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Semin Thromb Hemost 2022; 48(04): 465-480
DOI: 10.1055/s-0042-1748152
Review Article

Risk Factors for Major Adverse Cardiovascular Events and Major Adverse Limb Events after Venous Thromboembolism: A Large Prospective Cohort Study

Steve Raoul Noumegni
1   Departments of Internal Medicine, Vascular Medicine and Pneumology, Brest University Teaching Hospital, Brest Teaching Hospital, Brest, France
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
,
Romain Didier
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
3   Department of Cardiology, Brest Teaching Hospital, Brest, France
,
Vincent Mansourati
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
3   Department of Cardiology, Brest Teaching Hospital, Brest, France
,
Emmanuelle Le Moigne
1   Departments of Internal Medicine, Vascular Medicine and Pneumology, Brest University Teaching Hospital, Brest Teaching Hospital, Brest, France
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
,
Raphael Le Mao
1   Departments of Internal Medicine, Vascular Medicine and Pneumology, Brest University Teaching Hospital, Brest Teaching Hospital, Brest, France
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
,
Clément Hoffmann
1   Departments of Internal Medicine, Vascular Medicine and Pneumology, Brest University Teaching Hospital, Brest Teaching Hospital, Brest, France
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
,
Claire De Moreuil
1   Departments of Internal Medicine, Vascular Medicine and Pneumology, Brest University Teaching Hospital, Brest Teaching Hospital, Brest, France
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
,
Cécile Tromeur
1   Departments of Internal Medicine, Vascular Medicine and Pneumology, Brest University Teaching Hospital, Brest Teaching Hospital, Brest, France
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
,
Pierre-Yves Le Roux
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
4   Department of Nuclear Medicine, Brest Teaching Hospital, Brest, France
,
Bahaa Nasr
5   Department of Vascular Surgery, Brest Teaching Hospital, Brest, France
,
Jean-Christophe Gentric
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
6   Department of Neuroradiology, Brest Teaching Hospital, Brest, France
,
Marie Guegan
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
,
Elise Poulhazan
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
,
Karine Lacut
1   Departments of Internal Medicine, Vascular Medicine and Pneumology, Brest University Teaching Hospital, Brest Teaching Hospital, Brest, France
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
,
Luc Bressollette
1   Departments of Internal Medicine, Vascular Medicine and Pneumology, Brest University Teaching Hospital, Brest Teaching Hospital, Brest, France
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
,
Francis Couturaud
1   Departments of Internal Medicine, Vascular Medicine and Pneumology, Brest University Teaching Hospital, Brest Teaching Hospital, Brest, France
2   Western Brittany Thrombosis Study Group, Western Brittany University, Brest, France
› Author Affiliations Funding The study was supported by grants from the “Programme Hospitalier de Recherche Clinique” (French Department of Health), the Foundation “Archipel Santé” and the sponsor was the Brest Teaching Hospital. The funding source was not involved in designing or conducting the study; collecting, managing, analyzing, or interpreting the data; preparing, reviewing, or approving the manuscript; or deciding to submit this for publication. An academic steering committee led by F.C. assumed overall responsibility for all these steps. F.C. reported having received research grant support from Pfizer and fees for board memberships or symposia from Bayer and Astra Zeneca and having received travel support from Bayer, Daiichi Sankyo, Leo Pharma, InterMune, and Actelion.
› Further Information
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Abstract

Background There is an increased risk of arterial events including major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after venous thromboembolism (VTE). However, their risk factors remain little explored.

Methods We aimed to determine the risk factors for MACE (acute coronary syndrome/stroke/cardiovascular death) and MALE (limb ischemia/critical limb ischemia/non-traumatic amputation/any limb revascularization) after VTE. Competing risk models (Fine-Gray) were used in a multicenter prospective cohort of 4,940 patients (mean age: 64.6 years and median follow-up: 64 months).

Results MACE occurred in 17.3% of participants (2.35% per patient-years) and MALE in 1.7% (0.27% per patient-years). In multivariable analysis, the identified risk factors for MACE were the age of 50 to 65 years (vs. <50 years, hazard ratio [HR]: 2.00, 95% confidence interval [CI]: 1.38–2.91), age >65 years (vs. <50 years, HR 4.85, 95% CI: 3.35–7.02), pulmonary embolism + deep vein thrombosis (DVT) (vs. isolated-DVT, HR: 1.25, 95% CI: 1.02–1.55), unprovoked-VTE (vs. transient risk factor associated-VTE, HR: 1.29, 95% CI: 1.04–1.59), current tobacco use (vs. never, HR: 1.45, 95% CI: 1.07–1.98), hypertension (HR: 1.61, 95% CI: 1.30–1.98), past history of symptomatic atherosclerosis (HR: 1.52, 95% CI: 1.17–1.98), heart failure (HR: 1.71, 95% CI: 1.21–2.42), atrial fibrillation (HR: 1.55, 95% CI: 1.15–2.08), and vena cava filter insertion (HR: 1.46, 95% CI: 1.03–2.08). The identified risk factors for MALE were the age of 50–65 years (vs. <50 years, HR: 3.49, 95% CI: 1.26–9.65) and atrial fibrillation (HR: 2.37, 95% CI: 1.15–4.89).

Conclusions Risk factors for MACE and MALE after VTE included some traditional cardiovascular risk factors, patient's comorbidities, and some characteristics of VTE.

Keywords

venous thromboembolism - arterial cardiovascular event - MACE - MALE - prospective cohort

Ethics Approval and Consent to Participate

The study was approved by the Ethics Committee of Brest University Teaching Hospital (CCP-Ouest 6-390) with the last amendment approved on November 20, 2013 under reference number: EDITH II/RB 05.003. All participants signed a consent form.


Patient and Public Involvement

Patients or the public were not involved in the design, conduct, reporting, or dissemination plans of our research.


Availability of Data and Materials

The data that support the findings of this study are available from SRN or FC, upon reasonable request.


Author's Contributions

S.R.N., F.C., L.B., R.D., C.D.M., K.L., and E.L.M. were responsible for conception and design; E.P. for acquisition of data; S.R.N. for data analysis; S.R.N., F.C., and L.B. for the analysis and interpretation of data; S.R.N. for manuscript drafting; all authors for manuscript revision; all authors for the approval of the final version of the manuscript; F.C. for obtaining funding; F.C., C.T., R.D., K.L., R.L.M., and E.L.M. for administrative, technical, and material support; F.C. for study supervision; F.C. and S.R.N. for full access to all the data of the study; and all authors were responsible for all aspect of the study, reliability, and freedom from bias of the data presented.


Supplementary Material



Publication History

Article published online:
30 June 2022

© 2022. Thieme. All rights reserved.

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