Introduction: Abdominal aortic aneurysms (AAA) are an important manifestation of vascular disease in older age and rupture of an AAA is associated with high mortality. Traditional atherosclerotic disease risk factors contribute to the etiology of AAA. Biomarkers for novel etiopathogenic mechanisms, including extracellular matrix remodeling and inflammation, have been assessed primarily in cross-sectional studies of AAA. The objective of this study was to prospectively assess the association between biomarkers for these novel mechanisms and clinical AAA during 24 years of follow-up in the ARIC study, a large, community-based cohort.
Methods: Clinical AAAs were ascertained from baseline in 1987-1989 (45-64 years of age) to 2011 through hospital discharge codes, death codes, and Medicare outpatient claims. Over a maximum 24 years of follow-up, a total of 554 AAAs (85.3% whites) were identified. Using a nested case-cohort design, novel biomarkers, including MMP3, MMP9, IL6, IL1-beta, N-terminal propeptide of Type III procollagen (PIIINP), and osteopontin, were measured at baseline (90% of sample) or Visit 2 (1990-1992, 10% of sample) in all AAAs and a random sample of 747 participants who were selected from baseline and matched with AAAs by age (≤55 and >55), race, and gender. The association of the biomarkers with the risk of future AAA was estimated using multivariable Cox proportional hazard models with weighting to adjust for the varying sampling fractions of cases and controls across strata.
Results: MMP9, IL6, PIIINP, and osteopontin were significantly associated with future risk of AAA after adjusting for age, gender, race and field center (Table). The associations for PIIINP and osteopontin were no longer significant after further adjusting for other traditional risk factors for AAA.
Conclusions: Blood concentrations of MMP9, IL6, and osteopontin measured in middle-age were risk markers for incident AAA. These results highlight the role of inflammation and extracellular remodeling in the development of AAA.