[Relationship between serum levels of osteoproteins, inflammatory cytokines and coronary heart disease and disease severity]

Abstract

Objective: To explore the relationship between serum levels of osteoprotein (OPG), soluble nuclear factor-κB receptor activator ligand (sRANKL), inflammatory factors and coronary heart disease (CHD) and its severity.

Methods: The patients who underwent coronary angiography (CAG) due to chest pain admitted to department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled, and they were divided into CHD group and non-CHD group according to the CAG results. The gender, age, history of hypertension, smoking history, diabetes, the levels of cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB), lipoprotein (a) [Lp (a)], MB isoenzyme of creatine kinase (CK-MB) and other clinical data of patients were collected. The serum levels of OPG, sRANKL, matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1), insulin-like growth factor-1 (IGF-1) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). According to the results of CAG, the patients with CHD were divided into single-, double-, triple-branch coronary artery lesion groups, and the relationship between the levels of serum OPG, sRANKL, inflammatory factors and the degree of coronary artery lesions was observed. Multivariate Logistic regression was used to analyze the risk factors of CHD, and receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of main risk factors for CHD.

Results: A total of 472 patients were enrolled in the final analysis during the study period, including 264 patients in the CHD group, 208 patients in the non-CHD group, 79 patients in the CHD group with single-branch disease, 75 patients with double-branch disease, and 110 patients with three-branch disease. (1) Compared with the non-CHD group, the CHD group had more older male patients, as well as higher proportion of hypertension and diabetes, the levels of serum Lp (a) and CK-MB were significantly increased, and the levels of serum HDL-C and apoAI were significantly lowered. There was no statistically significant difference in serum TC, LDL-C, or apoB between the two groups. The levels of serum OPG, MMP-9, MCP-1, IGF-1 and IL-6 in the CHD group were significantly higher than those in the non-CHD group [OPG (μg/L): 1.79±0.50 vs. 1.50±0.30, MMP-9 (μg/L): 57.91 (33.50, 130.46) vs. 38.33 (29.43, 109.78), MCP-1 (μg/L): 298.30 (207.96, 537.16) vs. 252.73 (165.22, 476.01), IGF-1 (μg/L): 734.03±486.11 vs. 217.75±126.45, IL-6 (ng/L): 64.76±40.25 vs. 48.60±15.80, all P < 0.05], and the levels of serum sRANKL was significantly lower than that in the non-CHD group (ng/L: 344.31±122.14 vs. 378.74±109.27, P < 0.05). (2) The serum OPG level showed a slight upward tendency with the increase in the number of coronary artery lesions, and the sRANKL level showed a slight downward tendency [OPG (μg/L) in the single-, double-, triple-branch coronary artery lesion groups was 1.74±0.49, 1.76±0.50, 1.85±0.52, and sRANKL (ng/L) was 354.96±116.64, 340.05±124.24, 339.57±125.03, respectively) without statistically significant differences (all P > 0.05). The levels of IGF-1 and IL-6 were increased with the number of coronary artery lesions [IGF-1 (μg/L) in the single-, double- and triple-branch coronary artery lesions groups was 372.13±258.42, 676.06±350.29, 1 033.47±468.06, and IL-6 (ng/L) was 48.87±16.72, 65.36±18.84, 75.76±22.72, respectively], and the differences among different lesion groups were statistically significant (all P < 0.01). Correlation analysis showed that IGF-1 level was significantly positively correlated with the number of coronary artery lesions (r = 0.612, P < 0.01), while IL-6 was not correlated with the number of coronary artery lesions (r = 0.185, P > 0.05). (3) Multivariate Logistic regression analysis showed that elevated serum OPG and IGF-1 levels were risk factors for CHD [OPG: odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.936-2.067, P = 0.012; IGF-1: OR = 1.009, 95%CI = 1.004-1.015, P = 0.001]. (4) ROC curve analysis showed that the area under ROC curve (AUC) of OPG and IGF-1 was 0.716 and 0.867, respectively. When the cut-off value of OPG was 1.13 μg/L, the sensitivity was 81.7%, the specificity was 58.1%; when the cut-off value of sRANKL was 401.20 μg/L, the sensitivity was 69.7%, the specificity was 95.7%.

Conclusions: CHD was associated with increased in OPG, related inflammatory cytokines including MMP-9, MCP-1, IGF-1 and IL-6, and decreased in sRANKL. The level of IGF-1 was positively correlated with the severity of CHD. The serum levels of OPG and IGF-1 were risk factors for CHD, which had good predictive value for CHD.