Apelin and its ratio to lipid factors are associated with cardiovascular diseases: A systematic review and meta-analysis

BACKGROUND: The present systematic review and meta-analysis aimed to ascertain if the circulating levels of apelin, as an important regulator of the cardiovascular homeostasis, differ in patients with cardiovascular diseases (CVDs) and controls. METHODS: A comprehensive search was performed in electronic databases including PubMed, Scopus, EMBASE, and Web of Science to identify the studies addressing apelin in CVD up to April 5, 2021. Due to the presence of different units to measure the circulating levels of apelin across the included studies, they expressed the standardized mean difference (SMD) and their 95% confidence interval (CI) as summary effect size. A random-effects model comprising DerSimonian and Laird method was used to pool SMDs. RESULTS: Twenty-four articles (30 studies) comprised of 1793 cases and 1416 controls were included. Pooled results obtained through random-effects model indicated that apelin concentrations in the cases’ blood samples were significantly lower than those of the control groups (SMD = -0.72, 95% CI: -1.25, -0.18, P = 0.009; I(2) = 97.3%, P<0.001). New combined biomarkers showed a significant decrease in SMD of apelin/high-density lipoprotein cholesterol (apelin/HDL-C) ratio [-5.17; 95% CI, -8.72, -1.63, P = 0.000; I(2) = 99.0%], apelin/low-density lipoprotein cholesterol (apelin/LDL-C) ratio [-4.31; 95% CI, -6.08, -2.55, P = 0.000; I(2) = 98.0%] and apelin/total cholesterol (apelin/TC) ratio [-17.30; 95% CI, -22.85, -11.76, P = 0.000; I(2) = 99.1%]. However, no significant differences were found in the SMD of apelin/triacylglycerol (apelin/TG) ratio in cases with CVDs compared to the control group [-2.96; 95% CI, -7.41, 1.49, P = 0.000; I(2) = 99.2%]. CONCLUSION: The association of apelin with CVDs is different based on the region and disease subtypes. These findings account for the possible usefulness of apelin as an additional biomarker in the diagnosis of CVD in diabetic patients and in the diagnosis of patients with CAD. Moreover, apelin/HDL-c, apelin/LDL-c, and apelin/TC ratios could be offered as diagnostic markers for CVD.