الارتباط بين عامل تمايز النمو 15 , الزونولين,و أوستيوكالسين في أمراض القلب والأوعية الدموية مع / بدون مرض الكبد الدهني غير الكحولي للمرضى العراقيين

Association between Growth Differentiation Factor-15, Zonulin and osteocalcin in Cardiovascular Diseases with/without Non-Alcoholic Fatty Liver Disease of Iraqi Patients

The most common cardiovascular disease (CVD), coronary artery disease (CAD), is one of the leading causes of death worldwide and has lately increased in prevalence in low- and middle-income counteries. It is brought on by atherosclerosis, which results in a reduction in blood flow to the distal myocardium by narrowing the arterial lumen.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and is the hepatic manifestation of metabolic syndrome. NAFLD is linked to both liver-related and extrahepatic morbidity. Among extrahepatic consequences, cardiovascular disease (CVD) is the leading cause of death in NAFLD patients. Coronary artery disease (CAD) is the most common clinical manifestation of CVD. Epidemiological studies show a relationship between CAD and NAFLD.
This study aimed to investigate the role of biochemical markers; Growth differentiation factor 15, osteocalcin, and zonulin as early diagnostic markers of CAD and NAFLD.
A Case-control study approach was conducted on 180 subjects with age ranging between (40-70) years involving 135 patients and 45 apparently healthy controls in Kerbala Governorate. The subjects were collected throughout the period from October 2022 to January 2023. The patients were divided into three groups, (45) coronary artery with non-alcoholic fatty liver, (45) coronary artery, and (45) non-alcoholic fatty liver. The patients of CAD and NAFLD were exposed to a medical examination for signs and symptoms by a specialized doctor. Serum biomarker levels were measured for the following parameters: GDF-15, osteocalcin, and zonulin levels were measured using the ELISA technique.; Measurement of Iipid profile and liver function test levels in human serum was performed using autoanalyzer chemistry. The association between biochemical markers and disease severity was evaluated. The efficiency of the predicting value was assessed using the receiver operating characteristic (ROC) curve.
The observed results indicated that GDF-15 levels were shown significantly increased levels in the CAD with NAFLD cases compared to the CAD and NAFLD cases separately. The levels were (273.18 ng/L); (223.78 ng/L) and (237.34 ng/L) respectively. Also, zonulin showed higher levels in CAD+NAFLD group, the levels were (94.80 ng/ml); (73.42 ng/ml) and (63.42 ng/ml) respectively. On the other hand, patients showed significantly decreased levels of osteocalcin compared to the control group. Results also illustrated the receiver operating curve (ROC) and AUC analysis for the markers as possible diagnostic parameters. Zonulin level had shown good diagnostic performance for prediction CAD+NAFLD patients compared to the control group. The optimal diagnostic points for predicting CAD+NAFLD by GDF-15 was (sensitivity = 79%, specificity = 91%) at a level = 250.605 , osteocalcin (sensitivity = 88%, specificity = 60%) at a level = 8.732 and zonulin (sensitivity = 93%, specificity = 83%) at a level =69.79.
In conclusion, the increased serum level of GDF‐15 in NAFLD and CAD functions as an early predictor marker for cardiovascular risk, non-alcoholic fatty liver, and appears to be a direct participant in the atherosclerotic process and metabolic changes. The decreased level of osteocalcin in the NAFLD and CAD Patients groups might be returned to the potential role for improving endothelial function and reducing the pathological mechanisms that promote the development of atherosclerosis in patients with NAFLD. This effect is often a result of improved metabolic outcomes; however, whether there is a direct osteocalcin/vascular interaction is yet to be fully elucidated. The present results revealed that increased serum zonulin levels in NAFLD and coronary artery disease patients groups denote the possible role in the pathogenesis of NAFLD occurrence and progression.