Korean Diabetes J KDJ Korean Diabetes Journal 1976-9180 Korean Diabetes Association 10.4093/kdj.2008.32.1.53 Original Article Prevalence and Clinical Characteristics of Aspirin Resistance in the Patients with Type 2 Diabetes Mellitus Kang Mi Yeon Cho Young Min Kim Hyun Kyung 1 An Jee Hyun Ahn Hwa Young Yoon Ji Won Choi Hoon Sung Lee Jie Seon Park Kyong Soo Kim Seong Yeon Lee Hong Kyu Department of Internal Medicine, Seoul National University College of Medicine, Korea. Department of Laboratory Medicine, Seoul National University College of Medicine, Korea. 02 2008 29 02 2008 32 1 53 59 04 12 2007 01 02 2008 Copyright © 2008 Korean Diabetes Association 2008 Background

We examined the prevalence and clinical characteristics of aspirin resistance in the Korean patients with type 2 diabetes mellitus.

 Methods

We studied 181 Korean patients with type 2 diabetes mellitus who were taking aspirin (100 mg/day for ≥ 3 months) and no other antiplatelet agents. The VerifyNow System was used to determine aspirin responsiveness. Aspirin resistance was defined as an aspirin reaction unit (ARU) ≥ 550. We measured the cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) to evaluate arteriosclerosis. The anthropometric parameters, electrocardiogram, blood pressure, fasting plasma glucose, lipid profiles, hemoglobin A1c, highly sensitive C-reactive protein (hsCRP), homocysteine, and microalbuminuria were measured in each patient.

 Results

The prevalence of aspirin resistance in type 2 diabetic patients was 9.4% (17 of 181). Those who had aspirin resistance were older than those without aspirin resistance (64.6 ± 10.6 vs. 59.8 ± 8.1, P = 0.024). Aspirin resistance was not associated with fasting plasma glucose, total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, hemoglobin A1c, hsCRP, homocysteine, microalbuminuria, ABI, CAVI, and body mass index.

 Conclusion

Prevalence of aspirin resistance in the Korean patients with type 2 diabetes mellitus was 9.4%. Although aspirin resistance was associated with old age, we could not find any good clinical parameter to predict it. Therefore, aspirin resistance should be evaluated in diabetic patients taking aspirin for prevention of cardiovascular complications.

 Aspirin resistance Type 2 diabetes mellitus cardiovascular complication Nathan DM Long-term complications of diabetes mellitus N Engl J Med 1993 328 1676 1685 Ruderman NB Haudenschild C Diabetes as an atherogenic factor Prog Cardiovasc Dis 1984 26 373 412 Collaborative Group of the Primary Prevention Project (PPP) Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice: Collaborative Group of the Primary Prevention Project Lancet 2001 357 89 95 Anti-thrombotic Trialists Collaboration Collaborative metaanalysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high-risk patients BMJ 2002 324 71 86 Hankey GJ Eikelboom JW Aspirin resistance Lancet 2006 367 606 617 Mckee SA Sane DC Deliargyris EN Aspirin resistance in cardiovascular disease: A review of prevalence, mechanisms, and clinical significance Thrombo Haemost 2002 88 711 715 Mehta J Mehta P Burger C Pepine CJ Platelet aggregation studies in coronary artery disease. Effect of aspirin Atherosclerosis 1978 31 169 175 Buchanan MR Brister SJ Individual variation in the effects of ASA on platelet function: implications for the use of ASA clinically Can J Cardiol 1995 11 221 227 Pappas JM Westengard JC Bull BS Population variability in the effect of aspirin on platelet function Arch Pathol Lab Med 1994 118 801 804 Mueller MR Salat A Stangl P Murabito M Pulaki S Boehm D Koppensteiner R Ergun E Mittlboeck M Schreiner W Losert U Wolner E Variable platelet response to low-dose aspirin and the risk of limb deterioration in patients submitted to peripheral arterial angioplasty Thromb Haemost 1997 78 1003 1007 Eikelboom JW Hirsh J White JI Johnston M Yi Q Yusuf S Aspirin resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke or cardiovascular death in patients at risk of high for cardiovascular event Circulation 2002 105 1650 1655 Gum PA Kottke-Marchant K Welsh PA White J Topol EJ A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease J Am Coll Cardiol 2003 41 961 965 Fateh-Moghadam S Plöckinger U Cabeza N Htun P Reuter T Ersel S Gawaz M Dietz R Bocksch W Prevalence of aspirin resistance in patients with type 2 diabetes Acta Diabetol 2005 42 99 103 Mehta SS Silver RJ Aaronson A Abrahamson M Goldfine AB Comparison of aspirin resistance in type 1 versus type 2 diaberes mellitus Am J Cardiol 2006 97 567 570 Ultegra Rapid Platelet Function Assay-ASA (RPFA-ASA) [package insert] 2002 San Diego, CA Accumetrics Inc. Chen WH Lee PY Ng W Tse HF Lau CP Aspirin resistance is associated with a high incidence of myonecrosis after nonurgent percutaneous coronary intervention despite clopidogrel pretreatment J Am Coll Cardiol 2004 43 1122 1126 Schwartz KA Schwartz DE Pittsley RA Mantz SL Ens G Sami A Davis JM A new method for measuring inhibition of platelet function by nonsteroidal antiinflammatory drugs J Lab Clin Med 2002 139 227 233 Malinin A Spergling M Muhlestein B Steinhubl S Serebruany V Assessing aspirin responsiveness in subjects with multiple risk factors for vascular disease with a rapid platelet function analyzer Blood Coagulation and Fibrinolysis 2004 15 295 301 Lee PY Chen WH Ng W Cheng X Kwok JY Tse HF Lau CP Low-dose aspirin increases aspirin resistance in patients with coronary artery disease Am J Med 2005 118 723 727 Seok JI Joo IS Yoon JH Choi YJ Lee PH Huh K Bang OY Can aspirin resistance be clinically predicted in stroke patients? Clin Neurol Neurosurg 2008 110 110 116 Pamukcu B A review of aspirin resistance: definition, possible mechanisms, detection with platelet function tests, and its clinical outcomes J Thromb Thrombolysis 2007 23 213 222 Michelson AD Furman MI Goldschmidt-Clermont P Mascelli MA Hendrix C Coleman L Hamlington J Barnard MR Kickler T Christie DJ Kundu S Bray PF Platelet GP IIIa Pl(A) polymorphisms display different sensitivities to agonists Circulation 2000 101 1013 1018 Szczeklik A Undas A Sanak M Frolow M Wegrzyn W Bleeding time, aspirin and the PlA1/A2 polymorphism of platelet glycoprotein IIIa Br J Haematol 2000 110 965 967 Jefferson BK Foster JH McCarthy JJ Ginsburg G Parker A Kottke-Marchant K Topol EJ Aspirin resistance and a single gene Am J Cardiol 2005 95 805 808

Distribution of aspirin reaction unit (ARU) measured by VerifyNow system.

Prevalence of aspirin resistance. Seventeen (9.4%) of 181 Korean patients with type 2 diabetes mellitus had aspirin resistance. Aspirin resistance was detected in 10.0% (9 of 90 patients) of male patients and 8.8% (8 of 91 patients) of female patients.

Clinical characteristics of the patients

Values are mean ± SD. HDL-cholesterol, high density lipoprotein-cholesterol; LDL-cholesterol, low density lipoprotein-cholesterol; hsCRP, highly sensitive C-reactive protein.

Comparison of concurrent medications

ACE inhibitors, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor antagonists.

Markers of peripheral arterial diseases

Values are mean ± SD. ABI, Ankle-brachial index; CAVI, cardio-ankle vascular index.