Aim. To study the role of biomarkers in assessing the vulnerability of atherosclerotic plaques.Material and methods. A review of literature sources investigating the biomarker assessment of the vulnerability of atherosclerotic plaques published for the period 01.01.2016 to 31.12.2022 was carried out. Literature search was carried out in English and Russian in PubMed databases, in Google Academy, Elibrary.ru according to the following keywords: “biomarkers of plaque vulnerability”, “NLR and vulnerable plaque”, “CRP and vulnerable plaque”, ”MMP-9 and vulnerable plaque”, “TIMP-1 and vulnerable plaque”, ”galectin-3 and vulnerable plaque”, “NGAL and vulnerable plaque”. A total of 183 articles were found, of which 42 articles in full-text format containing original clinical studies were selected for the preparation of this review.Results. Numerous studies have shown that the vulnerability and rupture of the plaque, rather than its size and severity of stenosis, are the main cause of cardiovascular events in patients with coronary heart disease. Small plaques rich in lipids often become unstable due to an inflammatory reaction supported by the interaction between lipoproteins, monocytes, macrophages, T-lymphocytes and vascular wall cells. NLR, CRP, NGAL, Galectin-3, as well as markers of extracellular matrix degradation (MMP-9, TIMP-1) can play a special role in assessing the vulnerability of plaques.Conclusion. The development of acute coronary syndrome is based on the destabilization of the atherosclerotic plaque, which occurs not only due to changes in its lipid composition, but also infiltration by immuno-inflammatory cells, degradation of the extracellular matrix, as well as an active inflammatory reaction and neovascularization of the plaque. Therefore, traditional imaging methods that characterize the plaque by its appearance and size are not enough to predict the risk of rupture and the development of an acute thrombotic event. Thus, there is a need to identify new biomarkers that would correlate with the instability of plaque atheroma.
Aim. To study the effect of high-dose combined lipid-lowering therapy (statins + ezetimibe vs statins + PCSK9 inhibitors) on plaque vulnerability assessed using multimodal imaging (coronary computed tomography angiography (CCTA) and optical coherence tomography, as well as biomarkers in patients with acute coronary syndrome (ACS).Material and methods. This open, prospective, randomized, single-center study will include 120 patients admitted urgently with an ACS. All patients will undergo percutaneous coronary intervention of the infarct-related artery, as well as intracoronary imaging using optical coherence tomography of one or two noninfarct-related arteries. During hospitalization, patients will receive standard therapy for ACS according to clinical guidelines, while statins will initially be prescribed at a maximum dosage of atorvastatin 80 mg/rosuvastatin 40 mg.Patients who showed high compliance and did not reach the target low-density lipoprotein cholesterol (LDL-C) values (≤1,4 mmol/l) 1 month after myocardial infarction/unstable angina at the second visit will be randomized into two groups. Patients of group 1 will receive PCSK9 inhibitors (alirocumab 150 mg by subcutaneous injection once every 2 weeks or evolocumab 140 mg by subcutaneous injection once every 2 weeks) in addition to maximum statin therapy (atorvastatin 80 mg/rosuvastatin 40 mg), while group 2 participants will take ezetimibe at a dose of 10 mg in combination with the maximum dose of statins. In addition, at the second visit, patients will undergo CCTA, assess the cardio-ankle vascular index (CAVI) index and laboratory tests (complete blood count (neutrophil-to-lymphocyte ratio NLR), lipid profile, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Troponin I, Galectin-3, high-sensitivity C-reactive protein (hs-CRP), metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL). Total follow-up will last 52 weeks. At the final visit, patients will undergo CCTA, assessment of the CAVI index and laboratory status (NLR, lipid profile, ALT, AST), Troponin I, Galectin-3, hs-CRP, MMP-9, TIMP-1, NGAL).Primary endpoint: reduction in plaque vulnerability according CCTA in non-infarct-related coronary arteries Secondary endpoints: death, stent thrombosis/restenosis, non-fatal myocardial infarction, readmissions with progressive angina, repeat revascularization; changes of the lipid profile (total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides) against the background of maximum combination therapy with statin + PCSK9 inhibitors or statin + ezetimibe; changes of the biomarkers of cardiac injury (Troponin I), inflammation (NLR, hs-CRP, NGAL, Galectin-3) and matrix remodeling (MMP-9, TIMP-1).Conclusion. Our study will allow for the first time to compare and evaluate the effect of both PCSK9 inhibitors and ezetimibe in combination with high-dose statin therapy on reducing the plaque vulnerability according to CCTA in non-infarction-related coronary arteries in patients with ACS undergoing percutaneous coronary intervention, as well as to evaluate the diagnostic value of inflammatory biomarkers (NLR, hs-CRP, NGAL, Galectin-3) and matrix remodeling (MMP-9, TIMP-1).
Background: Atherosclerotic plaque (AP) vulnerability can be assessed by coronary artery imaging techniques. Modern lipid-lowering therapy (LLT) has a stabilizing effect on the AP and reduces the likelihood of progression of vascular remodeling. Methods: Databases searched comprised PubMed, and the Web of Science up to April 2023. In total, 8 relevant articles were selected, and all of them are original clinical studies. Results Based on the results of ODISSEY-J-IVUS, there was a decrease in the percentage change in the normalized total volume of AP by 3.1% in the monotherapy group and by 4.8% in the combined LLT group (p = 0.23). According to GLACOV study normalized total atheroma volume decreased by 0.9 mm3 in the placebo group and by 5.8 mm3 in the evolocumab group (95% CI -7.3 -2.5; p<0.001). Plaque regression was observed in 64.3% of patients receiving evolocumab versus 47.3% of those on placebo. The dynamics of the minimum thickness of the fibrous cap varied within 18.0-62.67 microns while on combined LLT and 13.2-33.19 microns on monotherapy (PACMAN-AMI, Gao F). In the HUYGENS study, a lipid arc regression of 57.5° was obtained on combined LLT and by 31.4° with the statin alone. Conclusion: significant progress in the development of cardiovascular imaging has made it possible to expand our understanding of the morphology of AP, the features of coronary vessel remodeling, and the development of acute cardiovascular complications.
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