Association Between Family History and Early-Onset Atrial Fibrillation Across Racial and Ethnic Groups

Key Points

Question

What is the association of family history with the pathogenesis of early-onset atrial fibrillation in patients of African, European, and Hispanic descent?

Findings

In this cohort study of 664 patients, probands with early-onset atrial fibrillation were significantly more likely to have a family history of arrhythmia in first-degree relatives than patients with non–early-onset atrial fibrillation. Compared with European American probands, African American and Hispanic/Latino probands with early-onset atrial fibrillation were more likely to have a first-degree relative with arrhythmia.

Meaning

These findings support genetic predisposition to early-onset atrial fibrillation across individuals of European, African, and Hispanic/Latino descent and have important implications for identifying family members at risk for atrial fibrillation and sequencing candidate genes.

Abstract

This cohort study compares the prevalence of family history of atrial fibrillation (AF) in patients of European, African, and Hispanic/Latino descent with early-onset AF vs non–early-onset AF.

Abstract

Importance

There is a genetic predisposition to early-onset atrial fibrillation (EOAF) in European American individuals. However, the role of family history in the pathogenesis of EOAF in racial and ethnic minorities remains unclear.

Objective

To determine whether probands with EOAF across racial and ethnic groups have a higher rate of AF in first-degree family members than racially and ethnically matched control patients with non–early-onset AF (non-EOAF).

Design, Setting, and Participants

In this cohort study, patients prospectively enrolled in a clinical and genetic biorepository were administered baseline questionnaires that included questions about family history of AF. Early-onset AF was defined as AF occurring in probands aged 60 years or younger in the absence of structural heart disease. All other forms were categorized as non-EOAF. Recruitment took place from July 2015 to December 2017. Analysis was performed in January 2018.

Main Outcomes and Measures

Primary analysis of reported family history of AF in first-degree relatives with sensitivity analysis restricted to those in whom a family history was confirmed by medical record review and electrocardiogram.

Results

Of 664 patients enrolled (mean [SD] age, 62 [12] years; 407 [61%] male), 267 (40%) were European American; 258 (39%), African American; and 139 (21%), Hispanic/Latino. There was a family history of AF in 36 probands with EOAF (49%) compared with 128 patients with non-EOAF (22%) (difference, 27%; 95% CI, 14%-40%; P < .001). On multivariable analysis, the adjusted odds of a proband with EOAF who was of African descent (odds ratio [OR], 2.69; 95% CI, 1.06-6.91; P < .001) or Hispanic descent (OR, 9.25; 95% CI, 2.37-36.23; P = .002) having a first-degree relative with AF were greater than those of European descent (OR, 2.51; 95% CI, 1.29-4.87; P = .006). Overall, probands with EOAF were more likely to have a first-degree relative with AF compared with patients with non-EOAF (adjusted OR, 3.02; 95% CI, 1.82-4.95; P < .001) across the 3 racial and ethnic groups. Atrial fibrillation in a first-degree family member was confirmed in 32% of probands with EOAF vs 11% of those with non-EOAF (difference, 21%; 95% CI, 11%-33%; P < .001). Furthermore, African American (28% vs 5%; difference, 23%; 95% CI, 4%-43%; P = .001), European American (35% vs 20%; difference, 15%; 95% CI, 1%-30%; P = .03), and Hispanic/Latino (30% vs 5%; difference, 25%; 95% CI, 4%-54%; P = .02) probands with EOAF were more likely to have a first-degree relative with confirmed AF vs racially and ethnically matched control patients with non-EOAF. The positive and negative predictive values for a family history of confirmed AF were both 89%.

Conclusions and Relevance

Probands of African or Hispanic/Latino descent with EOAF were more likely to have a first-degree relative with AF when compared with European American individuals. These findings support genetic predisposition to EOAF across all 3 races.