Progression of atherosclerosis in patients with peripheral arterial disease as a function of angiotensin-converting enzyme gene insertion/deletion polymorphism.

Abstract

Angiotensin-converting enzyme insertion/deletion (I/D) gene polymorphism plays a role in determining the inter-individual variability of circulating angiotensin-converting enzyme activity and intracellular angiotensin-converting enzyme levels. Angiotensin-converting enzyme, as a key enzyme in the renin-angiotensin system, catalyzes the activation of the vasoconstricting and proliferation-stimulating angiotensin II and breaks down the vasodilatory peptide bradykinin. It is assumed that the excess supply of angiotensin II (due to the deletion polymorphism of the angiotensin-converting enzyme gene) contributes to endothelial dysfunction and in this way promotes the onset and progression of atherosclerosis. The aim of this study was to test whether the presence of the deletion allele of the angiotensin-converting enzyme gene predisposes a more rapid systemic progression of a preexisting peripheral arterial disease. To this end, the course of disease was surveyed for an average of 5 years in 97 patients who were angiotensin-converting enzyme gene-typed and suffered from a stable stage II peripheral arterial disease according to Fontaine. These patients did not suffer from an additional coronary artery disease, a cerebrovascular disease, or other serious illness. A local progression in the periphery or a systemic progression in the coronary or cerebrovascular areas was regarded as study endpoints. Of the patients, 49.5% showed an atherosclerosis progression during the surveillance period. With II-carriers, a progression was registered in 42.1% and with DD carriers, progression was seen in 59.4%. D/I allele frequencies were seen in patients with progression at a level of 0.60/0.40 vs 0.55/0.45 for patients without progression. The average duration of disease in stable stage II (before progression appeared) amounted to 108 +/- 14 months for II carriers, 88 +/- 8 months for ID carriers, and 92 +/- 11 months for DD carriers (p = 0.21). Based on these findings, the deletion polymorphism of the angiotensin-converting enzyme gene is not an independent risk factor for progression of atherosclerosis in patients with peripheral arterial disease.