Clopidogrel Improves Skin Microcirculatory Endothelial Function in Persons With Heightened Platelet Aggregation
Background 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...
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| Veröffentlicht in: | Journal of the American Heart Association Jg. 5; H. 11 |
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| Format: | Journal Article |
| Sprache: | Englisch |
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England
John Wiley and Sons Inc
01.11.2016
Wiley |
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| ISSN: | 2047-9980, 2047-9980 |
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| Abstract | Background
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.
Methods and Results
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.
Conclusions
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.
Clinical Trial Registration
URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799396. |
|---|---|
| AbstractList | 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. BackgroundPlatelet 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. Methods and ResultsMicrocirculatory 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. ConclusionsThe 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. Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00799396. Background 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. Methods and Results 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. Conclusions 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. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799396. 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.BACKGROUNDPlatelet 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.METHODS AND RESULTSMicrocirculatory 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.CONCLUSIONSThe 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.CLINICAL TRIAL REGISTRATIONURL: https://www.clinicaltrials.gov. Unique identifier: NCT00799396. |
| Author | Mitchell, Braxton D. Perry, James A. Salimi, Shabnam Yerges‐Armstrong, Laura M. Shuldiner, Alan R. Lewis, Joshua P. O'Connell, Jeffry R. Ryan, Kathleen A. Saeed, Faisal Parsa, Afshin |
| AuthorAffiliation | 2 Division of Nephrology Department of Medicine University of Maryland School of Medicine Baltimore MD 1 Division of Endocrinology, Diabetes & Nutrition Department of Medicine University of Maryland School of Medicine Baltimore MD 4 Geriatrics Research and Education Clinical Center Baltimore Veterans Administration Medical Center Baltimore MD 5 Department of Medicine Baltimore Veterans Administration Medical Center Baltimore MD 3 Department of Epidemiology and Public Health University of Maryland School of Medicine Baltimore MD |
| AuthorAffiliation_xml | – name: 4 Geriatrics Research and Education Clinical Center Baltimore Veterans Administration Medical Center Baltimore MD – name: 1 Division of Endocrinology, Diabetes & Nutrition Department of Medicine University of Maryland School of Medicine Baltimore MD – name: 2 Division of Nephrology Department of Medicine University of Maryland School of Medicine Baltimore MD – name: 5 Department of Medicine Baltimore Veterans Administration Medical Center Baltimore MD – name: 3 Department of Epidemiology and Public Health University of Maryland School of Medicine Baltimore MD |
| Author_xml | – sequence: 1 givenname: Shabnam surname: Salimi fullname: Salimi, Shabnam email: ssalimi@som.umaryland.edu, shabnam.salimi.m.d@gmail.com organization: University of Maryland School of Medicine – sequence: 2 givenname: Joshua P. surname: Lewis fullname: Lewis, Joshua P. organization: University of Maryland School of Medicine – sequence: 3 givenname: Laura M. surname: Yerges‐Armstrong fullname: Yerges‐Armstrong, Laura M. organization: University of Maryland School of Medicine – sequence: 4 givenname: Braxton D. surname: Mitchell fullname: Mitchell, Braxton D. organization: Baltimore Veterans Administration Medical Center – sequence: 5 givenname: Faisal surname: Saeed fullname: Saeed, Faisal organization: University of Maryland School of Medicine – sequence: 6 givenname: Jeffry R. surname: O'Connell fullname: O'Connell, Jeffry R. organization: University of Maryland School of Medicine – sequence: 7 givenname: James A. surname: Perry fullname: Perry, James A. organization: University of Maryland School of Medicine – sequence: 8 givenname: Kathleen A. surname: Ryan fullname: Ryan, Kathleen A. organization: University of Maryland School of Medicine – sequence: 9 givenname: Alan R. surname: Shuldiner fullname: Shuldiner, Alan R. organization: University of Maryland School of Medicine – sequence: 10 givenname: Afshin surname: Parsa fullname: Parsa, Afshin organization: Baltimore Veterans Administration Medical Center |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27799230$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_36290_int_2018_058 crossref_primary_10_1016_j_jdcr_2017_09_003 crossref_primary_10_3389_fnut_2022_961301 crossref_primary_10_1177_23969873221144814 crossref_primary_10_1111_jpi_12438 crossref_primary_10_1161_ATVBAHA_121_317513 |
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| Copyright | 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. |
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| Keywords | clopidogrel endothelial function platelet aggregation women |
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Platelet activation can lead to enhanced oxidative stress, inflammatory response, and endothelial dysfunction. To quantify the effects of platelet... Platelet activation can lead to enhanced oxidative stress, inflammatory response, and endothelial dysfunction. To quantify the effects of platelet inhibition... BackgroundPlatelet activation can lead to enhanced oxidative stress, inflammatory response, and endothelial dysfunction. To quantify the effects of platelet... |
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| Title | Clopidogrel Improves Skin Microcirculatory Endothelial Function in Persons With Heightened Platelet Aggregation |
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