Abstract 4053: Serum Osteoprotegerin Levels are Related to Vascular Risk Factors and Vascular Calcification in the Community: The Framingham Heart Study
Background: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor family of proteins. Targeted deletion of the OPG gene in mice leads to calcification of the aorta and as such, the OPG pathway has been suggested to be a novel regulator of vascular calcification. Human data on the relations of OPG to atherosclerotic vascular disease risk factors and vascular calcification is limited.
Methods: In 3699 Framingham Heart Study offspring cohort participants (mean age 61 years, 53% women), we evaluated the cross-sectional relations of serum OPG to established vascular risk factors and prevalent cardiovascular disease using stepwise multivariable linear regression. We measured coronary artery calcification (CAC) and abdominal aortic calcification (AAC) in 1422 participants who underwent cardiac multi-detector computed tomography. We investigated the association of OPG to quartiles of CAC and AAC utilizing multivariable analysis of covariance.
Results: Mean serum OPG was 5.6 pmol/L (SD 1.9 pmol/L, coefficient of variation 3.7%). Women had higher OPG level compared with men. In stepwise linear regression models, vascular risk factors significantly related to higher serum OPG level were age, diabetes, smoking, fasting glucose, and systolic blood pressure (each P<0.05, model R2=0.25). OPG was higher in those with prevalent cardiovascular disease compared to those without (P<0.0001). Median CAC Agatston score was 164 in men and 6.4 in women whereas median AAC was 965 in men and 393 in women. After adjustment for age, sex, and vascular risk factors, OPG levels were higher in participants at the highest CAC quartile compared with those in the lowest CAC quartile (5.3 pmol/L versus 5.0 pmol/L; P=0.03). OPG was associated with AAC after adjustment for age and sex but not after considering vascular risk factors.
Conclusions: In a community-based sample, OPG is related to multiple atherosclerotic vascular disease risk factors, particularly age and diabetes. OPG is associated with CAC independent of vascular risk factors.