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521 Cardiovascular Biomarkers for the Prediction of Adverse Cardiovascular Events and Mortality in Patients with Cancer

Program: Oral and Poster Abstracts
Type: Oral
Session: 332. Thrombosis and Anticoagulation: Clinical and Epidemiological: Cancer-associated Thrombosis: Risk Stratification, Prevention, and Treatment
Hematology Disease Topics & Pathways:
Research, Bleeding and Clotting, adult, epidemiology, Clinical Research, thromboembolism, Diseases, real-world evidence, Study Population, Human
Sunday, December 11, 2022: 1:00 PM

Florian Moik1,2*, Simon Kraler3*, Fabrizio Montecucco4*, Luca Liberale4*, Stephan Nopp2*, Cornelia Englisch2*, Tetiana Lapikova-Bryhinska3*, Alexander Akhmedov3*, Arnold von Eckardstein5*, Florian A. Wenzl3*, Ingrid Pabinger, MD6, Thomas F. Lüscher7,8* and Cihan Ay, MD2*

1Department of Internal Medicine, Division of Oncology, Medical University of Graz, Graz, Austria
2Department of Medicine I, Clinical Divison of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
3Center for Molecular Cardiology, University of Zürich, Zurich, Switzerland
4First Clinic of Internal Medicine, Department of Internal Medicine; IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, University of Genoa, Genoa, Italy
5Institute of Clinical Chemistry, University Hospital of Zurich, Zurich, Switzerland
6Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
7Heart Division, Royal Brompton & Harefield Hospitals, Imperial College and Kings College London, London, United Kingdom
8Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland

Introduction: Patients with cancer are prone to develop both thromboembolic and atherothrombotic events. Continued advances in contemporary anti-cancer therapy leads to prolonged cancer-specific survival, thus putting an increasing number of patients at high risk of major adverse cardiovascular events (MACE). Therefore, tools to personalize risk stratification to predict and eventually prevent short- and long-term cardiovascular complications in patients with cancer are an unmet medical need. Here, we aimed to assess the predictive utility of cardiovascular biomarkers in a representative population of oncologic patients.

Methods: The study was conducted in the framework of a single-center prospective observational cohort study (Vienna Cancer & Thrombosis Study - CATS). Cardiovascular biomarkers (lipoprotein(a), NT-proBNP, P-selectin, E-selectin, L-selectin, ICAM-1, VCAM-1, sLOX-1) were explored for their predictive utility towards MACE (i.e. composite of non-fatal myocardial infarction or ischaemic stroke, and cardiovascular death), cardiovascular mortality, and all-cause mortality. Patients were followed for the occurrence of MACE for the maximum predefined prospective follow-up period in CATS of 2 years, whereas a prolonged follow-up period (5 years) for mortality outcomes was feasible due to data availability from the national Austrian death registry. MACE and cardiovascular mortality were analysed by competing-risk regression, accounting for non-cardiovascular death as competing outcome event and adjusting for patient age, sex and smoking status. All-cause mortality was analysed in Cox regression analysis, adjusting for age, sex, cancer stage, and tumour type in multivariable analysis.

Results: In total, 2,192 adult patients with newly diagnosed or recurrent cancer were included in the present analysis (median age: 62 years; 53% male). Over a median follow-up of 23 months 50 MACEs occurred, with a cumulative 1- and 2-year incidence of 1.7% [95% confidence interval, CI: 1.2-2.3] and 2.4% [95%CI: 1.8-3.1]. An independent association with risk of MACE was observed for baseline levels of NT-proBNP (sub-distribution hazard ratio, SHR, per double increase: 1.28 [95%CI: 1.06-1.54]), ICAM-1 (SHR: 1.53 [1.06-2.20], and L-selectin (SHR: 0.63 [0.44-0.90]), but not for lipoprotein(a), P-selectin, VCAM-1, or sLOX-1. An additive predictive effect of individual biomarkers was observed in the derivation of a point-based risk prediction score (+1 point: NT-proBNP≥75th percentile, ICAM-1≥75th percentile, and L-selectin ≤25th percentile), with a 2-year MACE risk in patents with 0-, 1-, and ≥2 points of 1.5%, 2.2%, and 5.9%, respectively (Figure 1). Furthermore, an independent association with risk of long-term cardiovascular mortality was observed for baseline levels of NT-proBNP (SHR: 1.42 [95%CI: 1.17-1.72]) and ICAM-1 (1.62 [1.05-2.48]). Accordingly, the risk of all-cause mortality independently increased with higher NT-proBNP levels (HR: 1.16 [95%CI: 1.10-1.22]) and ICAM-1 (1.15 [1.06-1.25]). No significant association with cardiovascular mortality or all-cause mortality was observed for levels of lipoprotein(a), P-selectin, E-selectin, L-selectin, VCAM-1, and sLOX-1.

Conclusion: Cancer patients are at substantial risk of cardiovascular events, with a predictive utility of NT-proBNP, L-selectin, and ICAM-1 for short-term MACE-risk. Further, NT-proBNP and ICAM-1 independently predict long-term risk of both cardiovascular mortality and all-cause mortality. Our findings suggest a possible benefit of incorporating cardiovascular biomarkers in personalized risk prediction models to develop individualized cardiovascular prevention strategies in patients with cancer.

Figure 1: Additive effect of biomarkers for the prediction of MACE in patients with cancer. Patients were assigned +1 point each for levels of NT-proBNP ≥75th percentile, ICAM-1 ≥75th percentile, and L-selectin ≤25th percentile. Cumulative incidences were obtained in competing risk analysis, accounting for non-cardiovascular mortality as the competing outcome event.

Disclosures: Liberale: Daiichi-Sankyo: Honoraria. Pabinger: Bayer AG, Boehringer Ingelheim, Daiichi Sanchyo, and BMS/ Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lüscher: Amgen, AstraZeneca, Daiichi-Sankyo, Sanofi, Abbott, Ablative Solutions, Boehringer Ingelheim, Novartis, Servier, and Vifor.: Research Funding; Daichi-Sankyo: Honoraria; DalCor: Honoraria; Novartis: Honoraria; Pfizer: Honoraria. Ay: Bayer, Daiichi Sankyo, BMS/Pfizer, and Sanofi: Honoraria; Bayer, Boehringer Ingelheim, Daiichi Sankyo, and BMS/Pfizer: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH