Abstract
Osteoprotegerin (OPG) is a glycoprotein involved in bone metabolism and cardiovascular health, with emerging evidence suggesting its role in heart failure (HF). Despite its potential as a biomarker, the association between circulating OPG levels and HF severity remains unclear. This systematic review and meta-analysis aimed to evaluate OPG levels in HF patients and their relationship with disease severity according to the New York Heart Association (NYHA) classification. A comprehensive search of PubMed, EMBASE, and Scopus was conducted to identify observational studies assessing OPG levels in HF patients. Studies were included if they reported OPG levels in HF patients and controls, with subgroup analyses according to NYHA classification when available. Risk of bias assessment was performed using the Newcastle-Ottawa Scale (NOS). The principal outcome was the mean difference (MD) in circulating OPG levels between HF patients and controls. Random-effects meta-analysis models were used to pool the data. Thirteen studies with a total of 1387 participants were included in the quantitative and qualitative synthesis. Overall, OPG levels were significantly elevated in HF patients compared to healthy controls (2.490 [95% CI 0.531, 4.449]). Subgroup analysis showed a significant decrease in OPG levels in controls versus NYHA II patients (-1.503 [95% CI -2.402, -0.604]). However, no statistically significant difference was found when comparing OPG levels between the combined NYHA II/III group and controls (-1.019 [95% CI -2.451, 0.412]). OPG levels are significantly elevated in HF patients compared to controls, with a progressive increase in NYHA II patients. However, the lack of significance in the NYHA II/III group highlights the need for further studies with a more comprehensive NYHA classification breakdown.