Osteoprotegerin levels in ST-elevation myocardial infarction: Temporal profile and association with myocardial injury and left ventricular function

Abstract

BackgroundElevated levels of osteoprotegerin (OPG) have been associated with adverse outcomes in ST-elevation myocardial infarction (STEMI). However, the role of OPG in myocardial injury and adverse remodeling in STEMI patients remains unclear. The aims of this observational cohort study were to evaluate: 1) the temporal profile of OPG during STEMI, 2) possible associations between OPG measured acutely and after 4 months, with infarct size, adverse left ventricular (LV) remodeling, microvascular obstruction (MVO) and myocardial salvage and 3) the effect of heparin administration on OPG levels.MethodsBlood samples were drawn repeatedly from 272 STEMI patients treated with primary percutaneous coronary intervention (PCI). Cardiac magnetic resonance imaging (CMR) was performed in the acute phase and after 4 months. The effect of heparin administration on OPG levels was studied in 20 patients referred to elective coronary angiography.ResultsOPG levels measured acutely were significantly higher than Day 1 and during follow-up. OPG levels were correlated with age. No association was found between early OPG levels and CMR measurements at 4 months. Patients with >median OPG levels measured at Day 1 had larger final infarct size, lower LV ejection fraction (LVEF) at 4 months and higher frequency of MVO. There were no associations between OPG and change in end-diastolic volume or myocardial salvage. OPG remained associated with infarct size and LVEF after adjustment for relevant covariates, except peak troponin T and CRP. A 77% increase in OPG levels following heparin administration was found in patients undergoing elective coronary angiography.ConclusionsOPG was found to be associated with myocardial injury, but not with LV remodeling or myocardial salvage. The use of OPG as a biomarker in STEMI patients seems to be limited by a strong association with age, confounding effect of heparin administration, and little additive value to established biomarkers.

MR findings of microvascular perfusion in infarcted and remote myocardium early after successful primary PCI

“…In the present study, the results on CMR first-pass perfusion at rest showed no significant differences between patients treated with PCI with or without postconditioning, which is in accordance with the findings in the main study [ 19 , 29 ].…”

Glycosylation is important for legumain localization and processing to active forms but not for cystatin E/M inhibitory functions

“…The anticoagulant heparin displays close structural relationship to HS [236], and is routinely administrated to patients prior to percutaneous coronary intervention (PCI) [237]. This drug has previously been shown to influence circulating levels of several cytokines [238,239]. To study whether heparin influenced the level of circulating legumain, a small population of patients (n=9) with suspected stable coronary artery disease was administrated with 5000 IU heparin.…”

Circulating osteogenic proteins are associated with coronary artery calcification and increase after myocardial infarction

“…Previous clinical studies have shown that the elevation of both OPG and oxLDL plasma levels in patients with recent MI was associated with the severity of MI, with heart failure, and with long-term adverse outcomes. [ 23 , 25 ]. In accordance with our results, Shetelig C et al demonstrated that circulating OPG levels were increased in the acute phase of ST-elevation MI patients and were only slightly decreased after 4 months, suggesting that OPG levels may remain increased after acute and subacute MI.…”

“…In accordance with our results, Shetelig C et al demonstrated that circulating OPG levels were increased in the acute phase of ST-elevation MI patients and were only slightly decreased after 4 months, suggesting that OPG levels may remain increased after acute and subacute MI. [ 25 ]…”

“…Finally, in patients with acute MI, the prognostic role of baseline circulating inflammatory and osteogenic proteins was clinically well established, but few studies followed the levels of OPs after the acute and subacute phases. [ 23 – 25 ]. Moreover, whether OPs expression is affected by increased atherothrombotic inflammation after MI remains largely unknown.…”