Leukocyte activation in atherosclerosis: correlation with risk factors

Leukocytes have been implicated in the development of atherosclerotic vascular diseases, and numerous abnormalities of leukocytes in conjunction with atherosclerosis have been reported. The aim of this study of middle-aged asymptomatic subjects with early atherosclerosis was to determine whether a relationship exists between the levels of plasma markers of leukocyte activation, i.e. cytokines and proteases and risk factors for atherosclerosis or the degree of atherosclerotic disease. Using ELISAs we measured the plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), neutrophil protease 4 (NP4) as markers for neutrophil activation, tumor necrosis factor alpha (TNF) and soluble TNF receptor-1 (sTNFR-1) as markers of monocyte/macrophage activation in 156 subjects with asymptomatic carotid artery plaque detected at ultrasound examination. Plasma TNF and sTNFR-1 levels were found to correlate with systolic blood pressure (r = 0.32, P < 0.04 and r = 0.22, P < 0.05, respectively). plasma NGAL level to correlate with diastolic blood pressure (r = 0.22; P < 0.005), the plasma levels of sTNFR-1 and NGAL to correlate with age (r = 0.28, P < 0.001 and r = 0.20, P < 0.05, respectively). As compared with non-smokers (n = 112), smokers (n = 43) had higher plasma levels of TNF (2.9 vs. 1.4 microg/l; P < 0.02) and of NP4 (27.5 vs. 23.4 microg/l; P < 0.05). The plasma NGAL level was higher in hypertensive women (n = 7) than in normotensive women (n = 85) (109 vs. 87 microg/l; P < 0.05). We thus demonstrated that, in subjects with asymptomatic early atherosclerosis, the plasma levels of markers of systemic leukocyte activation were correlated with age and blood pressure, and were higher in smokers and hypertensives. These results support the hypothesized relationship between the level of systemic leukocyte activation and risk factors for atherosclerotic vascular disease.