Familial risks of aortic aneurysms among siblings in a nationwide Swedish study

Abstract

Purpose: Aortic aneurysms have a high fatality rate that could be reduced with control of risk factors and use of available screening methods for detection of early changes in aortic walls. The available data on familial risks, a potential indication for screening, are mainly limited to abdominal aortic aneurysms. Methods: A nationwide Standardized incidence ratios (SIRs) were calculated for affected siblings by comparing with those whose siblings had no aneurysm. Results: A total of 71 affected siblings were identified with a familial SIR of 8.71; when one sibling was diagnosed before age 50 years, the SIR was 19.69. For concordant thoracic or concordant abdominal aneurysms, the SIRs were 21.68 and 13.06, respectively. For brothers, the risk of abdominal aneurysms was 14.63, and 49.50 for diagnosis before age 50 years. Familial risks and the effects of early diagnostic age were shared by the anatomic subtypes of aneurysms. Within limits of the sample size, no gender differences could be observed. Affected siblings constituted 2.2% of all diagnosed patients. Conclusions: A family history of any aortic aneurysms and age groups younger than 50 years should be considered in recommendations for screening. The Key Words: familial disease, sibling risk, heritability, screening, population-based Aneurysms are swellings of the blood vessels, and on rupture, they are often fatal. Aneurysms are most common in the abdominal and thoracic parts of the aorta. The lesions in the ascending aorta are often dissections, that is, separations of aortic media that extend to distal segments of the affected vessel. 1-3 The known risk factors for aortic aneurysms include male gender, atherosclerosis, hypertension, smoking, vascular malformations, heritable traits, and family history. 3-5 Atherosclerotic lesions preferentially affect the descending aorta, whereas medial degeneration is the most common lesion in the ascending aorta. 2 Aneurysms are usually a result of a degenerative or an autoimmune disease, including, historically, latestage syphilitic infections. 2,6,7 The pathogenesis of aneurysms involves reduction in elastic compliance of the aortic wall, reduction in medial matrix connective tissue fibers composed of fibrillin, elastin, and collagen, and proneness to progressive damage. 2,3 Important mechanical components in this cascade are extracellular matrix defects, proteolytic enzymes, matrix metalloproteinases capable of degrading elastin and collagen, proteinase inhibitors, and persistent inflammation. 3,5 Marfan syndrome is an autosomal dominant condition in which mutated fibrillin 1 prevents an orderly assembly of the elastic fibers. Dissections are one of the manifestations in this condition. 2 Various types of vascular fragility are also found in excess in one form of Ehlers-Danlos syndrome, which is caused by defects in collagen structure and metabolism. 2,8 Familial clustering of aneurysms is well known, based on anecdotal reports and clinical series, covering both abdominal and thoracic aorta. Some 5% to 20% of th...

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

“…12 Their study design only included 71 affected sib-pairs between 0 and 69-yearsold and included all types of aortic aneurysm.…”

Family history, comorbidity and risk of thoracic aortic disease: a population-based case-control study

“…Two studies using similar methods have been undertaken previously. Hemminki et al 8 in a study utilising the same registries for an earlier study era (1987–2001), but restricted to 71 identified sib-pairs, reported an overall standardised incidence ratio of 8.71 for individuals with an affected sibling. They, however, included all types of aneurysms in their study, noting that, since AAA constituted almost 40% and aneurysms with unspecified locations 6.7%, TAD constituted approximately 50% of the study population.…”

“…The family history of the index cases and controls was obtained by identifying all first-degree relatives in the Multigeneration Registry (Statistics Sweden)—a registry including first-degree relatives (parents, children, siblings and half-siblings) of subjects born 1932 or later—and identifying diagnoses of thoracic or AAA in these subjects, if any. Besides age and sex, atherosclerosis, hypertension and smoking are implied risk factors for TAD 8. Their influence on the risk of TAD was assessed in terms of occurrence of correlated clinical conditions identifiable in discharge records; ischaemic heart disease, congestive heart failure, hypertension and chronic obstructive pulmonary disease.…”

Familial Risks for Main Neurological Diseases in Siblings Based on Hospitalizations in Sweden

“…The usefulness of the Swedish family dataset has been demonstrated earlier in studies of familial migraine and aortic aneurysms (Hemminki et al, , 2006.…”