PLASMINOGEN-ACTIVATOR INHIBITOR-1, THE ACUTE-PHASE RESPONSE AND VITAMIN-C

Epidemiologial studies suggest that elevated plasma plasminogen activa tor inhibitor-1 (PAI-1) activity is associated with ischaemic heart di sease. Based on our earlier work suggesting a link between plasma fibr inogen, infection and low vitamin C status, we sought to determine whe ther similar relationships existed for PAI-1 activity. We performed a longitudinal study of cardiovascular disease risk factors in 96 volunt eers aged 65-74 years, living in the community in Cambridge. Each subj ect was visited at home 7 times over a 14 month period. Plasma PAI-1 a ctivity, serum ascorbate, markers of the acute phase response, serum l ipids and other cardiovascular disease risk factors were measured on e ach occasion. In a multiple regression analysis, the three significant predictors of PAI-1 activity were body mass index (P = 0.0001), blood neutrophil count (P = 0.03) and, inversely, serum ascorbate (P = 0.00 3). The inverse relationship between PAT-I activity and serum ascorbat e persisted even when vitamin C supplement takers or smokers were excl uded from the analysis. Serum ascorbate was strongly related to estima ted dietary intake of vitamin C (P < 0.0001). Low serum ascorbate is a ssociated with high PAI-I activity which is, in turn, associated with increased ischaemic heart disease risk. We hypothesise that activation of the acute phase response by infection could increase PAI-1 activit y and, consequently, also increase the risk of coronary artery thrombo sis. Furthermore, we suggest that vitamin C could attenuate this respo nse. (C) 1997 Elsevier Science Ireland Ltd.