Abstract 4204: Osteoprotegerin Levels and Risk of Future Cardiovascular Events in Apparently Healthy Men and Women: the Prospective EPIC-Norfolk Population Study 1993–2003
Introduction: The identification of osteoprotegerin (OPG) as a novel cardiovascular risk marker suggests an association between mediators of bone homeostasis and cardiovascular disease. OPG is a member of the tumour necrosis factor (TNF) superfamily, and functions as a soluble decoy receptor for RANKL. There is no epidemiological evidence that OPG levels predict future coronary events in healthy individuals. It was therefore our objective to study the prospective relationship between plasma levels of OPG and the risk of future CAD in such a population.
Methods and Results: A nested case-control study among participants of the European prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study, a prospective population study of 25 663 men and women between 45 and 79 years of which 988 apparently healthy individuals developed coronary artery disease (CAD) were matched by sex and age with 1812 healthy controls which did not develop CAD. Baseline OPG was higher in cases than in controls [6957 pg/ml (5778 – 8727) vs. 6602 pg/ml (5434–8242) (p<0.005) median and interquartile range], and significantly higher in women than men in both cases and controls. Using OPG quartiles based on the distribution among controls, baseline OPG levels were independently correlated with fatal and non fatal coronary events and the risk increased continuously (p for linearity= 0.008 men, p=0.01 women), also when adjusted for age, smoking, diabetes, body mass index, LDL, HDL, systolic blood pressure, this strong relationship still existed. When adjusted for log (CRP) as well, the OR in the highest OPG quartile was 2.17(0.86–5.49)(95% CI)(p=0.04) for women and 2.78 (1.45–5.32)(p<0.001) for men.
Conclusion: Among apparently healthy men and women, an elevated level of OPG is associated with increased risk of future fatal and non fatal CAD.