Purpose: To investigate the association of the heme oxygenase-1 (HO-1) genotype, which has potent anti-inflammatory capability, and the inflammatory response induced by balloon angioplasty.
Methods: Three hundred seventeen patients (188 men; median age 70 years, range 57-77) undergoing femoropopliteal balloon angioplasty (n=150) or stenting (n=61) were evaluated for upregulation of the HO-1 genotype; 106 patients undergoing lower limb angiography served as controls. The acute phase reactants C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen were measured 24 and 48 hours postintervention and compared to baseline values. An association of the relative increase (Delta, %) of these inflammatory markers with short (<25) (GT)(n) dinucleotide repeats in the HO-1 gene promoter was assessed.
Results: The HO-1 genotype was significantly associated with Delta CRP(24) (p<0.0001), Delta CRP(48) (p<0.0001), Delta SAA(24) (p=0.02), and Delta SAA(48) (p=0.006) after balloon angioplasty; Delta fibrinogen showed no association. Patients with a higher Delta CRP(48) after balloon angioplasty exhibited significantly reduced odds for the presence of short (<25) (GT)(n) repeats. The adjusted odds reduction in the multivariate model was 80% (p=0.002) in the third quartile of Delta CRP(48) values and 90% (p=0.001) in the fourth quartile. No association of HO-1 genotype and inflammatory response was found 24 and 48 hours after stenting (p=0.3, p=0.5) or angiography (p=0.2, p=0.6).
Conclusions: The HO-1 promoter genotype is independently associated with the inflammatory response seen after balloon angioplasty. Short alleles (<25 GT repeats) seem to be an intrinsic vascular anti-inflammatory factor.