Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial

Abstract

BackgroundElevated levels of osteoprotegerin, a secreted tumor necrosis factor–related molecule, might be associated with adverse outcomes in patients with coronary artery disease. We measured plasma osteoprotegerin concentrations on hospital admission, at discharge, and at 1 and 6 months after discharge in a predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO (Platelet Inhibition and Patient Outcomes) trial.Methods and ResultsThe associations between osteoprotegerin and the composite end point of cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke, and non–coronary artery bypass grafting major bleeding during 1 year of follow‐up were assessed by Cox proportional hazards models. Event rates of the composite end point per increasing quartile groups at baseline were 5.2%, 7.5%, 9.2%, and 11.9%. A 50% increase in osteoprotegerin level was associated with a hazard ratio (HR) of 1.31 (95% confidence interval [CI], 1.21–1.42) for the composite end point but was not significant in adjusted analysis (ie, clinical characteristics and levels of C‐reactive protein, troponin T, NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], and growth differentiation factor‐15). The corresponding rates of non–coronary artery bypass grafting major bleeding were 2.4%, 2.2%, 3.8%, and 7.2%, with an unadjusted HR of 1.52 (95% CI, 1.36–1.69), and a fully adjusted HR of 1.26 (95% CI, 1.09–1.46). The multivariable association between the osteoprotegerin concentrations and the primary end point after 1 month resulted in an HR of 1.09 (95% CI, 0.89–1.33); for major bleeding after 1 month, the HR was 1.33 (95% CI, 0.91–1.96).ConclusionsIn patients with acute coronary syndrome treated with dual antiplatelet therapy, osteoprotegerin was an independent marker of major bleeding but not of ischemic cardiovascular events. Thus, high osteoprotegerin levels may be useful in increasing awareness of increased bleeding risk in patients with acute coronary syndrome receiving antithrombotic therapy.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Plasma proteins associated with cardiovascular death in patients with chronic coronary heart disease: A retrospective study

“…Also, CHI3L1 [ 30 ] and TIM-1 [ 31 ] have been found associated with the development of coronary atherosclerosis. OPG, a member of the tumor necrosis factor receptor superfamily, has pleiotropic effects on bone metabolism, endocrine functions, and vascular inflammation [ 32 , 33 ]. It is expressed by inflammatory stimuli, during acute MI and heart failure, and OPG plasma levels are related to outcomes in patients with these conditions [ 34 – 36 ].…”

Association of serum sclerostin and osteoprotegerin levels with the presence, severity and prognosis in patients with acute myocardial infarction

“…The C-index was applied to preliminarily compare the prognostic value of serum OPG and cTNI on admission, the efficacy of OPG seemed to be superior to cTNI on admission. Conversely, insights from the PLATO (Platelet Inhibition and Patient Outcomes) trial showed plasma OPG was not an independent marker of ischemic cardiovascular events in patients with ACS [ 32 ]. Explanation for the discrepancy may be different reagent test kit.…”

Development and validation of a quantitative Proximity Extension Assay instrument with 21 proteins associated with cardiovascular risk (CVD-21)

“…In addition to these conventional proteins, the CVD-21 tool constitutes a number of potential novel biomarkers with specific pathways and biological functions with associations to different outcomes as exemplified below. Beyond GDF-15, we have previously shown that osteoprotegerin (OPG), OPN, fibroblast growth factor 23 (FGF-23), and TFF3 are important biomarkers for prediction of bleeding in patients with CAD or AF [21,34,35]. The phosphaturic hormone FGF-23 links calcium-phosphate metabolism with left-ventricular dysfunction [36].…”