C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men

Background There is much interest in reported associations between serum C- reactive protein and incident ischaemic heart disease. It is uncertain what this association represents. We aimed to assess the effect of confounding from a number of different sources in the Caerphilly Prospective Heart Dise ase Study and in particular whether the low grade inflammation indicated by C-reactive protein may be the mechanism whereby non-circulating risk facto rs may influence pathogenesis of ischaemic heart disease. Methods Plasma specimens collected during 1979-83 from 1395 men with suffic ient sample remaining were assayed for serum C-reactive protein by ELISA. S ubsequent mortality and incident ischaemic heart disease events were ascert ained from death certificates, hospital records and electrocardiographic ch anges at 5-yearly follow-up examinations. Results There was a positive association between C-reactive protein and inc ident ischaemic heart disease (P<0.005) mainly with fatal disease (P<0.002) . There was also a positive association with all-cause mortality (P<0.0001) . C-reactive protein was significantly associated with a number of non-circ ulating risk factors including body mass index (P<0.0001), smoking (P<0.000 1), low forced expiratory volume in Is (P<0.0001), height (P=0.025), low ch ildhood social class (P=0.014) and age (P=0.036). C-reactive protein was al so associated positively with circulating risk factors including viscosity, leukocyte count, fibrinogen (all P<0.0001) and insulin (P=0.0058). After a djustment for non-circulating risk factors the association with all-inciden t ischaemic heart disease and ischaemic heart disease death became non-sign ificant, but the association with all-cause mortality remained (P=0.033). F urther adjustment for fibrinogen however removed any hint of an increasing trend in odds for all three outcomes. Conclusion C-reactive protein levels are raised in association with a varie ty of established cardiovascular risk factors. Neither C-reactive protein n or the systemic inflammation it represents appears to play a direct role in the development of ischaemic heart disease. (C) 2000 The European Society of Cardiology.