Serum Osteoprotegerin Level Is Not a Localizing Biomarker of Atherosclerosis Affected by Kidney Function

Introduction: Osteoprotegerin (OPG) is recognized as an emerging biomarker for atherosclerosis. We hypothesized that atherosclerotic lesions localized across multiple vascular beds would result in greater elevations in OPG levels in the blood. Therefore, our study aimed to assess serum OPG levels and their confounding factors in patients with hemodynamically significant multivessel atherosclerosis in varying locations. Subjects and Methods: A case-control study included 222 selected outpatients aged 50 years or older (46.4% women) with atherosclerosis confirmed by imaging (Doppler ultrasound and CT angiography) treated at a single angiology clinic. Data concerning age, smoking status, comorbidity (hypertension, diabetes mellitus, history of stroke, myocardial infarction, coronary revascularization procedures), medication, lipid profile, serum creatinine, and homocysteine levels were retrieved from medical records. Additionally, serum OPG levels were measured. Patients were divided according to serum OPG levels into terciles and the number of involved vascular beds [carotid artery disease, coronary heart disease (CHD), lower-extremity peripheral artery disease (PAD), abdominal aorta aneurysm (AAA)]. Results: The distribution of carotid artery disease, CHD, PAD, and AAA did not differ across the OPG terciles. Additionally, we did not observe differences in OPG levels between specific and multiple locations of atherosclerotic lesions. Subjects with the highest OPG levels were the oldest (75.0 ± 8.4 vs. 69.8 ± 7.1 years in the lowest tercile; p < 0.001) and were characterized by the worst kidney function (eGFR 60.8 ± 16.8 vs. 74.1 ± 13.5 mL/min/1.73 m²; p < 0.001). Conclusions: The serum OPG level did not reveal the specific location of atherosclerosis. Impaired renal function appears to be the primary determinant of serum OPG levels and a key confounder, complicating the interpretation of serum OPG as a biomarker of atherosclerosis.