Highlights
- •We analyze the impact of MPO on plaque progression by intravascular ultrasound.
- •Increasing MPO level contributes to plaque progression in diabetics.
- •LDL-C lowering results in less progression in diabetics with low MPO level.
- •High-dose statin prevents plaque progression in diabetics with low MPO level.
- •These benefits are diminished in diabetics with high MPO level.
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.
Keywords
Abbreviations:
CAD (coronary artery disease), DM (diabetes mellitus), EEM (external elastic membrane), HDL (high-density lipoprotein), hsCRP (high sensitivity C-reactive protein), IVUS (intravascular ultrasound), LDL (low-density lipoprotein), MPO (myeloperoxidase), PAV (percent atheroma volume)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to AtherosclerosisAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies.BMJ. 2006; 332: 73-78
- Is diabetes mellitus a cardiovascular disease risk equivalent for fatal stroke in women? Data from the Women's Pooling Project.Stroke. 2003; 34: 2812-2816
- Effect of diabetes on progression of coronary atherosclerosis and arterial remodeling: a pooled analysis of 5 intravascular ultrasound trials.J Am Coll Cardiol. 2008; 52: 255-262
- Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial.Diabetes Care. 1993; 16: 434-444
- Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study.Diabetes. 2003; 52: 1799-1805
- Insulin resistance, inflammation, and the prediabetic state.Am J Cardiol. 2003; 92: 18J-26J
- New aspects in the pathogenesis of diabetic atherosclerosis.J Am Coll Cardiol. 2004; 44: 2293-2300
- Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions.J Am Coll Cardiol. 2005; 46: 1978-1985
- Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus.Circulation. 2000; 102: 2180-2184
- Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study.Arterioscler Thromb Vasc Biol. 2004; 24: 1266-1271
- Association of C-reactive protein with early-stage carotid atherosclerosis in Japanese patients with early-stage type 2 diabetes mellitus.Endocr J. 2006; 53: 693-698
- Combined effects of hemoglobin A1c and C-reactive protein on the progression of subclinical carotid atherosclerosis: the INVADE study.Stroke. 2006; 37: 351-357
- Myeloperoxidase and cardiovascular disease.Arterioscler Thromb Vasc Biol. 2005; 25: 1102-1111
- Myeloperoxidase, modified lipoproteins, and atherogenesis.J Lipid Res. 2009; 50: S346-S351
- Oxygen metabolism and the toxic properties of phagocytes.Ann Intern Med. 1980; 93: 480-489
- Immunocytochemicalidentification of azurophilic and specific granule markers in the giant granules of Chediak-Higashi neutrophils.N Engl J Med. 1978; 298: 693-698
- Spatial mapping of pulmonary and vascular nitrotyrosinereveals the pivotal role of myeloperoxidase as a catalyst for tyrosine nitration in inflammatory diseases.Free Radic Biol Med. 2002; 33: 1010
- Endothelial transcytosis of myeloperoxidase confers specificity to vascular ECM proteins as targets of tyrosine nitration.J Clin Invest. 2001; 108: 1759-1770
- 3-Chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima.J Clin Invest. 1997; 99: 2075-2081
- Myeloperoxidase-generated reactive nitrogen species convert LDL into an atherogenic form in vitro.J Clin Invest. 1999; 103: 1547-1560
- Apolipoprotein A-1 is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subject with cardiovascular disease.J Clin Invest. 2004; 114: 529-541
- Myeloperoxidase impairs ABCA1-dependent cholesterol efflux through methionine oxidation and site-specific tyrosine chlorination of apolipoprotein A-I.J Biol Chem. 2006; 281: 9001-9004
- Modification of high density lipoprotein by myeloperoxidase generates a pro-inflammatory particle.J Biol Chem. 2009; 284: 30825-30835
- Myeloperoxidase, a leukocyte-derived vascular NO oxidase.Science. 2002; 296: 2391-2394
- Serum myeloperoxidase levels independently predict endothelial dysfunction in humans.Circulation. 2004; 110: 1134-1139
- Nitric oxide modulates the catalytic activity of myeloperoxidase.J Biol Chem. 2000; 275: 5425-5430
- Endothelial-vasoprotective effects of high-density lipoprotein are impaired in patients with type 2 diabetes mellitus but are improved after extended-release niacin therapy.Circulation. 2010; 121: 110-122
- Intravascular ultrasound in cardiovascular medicine.Circulation. 2006; 114: e55-e59
- Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial.JAMA. 2004; 291: 1071-1080
- Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial.JAMA. 2004; 292: 2217-2225
- Effect of ACAT inhibition on the progression of coronary atherosclerosis.N Engl J Med. 2006; 354: 1253-1263
- Risk prediction with serial myeloperoxidase monitoring in patients with acute chest pain.Clin Chem. 2011; 57: 1762-1770
- Prognostic value of myeloperoxidase in patients with chest pain.N Engl J Med. 2003; 349: 1595-1604
- Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes.Circulation. 2003; 108: 1440-1445
- Serum myeloperoxidase levels are associated with the future risk of coronary artery disease in apparently healthy individuals: the EPIC-Norfolk Prospective Population Study.J Am Coll Cardiol. 2007; 50: 159-165
- Association between myeloperoxidase levels and risk of coronary artery disease.JAMA. 2001; 286: 2136-2142
- Myeloperoxidase and C-reactive protein have combined utility for long-term prediction of cardiovascular mortality after coronary angiography.J Am Coll Cardiol. 2010; 55: 1102-1109
- Leukocyte-derived myeloperoxidase amplifies high-glucose-induced endothelial dysfunction through interaction with high-glucose-stimulated, vascular non-leukocyte-derived reactive oxygen species.Diabetes. 2004; 53: 2950-2959
- Intravascular ultrasound-derived measures of coronary atherosclerotic plaque burden and clinical outcome.J Am Coll Cardiol. 2010; 55: 2399-2407
Article info
Publication history
Accepted:
November 27,
2013
Received in revised form:
November 26,
2013
Received:
June 5,
2013
Identification
Copyright
© 2013 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.