Subject(s)
Aspirin/pharmacology , Aspirin/therapeutic use , Blood Platelets/metabolism , Coronary Artery Disease/drug therapy , Coronary Artery Disease/metabolism , Monocytes/metabolism , P-Selectin/metabolism , Platelet Adhesiveness/drug effects , Humans , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic useABSTRACT
Vascular function is an important pathophysiological factor in cardiovascular disease, and is influenced by many factors, one of the principles being hypertension. Developing evidence suggests that inflammation may be another risk factor. Vascular function and blood pressure haemodynamics can be assessed by arterial stiffness, pulse pressure and plasma markers. Testing the hypothesis of a relationship between inflammatory markers, hypertension and vascular function, we recruited 222 stable coronary artery disease outpatients, assessing inflammation with levels of high sensitivity CRP and interleukin-6 (IL-6), vascular function/arterial stiffness by pulse-wave velocity (PWV), augmentation (SphygmoCor system Artcor, Sidney, Australia), aortic and brachial artery pulse pressure, Von Willebrand factor (vWf) and soluble E-selectin (both enzyme-linked immunosorbent assay). In multivariate regression analysis, PWVs, augmentation indices and pulse pressures were linked with age, blood pressure and (some) with heart rate (all P<0.01), while vWf was associated with age (P=0.01). We conclude that, in patients with stable coronary artery disease, arterial stiffness and pulse pressure are related strongly and independently with age, blood pressure and heart rate, and that any effect of inflammation is minimal.
Subject(s)
Coronary Artery Disease/physiopathology , Inflammation Mediators/blood , Inflammation/physiopathology , Pulse Wave Analysis , Vascular Stiffness , Age Factors , Aged , Biomarkers/blood , Blood Pressure , C-Reactive Protein/analysis , Coronary Artery Disease/blood , Coronary Artery Disease/diagnosis , Cross-Sectional Studies , Female , Heart Rate , Humans , Inflammation/blood , Inflammation/diagnosis , Interleukin-6/blood , Male , Middle Aged , Predictive Value of Tests , Risk FactorsABSTRACT
Aspirin resistance and chronic renal failure are both potentially important clinical issues in coronary artery disease. To test the hypothesis of a relationship between the two, we recruited 169 stable outpatients with proven coronary artery disease (myocardial infarction, coronary artery bypass grafting, intra-coronary stents) taking 75 mg aspirin daily. Blood was taken for light transmission aggregometry to agonists arachidonic acid (0.5mg/mL) and adenosine diphosphate (10 µmol/L), for platelet marker soluble P selectin (enzyme linked immunosorbent assay), resting and stimulated expression of CD62P (flow cytometry) and for renal function (estimated glomerular filtration rate). The estimated glomerular filtration rate was lower when aspirin resistance was defined by response to arachidonic acid after 3, 5 and 7 minutes (approximately 30% of patients) (p<0.021), and when defined by response to adenosine diphosphate after 3 minutes (approximately 17% of patients)(p=0.015) compared to those who were sensitive to aspirin. Mean [standard deviation] soluble P selectin levels were 57 [23] ng/mL in 49 patients with aspirin resistance, and 50 [15] ng/mL in the 119 aspirin sensitive patients (p=0.02). Estimated glomerular filtration rate correlated inversely with platelet CD62P expression at rest (r=-0.22, p=0.004), and when stimulated by arachidonic acid (r=-0.21, p=0.007) and by adenosine diphosphate (r=-0.17, p=0.023). Aspirin resistance was more than twice as prevalent in those with the greatest renal disease (50% of patients) compared to those with the best renal function (21.4%). Our data point to a weak relationship between worsening glomerular filtration rate and aspirin resistance. Nevertheless, we suspect that failure of patients to be fully responsive to aspirin may be important in the pathophysiology of thrombosis in renal dysfunction.
