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 conjunc tion with atherosclerosis have been reported. The aim of this study of middle-aged asymptomatic subjects with early atherosclerosis was to d etermine whether a relationship exists between the levels of plasma ma rkers of leukocyte activation. i.e. cytokines and proteases and risk f actors for atherosclerosis or the degree of atherosclerotic disease. U sing ELISAs we measured the plasma levels of neutrophil gelatinase-ass ociated lipocalin (NGAL), neutrophil protease 4 (NP4) as markers for n eutrophil activation, tumor necrosis factor alpha (TNF) and soluble TN F receptor-1 (sTNFR-1) as markers of monocyte/ macrophage activation i n 156 subjects with asymptomatic carotid artery plaque detected at ult rasound examination. Plasma TNF and sTNFR-1 levels were found to corre late 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 b lood 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 mu g/l; P < 0.02) and of NP4 (27.5 vs. 23.4 mu g/l; P < 0.05). The plasma NGAL level was hi gher in hypertensive women (it = 7) than in normotensive women (n = 85 ) (109 vs. 87 mu g/l; P < 0.05). We thus demonstrated that, in subject s with asymptomatic early atherosclerosis, the plasma levels of marker s 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 le ukocyte activation and risk factors for atherosclerotic vascular disea se. (C) 1997 Elsevier Science Ireland Ltd.