Optimized combination of circulating biomarkers as predictors of prognosis in AECOPD patients complicated with Heart Failure

Abstract

Background: Systematic inflammation, nutritional status, and cardiovascular function have been associated with the outcomes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients with heart failure (HF). However, the value of their relevant biomarkers in predicting mortality has not been well defined yet. We aimed to investigate the prognostic value of circulating biomarkers including C-reaction protein (CRP)/albumin (ALB), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and N-terminal pro-brain natriuretic peptide (NT-proBNP) for AECOPD patients with HF. Methods: A retrospective study was carried out in the Second Clinical College of Jinan University from January 1, 2013 to January 31, 2019. A total of 146 cases of AECOPD complicated with HF were enrolled and classified into survivor group (n=94) and non-survivor group (n=52). The baseline characteristics, CRP/ALB ratio, NLR, PLR, serum levels of NT-proBNP, and other indicators were collected. The predictors for prognosis were analyzed by multivariate logistic regression, and the ability to predict 28-day mortality was evaluated by receiver operating characteristics curve (ROC) and the area under the curve (AUC). Results: The patients in non-survivors had significantly higher levels of CRP, CRP/ALB, NLR, PCT and NT-proBNP, but lower ALB levels compared to the survivors [111.7 (56.9, 186.5) VS. 43.8 (10.3, 96.1) mg/L, 4.6 (2.0, 8.0) VS. 1.4 (0.3, 3.4), 22.2 (11.1, 40.1) VS. 12.0 (6.2, 24.8), 2.6 (0.2, 10.3) VS. 0.08 (0.1, 0.5) ng/ml, 17912.5 (9344.0, 34344.5) VS. 9809.0 (4415.9, 16387.2) ng/ml, 25.8 (23.2, 30.5) VS. 30.7 (27.9, 34.1) g/L; P < 0.001, <0.001, 0.001, <0.001, <0.001, and < 0.001, respectively]. No significant difference in PLR was found between the two groups ( P =0.413). The logistic analysis revealed that CRP/ALB (OR=1.303, 95%CI: 1.145-1.483, P <0.001), NT-proBNP (OR=1.041, 95%CI: 1.010-1.073, P =0.009) and NLR (OR=1.010, 95%CI: 0.999-1.022, P <0.001) are independent risk factors for predicting the 28-day mortality. The AUC of the ROC curves were 0.768, 0.767, 0.757, 0.723, 0.716, and 0.668 for CRP/ALB, PCT, CRP, NT-proBNP, ALB, and NLR, respectively. The combination of CRP/ALB, NLR and NT-proBNP as biomarkers was shown to have better accuracy for predicting prognosis (AUC=0.830, 95%CI: 0.761-0.899, P <0.001), with a higher specificity of 80.8% and specificity of 77.7% as compared with each single biomarkers. Conclusions: High levels of NLR, CRP/ALB and NT-proBNP may be clinical usefully predictors for death in AECOPD patients with HF. Combination of NLR with CRP/ALB and NT-proBNP can provide a higher accuracy for predicting 28-day mortality in these patients.

A Comprehensive Systematic Review and Meta-Analysis of the Association between the Neutrophil-to-Lymphocyte Ratio and Adverse Outcomes in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

“…Of them, 926 were excluded because they were either duplicates or irrelevant. Following a full-text review of the remaining 18 articles, a further 3 were excluded because they did not fulfill the inclusion criteria, leaving 15 articles for final analysis ( Figure 1 and Table 1 ) [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. In all studies, the NLR was assessed within the first 24–48 h of admission.…”

“…Fifteen studies (seventeen patient groups) of 10,038 AECOPD patients (57% males, mean age 74 years) reported associations between the NLR and adverse outcomes, expressed as ORs by multivariate logistic regression analysis. The adverse outcomes studied included mortality (nine studies) [ 33 , 34 , 35 , 36 , 37 , 38 , 40 , 43 , 45 ], transfer to ICU (one study) [ 36 ], length of hospital stay (one study) [ 46 ], invasive mechanical ventilation (IMV) (one study) [ 20 ], non-invasive mechanical ventilation failure (NIMVF) (one study) [ 44 ], pulmonary hypertension (one study) [ 39 ], and composite endpoints (two studies: ICU admission or death; one study: ICU admission, IMV, or death) [ 32 , 41 , 42 ]. Seven studies investigated in-hospital mortality [ 32 , 34 , 35 , 38 , 40 , 41 , 42 ], three 28-day mortality [ 36 , 43 , 45 ], and two 90-day mortality [ 33 , 37 ].…”

“…The adverse outcomes studied included mortality (nine studies) [ 33 , 34 , 35 , 36 , 37 , 38 , 40 , 43 , 45 ], transfer to ICU (one study) [ 36 ], length of hospital stay (one study) [ 46 ], invasive mechanical ventilation (IMV) (one study) [ 20 ], non-invasive mechanical ventilation failure (NIMVF) (one study) [ 44 ], pulmonary hypertension (one study) [ 39 ], and composite endpoints (two studies: ICU admission or death; one study: ICU admission, IMV, or death) [ 32 , 41 , 42 ]. Seven studies investigated in-hospital mortality [ 32 , 34 , 35 , 38 , 40 , 41 , 42 ], three 28-day mortality [ 36 , 43 , 45 ], and two 90-day mortality [ 33 , 37 ]. Eight studies were conducted in China [ 36 , 37 , 39 , 42 , 43 , 44 , 45 , 46 ], two in Iran [ 34 , 40 ], two in Turkey [ 35 , 38 ], one in Egypt [ 32 ], one in Australia [ 33 ], and one in Colombia [ 41 ] ( Table 1 ).…”

“…Seven studies investigated in-hospital mortality [ 32 , 34 , 35 , 38 , 40 , 41 , 42 ], three 28-day mortality [ 36 , 43 , 45 ], and two 90-day mortality [ 33 , 37 ]. Eight studies were conducted in China [ 36 , 37 , 39 , 42 , 43 , 44 , 45 , 46 ], two in Iran [ 34 , 40 ], two in Turkey [ 35 , 38 ], one in Egypt [ 32 ], one in Australia [ 33 ], and one in Colombia [ 41 ] ( Table 1 ).…”

Prediction of readmission in patients with acute exacerbation of chronic obstructive pulmonary disease within one year after treatment and discharge

“…Herein, patients with higher CAT scores were associated with a higher risk of readmission within one year. This maybe because higher CAT scores were correlated with higher concentrations of serum C-reactive protein and plasma fibrinogen, demonstrating that systemic inflammation were more serious in patients with higher CAT scores [ 31 ]. For AECOPD patients with high CAT score, timely intervention should be provided and after discharge, follow-up should be conducted regularly to prevent the occurrence of readmission.…”