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Published on: April 9, 2018
Platelet and leukocyte activation, atherosclerosis and inflammation in European and South Asian men
O Dotsenko1, N Chaturvedi, S A McG Thom
1International Centre for Circulatory Health, NHLI Division, Faculty of Medicine, St Mary's Hospital and Imperial College London, London, UK.
Insights
Platelet activation, indicated by platelet-monocyte complexes (PMC), is linked to aortic and femoral atherosclerosis, not coronary or carotid disease. Inflammation may drive this platelet activation in generalized atherosclerosis.
Area of Science:
- Cardiovascular Medicine
- Atherosclerosis Research
- Inflammation and Immunology
Background:
- Platelet activation is observed in ischemic heart disease (IHD) and other atherosclerotic conditions.
- The role of platelet activation as a marker for IHD versus generalized atherosclerosis and inflammation is unclear.
- Ethnic differences in platelet and leukocyte function between European and South Asian subjects at high risk for IHD are not well understood.
Purpose of the Study:
- To investigate the relationship between platelet and leukocyte activation markers and the extent of atherosclerosis in different vascular beds.
- To determine if platelet activation is associated with generalized atherosclerosis, inflammation, or specific vascular diseases.
- To explore potential ethnic differences in platelet and leukocyte function.
Main Methods:
- Fifty-four male subjects (age 49-79) underwent assessments for coronary artery calcification (CT), aortic atherosclerosis (aortic pulse wave velocity), and femoral/carotid atherosclerosis (ultrasound).
- Platelet and leukocyte activation were measured using flow cytometry, assessing platelet-monocyte complexes (PMC), platelet PAC-1 binding, CD62P expression, and leukocyte L-selectin expression.
- Multivariate analysis was used to identify independent predictors of PMC levels.
Main Results:
- Elevated circulating PMC significantly correlated with increased aortic pulse wave velocity and higher prevalence of femoral plaques.
- PMC levels did not differ based on coronary artery calcification severity or the presence of carotid plaques.
- Higher PMC counts were independently associated with elevated C-reactive protein (CRP), higher aortic pulse wave velocity, hypertension, and smoking.
- No significant ethnic differences were found in markers of platelet and leukocyte activation.
Conclusions:
- Increased platelet-monocyte complexes are associated with the extent of aortic and femoral atherosclerosis, but not coronary or carotid atherosclerosis.
- The strong association between elevated CRP and increased PMC suggests a significant role for inflammation in generalized atherosclerosis-related platelet activation.
- Platelet and leukocyte activation markers do not appear to differ significantly between European and South Asian subjects in this cohort.
Background:
Increased platelet activation occurs in ischemic heart disease (IHD), but increased platelet activation is also seen in cerebrovascular atherosclerosis and peripheral artery disease. It is not clear therefore whether platelet activation is an indicator of IHD or a marker of generalized atherosclerosis and inflammation. South Asian subjects are at high risk of IHD, but little is known regarding differences in platelet and leukocyte function between European and South Asian subjects.
Methods:
Fifty-four male subjects (age 49-79 years) had coronary artery calcification measured by multislice computed tomography (CT), aortic atherosclerosis assessed by measurement of carotid-femoral pulse wave velocity (aortic PWV), and femoral and carotid atherosclerosis measured by B-mode ultrasound. Platelet and leukocyte activation was assessed by flow cytometry of platelet-monocyte complexes (PMC), platelet expression of PAC-1 binding site and CD62P, and expression of L-selectin on leukocytes.
Results:
Elevated circulating PMC correlated significantly with elevated aortic PWV and PMC were higher in subjects with femoral plaques. In contrast PMC did not differ by increasing coronary artery calcification category or presence of carotid plaques. Higher numbers of PMC were independently related to elevated levels of C-reactive protein (CRP), higher aortic PWV, hypertension and smoking in a multivariate model. Markers of platelet and leukocyte activation did not differ significantly by ethnicity.
Conclusions:
Increased PMC are related to the extent of aortic and femoral atherosclerosis rather than coronary or carotid atherosclerosis. The association between elevated CRP and increased PMC suggests that inflammation in relation to generalized atherosclerosis may play an important role in PMC activation.
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