Obesity and Altered Aspirin Pharmacology.
Nicholas B NorgardPublished in: Clinical pharmacokinetics (2019)
Obesity is an independent risk factor for cardiovascular morbidity and mortality due to atherothrombotic events and represents a group of patients who are in need of optimized antithrombotic therapy. Central to the obesity-related risk of atherothrombosis is a pro-thrombotic state characterized by increased levels of coagulation factors, impaired fibrinolysis, and platelet hyper-reactivity, which results from the interaction among the features clustering in obesity: insulin resistance, inflammation, oxidative stress, and endothelial dysfunction. Aspirin is a cornerstone antiplatelet drug that has substantial interpatient variability in pharmacodynamic response and a number of reports have demonstrated that obesity is a risk factor for a reduced aspirin pharmacodynamic response. The inflammatory state associated with obesity, particularly a metabolic endotoxemia, may set in motion a number of mechanisms that increase platelet reactivity and platelet turnover and decrease aspirin bioavailability, all contributing to a poor aspirin response. A greater understanding of the mechanisms underlying obesity-related high on-aspirin platelet reactivity will help in optimization of antithrombotic therapy in this patient population.
Keyphrases
- insulin resistance
- metabolic syndrome
- high fat diet induced
- weight loss
- low dose
- type diabetes
- oxidative stress
- weight gain
- cardiovascular events
- adipose tissue
- antiplatelet therapy
- high fat diet
- skeletal muscle
- end stage renal disease
- polycystic ovary syndrome
- chronic kidney disease
- body mass index
- dna damage
- atrial fibrillation
- acute coronary syndrome
- single cell
- high resolution
- percutaneous coronary intervention
- newly diagnosed
- peritoneal dialysis
- inflammatory response
- high speed
- postmenopausal women
- signaling pathway
- rna seq
- smoking cessation
- adverse drug
- endoplasmic reticulum stress
- anti inflammatory drugs