title: Clopidogrel Improves Skin Microcirculatory Endothelial Function in Persons With Heightened Platelet Aggregation.
abstract: Platelet activation can lead to enhanced oxidative stress, inflammatory response, and endothelial dysfunction. To quantify the effects of platelet inhibition on endothelial function, we assessed platelet activity of healthy persons before and after clopidogrel administration and evaluated its effects on endothelial function. We hypothesized that clopidogrel, by attenuating platelet activity, would result in enhanced endothelial function.
  
  
  
  Microcirculatory endothelial function was quantified by laser Doppler flowmetry (LDF) mediated by thermal hyperemia (TH) and postocclusive reactive hyperemia, respectively, in 287 and 241 relatively healthy and homogenous Old Order Amish persons. LDF and platelet aggregation measures were obtained at baseline and after 7 days of clopidogrel administration. Our primary outcome was percentage change in post- versus preclopidogrel LDF measures. Preclopidogrel TH-LDF and platelet aggregation were higher in women than in men (P<0.001). Clopidogrel administration was associated with ≈2-fold higher percentage change in TH-LDF in participants with high versus low baseline platelet aggregation (39.4±10.1% versus 17.4±5.6%, P=0.03). Clopidogrel also increased absolute TH-LDF measures in persons with high platelet aggregation (1757±766 to 2154±1055, P=0.03), with a more prominent effect in women (1909±846 to 2518±1048, P=0.001). There was no evidence that clopidogrel influenced postocclusive reactive hyperemia LDF measures.
  
  
  
  The administration of clopidogrel in healthy persons with high baseline platelet aggregation results in improved TH-induced microcirculatory endothelial function. These data suggest that clopidogrel may have a beneficial effect on microcirculatory endothelial function, presumably through antiplatelet activity, and may confer additional vascular benefits.
  
  
  
  URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799396.
authors: Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD ssalimi@som.umaryland.edu shabnam.salimi.m.d@gmail.com.
authors: Shabnam
authors: S
authors: Salimi
authors: Division of Endocrinology, Diabetes & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.
authors: Joshua P
authors: JP
authors: Lewis
authors: Division of Endocrinology, Diabetes & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.|Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD.
authors: Laura M
authors: LM
authors: Yerges-Armstrong
authors: Division of Endocrinology, Diabetes & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.|Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD.|Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD.
authors: Braxton D
authors: BD
authors: Mitchell
authors: Department of Medicine, Baltimore Veterans Administration Medical Center, Baltimore, MD.
authors: Faisal
authors: F
authors: Saeed
authors: Division of Endocrinology, Diabetes & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.
authors: Jeffry R
authors: JR
authors: O'Connell
authors: Division of Endocrinology, Diabetes & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.
authors: James A
authors: JA
authors: Perry
authors: Division of Endocrinology, Diabetes & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.
authors: Kathleen A
authors: KA
authors: Ryan
authors: Division of Endocrinology, Diabetes & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.|Department of Medicine, Baltimore Veterans Administration Medical Center, Baltimore, MD.
authors: Alan R
authors: AR
authors: Shuldiner
authors: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.|Department of Medicine, Baltimore Veterans Administration Medical Center, Baltimore, MD.
authors: Afshin
authors: A
authors: Parsa
mesh_terms: D000328:Adult; D000368:Aged; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D006940:Hyperemia / Q000235:genetics / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000235:genetics; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects / Q000235:genetics; D010974:Platelet Aggregation / Q000187:drug effects* / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: clopidogrel; endothelial function; platelet aggregation; women