Familial Atrial Fib ups AF Risk Independent of Known AF Gene Variants: Framingham

November 13, 2010

November 13, 2010 (Chicago, Illinois) — Relatively speaking, a presence of atrial fibrillation (AF) in a parent or sibling ups one's own risk of developing the arrhythmia by about 40%, independently of four known AF-related gene variants and more conventional risk factors, according to an analysis based on several Framingham Heart Study cohorts [1].

"Assessment of familial AF enhanced risk prediction slightly beyond traditional risk factors, particularly when familial AF occurred prematurely," that is, at age 65 or younger, write the authors, led by Dr Steven A Lubitz (Massachusetts General Hospital, Boston). In particular, premature AF in a first-degree relative tripled one's risk of new-onset AF by age 65.

The group's report is published online today in the Journal of the American Medical Association, to coincide with presentation of the study by Lubitz here at the American Heart Association 2010 Scientific Sessions.

"You'd Want Them to Know . . ."

That AF is heritable is far from a new insight, but not much is known about the degree of risk associated with the arrhythmia in close relatives, according to senior author Dr Emelia J Benjamin (Boston University, MA).

"And for clinicians," she told heartwire , "if [patients] say they have a family history of atrial fibrillation, you'd want them to know if they have palpitations, if their heart is racing or irregular, it's probably a good idea to have it checked out by a doctor--because for some people, the first manifestation of atrial fibrillation is when they have a stroke or heart failure."

Lubitz et al looked at 4421 members of the Framingham Heart Study original and offspring cohorts who were at least 30 years of age and AF-free at baseline examination and had at least one parent or sibling who was also in the study (median three first-degree relatives per participant).

At a total of 11 971 examinations conducted from 1968 to 2007, 440 participants were found with AF during predefined follow-up windows of eight years.

Familial AF--that is, presence of AF in a first-degree relative prior to the examination that started the eight-year follow-up--was identified in 26.8% of participants. A subset amounting to 7.9% of the total had premature familial AF--the first-degree relative developed AF at 65 or younger.

In an age- and sex-adjusted analysis, familial AF raised the risk of new-onset AF by almost 40% (hazard ratio [HR] 1.39, 95% CI 1.12–1.73; p=0.003).

The risks weren't much altered after further adjustment for other AF risk factors (HR 1.40, p=0.002), nor did adding diabetes or removing PR interval from the model make much of a difference.

Atrial fib in a sibling similarly increased AF risk even after adjustment for AF in a parent (HR 1.39, p=0.04).

Influence of Age, Genotype

In multivariate analysis, the risk of developing AF at 65 years or younger shot up for participants with a first-degree relative also with such premature AF (HR 3.03, p<0.001). The younger the relative at AF diagnosis, the greater was the risk.

Familial AF similarly affected AF risk in multivariate analysis in a subgroup of 2861 participants who had been genotyped (HR 1.43, p=0.003).

Their risk wasn't influenced much by further adjustment for presence of four single-nucleotide polymorphisms (SNPs) determined to be related to AF in genomewide association studies: rs2200733, rs10033464, rs2106261, and rs13376333 (HR 1.38, p=0.01).

The findings, said Benjamin, "emphasize that updates to the family history are important as part of routine healthcare maintenance. 'Are there any other conditions that have been diagnosed in your first-degree family members since the last time I saw you?' It may be a heart attack, it may be heart failure, or it may be atrial fibrillation, but for all of them, it has some clinical implication."

With his scheduled oral presentation of the analysis, Lubitz is a finalist for the AHA's Samuel A Levine Young Clinical Investigator Award.

The authors had no disclosures. The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute. This analysis or its coauthors received further support from the American Heart Association, the Netherlands Organization for Scientific Research, and other public sources.

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