Osteopontin and Osteoprotegerin Investigated In Peripheral Artery Disease

Atherosclerosis is a complex procedure of different pathways. Among other cytokines, inflammation and calcification are known to be regulated also by well-known bone regulators, such as osteoprotegerin (OPG) and osteopontin (OPN). OPG is a secretory basic glycoprotein and a member of the tumor necrosis factor (TNF) receptor superfamily, acting as an inhibitor of bone resorption. OPN is a highly phosphorylated glycophosphoprotein having acidic characteristics and rich in aspartic acid.

Clinical Scientists at the Medical School University of Cyprus (Nicosia, Cyprus) and their colleagues enrolled 203 consecutive patients with symptomatic, established PAD requiring endovascular revascularization (percutaneous transluminal angioplasty–PTA and/or stent placement) of any or both of their lower limbs (PAD group–PADG). They also recruited 78 age- and sex-matched subjects with less than two classical cardiovascular risk factors (hypertension, diabetes, hyperlipidemia, smoking, family history of premature CAD) who served as control group (COG).

Overnight fasting, blood samples were obtained and glycemic and lipid parameters were immediately assayed in an AU560 automatic enzymatic analyzer (Olympus, Hamburg, Germany). The glycated hemoglobin (HbA1c) was determined by high-performance liquid chromatography (Menarini Diagnostics, Florence, Italy) only in diabetic patients. Serum OPN and OPG were assayed using quantikine immunoassay EIA kits (R&D Systems Inc., Minneapolis, MN, USA) and Metra, San Diego, CA, USA). The high-sensitivity C-Reactive Protein (hsCRP) levels were measured with latex-enhanced immunonephelometry (Dade Behring, Marburg, Germany).

The investigators reported that during 12-month follow-up, 82 major adverse cardiovascular events (MACE) were recorded (MACE subgroup). The rest of 124 PAD patients remained free of MACE (non-MACE subgroup). At baseline, OPG (9.89 ± 2.85 ng/mL versus 3.47 ± 1.95 ng/mL) and OPN (79.99 ± 38.29 ng/mL versus 35.21 ± 14.84 ng/mL) levels were significantly higher in PADG compared to COG, as well as in MACE subgroup compared to non-MACE subgroup (13.29 ± 3.23 ng/mL versus 10.86 ± 3 ng/mL and 96.45 ± 40.12 ng/mL versus 78.1 ± 38.29 ng/mL, respectively). An independent association of PAD with OPG and OPN was found in the whole patient cohort.

The authors concluded that baseline high OPG and OPN levels were independently associated with the presence of PAD. Even higher levels of those biomarkers were detected among PAD patients with MACE. The study was published on September 1, 2022 in the journal Cardiovascular Diabetology.