Obesity is associated with impaired responsiveness to once‐daily low‐dose aspirin and in vivo platelet activation
Author(s): ,
Giovanna Petrucci
Affiliations:
Istituto di Farmacologia, Università Cattolica, Rome, Italy. Fondazione Policlinico Universitario IRCCS, A. Gemelli, Rome, Italy
,
Francesco Zaccardi
Affiliations:
Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK
,
Alberto Giaretta
Affiliations:
Department of Information Engineering, University of Padova, Padova, Italy
,
Viviana Cavalca
Affiliations:
Centro Cardiologico Monzino, IRCCS, Italy
,
Esmeralda Capristo
Affiliations:
Fondazione Policlinico Universitario IRCCS, A. Gemelli, Rome, Italy. Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
,
Carmine Cardillo
Affiliations:
Fondazione Policlinico Universitario IRCCS, A. Gemelli, Rome, Italy. Istituto di Patologia Medica, Università Cattolica del Sacro Cuore, Rome, Italy
,
Dario Pitocco
Affiliations:
Fondazione Policlinico Universitario IRCCS, A. Gemelli, Rome, Italy. Diabetology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
,
Benedetta Porro
Affiliations:
Centro Cardiologico Monzino, IRCCS, Italy
,
Francesca Schinzari
Affiliations:
Istituto di Patologia Medica, Università Cattolica del Sacro Cuore, Rome, Italy
,
Gianna Toffolo
Affiliations:
Department of Information Engineering, University of Padova, Padova, Italy
,
Elena Tremoli
Affiliations:
Centro Cardiologico Monzino, IRCCS, Italy
Bianca Rocca
Affiliations:
Istituto di Farmacologia, Università Cattolica, Rome, Italy. Fondazione Policlinico Universitario IRCCS, A. Gemelli, Rome, Italy
Correspondence |Bianca Rocca, Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.|Emails: ; bianca.rocca@unicatt.it
ISTH Academy. Rocca . May 31, 2019; 273622
Correspondence |Bianca Rocca

Correspondence
|Bianca  Rocca
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Journal Abstract
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Background
The prevalence and degree of obesity is rising worldwide, increases cardiovascular risk, modifies body composition and organ function, and potentially affects the pharmacokinetics and/or pharmacodynamics of drugs.
Objectives
To investigate the pharmacodynamics of once‐daily low‐dose aspirin in healthy obese subjects, and to assess whether body weight (BW) and body mass index (BMI) affect the pharmacology of aspirin.
Patients/Methods
Otherwise healthy, obese (BMI > 30 kg/m) subjects were studied before and after 3‐4 weeks of 100‐mg once‐daily aspirin intake. Aspirin pharmacodynamics were assessed according to serum thromboxane (TX) B levels measured at 4 hours, 24 hours (i.e., posologic interval) and 48 hours after the last witnessed intake; age‐matched and sex‐matched non‐obese controls were included. A previously calibrated pharmacokinetic/pharmacodynamic in silico model of aspirin was used to fit serum TXB data from obese subjects. At baseline, the major urinary TXA and prostacyclin metabolites, urinary isoprostane and plasma inflammatory biomarkers were measured.
Results
In 16 obese subjects (aged 47 ± 11 years; BMI of 39.4 ± 5.1 kg/m), residual serum TXB values between 4 and 48 hours after aspirin intake were increased 3‐ to 5‐fold as compared with controls. At 24 hours, the residual serum TXB level was log‐linearly associated with body size over a wide range of BMI and BW values, without any apparent threshold. The in silico model predicted that reduced aspirin bioavailability would be inversely related to body size and rescued by 200 mg of aspirin once daily or 85 mg twice daily. Baseline urinary TXA metabolite, isoprostane and plasma C‐reactive protein levels were significantly increased in obese subjects.
Conclusions
Obesity is associated with impaired aspirin responsiveness, largely because of body size. Impaired inhibition of platelet activation by conventional low‐dose aspirin may affect antithrombotic efficacy.
Keyword(s)
aspirin, body mass index, obesity, platelets, thromboxane A
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