A population-based case-control study of the familial risk of abdominal aortic aneurysm.

Department of Molecular Medicine and Surgery, Stockholm, Sweden.
Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter (Impact Factor: 3.52). 12/2008; 49(1):47-50; discussion 51. DOI: 10.1016/j.jvs.2008.08.012
Source: PubMed

ABSTRACT Several studies have reported a familial clustering of abdominal aortic aneurysm (AAA) supporting that AAA is an inheritable disease, but few population-based studies can be found. Possible gender differences regarding hereditary patterns have been reported.
The aim of this study was to investigate the risk of developing an AAA for first-degree relatives of patients with AAA in Sweden and compare them with matched controls and their relatives.
All persons (3183) born after 1932, diagnosed with AAA between 2001 and 2005, and a random selection of 15,943 age-, gender-, and region-matched controls were included. First-degree relatives of cases and controls were identified via the Multigeneration Register. Family history of AAA for cases and controls was assessed by linking the relatives to the Hospital Discharge Register and Cause of Death Register. The data were analyzed by conditional logistic regression.
The overall relative risk of AAA associated with family history compared to no family history was 1.9 (95% confidence interval [CI] 1.6-2.2). Comorbidities were more common among the cases than the controls (P < .0001) but the relative risks remained unchanged after adjustment for comorbidities. Stratification for absence or presence of comorbidities showed no significant difference between the two groups (P = .29). The relative risk of AAA for first-degree relatives was similar for women and men (P = .22 for gender differences), ie, the relative risk of AAA was not dependent on the gender of the index person.
In this nationwide survey, the relative risk of developing AAA for first-degree relatives to persons diagnosed with AAA was approximately doubled compared to persons with no family history. Neither the gender of the index person nor the first-degree relative influenced the risk of AAA.

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    ABSTRACT: Abdominal aortic aneurysm (AAA) is a complex multifactorial disease with genetic and environmental components. AAA is more common in males, whereas women have a greater risk of rupture and more frequently have concomitant thoracic aortic aneurysms. Moreover, women are diagnosed with AAA about 10 years later and seem to be protected by female sex hormones. In this MEDLINE-based review of literature we examined human and animal, in vivo and in vitro studies, to further deepen our understanding of the sexual dimorphism of AAA. We focus on the role of sex hormones during the formation and growth of AAA. Endogenous estrogens and exogenous 17β-estradiol were found to exert favorable actions protecting from AAA in animal models, whereas exogenous hormone replacement therapy in humans had inconclusive results. Androgens, known to have detrimental effects in the vasculature, in sufficient levels maintain the integrity of the aortic wall through their anabolic actions and act differentially in males and females, whereas lower levels of testosterone have been associated with AAA in humans. In conclusion, sex differences remain an important area of AAA research, but further studies especially in humans are needed. Furthermore, differential molecular mechanisms of sex hormones constitute a potential therapeutic target for AAA.
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