Selma Hasific - PhD Scholarship 2021

Project summary:
The role of vitamin K in reduction of coronary heart disease

Coronary heart disease (CHD) is the leading cause of death in the world. Identifying risk factors, preventive treatments and good diagnostic tests is essential in the reduction of CHD. This research project is dedicated to investigate the role of vitamin K in heart health. The effect of vitamin K2 supplementation on coronary plaque and inflammation is investigated in a randomized multicenter trial. Moreover, coronary calcification and events are evaluated in Danish patients treated with vitamin K antagonists.

Project Title

Coronary artery atherosclerosis and clinical consequences associated to vitamin K2 supplementation and vitamin K antagonist treatment

Background

Coronary artery calcification (CAC) and especially progression in CAC is a strong predictor of acute myocardial infarction (AMI) and cardiovascular mortality. Observational studies suggest a protective role of vitamin K2 in the development of CAC. On the other hand, vitamin K antagonists (VKA), the most frequently prescribed oral anticoagulants worldwide, have been shown to increase the progression of calcification. Measurement of CAC score in Agatston Units (AU) is common practice, while novel software as AutoPlaque introduces new opportunities to measure coronary plaques.

Aim

The overall aim of this study is to examine the pathophysiological, subclinical and clinical consequences of vitamin K2 supplementation and VKA treatment. The specific aims are to investigate the effect of vitamin K2 supplementation on progression of atherosclerosis and inflammation in a randomized clinical trial. Also, we aim to investigate the progression of CAC and development of cardiovascular disease between VKA and direct oral anticoagulants (DOACs) users compared to the background population.

Methods

AVADEC is a multicenter trial investigating 389 participants randomized to vitamin K2 (720 µg/day) and vitamin D (25 µg/day) versus placebo with a 2-year follow-up. In two substudies, the effect on coronary plaque and inflammation is investigated. Cardiac CT scans are analyzed traditionally but also with AutoPlaque. In prospective cohort - and Danish nationwide registry studies, respectively, CAC progression and incidence of cardiac events are evaluated in patients treated with VKA and DOACs.

Selma Hasific

  • MD
  • University of Southern Denmark
  • Odense University Hospital, Department of Cardiology

Mentors:

Professor Axel Diederichsen, Department of Cardiology, Odense University Hospital, Denmark (main supervisor)

Professor Damini Dey, Biomedical Imaging Research Institute, Cedars Sinai Medical Center, Los Angeles, USA (co-supervisor)

Professor Jesper Hallas, Department of Clinical Pharmacology, University of Southern Denmark, Denmark (co-supervisor)

Associate professor, PhD, MD Kristian Øvrehus, Department of Cardiology, Odense University Hospital, Denmark (co-supervisor)

Partners:

  • Professor Oke Gerke, Department of Nuclear Medicine, Odense University Hospital, Denmark

  • Professor Lars Melholt Rasmussen, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Denmark

Contact: