Qi Jin1, Yi Tang1,2, Zhihong Liu3, Wenlin Xie4, Qin Luo1, Zhihui Zhao1, Qing Zhao1, Zhiwei Huang1, Xue Yu1, Lu Yan1, Changming Xiong1, Xinhai Ni1, Yinkun Yan5. 1. State Key Laboratory of Cardiovascular Disease, Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. 2. Department of Cardiology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, The College of Clinical Medicine of Hunan Normal University, Changsha, China. 3. State Key Laboratory of Cardiovascular Disease, Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, China. zhihongliufuwai@163.com. 4. Department of Pathology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China. 5. Department of Epidemiology, Capital institute of Pediatrics, Beijing, China.
Abstract
BACKGROUND: Human epididymis protein 4 (HE4) was proved to be a novel biomarker for left heart failure. The purpose of this exploratory study was to evaluate the role of HE4 in patients with idiopathic pulmonary arterial hypertension (IPAH) who usually have concurrent right heart failure. METHODS: 55 patients with newly diagnosed IPAH were continuously enrolled and serum HE4 levels were assessed at baseline. All patients were followed up from the date of blood sampling, and a composite endpoint of clinical worsening was detailedly recorded. RESULTS: Serum levels of HE4 were significantly higher in IPAH patients than healthy controls (6.9 ± 2.2 vs 4.4 ± 0.9 ng/ml, p < 0.05) and increased as cardiac function deteriorated. HE4 levels correlated with endothelin-1 (r = 0.331, p < 0.01) and right atrial pressure (r = 0.30, p < 0.03). After a mean follow-up of 20 ± 10 months, 13 patients experienced clinical worsening. Receiver operating characteristic analysis showed that HE4 levels > 6.5 ng/ml discriminated clinical worsening with a sensitivity of 92.31% and a specificity of 59.52% (area under the curve [AUC] = 0.81). Multivariate Cox regression analysis demonstrated that HE4 (χ2: 5.10; hazard ratio [HR] = 1.26; 95% confidence interval: 1.03 to 1.55, p < 0.02) and pulmonary vascular resistance (χ 2: 4.19; HR = 1.14; 95% confidence interval: 1.00-1.29, p < 0.04) were independently predictive of clinical worsening. Patients with HE4 > 6.5 ng/ml had a worse 2-year survival rate than those with HE4 ≤ 6.5 ng/ml (58.9% vs 96.2%, p < 0.001). CONCLUSIONS: Serum levels of HE4 were elevated in IPAH patients and correlated with disease severity. HE4 was an independent predictor of clinical worsening in IPAH patients.
BACKGROUND:Human epididymis protein 4 (HE4) was proved to be a novel biomarker for left heart failure. The purpose of this exploratory study was to evaluate the role of HE4 in patients with idiopathic pulmonary arterial hypertension (IPAH) who usually have concurrent right heart failure. METHODS: 55 patients with newly diagnosed IPAH were continuously enrolled and serum HE4 levels were assessed at baseline. All patients were followed up from the date of blood sampling, and a composite endpoint of clinical worsening was detailedly recorded. RESULTS: Serum levels of HE4 were significantly higher in IPAHpatients than healthy controls (6.9 ± 2.2 vs 4.4 ± 0.9 ng/ml, p < 0.05) and increased as cardiac function deteriorated. HE4 levels correlated with endothelin-1 (r = 0.331, p < 0.01) and right atrial pressure (r = 0.30, p < 0.03). After a mean follow-up of 20 ± 10 months, 13 patients experienced clinical worsening. Receiver operating characteristic analysis showed that HE4 levels > 6.5 ng/ml discriminated clinical worsening with a sensitivity of 92.31% and a specificity of 59.52% (area under the curve [AUC] = 0.81). Multivariate Cox regression analysis demonstrated that HE4 (χ2: 5.10; hazard ratio [HR] = 1.26; 95% confidence interval: 1.03 to 1.55, p < 0.02) and pulmonary vascular resistance (χ 2: 4.19; HR = 1.14; 95% confidence interval: 1.00-1.29, p < 0.04) were independently predictive of clinical worsening. Patients with HE4 > 6.5 ng/ml had a worse 2-year survival rate than those with HE4 ≤ 6.5 ng/ml (58.9% vs 96.2%, p < 0.001). CONCLUSIONS: Serum levels of HE4 were elevated in IPAHpatients and correlated with disease severity. HE4 was an independent predictor of clinical worsening in IPAHpatients.
Entities:
Keywords:
Cardiac function; Clinical worsening; Human epididymis protein 4; Idiopathic pulmonary arterial hypertension; Predictor