Yu Kataoka1, Mingyuan Shao2, Kathy Wolski2, Kiyoko Uno2, Rishi Puri2, E Murat Tuzcu2, Stanley L Hazen3, Steven E Nissen2, Stephen J Nicholls2. 1. Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Electronic address: jimmyk67@yahoo.co.jp. 2. Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. 3. Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA; Department of Cell Biology, Cleveland Clinic and the Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Abstract
OBJECTIVE: While inflammation has been proposed to contribute to the adverse cardiovascular outcome in diabetic patients, the specific pathways involved have not been elucidated. The leukocyte derived product, myeloperoxidase (MPO), has been implicated in all stages of atherosclerosis. The relationship between MPO and accelerated disease progression observed in diabetic patients has not been studied. METHODS: We investigated the relationship between MPO and disease progression in diabetic patients. 881 patients with angiographic coronary artery disease underwent serial evaluation of atherosclerotic burden with intravascular ultrasound. Disease progression in diabetic (n = 199) and non-diabetic (n = 682) patients, stratified by baseline MPO levels was investigated. RESULTS: MPO levels were similar in patients with and without diabetes (1362 vs. 1255 pmol/L, p = 0.43). No relationship was observed between increasing quartiles of MPO and either baseline (p = 0.81) or serial changes (p = 0.43) in levels of percent atheroma volume (PAV) in non-diabetic patients. In contrast, increasing MPO quartiles were associated with accelerated PAV progression in diabetic patients (p = 0.03). While optimal control of lipid and the use of high-dose statin were associated with less disease progression, a greater benefit was observed in diabetic patients with lower compared with higher MPO levels at baseline. CONCLUSIONS: Increasing MPO levels are associated with greater progression of atherosclerosis in diabetic patients. This finding indicates the potential importance of MPO pathways in diabetic cardiovascular disease.
OBJECTIVE: While inflammation has been proposed to contribute to the adverse cardiovascular outcome in diabeticpatients, the specific pathways involved have not been elucidated. The leukocyte derived product, myeloperoxidase (MPO), has been implicated in all stages of atherosclerosis. The relationship between MPO and accelerated disease progression observed in diabeticpatients has not been studied. METHODS: We investigated the relationship between MPO and disease progression in diabeticpatients. 881 patients with angiographic coronary artery disease underwent serial evaluation of atherosclerotic burden with intravascular ultrasound. Disease progression in diabetic (n = 199) and non-diabetic (n = 682) patients, stratified by baseline MPO levels was investigated. RESULTS:MPO levels were similar in patients with and without diabetes (1362 vs. 1255 pmol/L, p = 0.43). No relationship was observed between increasing quartiles of MPO and either baseline (p = 0.81) or serial changes (p = 0.43) in levels of percent atheroma volume (PAV) in non-diabeticpatients. In contrast, increasing MPO quartiles were associated with accelerated PAV progression in diabeticpatients (p = 0.03). While optimal control of lipid and the use of high-dose statin were associated with less disease progression, a greater benefit was observed in diabeticpatients with lower compared with higher MPO levels at baseline. CONCLUSIONS: Increasing MPO levels are associated with greater progression of atherosclerosis in diabeticpatients. This finding indicates the potential importance of MPO pathways in diabetic cardiovascular disease.
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