Family history as a risk factor for recurrent hospitalization for lone atrial fibrillation: a nationwide family study in Sweden

BMC Cardiovascular Disorders, Dec 2012

Background Although the heritability of atrial fibrillation (AF) has been determined, the relevance of family history of AF for the likelihood of recurrent hospitalization for AF is unknown. The aim of this nationwide study was to determine whether family history of AF is a risk factor of recurrent hospitalization for lone AF (LAF), i.e., AF with unknown etiology. The familial risk for first time LAF hospitalization was also determined and compared to the risk of recurrent hospitalization for LAF. Methods We examined whether family history of AF is a risk factor for recurrent hospitalization for LAF in the whole Swedish population. We linked Multigeneration Register data on individuals aged 0–60 years to Hospital Discharge Register data for the period 1987–2009 to compare LAF recurrent hospitalization risk among individuals with and without parental or sibling history of AF. We calculated hazard ratios (HRs) to determine the familial HR of recurrent hospitalization for LAF. Odds ratios (OR) were calculated for familial risk of first time LAF hospitalization. Results The risk of recurrent LAF hospitalization was 1.23 (95% CI 1.17-1.30) for individuals with affected parents compared to 1.30 (95% CI 1.22-1.38) for those with affected siblings. After 10 years of follow up 50% of those without and 60% of those with family history had recurrent hospitalization for LAF. The risk of recurrent LAF hospitalization in individuals with two affected parents was 1.65 (95% CI 1.44-1.90). There was an interaction between age and family history, with family history having a weaker effect on LAF hospitalization risk in older age groups. The OR for first time LAF hospitalization was 2.08 (95% CI 2.02-2.15) for offspring with affected parents and 3.23 (95% CI 3.08-3.39) for individuals with affected siblings. Conclusions Family history of AF is a novel risk factor for recurrent LAF hospitalization. The higher recurrence hospitalization risk in multiplex families and younger individuals suggests a genetic contribution. However, the familial risk for recurrent LAF hospitalization was much lower than the risk for first time LAF hospitalization, suggesting that familial and possibly genetic factors are more important for first time LAF hospitalization than recurrent LAF hospitalization.

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Family history as a risk factor for recurrent hospitalization for lone atrial fibrillation: a nationwide family study in Sweden

BMC Cardiovascular Disorders Family history as a risk factor for recurrent hospitalization for lone atrial fibrillation: a nationwide family study in Sweden Bengt Zller 0 2 Henrik Ohlsson 0 2 Jan Sundquist 0 1 2 Kristina Sundquist 0 1 2 0 Center for Primary Health Care Research, CRC, Skane University Hospital , Building 28, Floor 11, Jan Waldenstroms gata 35, Malmo S-205 02 , Sweden 1 Stanford Prevention Research Center, Stanford University School of Medicine , Stanford, California , USA 2 Center for Primary Health Care Research, CRC, Skane University Hospital , Building 28, Floor 11, Jan Waldenstroms gata 35, Malmo S-205 02 , Sweden Background: Although the heritability of atrial fibrillation (AF) has been determined, the relevance of family history of AF for the likelihood of recurrent hospitalization for AF is unknown. The aim of this nationwide study was to determine whether family history of AF is a risk factor of recurrent hospitalization for lone AF (LAF), i.e., AF with unknown etiology. The familial risk for first time LAF hospitalization was also determined and compared to the risk of recurrent hospitalization for LAF. Methods: We examined whether family history of AF is a risk factor for recurrent hospitalization for LAF in the whole Swedish population. We linked Multigeneration Register data on individuals aged 0-60 years to Hospital Discharge Register data for the period 1987-2009 to compare LAF recurrent hospitalization risk among individuals with and without parental or sibling history of AF. We calculated hazard ratios (HRs) to determine the familial HR of recurrent hospitalization for LAF. Odds ratios (OR) were calculated for familial risk of first time LAF hospitalization. Results: The risk of recurrent LAF hospitalization was 1.23 (95% CI 1.17-1.30) for individuals with affected parents compared to 1.30 (95% CI 1.22-1.38) for those with affected siblings. After 10 years of follow up 50% of those without and 60% of those with family history had recurrent hospitalization for LAF. The risk of recurrent LAF hospitalization in individuals with two affected parents was 1.65 (95% CI 1.44-1.90). There was an interaction between age and family history, with family history having a weaker effect on LAF hospitalization risk in older age groups. The OR for first time LAF hospitalization was 2.08 (95% CI 2.02-2.15) for offspring with affected parents and 3.23 (95% CI 3.08-3.39) for individuals with affected siblings. Conclusions: Family history of AF is a novel risk factor for recurrent LAF hospitalization. The higher recurrence hospitalization risk in multiplex families and younger individuals suggests a genetic contribution. However, the familial risk for recurrent LAF hospitalization was much lower than the risk for first time LAF hospitalization, suggesting that familial and possibly genetic factors are more important for first time LAF hospitalization than recurrent LAF hospitalization. Atrial fibrillation; Family history; Risk factors; Genetics - Background Atrial fibrillation (AF) is a major public health problem because of its increasing prevalence and because it is associated with increased morbidity and mortality [1,2]. Many risk factors for AF have been described and they include, e.g., old age, cardiomyopathy, valvular disease, ischemic heart disease, heart failure, thyroid disease, hypertension and diabetes mellitus [1-3]. In some patients, its etiology remains unknown. AF occurring before the age of 60 years without any evidence of associated cardiopulmonary or other comorbid disease has been termed lone AF (LAF) [4,5]. Familial AF was first reported in 1943 [6], and familial clustering of AF has been repeatedly demonstrated [7-15]. The first chromosomal location of an AF susceptibility gene was reported in 1997 based on genetic mapping studies in three families [16]. Several genetic variants have since then been linked to risk of AF [17-25]. The importance of family history for LAF has been determined in several studies [9,11,12,14]. Despite the use of antiarrhythmic agents for sinus rhythm maintenance in cardioverted AF patients, a considerable proportion of patients relapse to AF [2]. It is generally believed that these recurrences are associated with older age, atrial dilatation, and long duration of AF [26]. Studies have also suggested that female sex, obesity, personal history of two or more AF events, decreased renal function, increased circulating markers of cardiomyocyte injury/strain (high-sensitivity troponin T, Nterminal probrain natriuretic peptide and mid-regional proatrial natriuretic peptide) and endothelin, and increased C-reactive protein to be risk factors for relapse to AF [26-32]. The tendency of AF to become sustained over time is not easily managed, and represents a challenging therapeutic problem. Although family history is a risk factor for first event of AF [6-15], the risk of AF recurrence in patients with a family history of AF has not yet been determine (...truncated)


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Bengt Zöller, Henrik Ohlsson, Jan Sundquist, Kristina Sundquist. Family history as a risk factor for recurrent hospitalization for lone atrial fibrillation: a nationwide family study in Sweden, BMC Cardiovascular Disorders, 2012, pp. 121, 12, DOI: 10.1186/1471-2261-12-121