OPEN Research Support
head

consultant
Axel Diederichsen
Department of Cardiology


Projekt styring
Projekt status    Planning
 
Data indsamlingsdatoer
Start 01.02.2018  
Slut 15.04.2019  
 



Risk of arterial calcification by conventional vitamin K antagonist treatment

Short summary

Atrial fibrillation (AF) is the most common type of arrhythmia. Because of the major risk of AF causing stroke and systemic thromboembolism, the condition is often treated with vitamin K antagonists (VKA). However it has been suggested that VKA treatment is associated with enhanced tissue calcification including coronary artery calcification (CAC). The major objective of this study is to clarify if VKA treatment is inducing progression of CAC. Around 23.000 subjects are investigated in a retrospective part of the study, and around 500 patients will be invited to the prospective part. 


Rationale

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice, and a cause of increasing health care costs. Additionally, prevalence of AF is expected to increase, which is explained by an aging population. By 2030, 120.000-225.000 newly diagnosed AF patients per year are anticipated solely in the European Union. 

It is well known, that AF is a major cause of stroke and systemic thromboembolism, thus one of the challenges is management of anticoagulation. Vitamin K antagonist (VKA) is currently the most frequently used oral anticoagulant. The most familiar vitamin K is phylloquinone, which is essential for the synthesis of functional clotting factors II, VII, IX and X, and VKA inhibits this activation. Menaquinone (MK) is another important vitamin K species. MK is deemed necessary for ?-carboxylation of proteins involved in inhibition of arterial calcification, i.e. matrix-Gla proteins (MGP). Without these activated proteins, the balance of cellular calcium uptake and the mineralization process in bone and blood vessels is impaired. The inhibiting process was originally showed in a mice model in 1997. In other animal studies, the inhibition of the vitamin K-dependent proteins by VKA resulted in arterial and soft tissue calcification. It has also been suggested that VKA treatment is associated with enhanced tissue calcification including coronary artery calcification (CAC) in humans. 

CAC is a strong and independent predictor of cardiovascular disease (CVD) including stroke, and has additionally been associated with an increased risk for AF. The association between CAC and AF may be an independent association, due to mutual risk factors (confounding variables) or as suggested above caused by the VKA treatment related to AF.

The major objective of this study is to clarify if VKA treatment is inducing progression of CAC.

Objectives of our three substudies of which 1 and 2 are retrospective and 3 is prospective:

1. The aim of this study is to evaluate the presence and extent of CAC in AF patients treated with VKA compared to patients treated with NOAC and without anticoagulants. 

2. The aim of this study is to examine the presence and extent of CAC in patients treated with VKA compared to patients not treated with VKA. 

3. The aim of this study is to investigate the progression of CAC in patients with AF treated with or without VKA or NOAC and compared to the background population. 


Description of the cohort

Registry data on around 23.000 patients and trial participants, who had a CT scan of their heart in the period 2007-2017, is evaluated in the retrospective part of the project. 

In the prospective clinical part, around 500 AF patients ? 65 years of age and no previous CVD, who underwent a non-contrast CT scan prior to ablation in the period 2007-2012 will be invited for a follow-up CT scan. 


Data and biological material

Registry data, questionnaires and CT-scans of the heart.  

The collected registry data consists of CAC score, cardiovascular risk factors (age, gender, hypertension, hypercholesterolemia, diabetes mellitus, body mass index (BMI), smoking, family history of CVD), prior CVD, renal function, statin and dose and duration of VKA/NOAC therapy. 


Collaborating researchers and departments

Department of Cardiology, Odense University Hospital 

  • Pregraduate research student, Selma Hasific
  • PhD student, Kristian Altern Øvrehus 

Department of Clinical Pharmacology, Odense University Hospital

  • Professor Jesper Hallas

Centre of Health Economics Research, University of Southern Denmark

  • Statistician PhD, Oke Gerke