Association Between Serum HER2/ErbB2 Levels And Risk Of Coronary Artery Disease

Background: Coronary artery disease(CAD)is the leading cause of death worldwide.The understanding of the relevant risk factors is critical to the prevention of and treatment of CAD.Human epidermal growth factor receptor 2(HER2)is a transmembrane receptor with tyrosine kinase catalytic activity.HER2 signaling can mediate cell proliferation,differentiation,migration and apoptosis through various pathways.Besides its important role in cancers,animal studies have shown that HER2 signaling is related to vascular dysfunction and arteriosclerosis.Of note,clinical evidence has recently associated circulating HER2 levels with glucose and lipid metabolism.Moreover,circulating HER2 has been identified as a causal mediator of chronic kidney disease.Objective: this case–control study aimed to investigate whether circulating HER2 levels are associated with CAD risk.Methods: We selected participants who underwent diagnostic coronary angiography in our hospital from September 2018 to January 2020.Based on the angiographic results recorded by experienced angiographers,patients with stenosis?≥?50% of at least one epicardial vessel were enrolled as CAD group,and patients without any visible lesion were chosen as control group.Blood samples were collected at admission,and were measured with enzyme-linked immunosorbent assay kits.Results: Exploratory data analysis initially included 435 participants(CAD group,n?=?237;control group,n?=?198).Multivariable logistic regression analysis showed that,after adjustment of conventional CAD risk factor,increased serum HER2 levels were independently associated with the presence of CAD(odds ratio(OR)per 1-standard deviation(SD)increase: 1.438,95% confidence interval(CI):1.13–1.83;P=0.003).In the subgroup analysis,a significant interaction of HER2 with body mass index(BMI)on the presence of CAD was observed.Increased serum HER2 levels were strongly associated with the presence of CAD in participants with BMI≥25kg/m2(OR per 1-SD increase: 2.143,95% CI: 1.37–3.35;P=0.001),whereas no significant association was found in patients with BMI<25kg/m2.To bridge the age and gender gaps between groups and rule out the residual unknown confounders as many as possible,we finally enrolled 92 participants with BMI≥27kg/m2(CAD group,n?=?46;1:1 age and gendermatched control group,n?=?46),and measured important adipokine and inflammatory factors levels(leptin,high-sensitivity C-reactive protein [hs-CRP],and S100A8/A9).We found that HER2 levels are not correlated with leptin,hsCRP,and S100A8/A9.The association between HER2/Erb B2 Levels and CAD remains significant after adjustment of leptin,hs-CRP,and S100A8/A9 respectively.Conclusion: Elevated HER2 level is associated with the presence of CAD in people with obesity.Circulating HER2 is probably a risk factor of CAD and need to be confirmed by large cohort studies.Further research regarding HER2 as a preventive and therapeutic target of CAD is required.