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Genetic Predisposition, Clinical Risk Factor Burden, and Lifetime Risk of Atrial Fibrillation

Lu-Chen Weng1,2, Sarah R Preis3,4, Olivia L Hulme1,2

  • 1Cardiovascular Research Center (L.-C.W., O.L.H., P.T.E., S.A.L.).

Circulation
|November 14, 2017
PubMed

Insights

The lifetime risk of developing atrial fibrillation (AF) is 37%, influenced by both genetic predisposition and clinical factors. Individuals with high genetic and clinical risk have a nearly 50% lifetime risk of AF.

Area of Science:

  • Cardiology
  • Genetics
  • Epidemiology

Background:

  • The long-term probability of developing atrial fibrillation (AF) is not well understood, particularly concerning genetic and clinical risk factors.
  • Assessing lifetime AF risk requires integrating genetic predisposition with the burden of clinical risk factors.

Purpose of the Study:

  • To estimate the lifetime risk of AF in individuals from a community-based cohort.
  • To determine the influence of polygenic risk and clinical risk factors on the long-term probability of developing AF.

Main Methods:

  • Utilized data from the Framingham Heart Study, including approximately 1000 AF-associated single-nucleotide polymorphisms for polygenic risk scoring.
  • Calculated clinical risk factor burden using a validated score encompassing height, weight, blood pressure, smoking, medication use, diabetes, myocardial infarction, and heart failure history.
  • Estimated lifetime AF risk stratified by tertiles of polygenic and clinical risk.

Main Results:

  • Among 4606 participants AF-free at age 55, the overall lifetime risk of AF was 37.1%.
  • Individuals in the lowest tertiles of both polygenic and clinical risk had a 22.3% lifetime AF risk.
  • Those in the highest tertiles of both risk categories faced a significantly higher lifetime AF risk of 48.2%.
  • Lower clinical risk factor burden was independently associated with a later onset of AF.

Conclusions:

  • The lifetime risk of AF in this community cohort is substantial at 37%.
  • Polygenic risk estimation is feasible and, combined with clinical risk factors, explains a significant portion of the variation in long-term AF risk.
  • Integrating genetic and clinical risk assessment can identify individuals at higher lifetime risk for atrial fibrillation.
Abstract

Keywords:
atrial fibrillationepidemiologygeneticslifetime riskpolygenic riskrisk factorrisk stratification

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