Lack of observed association between high plasma osteoprotegerin concentrations and ischemic stroke risk in a healthy population

Several studies suggest that osteoprotegerin (OPG) concentrations may be associated with the risk of ischemic stroke, but no large prospective studies have been conducted. We conducted a nested case-control study within a large cohort to elucidate a possible relation.

The study was done within a follow-up study including 57 053 men and women. Baseline data included OPG concentrations, lifestyle factors, and medical history. Median length of follow-up was 3.1 years. We assessed the relationship between OPG and stroke risk using conditional logistic regression to adjust for known risk factors (smoking, blood pressure, cholesterol, diabetes, body mass index, alcohol use, polyunsaturated fatty acids, and education).

We identified 254 cases with verified incident acute ischemic stroke and 254 age- and sex-matched controls. Median plasma OPG concentration among cases was 1.84 microg/L (25th-75th percentile 1.45-2.30 microg/L) compared with 1.87 microg/L (1.49-2.27 microg/L) in the control group. The adjusted odds ratio was 0.87 (95% CI 0.46-1.63) comparing participants in the highest quartile of OPG concentrations with those in the lowest quartile.

These findings provide no support for the hypothesis that plasma OPG concentrations are associated with an increased risk of ischemic stroke. This result could indicate a different pathogenic process in stroke development from that in ischemic heart disease, where OPG is a strong predictor.