title: Microvascular dysfunction is associated with plasma osteoprotegerin levels in patients with acute myocardial infarction.
abstract: OBJECTIVE
  Osteoprotegerin (OPG) is a glycoprotein that inhibits nuclear factor-κB's regulatory effects on inflammation, skeletal, and vascular systems, and is a potential biomarker of atherosclerosis and seems to be involved in vascular calcifications. The objective of this study was to assess the relationship between OPG, left ventricular function, and microvascular function in patients with acute myocardial infarction (AMI).
  
  
  METHODS
  After successful revascularization, noninvasive assessment of coronary flow reserve (CFR) was performed in the distal part of the left anterior descending artery in 183 patients with first AMI. We performed low-dose dobutamine stress echocardiography to assess viability and finally we assessed the ventriculoarterial coupling (VAC). Plasma OPG was determined by ELISA.
  
  
  RESULTS
  Plasma OPG concentrations were higher in patients with impaired microcirculation (CFR<2) than in patients without [median (first; third quartile), 1.939 (1.366; 2.724) vs. 1.451 (0.925; 2.164) ng/l; P=0.001]. OPG was associated with CFR both in linear regression single-variable analysis (P=0.001) and in multivariable analysis adjusting for possible confounders (P=0.024).Eighty-seven patients had resting wall motion abnormalities and 28 patients fulfilled the criteria for viability. In the group with low OPG 20 patients had viability, and in patients with high OPG only eight patients had viability (P=0.03).Both the E/A ratio (1.22±0.65 vs. 1.06±0.39; P=0.04) and the E/e' ratio (10.4±3.1 vs. 12.2±4.6; P=0.002) indicated worse diastolic function in patients with increased levels of OPG.Overall, an increase in the VAC point was observed in the population (1.11±0.6). The VAC point was higher in patients with increased OPG compared with low OPG (1.01±0.51 vs. 1.2±0.67; P=0.03).
  
  
  CONCLUSIONS
  This is the first study to show an association between OPG levels and CFR, decreased diastolic function, and increased VAC in the setting of AMI. Our results indicate a relationship between OPG and the degree of microvascular dysfunction.
authors.affiliation: Department of Medical Research, Funen Svendborg Hospital, University of Odense, Svendborg, Denmark. bbl@dadlnet.dk
authors.forename: Brian B
authors.initials: BB
authors.lastname: Løgstrup
authors.forename: Dan E
authors.initials: DE
authors.lastname: Høfsten
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Christophersen
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Møller
authors.forename: Mette
authors.initials: M
authors.lastname: Bjerre
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Hans E
authors.initials: HE
authors.lastname: Bøtker
authors.forename: Kenneth
authors.initials: K
authors.lastname: Egstrup
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000503:physiopathology*; D015150:Echocardiography, Doppler; D025401:Echocardiography, Stress; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D053805:Fractional Flow Reserve, Myocardial; D006801:Humans; D016014:Linear Models; D008297:Male; D008833:Microcirculation; D055806:Microvessels / Q000503:physiopathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy; D009204:Myocardial Revascularization; D053244:Osteoprotegerin / Q000097:blood*; D012307:Risk Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human