Myeloperoxidase levels predict accelerated progression of coronary atherosclerosis in diabetic patients: insights from intravascular ultrasound.
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.
Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Electronic address: jimmyk67@yahoo.co.jp.
Yu
Y
Kataoka
Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Mingyuan
M
Shao
Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Kathy
K
Wolski
Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Kiyoko
K
Uno
Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Rishi
R
Puri
Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
E
E
Murat Tuzcu
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.
Stanley L
SL
Hazen
Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Steven E
SE
Nissen
Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Stephen J
SJ
Nicholls
D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D048909:Diabetes Complications / Q000097:blood* / Q000150:complications; D003920:Diabetes Mellitus / Q000097:blood; D018450:Disease Progression; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000097:blood*; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging; D018084:Ultrasonography, Interventional
D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009195:Peroxidase
Atheroma progression; CAD; Coronary atherosclerosis; DM; Diabetes mellitus; EEM; HDL; IVUS; Intravascular ultrasound; LDL; MPO; Myeloperoxidase; PAV; coronary artery disease; diabetes mellitus; external elastic membrane; high sensitivity C-reactive protein; high-density lipoprotein; hsCRP; intravascular ultrasound; low-density lipoprotein; myeloperoxidase; percent atheroma volume