European Heart Journal Advance Access originally published online on January 24, 2006
European Heart Journal 2006 27(7):817-823; doi:10.1093/eurheartj/ehi746
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Elevated levels of remnant lipoproteins are associated with plasma platelet microparticles in patients with type-2 diabetes mellitus without obstructive coronary artery disease
1Department of Cardiovascular Medicine, Graduate School of Medical Sciences Kumamoto University, 1-1-1 Honjo, Kumamoto City, Kumamoto 860-8556, Japan
2Second Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan
3Department of Internal Medicine, Jinnouchi Clinic, Kumamoto, Japan
Received 4 January 2005; revised 21 October 2005; accepted 5 January 2006; online publish-ahead-of-print 24 January 2006.
* Corresponding author. Tel: +81 96 373 5175; fax: +81 96 362 3256. E-mail address: ssugiyam{at}kumamoto-u.ac.jp
Aims Platelets participate in the pathogenesis of arterial thrombosis and it has been demonstrated that enhanced platelet activation occurs in patients with diabetes mellitus (DM). Dyslipidaemia is a common feature of diabetes. We investigated the association between certain lipid fractions and plasma platelet-derived microparticle (PMP) levels in patients with type-2 DM.
Methods and results We measured fasting serum levels of remnant-like lipoprotein particles-cholesterol (RLP-cholesterol) and assessed in vivo platelet activation by quantifying the number of PMP in the plasma detected as CD42b-positive microparticles by flow cytometry in Japanese type-2 DM patients without obstructive coronary artery disease who were more slender when compared with Western diabetic patients. The levels of total cholesterol, triglycerides, RLP-cholesterol, and plasma glucose were significantly higher in patients with type-2 DM (n=105) than in non-diabetic patients (n=92). The plasma levels of PMP were elevated significantly in type-2 DM patients when compared with non-diabetic control subjects [7.41(5.39–10.50)x106 vs. 3.44(2.43–4.41)x106, P<0.001]. We found that RLP-cholesterol levels were the best predictor of PMP in multivariable linear regression analyses (ß=0.375, P<0.001). Lipid-lowering medication with bezafibrate successfully reduced levels of both RLP-cholesterol and PMP in patients with type-2 DM (P<0.05).
Conclusions RLP-cholesterol and platelet microparticles are both elevated in type-2 DM patients when compared with controls. RLP-cholesterol is the primary and only predictor of platelet microparticles in the multivariable analysis, which include several standard atherosclerosis risk factors. This suggested that reducing elevated RLP-cholesterol with lipid-lowering therapy may be an effective strategy to prevent thrombogenic vascular complications in type-2 DM.
Key Words: Remnant lipoprotein • Diabetes mellitus • Platelet-derived microparticles
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