1. Genetic Risk Score to Identify Risk of Venous Thromboembolism in Patients With Cardiometabolic Disease
- Author
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Ofri Mosenzon, Marc P. Bonaca, Ilaria Cavallari, Anthony C Keech, Itamar Raz, Marc Cohen, Philippe Gabriel Steg, Nicholas A Marston, Yared Gurmu, Marc S. Sabatine, Robert F. Storey, Carolina Roselli, Giorgio E. M. Melloni, Benjamin M. Scirica, Deepak L. Bhatt, Patrick T. Ellinor, Christina J.-Y. Lee, Frederick K. Kamanu, Christian T. Ruff, Robert P. Giugliano, Eugene Braunwald, and Steven A. Lubitz
- Subjects
Male ,medicine.medical_specialty ,pulmonary embolism ,venous thromboembolism ,Article ,Risk Factors ,Internal medicine ,genomics ,Humans ,Medicine ,In patient ,genetics ,Myocardial infarction ,cardiovascular diseases ,Genetic risk ,Aged ,Proportional Hazards Models ,Metabolic Syndrome ,business.industry ,General Medicine ,Middle Aged ,Cardiometabolic disease ,medicine.disease ,Pulmonary embolism ,myocardial infarction ,Female ,Proprotein Convertase 9 ,business ,Venous thromboembolism - Abstract
Background: Venous thromboembolism (VTE) is a major cause of cardiovascular morbidity and mortality and has a known genetic contribution. We tested the performance of a genetic risk score for its ability to predict VTE in 3 cohorts of patients with cardiometabolic disease. Methods: We included patients from the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk), PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin), and SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus) trials (history of a major atherosclerotic cardiovascular event, myocardial infarction, and diabetes, respectively) who consented for genetic testing and were not on baseline anticoagulation. We calculated a VTE genetic risk score based on 297 single nucleotide polymorphisms with established genome-wide significance. Patients were divided into tertiles of genetic risk. Cox proportional hazards models were used to calculate hazard ratios for VTE across genetic risk groups. The polygenic risk score was compared with available clinical risk factors (age, obesity, smoking, history of heart failure, and diabetes) and common monogenic mutations. Results: A total of 29 663 patients were included in the analysis with a median follow-up of 2.4 years, of whom 174 had a VTE event. There was a significantly increased gradient of risk across VTE genetic risk tertiles ( P -trend P =0.004) and 2.70-fold (95% CI, 1.81–4.06; P P Conclusions: In a broad spectrum of patients with cardiometabolic disease, a polygenic risk score is a strong, independent predictor of VTE after accounting for available clinical risk factors, identifying 1/3 of patients who have a risk of VTE comparable to that seen with established monogenic thrombophilia.
- Published
- 2021