Osteoprotegerin Improves Risk Detection by Traditional Cardiovascular Risk Factors and hsCRP

Study Questions:

What is the association of plasma osteoprotegerin (OPG) to hospitalization for ischemic heart disease (IHD), ischemic stroke, and all-cause mortality, and the effect of combining plasma OPG and high-sensitivity C-reactive protein (hsCRP)?

Methods:

OPG and hsCRP concentrations were measured at baseline in a large Danish prospective community-based population study, the 4th Copenhagen City Heart Study. A total of 5,863 men and women ages 20-95 were recruited from the general population. The main outcome measure was the combined endpoint of IHD, ischemic stroke, or all-cause mortality. Cox proportional hazards regression models were used to examine the associations of plasma OPG and traditional risk factors (age, male sex, hypertension, diabetes, hypercholesterolemia, present or former smoking, glomerular filtration rate, prior IHD, prior ischemic stroke, and hsCRP) with the risk of the combined endpoint.

Results:

During a median follow-up of 7.8 years (interquartile range 7.3-8.3), 1,270 subjects (21.7%) reached the combined endpoint. A twofold increase in plasma OPG was a significant predictor of the combined endpoint (univariable hazard ratio [HR], 1.85; 95% confidence interval [CI], 1.75-1.96; p < 0.001). In a multivariable Cox-regression model containing age, male sex, hypertension, diabetes, hypercholesterolemia, present or former smoking, glomerular filtration rate, prior IHD, prior ischemic stroke, hsCRP, and plasma OPG, high concentrations of hsCRP and plasma OPG were independent predictors of the combined endpoint. The two biomarkers interacted statistically (p < 0.001). Compared to low hsCRP and low OPG (n = 1,927), either high hsCRP or high OPG (univariable HR, 2.38; 95% CI, 2.02-2.80; p < 0.001; n = 2,816), or both high hsCRP and high OPG (univariable HR, 5.13; 95% CI, 4.29-6.13; p < 0.001; n = 775) conferred increased risk of the combined endpoint.

Conclusions:

The authors concluded that OPG is an independent predictor of the combined endpoint of hospitalization of IHD, ischemic stroke, and all-cause mortality.

Perspective:

This study reports that increased baseline levels of plasma OPG are associated with the combined endpoint of hospitalization for ischemic stroke or heart disease and all-cause mortality independently of traditional risk factors and hsCRP. Furthermore, the combination of plasma OPG and hsCRP provides more prognostic information than the individual effect of the two biomarkers. Future studies should evaluate the benefit and cost-effectiveness of screening and monitoring strategies based on the combination of these and other biomarkers of different atherosclerotic mechanisms.

Clinical Topics: Dyslipidemia, Prevention, Homozygous Familial Hypercholesterolemia, Hypertension

Keywords: Prognosis, Stroke, Myocardial Ischemia, C-Reactive Protein, Biological Markers, Osteoprotegerin, Cardiovascular Diseases, Hypercholesterolemia, Hypertension, Diabetes Mellitus


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