Biomarkörer för en ökad förståelse och bättre behandling av förmaksflimmer

Background

Atrial fibrillation (AF) confer substantial morbidity and health care costs due to increased risk of stroke and death. The treatment recommendations in AF are based on insensitive risk models. Biochemical markers influencing the pathophysiology of AF and the risk of stroke and death provides opportunities to increase the understanding and individualize treatment to improve patient outcomes.

Hypothesis

Biomarkers indicating AF pathophysiology and/or organ dysfunction-damage will provide key information to guide personalized treatment of patients with AF. Objectives

1.Use proteomics to increase the understanding of pathophysiology, improve prognostication and identify new targets for improved treatments of stroke and death.

2.Evaluate the clinical usefulness of 4 novel biomarkers recently identified in advanced proteomic screening programs in patients with AF concerning risk of stroke and death.

3.Evaluate and calibrate biomarker-based risk scores for stroke and death in patients with AF not treated with oral anticoagulation (OAC) to improve the risk prediction. Work plan

-For objective 1. Employ new technologies, proximity extension assay (PEA) multiplex panels, in search of novel plasma biomarkers (a total of 184 markers representing remodelling, cellular growth, metabolism, cellular function/damage, inflammation, and platelet markers).

-For objectives 2, 3. Use ELISA and prototype assays (Roche, Uppsala Clinical Research Center [UCR] laboratory) to evaluate the clinical usefulness of newly discovered biomarkers and biomarker-based risk scores to improve outcomes by better treatment decision support in AF with/without OAC treatment.

Materials

–Newly created biobanks at UCR containing plasma samples from 4,500 well characterized patient materials with AF from international prospective clinical trials not treated with OAC sent from PHRI (ACTIVE and AVERROES). [Aims 1-3]

–Biobanks at UCR containing plasma samples from more than 23,000 well characterized patient materials with AF from international prospective clinical trials treated with OAC (ARISTOTLE and RE-LY). [Aim 2] Significance

Results have shown that a biomarker-based approach provides superior prognostic abilities making it suitable for individualized treatment options and improved patient outcomes. Novel biochemical markers provide a distinct opportunity to expand the knowledge and further improve the risk assessment in order to improve health and optimize the health care system.