Association of serum sclerostin and osteoprotegerin levels with the presence, severity and prognosis in patients with acute myocardial infarction

Abstract

Background Bone-related proteins (such as sclerostin and osteoprotegerin [OPG]) are involved in the development of atherosclerosis. However, the relationship between bone-related proteins and acute myocardial infarction (AMI) has not been extensively evaluated. The purpose of this study was to assess the association of serum sclerostin and OPG with the presence, severity and prognosis in patients with AMI. Methods This study prospectively enrolled 152 patients attacked by acute chest pain. Serum sclerostin and OPG were detected within the first 24 h after AMI diagnosis by ELISA kits. The AMI predictive efficacy of sclerostin and OPG were analyzed by receiver operating characteristics (ROC) curve. Univariable and multivariable linear regression analyses were performed to determine the association between bone-related proteins and scores indicating the severity of coronary artery occlusion. Moreover, prognostic values were assessed by Kaplan–Meier curves and Cox regression analysis. Results There were 92 patients in AMI group, 60 in non-AMI group. Serum levels of sclerostin and OPG were significantly higher in AMI group than in non-AMI group (all p < 0.001), which showed predictive value for the presence of AMI (all p < 0.001). The area under the ROC curve values of sclerostin and OPG were 0.744 and 0.897, respectively. A multivariable linear regression analysis demonstrated that Ln-transformed sclerostin (β = 0.288, p = 0.009) and Ln-transformed OPG (Ln-OPG: β = 0.295, p = 0.019) levels were associated with GENISINI score, independently of conventional clinical parameters. In addition, Ln-OPG levels were still positively associated with GRACE score after adjustments (β = 0.320, p = 0.001). During a 1-year follow-up, patients above the median of sclerostin levels had higher incidence of major adverse cardiac events (MACE) than those below the median (p = 0.028). It was also observed that the MACE rates were higher in patients above the median of OPG levels, though no statistic importance (p = 0.060). After adjusting conventional risk factors by multivariate Cox regression, Ln-OPG was associated with incident MACE (hazard ratio = 2.188 [95% confidence intervals 1.102–4.344], p = 0.025). Conclusions Bone-related proteins could exert a potential role in early risk stratification and prognosis assessment in patients with AMI.

El papel del eje osteoprotegerina/RANKL/RANK y la osteopontina en el síndrome coronario agudo

“…The main objective of this study was to assess the usefulness of possible biomarkers within the bone-vessel axis in patients with ACS. Our findings confirm the previously known relation between OPG and ACS patients 19 . However, neither OPG nor OPN values correlated with specific SYNTAX scores and only ORR showed a slight increase in the RR for high scores.…”

Causal effects for genetic variants of osteoprotegerin on the risk of acute myocardial infarction and coronary heart disease: A two-sample Mendelian randomization study

“…Although several clinical experiments have proved that OPG is closely related to CHD or AMI ( 9 , 21 , 27 ), and this relationship is positive, there is still controversy about this relationship in academic circles. In addition, other studies have found an association between OPG and other cardiovascular diseases, including congestive heart failure, aortic stenosis, and aortic valve calcification ( 8 , 28 ). At the same time, it is not only related to the occurrence of cardiovascular diseases, but also firmly to the prognosis of related cardiovascular diseases ( 29 – 33 ).…”

“…MI patients may benefit from the use of bone-related proteins for early risk stratification and prognosis evaluation. In patients with AMI, OPG levels are correlated with the complexity of coronary artery disease(CAD) ( 7 , 8 ). Healthy subjects with low or high coronary artery calcification cannot be distinguished by using OPG.…”

Correlation between osteoprotegerin and coronary artery calcification in diabetic subjects: a systematic review of observational studies

“…There is increasing evidence indicating the predictive role of OPG in CAD risk stratification among various populations. For instance, in a recent study that patients with acute myocardial infraction (AMI) were recruited, OPG was an independent prognostic marker for major adverse cardiovascular events (MACE) during one year follow-up and was also positively associated with AMI [ 40 ].…”