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

M.A Mendall, D.P Strachan, B.K Butland, L Ballam, J Morris, P.M Sweetnam, P.C Elwood
DOI: http://dx.doi.org/10.1053/euhj.1999.1982 1584-1590 First published online: 1 October 2000


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 Disease Study and in particular whether the low grade inflammation indicated by C-reactive protein may be the mechanism whereby non-circulating risk factors may influence pathogenesis of ischaemic heart disease.

Methods Plasma specimens collected during 1979–83 from 1395 men with sufficient sample remaining were assayed for serum C-reactive protein by ELISA. Subsequent mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records and electrocardiographic changes at 5-yearly follow-up examinations.

Results There was a positive association between C-reactive protein and incident 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-circulating risk factors including body mass index (P<0·0001), smoking (P<0·0001), low forced expiratory volume in 1s (P<0·0001), height (P=0·025), low childhood social class (P=0·014) and age (P=0·036). C-reactive protein was also associated positively with circulating risk factors including viscosity, leukocyte count, fibrinogen (all P<0·0001) and insulin (P=0·0058). After adjustment for non-circulating risk factors the association with all-incident ischaemic heart disease and ischaemic heart disease death became non-significant, but the association with all-cause mortality remained (P=0·033). Further 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 variety of established cardiovascular risk factors. Neither C-reactive protein nor the systemic inflammation it represents appears to play a direct role in the development of ischaemic heart disease.