ADAMTS4 is a serum biomarker for pulmonary arterial hypertension associated with congenital heart disease.
Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a cardiopulmonary disorder characterized by pathological pulmonary vascular remodeling and perivascular inflammatory cell infiltration. ADAMTS4 is a secreted, zinc-dependent metalloprotease critically involved in extracellular matrix degradation and turnover and has recently emerged as a potential biomarker in vascular remodeling diseases. This study aimed to evaluate the diagnostic performance and prognostic value of serum ADAMTS4 in patients with PAH-CHD.
This study included patients with PAH-CHD, patients with CHD, and healthy controls. Serum ADAMTS4 levels were measured by ELISA. Correlations with clinical parameters were assessed using Spearman's rank correlation. The diagnostic efficacy was evaluated by ROC curve analysis. Univariate and multivariable logistic regression were used to identify independent risk factors associated with the presence of PAH-CHD. PAH-CHD patients were followed up for a median duration of 40.5 months, and Kaplan-Meier and Cox regression analyses were used to analyze prognosis.
Compared with those in CHD patients and healthy controls, serum ADAMTS4 levels were elevated in PAH-CHD patients. ADAMTS4 was positively correlated with NT-proBNP (r = 0.45, p = 0.002), CRP (r = 0.60, p < 0.001), and WHO functional class (r = 0.49, p < 0.001). ROC analysis demonstrated good discriminatory ability for differentiating PAH-CHD from CHD (AUC = 0.78; 95% CI: 0.69-0.87; p < 0.001), with an optimal cutoff value of 42.2 ng/mL. After multivariable adjustment, logistic regression revealed that ADAMTS4 remained an independent factor associated with the presence of PAH-CHD (OR = 1.189; 95% CI: 1.036-1.365; p = 0.014). Kaplan-Meier analysis revealed significantly shorter event-free survival in patients with ≥ 42.2 ng/mL ADAMTS4 than in those with lower levels (log-rank p = 0.046). After multivariable adjustment, Cox regression confirmed ADAMTS4 as an independent predictor of adverse clinical events (HR = 1.038; 95% CI: 1.007-1.071; p = 0.017).
Serum ADAMTS4 is elevated in patients with PAH-CHD and is correlated with disease severity and adverse outcomes. These findings support its utility as a noninvasive serum biomarker for diagnosis, risk stratification and prognostic assessment in PAH-CHD patients.
This study included patients with PAH-CHD, patients with CHD, and healthy controls. Serum ADAMTS4 levels were measured by ELISA. Correlations with clinical parameters were assessed using Spearman's rank correlation. The diagnostic efficacy was evaluated by ROC curve analysis. Univariate and multivariable logistic regression were used to identify independent risk factors associated with the presence of PAH-CHD. PAH-CHD patients were followed up for a median duration of 40.5 months, and Kaplan-Meier and Cox regression analyses were used to analyze prognosis.
Compared with those in CHD patients and healthy controls, serum ADAMTS4 levels were elevated in PAH-CHD patients. ADAMTS4 was positively correlated with NT-proBNP (r = 0.45, p = 0.002), CRP (r = 0.60, p < 0.001), and WHO functional class (r = 0.49, p < 0.001). ROC analysis demonstrated good discriminatory ability for differentiating PAH-CHD from CHD (AUC = 0.78; 95% CI: 0.69-0.87; p < 0.001), with an optimal cutoff value of 42.2 ng/mL. After multivariable adjustment, logistic regression revealed that ADAMTS4 remained an independent factor associated with the presence of PAH-CHD (OR = 1.189; 95% CI: 1.036-1.365; p = 0.014). Kaplan-Meier analysis revealed significantly shorter event-free survival in patients with ≥ 42.2 ng/mL ADAMTS4 than in those with lower levels (log-rank p = 0.046). After multivariable adjustment, Cox regression confirmed ADAMTS4 as an independent predictor of adverse clinical events (HR = 1.038; 95% CI: 1.007-1.071; p = 0.017).
Serum ADAMTS4 is elevated in patients with PAH-CHD and is correlated with disease severity and adverse outcomes. These findings support its utility as a noninvasive serum biomarker for diagnosis, risk stratification and prognostic assessment in PAH-CHD patients.
Authors
Xiao Xiao, Chen Chen, Meng Meng, Wang Wang, Cai Cai, Cao Cao, Zeng Zeng, Liang Liang, Yu Yu, Wang Wang, Nie Nie, Liu Liu, Liao Liao
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