AF in the family raises individual risk
MedWire News: People are at increased risk for atrial fibrillation (AF) if they have first-degree relatives with the condition, shows an analysis of the Framingham Heart Study.
The effect was independent of genetic variants already known to increase AF risk, report Emelia Benjamin (Framingham Heart Study, Massachusetts, USA) and colleagues.
"The concept of 'missing heritability' has received much attention in the current era of genome-wide association studies," they write in JAMA.
"Our results justify future efforts to identify novel genetic variants, unmeasured environmental factors, and potential joint effects of genetic and environmental factors involved in the pathogenesis of AF."
The 4421 participants in the team's analysis were free of AF at baseline and had at least one parent or sibling enrolled in the study. In all, 26.8% of the participants had familial AF, and 5.8% of these developed incident AF during follow-up from 1968 through 2007, compared with 3.1% of those without familial AF.
Having familial AF increased participants' individual risk by 40%, after adjustment for age, gender, and AF risk factors including body mass index, blood pressure, PR interval, heart murmur, and heart failure.
Accounting for four genetic variants known to influence AF risk, in a subset of 2861 previously genotyped participants, did not influence the association between familial AF and individual risk.
Adding features of familial AF to a base model of established AF predictors slightly, but significantly, improved its ability to discriminate between participants who did and did not develop AF. The greatest improvement to the model came with the addition of premature familial AF, defined as occurring by the age of 65 years.
The base model had a C statistic of 0.842, so already provided excellent discrimination, and only improved to 0.846 with the addition of premature familial AF.
But Benjamin et al say this is in line with the reported effect of family history on cardiovascular disease and "reflects the difficulty of assessing novel risk factors for incremental benefit beyond established risk factors."
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By Eleanor McDermid