Association between serum HER2/ErbB2 levels and coronary artery disease: a case-control study.

BACKGROUND: Research has associated human epidermal growth factor receptor (HER2) with glucose and lipid metabolism. However, the association between circulating HER2 levels and coronary artery disease (CAD) remains to be elucidated. METHODS: We performed a case-control study with 435 participants (237 CAD patients and 198 controls) who underwent diagnostic coronary angiography from September 2018 to October 2019. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CAD were calculated with multiple logistic regression models after adjustment for confounders. RESULTS: Overall, increased serum HER2 levels were independently associated with the presence of CAD (OR per 1-standard deviation (SD) increase: 1.438, 95% CI 1.13-1.83; P = 0.003) and the number of stenotic vessels (OR per 1-SD increase: 1.399, 95% CI 1.15-1.71; P = 0.001). In the subgroup analysis, a significant interaction of HER2 with body mass index (BMI) on the presence of CAD was observed (adjusted interaction P = 0.046). Increased serum HER2 levels were strongly associated with the presence of CAD in participants with BMI ≥ 25 kg/m2 (OR per 1-SD increase: 2.143, 95% CI 1.37-3.35; P = 0.001), whereas no significant association was found in participants with BMI < 25 kg/m2 (OR per 1-SD increase: 1.225, 95% CI 0.90-1.67; P = 0.201). CONCLUSION: Elevated HER2 level is associated with an increased risk of CAD, particularly in people with obesity. This finding yields new insight into the pathological mechanisms underlying CAD, and warrants further research regarding HER2 as a preventive and therapeutic target of CAD.

Angiopoietin-2 provides no incremental predictive value for the presence of obstructive coronary artery disease over N-terminal pro-brain natriuretic peptide.

BACKGROUND: Using circulating biomarkers as a noninvasive method to assist the evaluation of coronary artery disease (CAD) is beneficial for reducing the unnecessary diagnostic cardiac catheterization. This study aimed to assess the predictive role of angiopoietin-2 (Ang-2) for the presence of obstructive coronary stenosis as compared with N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with symptoms of CAD. METHODS: The study enrolled 222 consecutive symptomatic patients who underwent elective diagnostic cardiac catheterization from July to December 2018. Blood samples were collected in the first morning after admission. The severity of coronary stenosis was assessed by coronary angiography. The obstructive CAD was defined as stenosis ≥50% of the left main coronary artery or stenosis ≥70% of a major epicardial vessel (left anterior descending artery, left circumflex artery and right coronary artery). RESULTS: Patients with obstructive CAD (n = 120) had significantly higher levels of Ang-2 and NT-proBNP compared with those without. In multivariable regression analysis, only NT-proBNP levels were independently associated with Ang-2 levels. NT-proBNP was superior to Ang-2 as a predictor for the presence of obstructive CAD (NT-proBNP, area under curve [AUC] = 0.733, vs Ang-2, AUC = 0.626, P = 0.004). In multiple logistic regression analysis, NT-proBNP, but not Ang-2, was the independent predictor of obstructive CAD. The combination of Ang-2 with NT-proBNP did not provide the incremental value over NT-proBNP alone. CONCLUSION: Serum Ang-2 levels are associated with NT-proBNP levels in patients suspected for CAD. NT-proBNP is superior to Ang-2 as a predictor for the presence of obstructive CAD. However, Ang-2 does not further increase diagnostic accuracy on top of NT-proBNP.

Association between serum angiopoietin-2 concentrations and periprocedural myocardial injury in patients undergoing elective percutaneous coronary intervention.

Angiopoietin-2 (Ang-2) is a proangiogenic factor that mediates inflammation and atherosclerosis. We evaluated the predictive value of circulating Ang-2 levels for periprocedural myocardial injury (PMI) in 145 patients undergoing elective percutaneous coronary intervention (PCI), and investigated whether post-PCI Ang-2 levels are influenced by PMI. PMI was defined as a post-procedural troponin elevation above the 5×99th percentile upper reference limit. Blood samples for Ang-2 analysis were collected at admission and on postoperative days 1 and 3. PMI occurred in 40 patients (28%). At baseline, there was no difference in Ang-2 levels between PMI and non-PMI patients (P=0.554). However, a significant interaction effect between PMI occurrence and time on Ang-2 levels was observed (interaction P=0.036). Although serum Ang-2 levels in non-PMI patients gradually decreased, Ang-2 levels in PMI patients did not change between different time-points. Multiple logistic regression analysis revealed that age, total stent length, and serum levels of N-terminal pro-brain natriuretic peptide were independent PMI predictors. These findings indicate that pre-procedural Ang-2 levels do not impact PMI occurrence after elective PCI. However, changes in Ang-2 levels after the procedure are closely related to PMI.