Plasminogen activator inhibitor-1, the acute phase response and vitamin C

Epidemiologial studies suggest that elevated plasma plasminogen activator inhibitor-1 (PAI-1) activity is associated with ischaemic heart disease. Based on our earlier work suggesting a link between plasma fibrinogen, infection and low vitamin C status, we sought to determine whether similar relationships existed for PAI-1 activity. We performed a longitudinal study of cardiovascular disease risk factors in 96 volunteers aged 65-74 years, living in the community in Cambridge. Each subject was visited at home 7 times over a 14 month period. Plasma PAI-1 activity, serum ascorbate, markers of the acute phase response, serum lipids and other cardiovascular disease risk factors were measured on each 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 = 0.003). The inverse relationship between PAI-1 activity and serum ascorbate persisted even when vitamin C supplement takers or smokers were excluded from the analysis. Serum ascorbate was strongly related to estimated dietary intake of vitamin C (P < 0.0001). Low serum ascorbate is associated with high PAI-1 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 activity and, consequently, also increase the risk of coronary artery thrombosis. Furthermore, we suggest that vitamin C could attenuate this response.