Genetic Risk Score Could Improve Diagnosis of Atrial Fibrillation

A genetic risk score (GRS) may identify patients at highest risk for developing atrial fibrillation (AF), according to a study published March 13 in PLOS Medicine. The authors say that patients with a high GRS were three times more likely to be diagnosed with AF through use of ambulatory cardiac rhythm monitoring in the two weeks following presentation of symptoms, compared to those with a low GRS.

AF is the most common heart rhythm disturbance and substantially increases the risk of stroke. Efforts to better diagnose subclinical, asymptomatic AF could lead to initiation of preventive measures that would reduce stroke risk.

The study included 903 patients aged 40 years of age or older presenting with symptoms of AF and at least one clinical risk factor for AF. Participants subsequently underwent genetic testing and ambulatory cardiac rhythm monitoring for two weeks. The AF GRS was based on the weighted contribution of 12 single nucleotide polymorphisms (minor allele frequency of more than 5 percent) that previously have been determined to be associated with AF at a genome-wide significance level.

Over the two-week study period, approximately 9 percent of the patients had an AF episode. Participants in the highest quintile of AF GRS were more than three times more likely to have had a recorded AF event than participants in the lowest quintile, even after adjusting for age, sex, smoking status, body mass index, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction.

“The ability to combine common single nucleotide polymorphisms [SNPs] into an AF GRS with the ability to differentiate a greater than 3-fold increased risk of AF in a population on a prospective basis may be useful,” write the authors led by Evan Muse, from the Scripps Translational Science Institute in La Jolla, Calif. “Such a panel of SNPs could be assayed at low cost and be used in conjunction with an evaluation of a patient with possible AF.”

Takeaway: This prospective validation of a GRS may enable tailoring of diagnostic strategies in patients presenting with AF symptoms.