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- Title
Elevated carbonylated proteins are associated with major cardiovascular events in patients with chronic coronary syndrome: A cohort study.
- Authors
Mróz, Krystian; Paszek, Elżbieta; Baran, Mateusz; Ząbczyk, Michał; Butenas, Saulius; Undas, Anetta
- Abstract
Background: Protein carbonylation is reported in atherosclerosis, but its predictive value is unknown. Aims: We evaluated plasma carbonylated protein (PC) levels in association with clinical outcomes in coronary artery disease (CAD) in long-term follow-up. Methods: In patients with advanced stable CAD, we assessed plasma PC content along with fibrin clot properties, i.e., permeability (Ks) and clot lysis time, and its determinants: plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor. We recorded a composite of myocardial infarction, ischemic stroke, systemic embolism, and cardiovascular death during a follow-up of 8.3 (1.8) years. Results: The analysis involved 178 patients aged 64.0 (57.0-70.0) years. The baseline PC content was 2.9 (2.2-3.7) nmol/mg protein and was elevated above the reference value obtained for a control group (2.03 nmol/mg protein) in 82.6% of patients. In linear regression models, high PC adjusted for age was associated with lower Ks, longer clot lysis time, and elevated PAI-1 and thrombin-activatable fibrinolysis inhibitor. Baseline PC was 48% higher in patients with the composite endpoint (n = 67, 37.6%) compared with others (P <0.001). Patients with PC in the highest quartile (3.7-5.1 nmol/mg protein) were more likely to develop the composite endpoint compared to the lowest quartile (hazard ratio [HR] 4.9; 95% confidence interval, 2.1-11.3; P <0.001). Conclusions: This is the first study showing that in CAD the extent of protein carbonylation, in part via its antifibrinolytic effects, predisposes to cardiovascular events in long-term follow-up, highlighting the role of persistent oxidative protein modifications in atherosclerotic vascular disease.
- Subjects
CARDIOVASCULAR disease related mortality; MYOCARDIAL infarction; RESEARCH funding; T-test (Statistics); DATA analysis; MAJOR adverse cardiovascular events; BLOOD proteins; FIBRIN; KRUSKAL-Wallis Test; FISHER exact test; TREATMENT effectiveness; OXIDATIVE stress; MANN Whitney U Test; MULTIVARIATE analysis; DESCRIPTIVE statistics; ACUTE coronary syndrome; LONGITUDINAL method; PERMEABILITY; EMBOLISMS; KAPLAN-Meier estimator; PLASMINOGEN activators; FIBRINOLYSIS; ISCHEMIC stroke; ANALYSIS of variance; STATISTICS; CORONARY artery disease; CONFIDENCE intervals; DATA analysis software; PATIENT aftercare; BIOMARKERS; REGRESSION analysis; PROPORTIONAL hazards models
- Publication
Polish Heart Journal / Kardiologia Polska, 2024, Vol 82, Issue 7/8, p708
- ISSN
0022-9032
- Publication type
Article
- DOI
10.33963/v.phj.100609