Value of C-reactive protein levels and IL-6 in predicting events levels in women at increased cardiovascular risk

Abstract

Background: Elevated C-reactive protein (CRP) levels due to of heightened vascular inflammatory state in vascular conditions are often associated with elevated interleukin-6 (IL-6) levels since during inflammation CRP production in the liver is induced by IL-6. It has been suggested that CRP may be a predictors of unfavourable outcome in postmenopausal women (PMW) receiving hormone replacement therapy. Because of the possible metabolic effect of hormone replacement therapy (HRT) on CRP, the relative predictive importance of CRP and IL-6 levels in PMW receiving HRT remains to be elucidated. Methods: We measured plasma levels of CRP and IL-6 levels in 346 consecutive PMW (mean age 66±9 years) with cardiovascular risk >20 in 10 years followed during a 36 month period. Women underwent measurement of inflammatory cytokines at baseline and were allocated to two groups according to the willingness to take hormone replacement therapy. All women underwent a further measurement of CRP and IL-6 at 3 and 6 months. Health status was assessed by out patient visits and hospital charts. Results: During 1 year follow up, three patient died, four had a major cardiovascular event, three had a unstable angina, two had a transient ischemic attack and two patients underwent PTCA. PMW with events had higher CRP levels compared with patients with no events (1.94±0.61 versus 1.43±0.21, P<0.05) but still within the limits of normal. Also baseline IL-6 plasma levels were significantly higher in PMW with events than in those without events (0.87±0.23 versus 0.54±0.18, P<0.05). The increase in CRP and IL-6 with HRT was significantly higher in patients with events than in those with no events (CRP: 81±12% versus 76±21%, P<0.05; IL-6 9±3% versus −14±7%, P<0.05). In a stepwise multivariate analysis, IL-6 levels resulted a stronger predictor of outcome than CRP. CRP levels were predictors of future events only after removal of IL-6 levels and presence of cardiovascular symptoms from the analysis. CRP levels were associated with an unfavourable outcome only when IL-6 levels were also elevated. The increase in CRP with HRT during follow up was not associated to an increased event rate. Conclusion: Our study showed that CRP levels are increased in PMW receiving HRT. Elevated IL-6 levels may identify those PMW at increased 1 year risk. CRP levels predict events only when they are coupled with elevated IL-6 levels.