A mathematical model using routine serum biomarkers for predicting of pulmonary hypertension in patients with left heart disease

Abstract Background: Pulmonary hypertension (PH) insidiously occurs in patients with left heart disease (LHD), but its diagnosis is often delayed due to the lack of specific symptoms. This observational study aimed to identify a biomarker panel for the noninvasive detection of PH in LHD patients. Methods: Patients with LHD were consecutively recruited and analyzed for correlations between the pulmonary artery systolic pressure (PASP) and levels of routine serum biomarkers, and 100 age-matched subjects served as healthy controls. The diagnostic accuracy of biomarkers was assessed by receiver operating characteristic (ROC) curve analysis. Forward stepwise binary logistic regression was performed to determine the optimal combination of biomarkers for predicting PH.Results: A total of 426 LHD patients were divided into the LHD group (n=216, PASP <35 mmHg) and PH-LHD group (n=210, PASP ≥35 mmHg). The ranges of routinely examined biomarkers were significantly different between the two groups. The levels of biomarkers, including brain natriuretic peptide (BNP), total bilirubin (TB), direct bilirubin (DB), indirect bilirubin (IB), red cell distribution width (RDW), uric acid (UA), and cystatin c (Cys-C), were higher, while high-density lipoprotein (HDL) levels were lower in the PH-LHD group than in the LHD and healthy control groups. Positive correlations were found between the PASP and levels of BNP, Cys-C, UA, bilirubin, and RDW, while a negative correlation was found between the PASP and HDL level. A mini program based on the formula “P=1/(1+exp(6,314-0.898×[BNP]/1000-0.146×[DB]-0.318×[RDW]))” was developed using forward stepwise binary regression for calculating the probability of PH. The combination of BNP, DB, and RDW (cutoff, 0.256) demonstrated a better predictive value than did individual biomarkers, with a sensitivity of 0.822 and specificity of 0.783 in the prediction of PH in LHD patients. Conclusion: The combination of BNP, bilirubin, and RDW shows promise as a simple method for screening LHD patients for PH.