP using biomarkers and invasive imaging methods. First, we focused on the detection of microRNAs (miRs), which have been investigated in recent years as promising biomarkers for a number of diseases, including atherosclerosis. We determined miR levels using quantitative polymerase chain reaction in peripheral venous blood samples from patients in very early phase of ST-elevation myocardial infarction (STEMI), which served as the closest clinical model of acute VP rupture. The results led to the identification of two miRs (miR-331 and miR-151-3p) that were deregulated in STEMI and could be biomarkers of VP. In the next part of the research, we dealt with the possibilities of invasive imaging of VP using intravascular ultrasound and near- infrared spectroscopy (IVUS and NIRS). We confirmed...
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Biomarkers, intravascular ultrasound and near-infrared spectroscopy in the assessment of vulnerable atherosclerotic plaque
Štěchovský, Cyril ; Hájek, Petr (advisor) ; Krajina, Antonín (referee) ; Kaňovský, Jan (referee)
Biomarkers, Intravascular Ultrasound and Near-Infrared Spectroscopy in the Assessment of Vulnerable Atherosclerotic Plaque Abstract The thesis describes pathophysiology of a vulnerable atherosclerotic plaque, detection of the vulnerable plaque in the stenosis of the internal carotid artery (ICA), and optimalization of carotid stenting (CAS) with near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) imaging. NIRS detects lipid core of the vulnerable lipid rich plaque (LRP). We demonstrated safety of NIRS-IVUS imaging during CAS. LRP was detected in one third of ICAs before CAS. Lipid signal was not correlated with plaque morphology (IVUS), biomarkers or clinical variables. CAS caused significant decrease of the lipid signal. Angiography overestimated severity of stenosis of the ICA and vastly underestimated residual stenosis after CAS. Presence of the LRP in the stenosis was neither associated with periprocedural neurological complications of CAS nor long-term adverse cardiovascular events. IVUS identified planimetric features associated with long-term restenosis or stent occlusion. After a median follow-up of 31 months, repeated NIRS-IVUS of the implanted stents showed significant expansion of the stents, diffuse neointimal hyperplasia and further reduction of the lipid signal. We assume,...
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The coronary atherosclerosis regression during hypolipidemic therapy
Kovárník, Tomáš ; Aschermann, Michael (advisor) ; Rokyta, Richard (referee) ; Pudil, Radek (referee)
Background: There is no study focusing on changes of coronary atherosclerosis during dual hypolipidemic therapy with statin and ezetimibe. Methods: 107 patients with stable angina were enrolled and the final analysis was performed in 89 patients. Randomization was 1:1 to the group A (atorvastatin 80mg and ezetimibe 10mg) and to the standard group S. Treatment period was 12 months. Results: Changes of percent atheroma volume (PAV) were -0,4% in group A and + 1,4% in group S, p=0,014. Combine atherosclerosis regression (increase of lumen volume together with decrease of PAV) was found more frequent in group A (40,5%) than the group S (14,9%), p=0,007. The target LDLc level < 2mmol/l, presence of at least four of five atherosclerotic risk factors, and decrease of VCAM level were independent predictors for plaque regression. There were no significant differences in plaque composition between the two groups over the duration of the study. However during analysis the two groups together, fibrous and fibro-fatty tissues decreased and dense calcification and necrotic core increased during follow-up. Conclusion: The dual hypolipidemic therapy starts atherosclerosis regression. Despite significant decrease of lipid levels the continuous plaque shift from fibro and fibro-fatty to necrotic with calcification...
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The coronary atherosclerosis regression during hypolipidemic therapy
Kovárník, Tomáš ; Aschermann, Michael (advisor) ; Rokyta, Richard (referee) ; Pudil, Radek (referee)
Background: There is no study focusing on changes of coronary atherosclerosis during dual hypolipidemic therapy with statin and ezetimibe. Methods: 107 patients with stable angina were enrolled and the final analysis was performed in 89 patients. Randomization was 1:1 to the group A (atorvastatin 80mg and ezetimibe 10mg) and to the standard group S. Treatment period was 12 months. Results: Changes of percent atheroma volume (PAV) were -0,4% in group A and + 1,4% in group S, p=0,014. Combine atherosclerosis regression (increase of lumen volume together with decrease of PAV) was found more frequent in group A (40,5%) than the group S (14,9%), p=0,007. The target LDLc level < 2mmol/l, presence of at least four of five atherosclerotic risk factors, and decrease of VCAM level were independent predictors for plaque regression. There were no significant differences in plaque composition between the two groups over the duration of the study. However during analysis the two groups together, fibrous and fibro-fatty tissues decreased and dense calcification and necrotic core increased during follow-up. Conclusion: The dual hypolipidemic therapy starts atherosclerosis regression. Despite significant decrease of lipid levels the continuous plaque shift from fibro and fibro-fatty to necrotic with calcification...
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