The Influence of Haemoglobin A1c Levels on Platelet Aggregation and Platelet Turnover in Patients with Coronary Artery Disease Treated with Aspirin

PLoS One. 2015 Jul 6;10(7):e0132629. doi: 10.1371/journal.pone.0132629. eCollection 2015.

Abstract

Background: Hyperglycaemia may attenuate the antiplatelet effect of aspirin and thereby increase the risk of cardiovascular events. We investigated the influence of increased haemoglobin A1c (HbA1c) levels on platelet aggregation and turnover in a large cohort of patients with coronary artery disease (CAD) with type 2 diabetes, prediabetes or no diabetes.

Methods: In this observational study, we included 865 stable CAD patients on 75 mg aspirin as mono-therapy of whom 242 patients had type 2 diabetes and were receiving antidiabetic drugs. Among 623 patients without diabetes, we classified 303 patients with prediabetes (HbA1c ≥5.7-6.4% [39-47 mmol/mol]) naive to antidiabetic drugs. Platelet aggregation was evaluated by the Multiplate Analyzer using arachidonic acid and collagen and by the VerifyNow Aspirin. Platelet turnover was evaluated by immature platelets using flow cytometry and platelet activation by soluble P-selectin.

Results: CAD patients with type 2 diabetes had higher platelet aggregation (all p-values <0.01), platelet turnover (immature platelet count, p<0.01) and platelet activation (p<0.001) than patients without diabetes. CAD patients with prediabetes had increased platelet aggregation (p = 0.02) and platelet count (p = 0.02) compared with patients without diabetes. Increased levels of HbA1c correlated positively with increased platelet aggregation using arachidonic acid (r = 0.19, p<0.0001), collagen (r = 0.10, p<0.01) and VerifyNow (r = 0.15, p<0.0001), and with platelet count (r = 0.08, p = 0.01), immature platelet count (r = 0.11, p<0.001) and soluble P-selectin (r = 0.15, p<0.0001). These associations were mainly evident in non-diabetic and prediabetic CAD patients.

Conclusions: CAD patients with prediabetes and diabetes may have attenuated antiplatelet effect of aspirin compared with CAD patients without diabetes. This may be related to increased platelet count in patients with prediabetes. Increased levels of HbA1c correlated positively, though weakly, with increased platelet aggregation, platelet turnover and platelet activation.

Publication types

  • Clinical Trial
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin / administration & dosage*
  • Blood Platelets / metabolism*
  • Blood Platelets / pathology
  • Cohort Studies
  • Coronary Artery Disease* / blood
  • Coronary Artery Disease* / drug therapy
  • Coronary Artery Disease* / etiology
  • Diabetes Complications* / blood
  • Diabetes Complications* / drug therapy
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Female
  • Glycated Hemoglobin / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation*

Substances

  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • Aspirin

Grants and funding

Financial support: This study was financially supported by the Danish Agency for Science Technology and Innovation (grant no. 2101-05-0052), The Faculty of Health Sciences, Aarhus University, Eva and Henry Fraenkels foundation, A.P. Moeller Foundation and Novo Nordisk Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.