Medline ® Abstracts for References 9,23-25

BACKGROUND: Abdominal aortic aneurysm (AAA) is a relatively common disease, with 1% to 2% of the population harboring aneurysms. Genetic risk factors are likely to contribute to the development of AAAs, although no such risk factors have been identified.

METHODS AND RESULTS: We performed a whole-genome scan of AAA using affected-relative-pair (ARP) linkage analysis that includes covariates to allow for genetic heterogeneity. We found strong evidence of linkage (logarithm of odds [LOD]score=4.64) to a region near marker D19S433 at 51.88 centimorgans (cM) on chromosome 19 with 36 families (75 ARPs) when including sex and the number of affected first-degree relatives of the proband (N(aff)) as covariates. We then genotyped 83 additional families for the same markers and typed additional markers for all families and obtained a LOD score of 4.75 (P=0.00014) with sex, N(aff), and their interaction as covariates near marker D19S416 (58.69 cM). We also identified a region on chromosome 4 with a LOD score of 3.73 (P=0.0012) near marker D4S1644 using the same covariate model as for chromosome 19.

CONCLUSIONS: Our results provide evidence for genetic heterogeneity and the presence of susceptibility loci for AAA on chromosomes 19q13 and 4q31.

BACKGROUND: Abdominal aortic aneurysm is a multifactorial disorder in which inflammation is an important pathophysiological feature. In explant culture, aneurysm biopsies secrete large amounts of interleukin-6 (IL-6), and among aneurysm patients, the circulating concentration of IL-6 appears to be increased.

METHODS AND RESULTS: We investigated, in 19 patients, whether aneurysm wall was an important source of circulating IL-6. We also tested the hypotheses, in 466 patients with a small aneurysm, that (1) high concentrations of circulating IL-6 signaled rapid aneurysm growth and (2) the -174 G-->C polymorphism in the IL-6 promoter predicted survival. For 19 patients with large or inflammatory aneurysms, the concentration of IL-6 was higher in the iliac arteries than the brachial arteries (median difference 26.5 pg/mL, this difference increasing with aneurysm diameter, P=0.01). In 466 patients with small aneurysms, the frequency of the -174 C allele (0.40) was similar to that in a normal healthy population. Patients of GG genotype had lower plasma concentrations of IL-6 than patients of GC and CC genotypes (medians 1.9, 4.8, and 15.6 pg/mL, respectively, Kruskal-Wallis P=0.047). Cardiovascular and all-cause mortalities were lower for patients of GG genotype than forpatients of GC and CC genotype: hazard ratios 0.32 (95% CI 0.12 to 0.93), P=0.036, and 0.51 (95% CI 0.25 to 1.00), P=0.05, respectively. There was no association between plasma IL-6 or IL-6 genotype and aneurysm growth.

CONCLUSIONS: Aortic aneurysms appear to be an important source of circulating IL-6, the concentration being influenced by genotype. For patients with small aneurysms, the -174 G-->C IL-6 genotype predicts future cardiovascular mortality.

OBJECTIVE: The authors present a review of abdominal aortic aneurysms (AAAs) and to examine the literature on the diagnosis, operative management, and long-term survival of patients with inflammatory AAAs. Furthermore, to review current theories on the cause of inflammatory AAAs and present recent studies that provoke new thought on the cause of these aneurysms.

BACKGROUND DATA: Inflammatory AAAs represent 3% to 10% of all AAAs and present the surgical team with a unique challenge. Progress has occurred in the technical approach to these aneurysms, and operative morbidity and mortality have been reduced. However, the pathogenesis remains an enigma. Recent studies raise questions regarding the influence of tobacco and genetic factors that accentuate an antigen-driven inflammatory response.

METHODS: The authors conduct a review of the literature on both noninflammatory and inflammatory AAAs.

RESULTS: Review of the literature of inflammatory AAAs reveals advancement in the definition, diagnosis, management, and long-term survival of patients with inflammatoryAAAs. This review found an evolution in thought regarding the cause of inflammatory AAAs. In contrast to initial reports describing a distinct clinical entity, recent evidence suggests that inflammatory AAAs arise from the same causal stimulus responsible for noninflammatory AAAs. Finally, recent studies show an influence of tobacco and genetic factors on the pathogenesis.

CONCLUSIONS: The literature supports the theory that inflammatory AAAs arise from the same or similar antigenic stimulus which is responsible for the noninflammatory AAA. Genetic and chemical factors such as tobacco use predispose certain persons to the development of noninflammatory AAAs and others to develop the extreme end of an inflammatory spectrum, the inflammatory AAA. Furthermore, inflammatory AAAs can be managed with the same operative morbidity, mortality, and long-term survival as noninflammatory AAAs.