Platelet Surface CD62p and Serum Vitamin D Levels are Associated with Clopidogrel Resistance in Chinese Patients with Ischemic Stroke

J Stroke Cerebrovasc Dis. 2019 May;28(5):1323-1328. doi: 10.1016/j.jstrokecerebrovasdis.2019.01.031. Epub 2019 Feb 20.

Abstract

Background: To explore the association of platelet activation markers, vitamin D, and antiplatelet drugs resistance in ischemic stroke patients.

Methods: A total of 230 patients with ischemic stroke were enrolled in this study. Platelet aggregation, platelet activation marker (CD62p), and vitamin D were measured after 7-14 days of dual antiplatelet treatment (aspirin + clopidogrel). All individuals were divided into a drug resistance group and a drug sensitive group according to the platelet maximum aggregation rate induced by antagonist adenosine diphosphate or arachidonic acid.

Results: In this study, the prevalence of aspirin resistance was low (1.2%), while the prevalence of clopidogrel resistance (CR) was 24.8%, so we focused on CR. The percentage of CD62p on activated platelet [(25.74 ± 4.61) versus (12.41 ± 3.93), P < .001] and the prevalence of hypertension [93.0% (53) versus 79.8% (138), P = .021] in CR group were significantly higher than those in clopidogrel sensitive (CS) group, while the vitamin D concentration [(8.96 ± 4.41) versus (13.9 ± 4.84) ng/mL, P = .003] in CR group was significantly lower compared with the CS group. No significant difference was found in soluble P-selectin between these 2 groups [(56.2 ± 16.13) versus (54.2 ± 14.87) ng/mL, P = .258], neither in calcium [(2.29 ± .12) versus (2.33 ± .13) mmol/L, P = .821]. Logistic regression analysis showed that hypertension (odds ratio [OR] = 5.348, 95% confidence intervals [CI] 1.184-23.350, P = .026), expression of platelet CD62p (OR = 1.095, 95% CI 1.052-1.201, P = .018) and vitamin D level (OR = .832, 95% CI .763-.934, P = .005) were associated with CR in ischemic stroke patients.

Conclusions: CR in ischemic stroke patients is associated with several independent predictors, including increased platelet activation marker CD62p, decreased vitamin D level, and hypertension.

Keywords: Ischemic stroke; clopidogrel resistance; platelet activation; vitamin D.

MeSH terms

  • Aged
  • Asian People
  • Aspirin / therapeutic use
  • Biomarkers / blood
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Brain Ischemia / blood
  • Brain Ischemia / diagnosis
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / ethnology
  • China
  • Clopidogrel / therapeutic use*
  • Drug Resistance*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypertension / blood
  • Hypertension / ethnology
  • Male
  • Middle Aged
  • P-Selectin / blood*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prevalence
  • Risk Factors
  • Stroke / blood
  • Stroke / diagnosis
  • Stroke / drug therapy*
  • Stroke / ethnology
  • Treatment Outcome
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / diagnosis
  • Vitamin D Deficiency / ethnology

Substances

  • Biomarkers
  • P-Selectin
  • Platelet Aggregation Inhibitors
  • SELP protein, human
  • Vitamin D
  • 25-hydroxyvitamin D
  • Clopidogrel
  • Aspirin