A study led by University of Oxford researchers has established that different biological mechanisms underlying a common heart disorder result in different characteristics and complications.
The results, published in Circulation: Genomic and Precision Medicine, could enable more tailored approaches to treatment of those with irregular heartbeats.
Atrial fibrillation (AF) is the most common sustained heart rhythm disorder, with recent estimates suggesting that one-in-three individuals will experience AF in their lifetime. Its most serious complication is stroke. Currently, stroke risk in AF is assessed and managed based on other cardiovascular risk factors, rather than on the underlying features of the AF itself.
This new genetic study, carried out by researchers at Oxford Population Health, supported by the NIHR Oxford Biomedical Research Centre (BRC), provides a more precise understanding of the effects and consequences of specific mechanisms that lead to AF ─ potentially guiding new approaches to stroke prevention in people with the condition.
The researchers analysed genetic data from several large-scale studies to investigate biological pathways linked to AF. They focused on common genetic variants identified in previous genome-wide association studies and examined their effects on a range of heart-related measures and outcomes.
The researchers focused on three main genetic pathways leading to AF: one related to heart muscle function; another to cardiac development; and a third to electrical ion channel regulation.
Each pathway was associated with specific patterns of electrocardiogram (ECG) measurements, cardiac magnetic resonance imaging (MRI) parameters, and blood biomarkers.
Crucially, the different AF-related pathways were linked with different risks of cardioembolic stroke (when a blood clot forms in the heart and travels to the brain). In particular, the cardiac muscle and development pathways were associated with a higher risk of cardioembolic stroke than the ion channel pathway.
This large-scale genetic study suggests that different biological mechanisms underlying AF may influence the risk of stroke in distinct ways.
Joint senior author of the paper Jemma Hopewell, Professor of Precision Medicine and Epidemiology at Oxford Population Health and Oxford BRC Theme Lead for Cardiovascular Medicine, said: “Our study uses the strengths of large-scale genetic data to elucidate our understanding of the causes and consequences of AF.
“In particular, we found how different biological mechanisms involved in the development of AF influence other measures of disease and, importantly, the risk of stroke. This is an exciting example of how research capitalising on the wealth of health data available is getting us closer to precision approaches to patient care.”
Barbara Casadei, Professor of Cardiovascular Medicine, Head of the National Heart and Lung Institute and joint senior author of the paper, commented “As we begin to unravel the impact of different genetic pathways underpinning atrial fibrillation, we take an important step toward informing more personalised AF treatment and stroke prevention strategies.”
First author on the paper Parag Gajendragadkar, Senior Clinical Research Fellow at Oxford Population Health, Consultant Cardiologist and Electrophysiologist, added: “Not all AF is created equal. This study offers hope that understanding an individual’s biological pathway to AF may help guide future treatment approaches to AF, bringing us one step closer to care that is tailored to individual patients.”