Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Mourouzis Konstantinos
Dissertation committee:
Γεράσιμος Σιάσος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Δημήτριος Τούσουλης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Χριστόδουλος Στεφανάδης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Εμμανουήλ Βαβουρανάκης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Τσιούφης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνα Αγγέλη, Καθηγήτρια, , Ιατρική Σχολή, ΕΚΠΑ
Ευάγγελος Οικονόμου, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Ο προγνωστικός ρόλος των κυκλοφορούντων βιοδεικτών σε ασθενείς με υποκλινική αθηροσκλήρωση
Translated title:
The prognostic role of circulating biomarkers in patients with subclinical atherosclerosis
Summary:
Introduction: Coronary heart disease is one of the most frequent causes of death worldwide. Finding biomarkers to better predict prognosis and, by extension, stratify the risk of patients with subclinical coronary artery disease is of great importance.
Purpose: To investigate the predictive ability of newer biomarkers [copeptin, transforming growth factor-15 (GDF-15) and pentraxin (PTX-3)] alone or in combination with other clinical biomarkers in patients with subclinical atherosclerosis.
Material and method: The study included consecutive 205 patients (67.8% male), with a mean age of 59±9 years with subclinical coronary artery disease, as confirmed by percutaneous coronary angiography (defined as <50% stenosis of any major epicardial coronary vessel). In addition to basic clinical and demographic data, echocardiographic data, nutrition and fitness data, socio-economic data, medication, and routine biochemical markers, circulating levels of copeptin, GDF-15 and PTX-3 were assessed in whole blood by the ELISA method with commercially available kits. The primary composite endpoint was defined as the combination of the incidence major cardiovascular event, all-cause death, or all-cause hospitalization, and worsening of cardiovascular disease. Patients were prospectively followed for the final endpoint for 71 (64-83) months by telephone follow-up.
Results: 28.4% of patients (n=54) experienced primary composite endpoint, which occurred at a median of 65 (58-79) months. No deaths were observed. Patients who met the primary composite endpoint had on average a higher plasma copeptin value than those who did not [250.38 (209.81-292.81) pg/ml vs. 223.63 (199.02-246.00 pg/ml, p=0.012) while they demonstrated no differences regarding the levels of other biomarkers and especially for GDF-15 and PTX-3 (p=NS for all). After Cox multivariate analysis with adjustment for classical cardiovascular risk factors, a 10 pg/mL change in copeptin resulted in a 5% increase in the odds of the primary composite endpoint [hazard ratio (HR)=1.05 (95%CI: 1.01- 1.08), p=0.01]. Kaplan-Meier survival analysis showed that patients with plasma copeptin values greater than the median value of 232.58 pg/ml had a significantly shorter time for the incidence of the primary composite endpoint than those with plasma copeptin values lower than the median value [59 (49-68) months vs. 76 (70-83) months, p=0.01]. The Area Under the Curve (AUC) estimate for copeptin was 0.723 (p=0.01), for GDF-15 0.529 (p=0.64), for PTX-3 0.512 (p=0.85) and the corresponding cut-off values 222.23 pg/mL, 639.89 pg/mL, 0.66 ng/mL for the primary composite endpoint. The inclusion of copeptin in a clinical model that included the SCORE 2 determinants increased the C-statistic from 0.634 to 0.766 while the inclusion of GDF-15 improved C-statistic to 0.688 and PTX-3 to 0.748, respectively. Including all 3 biomarkers in the basic clinical model led to the most optimal model with an increase in the C-statistic to 0.788.
Conclusion: Copeptin alone exhibits the best prognostic capacity for predicting the occurrence of the combination of all-cause hospitalization, hospitalization for major cardiovascular events, and worsening of cardiovascular disease relative to other biomarkers in patients with subclinical coronary artery disease. The inclusion of copeptin, GDF-15 and PTX-3 demonstrates the best predictive ability of all models considered
Main subject category:
Health Sciences
Keywords:
Atherosclerosis, Subclinical atherosclerosis, Copeptin, GDF-15, PTX-3, Inflammation
Number of references:
553
File:
File access is restricted until 2025-12-13.
Διατριβή_Pergamos_.pdf
3 MB
File access is restricted until 2025-12-13.
