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Lifetime Risk for Atrial Fibrillation Higher Than Expected

Key findings

  • After 55 years of age, the lifetime risk of atrial fibrillation is 37% and highly influenced by genetics and modifiable clinical factors
  • The range of lifetime risk for atrial fibrillation was between 20% and 50%, with greater polygenic and clinical risks associated with higher rates.
  • Regardless of genetic predisposition, patients with a lower clinical risk factor burden were associated with a lowered probability of developing atrial fibrillation.
  • Genome-wide single nucleotide polymorphism data can be successfully used to estimate atrial fibrillation risk.

The degree to which atrial fibrillation (AF) is inherited or caused by other risk factors is unknown. To learn more about the origins of AF, researchers led by Cardiac Electrophysiologist Steven Lubitz, MD, MPH, and Lu-Chen Weng, PhD, at Massachusetts General Hospital analyzed lifetime risk of AF estimates using available genetic data from the Framingham Heart Study.

Published in Circulation, they found that the lifetime AF risk for a person at age 55 years or older was higher than expected at 37%. The team further realized that the lifetime risk of AF ranged from between 20% to 50%, and was heavily influenced by genetic predisposition, as well as modifiable clinical factors such as weight or blood pressure.

The team analyzed data from three community-based cohort samples of patients at ages 55, 65 and 75. They examined how profiles of single nucleotide polymorphisms (SNPs), common genetic variants with a less obvious genetic relationship to AF, may allow for more varied patient segmenting based on inherited AF predisposition. It defined genetic profiles for AF using about 1,000 SNPs associated with AF. These SNPs came from a prior analysis of 133,073 individuals with 17,931 having had AF.

Together, genetic and clinical risk factors resulted in substantial stratification of lifetime risk of developing AF. For example, for a person 55 years of age who does not have AF and has relatively low levels of genetic and clinical risk factors, there is a 22.3% chance of developing AF during his or her life. A person who is free of AF at 55 but has a high genetic and clinical risk profile has a risk of 48.2%.

The team determined that both genetic and clinical risk factors were substantial contributors to risk for AF. Yet regardless of inherited predisposition to AF, a lower level of clinical risk factors was associated with both a lower risk of AF, as well as a delay in AF onset among those who eventually developed AF. Dr. Weng won the Elizabeth Barrett-Connor Research Young Investigator Competition for this work.

Learn more about the Telemachus & Irene Demoulas Family Foundation Center for Cardiac Arrhythmias

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Patrick Ellinor, MD, PhD, director of the Telemachus & Irene Demoulas Family Foundation Center for Cardiac Arrhythmias at Massachusetts General Hospital, discusses his team’s recent work leveraging genome-wide association studies to identify over 100 different genetic determinants of atrial fibrillation, and his hope of using those variants to develop new drugs to treat atrial fibrillation in the years to come.

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Steve Lubitz, MD, MPH, discusses his team’s work focusing on understanding the mechanisms of atrial fibrillation through human genetics, and understanding how best to identify patients at risk for the arrhythmia.