TY - JOUR

T1 - Platelet responses to pharmacological and physiological interventions in middle-aged men with different habitual physical activity levels

AU - Lundberg Slingsby, Martina Helena

AU - Gliemann, Lasse

AU - Thrane, Mette Nørmark

AU - Rytter Mortensen, Nicolai

AU - Egelund, Jon

AU - Chan, M V

AU - Armstrong, P C

AU - Warner, T D

AU - Hellsten, Ylva

N1 - CURIS 2018 NEXS 029

PY - 2018

Y1 - 2018

N2 - The current guidelines following an acute coronary syndrome recommend dual anti-platelet therapy (aspirin plus a P2Y12 antagonist) alongside lifestyle modifications, including more regular physical activity. It is currently unknown if regular exercise affects the pharmacology of dual anti-platelet therapy.AIM: To explore how exercise-induced improvements in vascular and platelet function affect the efficacy of dual anti-platelet therapy, in a cross-sectional study of men with different physical activity level (training status).METHODS: 42 healthy, normal-weight, middle-aged men were divided into 3 groups; untrained, moderately- and well-trained. Their platelet reactivity (agonist-induced %aggregation) was investigated in platelet rich plasma at rest and after inhibition with aspirin and ticagrelor and/or prostacyclin and nitric oxide added to the blood in vitro, and after physiological tests of vascular function; passive movement of the leg, flow-mediated dilation and one-leg knee-extensor exercise. Vascular function of the femoral artery (changes in arterial blood flow) was assessed by ultrasound doppler.RESULTS: Platelets from the well-trained subjects had lower basal reactivity, a higher sensitivity to the anti-aggregatory effects of prostacyclin and were more potently inhibited by dual anti-platelet therapy compared to the untrained subjects. The moderately- and well-trained subjects had a superior vascular function compared to untrained subjects and their platelets were more inhibited by the passive movement, flow-mediated dilation and one-leg knee extensor exercise.CONCLUSION: A habitually active lifestyle leads to an increased platelet sensitivity to pharmacological and physiological platelet inhibitors. We suggest that physical activity habits (training status) should be considered when personalising and optimizing anti-thrombotic treatment strategies. This article is protected by copyright. All rights reserved.

AB - The current guidelines following an acute coronary syndrome recommend dual anti-platelet therapy (aspirin plus a P2Y12 antagonist) alongside lifestyle modifications, including more regular physical activity. It is currently unknown if regular exercise affects the pharmacology of dual anti-platelet therapy.AIM: To explore how exercise-induced improvements in vascular and platelet function affect the efficacy of dual anti-platelet therapy, in a cross-sectional study of men with different physical activity level (training status).METHODS: 42 healthy, normal-weight, middle-aged men were divided into 3 groups; untrained, moderately- and well-trained. Their platelet reactivity (agonist-induced %aggregation) was investigated in platelet rich plasma at rest and after inhibition with aspirin and ticagrelor and/or prostacyclin and nitric oxide added to the blood in vitro, and after physiological tests of vascular function; passive movement of the leg, flow-mediated dilation and one-leg knee-extensor exercise. Vascular function of the femoral artery (changes in arterial blood flow) was assessed by ultrasound doppler.RESULTS: Platelets from the well-trained subjects had lower basal reactivity, a higher sensitivity to the anti-aggregatory effects of prostacyclin and were more potently inhibited by dual anti-platelet therapy compared to the untrained subjects. The moderately- and well-trained subjects had a superior vascular function compared to untrained subjects and their platelets were more inhibited by the passive movement, flow-mediated dilation and one-leg knee extensor exercise.CONCLUSION: A habitually active lifestyle leads to an increased platelet sensitivity to pharmacological and physiological platelet inhibitors. We suggest that physical activity habits (training status) should be considered when personalising and optimizing anti-thrombotic treatment strategies. This article is protected by copyright. All rights reserved.

KW - Aspirin

KW - Nitric oxide

KW - Physical activity

KW - Platelet aggregation inhibitors

KW - Prostacyclin

U2 - 10.1111/apha.13028

DO - 10.1111/apha.13028

M3 - Journal article

C2 - 29297976

VL - 223

JO - Acta Physiologica

JF - Acta Physiologica

SN - 1748-1708

IS - 1

M1 - e13028

ER -