Table 2

Studies Evaluating the Association Between OPG/RANKL/RANK and Cardiovascular Disease

First Author (Ref. #)Target PopulationStudy DesignPrimary Outcome MeasureMain Findings
Shin et al. (84)Type 2 diabetesCross-sectional, n = 104FMAD as an indicator of endothelial functionIncreased OPG levels were associated with endothelial dysfunction indicated by decreased FMAD
Xiang et al. (83)Type 1 and 2 diabetes patientsProspective, n = 50 (type 1); n = 86 (type 2)Endothelial function measured as FMAD pre- and post-treatment with insulinAfter 6 months of insulin therapy, FMAD was significantly increased, whereas serum OPG levels decreased significantly
Rasmussen et al. (113)Type 1 diabetes patientsCross-sectional, n = 291Cardiovascular disease prevalenceHigher OPG levels associated with cardiovascular disease, worse kidney function, glycemic control, and presence of nephropathy
Avignon et al. (86)Asymptomatic patients with type 1 and 2 diabetesCross-sectional, n = 465Prevalence of silent myocardial ischemia by myocardial perfusion imagingOPG levels were independently associated with presence of silent myocardial ischemia
Anand et al. (44)Asymptomatic type 2 diabetesProspective, n = 510Presence of CAC and coronary eventsSerum OPG levels associated with severity and progression of CAC and short-term cardiovascular events
Omland et al. (112)Patients presenting with acute coronary syndromesProspective, n = 897Death, recurrent MI, HF hospitalization, and strokeDuring an 89-month follow-up, higher baseline OPG levels were associated with mortality and HF hospitalization independent of C-reactive protein and troponin
Abedin et al. (114)General population (unselected)Cross-sectional, n = 3,386Prevalence of CAC and aortic plaqueHigher quartiles of OPG were independently associated with prevalence of CAC and aortic plaque
Sandberg et al. (56)Patients with unstable and stable anginaCross-sectional, n = 100OPG levels in stable vs. unstable anginaOPG was significantly higher in patients with unstable angina than in patients with stable angina
Helske et al. (115)Patients with aortic stenosisCross-sectional, n = 131Prevalence of HFHF was significantly associated with increasing levels of OPG that decreased after valve replacement
Omland et al. (116)General populationCross-sectional, n = 2,715Left ventricular structure and functionHigher OPG levels were associated with higher left ventricular mass and thickness and lower LVEF in male patients; higher LVESV and lower LVEF in female patients
Kiechl et al. (117)General populationProspective, n = 915Progression of carotid atherosclerosis and cardiovascular eventsOver a 10-yr follow-up, higher OPG levels were associated with severity and progression of carotid atherosclerosis, vascular mortality, and incident cardiovascular disease
Semb et al. (64)General population (nested case-control study)Prospective, 951 cases and 1,705 controlsCoronary eventHigher baseline OPG but not RANKL levels were associated with coronary events
Kiechl et al. (65)General populationProspective, n = 909Cardiovascular disease incidenceIncreasing serum RANKL levels were independently associated with increasing vascular risk but not atherosclerosis
Crisafulli et al. (66)Patients with AMI (n = 58), asymptomatic CAD (n = 52), and normal controls (n = 52)Cross-sectional, n = 162Serum OPG and RANKL levels in the different groupsOPG levels were significantly higher and RANKL levels significantly lower in AMI patients compared with asymptomatic CAD patients and normal subjects

AMI = acute myocardial infarction; CAC = coronary artery calcium; CAD = coronary artery disease; FMAD = flow-mediated arterial dilation; HF = heart failure; LVEF = left ventricular ejection fraction; LVESV = left ventricular end-systolic volume; OPG = osteoprotegerin; RANK = receptor activator of nuclear factor κB; RANKL = receptor activator of nuclear factor κB ligand.