Haptoglobin 2-1 phenotype predicts rapid growth of abdominal aortic aneurysms

Abstract

Haptoglobin (Hp) polymorphism is associated with the prevalence and clinical evolution of many inflammatory diseases and atherosclerosis. Circulating neutrophils and neutrophil-associated proteases are an important initial component of experimental abdominal aortic aneurysm (AAA) formation. Elastase and C-reactive protein (CRP) levels are elevated in patients with AAAs. This study assessed the relationship between AAA expansion and Hp phenotypes, neutrophil count, elastase, and CRP levels. Eighty-three consecutive AAA patients underwent annual ultrasound scans. Three major Hp phenotypes (1-1, 2-1, and 2-2) were determined, and the neutrophil count, serum elastase, and high-sensitivity (hs) CRP levels were measured at the initial examination. After initial screening, patients were rescanned at 6- to 12-month intervals up to a period of 2 to 7 years. The mean yearly growth of the AAA largest transverse diameter was estimated for each group of Hp patients. The results are presented as median (interquartile range). Hp 2-1 patients had a significantly higher growth rate (3.69 [2.40] mm/y) of AAA compared with patients with Hp 2-2 (1.24 [0.79], P < .00001) and Hp 1-1 (1.45 [0.68], P = .00004). This association remained significant in the multivariate analysis. Elevated elastase serum activity was also evident in AAA patients with Hp 2-1 (0.119 [0.084] arbitrary units) in contrast to Hp 2-2 (0.064 [0.041], P < .00001) and Hp 1-1 (0.071 [0.040], P = .0006) patients. CRP serum levels (mg/L) were significantly higher in patients with Hp 2-1 (7.2 [7.1]) than in Hp 2-2 (3.4 [3.1], P = .0058) and Hp 1-1 (2.8 [4.1], P = .044). The neutrophil count was not significantly different among Hp groups. The Hp 2-1 phenotype showed a strong association with increased rates of the expansion of AAAs and may be a useful independent predictor of growth rate. Further large follow-up studies will be needed to investigate the pathomechanisms of association and the role of elastase and inflammation in the progression of AAA.