Carotid and Peripheral Atherosclerosis Myeloperoxidase Predicts Progression of Carotid Stenosis in States of Low High-Density Lipoprotein Cholesterol

OBJECTIVES We investigated the effect of myeloperoxidase (MPO) on progression of carotid stenosis in states of high and low high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) levels. BACKGROUND Myeloperoxidase is pivotally involved in the pathogenesis of atherosclerosis. In vitro data suggest that MPO exerts deleterious effects via oxidative modulation of lipoproteins. METHODS We prospectively studied 1,019 of 1,268 consecutive patients who were asymptomatic with respect to carotid artery disease. Patients underwent serial carotid ultrasound investigations at baseline and after a follow-up interval of median 7.5 months (range 6 to 9 months), categorizing carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed or occluded. The MPO, HDL-C, and LDL-C levels were measured at baseline, grouped by medians, and correlated with progression of carotid atherosclerosis. RESULTS Progression of carotid atherosclerosis was found in 100 of 1,019 patients (9.8%). Myeloperoxidase (p 0.014) but not HDL-C (p 0.95) or LDL-C (p 0.30) were associated with progressive disease. However, MPO 310 ng/ml was significantly associated with progressive disease (adjusted odds ratio [OR] 2.57, 95% confidence interval [CI] 1.39 to 4.75) only in patients with HDL-C levels 49 mg/dl. Otherwise, in patients with higher HDL-C levels (49 mg/dl), MPO 310 ng/ml did not predict disease progression (adjusted OR 1.42, 95% CI 0.72 to 2.78). No interaction of MPO with LDL-C was observed. CONCLUSIONS Myeloperoxidase was associated with progression of carotid atherosclerosis in patients with HDL cholesterol levels below 49 mg/dl. (J Am Coll Cardiol 2006;47:2212– 8) © 2006 by the American College of Cardiology Foundation Recent evidence suggests that myeloperoxidase (MPO), a hemoprotein with mainly microbicidal properties, is fundamentally involved in the development of atherosclerotic lesions (1). Myeloperoxidase seems to play a potentially important role in promoting the progression of pre-existent atherosclerosis, thus triggering the occurrence of acute vascular events. Leukocyte- and blood-MPO levels are significantly higher in patients with coronary artery disease compared with healthy control subjects (2), and elevated MPO levels in patients with acute chest pain and acute coronary syndromes identify individuals with increased risk for an adverse cardiovascular outcome (2– 4). Imbalance between oxidative proatherogenic factors and antiatherogenic mechanisms is a key feature in the pathogenesis of atherosclerosis (5,6). Myeloperoxidase has been detected in human atherosclerotic lesions (7) and is essentially involved in the catalytic consumption of nitric oxide, impairing endothelium-dependent vasorelaxation (8 –10). Myeloperoxidase directly activates metalloproteinases and