Study Determines Atrial Fibrillation Heritability Among 3 Key Probands

The heritability of atrial fibrillation (AF) has remained largely unexplained.

However, a recent study that sought determine whether probands of African, European, and Hispanic descent with early onset AF (EOAF) were more likely to have a first-degree relative with arrhythmia when compared with racially and ethnically matched control patients with non-EOAF has addressed that long-answered question.

The genetic predisposition to EOAF in European-American individuals has long been established. Though it has been largely proven that non-Europeans are at a lower risk of developing AF, racial and ethnic minorities, specifically African American and Hispanic patients, have a proven increased rate of stroke, heart failure and death when compared to white patients.

Despite this correlation, the relationship between family history and the pathogenesis of EOAF in these minority groups has remained largely undetermined until recently.

Investigators solidified the significance of the relationship between family history and the likelihood of being diagnosed with EOAF, thus supporting the theory of genetic predisposition and proving significant in identifying at-risk patients.

The study followed 664 patients of European, African and Hispanic descent. Of this group, of whom 40% were European American, 39% were African American, and 21% were Hispanic/Latino. Eleven percent were diagnosed with EOAF and 89% had non-EOAF. The prevalence of EOAF in African American, European American, and Hispanic/Latino patients was 9%, 15% and 7%, respectively, according to the study.

Investigators found that proband with EOAF were significantly more likely to have a family history of arrhythmia in first-degree relatives than patients with non-EOAF. In examining the results of the study through the scope of race and ethnicity, they noted that European-Americans maintained their likelihood for a genetic predisposition to EOAF.

However, African American and Hispanic/Latino probands with EOAF were more likely to have a first-degree relative with arrhythmia when compared to their European counterparts.

One-third of European American participants with EOAF had a first-degree relative with confirmed AF, consistent with earlier studies reporting a 30% to 40% family history, according to the study.

Among the minority groups, results showed that 28% of African American and 60% of Hispanic/Latino probands with EOAF had a confirmed history of AF in first-degree relatives. The higher correlation rate among Hispanic/Latino probands with EOAF were due to the lower prevalence of AF among this group, according to the study.

Furthermore, results also showed that family members of probands of African and Hispanic descent with EOAF are at high risk for AF. However, penetrance in a family history of AF is significantly variable. Investigators postulated that this may relate to the “two-hit” hypothesis for the development of AF, which states that a proband carrying a mutation in a known AF gene only develops the arrhythmia in the presence of a second anomaly or “hit,” such as HTN or a single- nucleotide polymorphism commonly associated with AF risk, according to the study, which ultimately emphasized the importance of obtaining a family history of AF.

Ultimately, the study underscored the significance of determining a detailed family history in all patients diagnosed with EOAF, regardless of proband, due to the correlation between these probands with EOAF and first-degree family members with AF. With new clarity now established in terms of heritability of AF, investigators have opened the doors to innovative new treatments and research within the field of AF.

The study, "Association Between Family History and Early-Onset Atrial Fibrillation Across Racial and Ethnic Groups," was published online in JAMA on Friday.