Osteoprotegerin improves risk detection by traditional cardiovascular risk factors and hsCRP

Objective To evaluate the association of plasma osteoprotegerin (OPG) to hospitalisation for ischaemic heart disease (IHD), ischaemic stroke and all-cause mortality, and the effect of combining plasma OPG and high-sensitivity C-reactive protein (hsCRP). Design OPG and hsCRP concentrations were measured at baseline in a large Danish prospective community-based population study. Setting The 4th Copenhagen City Heart Study. Participants 5863 men and women aged 20-95 were recruited from the general population. Main outcome measures Combined end-point of IHD, ischaemic stroke or all-cause mortality. Results During a median follow-up of 7.8 years (IQR 7.3-8.3), 1270 subjects (21.7%) reached the combined end-point. A twofold increase in plasma OPG was a significant predictor of the combined end-point (univariable HR 1.85, 95% CI 1.75 to 1.96; p<0.001). In a multivariable Cox-regression model containing age, male sex, hypertension, diabetes, hypercholesterolaemia, present or former smoking, glomerular filtration rate, prior IHD, prior ischaemic stroke, hsCRP and plasma OPG, high concentrations of hsCRP and plasma OPG were independent predictors of the combined end-point. The two biomarkers interacted statistically (p<0.001). Compared to low hsCRP and low OPG (n=1927), either high hsCRP or high OPG (univariable HR 2.38, 95% CI 2.02 to 2.80, p<0.001; n=2816), or both high hsCRP and high OPG (univariable HR 5.13, 95% CI 4.29 to 6.13, p<0.001; n=775) conferred increased risk of the combined end-point. Conclusions OPG is an independent predictor of the combined end-point of hospitalisation of IHD, ischaemic stroke and all-cause mortality. The combination of plasma OPG and hsCRP provides more prognostic information than the individual effect of the two biomarkers.