NT-ProBNP and Mortality After Acute Exacerbation of COPD
NT-ProBNP and Mortality After Acute Exacerbation of COPD
99 patients were included. Mean age at inclusion was 71.5 years (standard deviation (SD) 9.0 years), and 47 (47%) were female. Spirometry measurement from the stable state was available in 88 patients. Mean FEV1 was 0.91 liter (SD 0.45 liter), and mean FEV1/FVC was 45.3% (SD 14.2%). Median NT-proBNP concentration at inclusion was 423.3 pg/mL, and the tertile limits were 264.4 and 909 pg/mL. 41 patients were readmitted during the inclusion period, adding to a total of 219 admissions. In 217 of these, we had NT-proBNP measured, with a median of 560.4 pg/mL. Among the patients with more than one NT-proBNP measurement, the median change (absolute value) from the previous measurement was 66% (IQR 41–150%). Three patients had two consecutive NT-proBNP measurements less than 5% apart, but none of these changed tertiles. The prevalence of categorical variables and the mean of continuous variables in each tertile of NT-proBNP at inclusion are reported in Table 1 for those variables associated with NT-proBNP (p<0.20). Among the variables not associated with NT-proBNP were: a history of coronary artery disease (27%), arterial hypertension (31%), smoking status (48% current smokers), chest pain on admission (10%), kidney function (mean creatinine 76 μg/L), P pulmonale (25%), right axis deviation (10%), atrial fibrillation (7%), prior MI (40%), and ischemia in ECG (27%). Median NT-proBNP concentrations (with interquartile range) among patients with 0, 1 and ≥2 admissions the past 12 months were 339 (183–1054), 679 (154–1438) and 421 (157–1389) pg/mL, respectively (p=0.826). The correlation between NT-proBNP and hs-cTnT was moderate (both logarithmically transformed, Pearson rho=0.34, p=0.0006).
During a median follow-up of 1.9 years, 57 (58%) patients died, with an overall mortality rate of 28.7 per 100 patient-years. NT-proBNP tertiles on inclusion were associated with increasing mortality rates, i.e. 8.6 (95% confidence interval 4.3–17), 35 (23–54) and 62 (43–91) per 100 patient-years, respectively (Figure 1, age-adjusted log-rank p-value<0.0001). When applying the cut-offs suggested by Abroug, the mortality rates were 19, 25 and 120 per 100 patient-years among patients with NT-proBNP <1000, 1000–2500 and ≥2500 pg/mL, respectively (age-adjusted log-rank p-value<0.0001).
(Enlarge Image)
Figure 1.
Mortality after acute exacerbation of COPD stratified by level of NT-proBNP. Based on 217 admissions and 57 mortalities in 99 patients.
Of the variables that were associated with NT-proBNP concentrations, history of diabetes and lung function failed to show any association with mortality and were therefore not included in further analyses. For the remaining covariables, stratified analyses of mortality through the tertiles of NT-proBNP were then performed (Table 2). Mantel-Haenszel tests showed no statistically significant effect modification of the association between NT-proBNP and mortality by any of the covariables listed in Table 2, and the following variables were included in the initial multivariable model: age, gender, BMI, history of heart failure, atrial fibrillation on admission, peripheral edema, cephalization of the lung veins, CRP, and hs-cTnT. Reduction of the model gave the final model in Table 3, showing increasing mortality with increasing levels of NT-proBNP (p =0.013 for trend). hs-cTnT, gender, peripheral edema, and cephalization of the lung veins were also independently associated with mortality. None of the interaction terms investigated proved statistically significant (p-values >0.05). Using the natural logarithm of the NT-proBNP concentration (lnBNP) as a continuous variable in the final model showed a hazard ratio of 1.5 (95% CI: 1.2–1.9, p=0.0005) per unit increase in lnBNP. By adhering to the model reduction described, BMI and CRP were eliminated from the model both when analyzed as continuous and dichotomized variables. Similarly, analyzing hs-cTnT continuously and categorized made no noteworthy change in the model. Patients with a history of heart failure had non-significantly higher NT-proBNP concentrations (median 1554 vs. 400 pg/mL, p=0.102), and when restricting the analysis to the 85 patients without history of heart failure, the associations with mortality remained practically unchanged (Table 3). At the index admission, patients with (n=35) and without (n=64) chest pain or ECG signs of acute ischemia had median NT-proBNP concentrations 655 (IQR 197–1311) and 345 (IQR 145–1312) pg/mL, respectively (p-value 0.219). When restricting the analysis to admissions without chest pain or ST-T changes, the association between cTnT and mortality increased markedly while the association between NT-proBNP and mortality was moderately attenuated and was no longer statically significant (Table 3).
None of the models violated the proportional hazards assumption.
Results
99 patients were included. Mean age at inclusion was 71.5 years (standard deviation (SD) 9.0 years), and 47 (47%) were female. Spirometry measurement from the stable state was available in 88 patients. Mean FEV1 was 0.91 liter (SD 0.45 liter), and mean FEV1/FVC was 45.3% (SD 14.2%). Median NT-proBNP concentration at inclusion was 423.3 pg/mL, and the tertile limits were 264.4 and 909 pg/mL. 41 patients were readmitted during the inclusion period, adding to a total of 219 admissions. In 217 of these, we had NT-proBNP measured, with a median of 560.4 pg/mL. Among the patients with more than one NT-proBNP measurement, the median change (absolute value) from the previous measurement was 66% (IQR 41–150%). Three patients had two consecutive NT-proBNP measurements less than 5% apart, but none of these changed tertiles. The prevalence of categorical variables and the mean of continuous variables in each tertile of NT-proBNP at inclusion are reported in Table 1 for those variables associated with NT-proBNP (p<0.20). Among the variables not associated with NT-proBNP were: a history of coronary artery disease (27%), arterial hypertension (31%), smoking status (48% current smokers), chest pain on admission (10%), kidney function (mean creatinine 76 μg/L), P pulmonale (25%), right axis deviation (10%), atrial fibrillation (7%), prior MI (40%), and ischemia in ECG (27%). Median NT-proBNP concentrations (with interquartile range) among patients with 0, 1 and ≥2 admissions the past 12 months were 339 (183–1054), 679 (154–1438) and 421 (157–1389) pg/mL, respectively (p=0.826). The correlation between NT-proBNP and hs-cTnT was moderate (both logarithmically transformed, Pearson rho=0.34, p=0.0006).
During a median follow-up of 1.9 years, 57 (58%) patients died, with an overall mortality rate of 28.7 per 100 patient-years. NT-proBNP tertiles on inclusion were associated with increasing mortality rates, i.e. 8.6 (95% confidence interval 4.3–17), 35 (23–54) and 62 (43–91) per 100 patient-years, respectively (Figure 1, age-adjusted log-rank p-value<0.0001). When applying the cut-offs suggested by Abroug, the mortality rates were 19, 25 and 120 per 100 patient-years among patients with NT-proBNP <1000, 1000–2500 and ≥2500 pg/mL, respectively (age-adjusted log-rank p-value<0.0001).
(Enlarge Image)
Figure 1.
Mortality after acute exacerbation of COPD stratified by level of NT-proBNP. Based on 217 admissions and 57 mortalities in 99 patients.
Of the variables that were associated with NT-proBNP concentrations, history of diabetes and lung function failed to show any association with mortality and were therefore not included in further analyses. For the remaining covariables, stratified analyses of mortality through the tertiles of NT-proBNP were then performed (Table 2). Mantel-Haenszel tests showed no statistically significant effect modification of the association between NT-proBNP and mortality by any of the covariables listed in Table 2, and the following variables were included in the initial multivariable model: age, gender, BMI, history of heart failure, atrial fibrillation on admission, peripheral edema, cephalization of the lung veins, CRP, and hs-cTnT. Reduction of the model gave the final model in Table 3, showing increasing mortality with increasing levels of NT-proBNP (p =0.013 for trend). hs-cTnT, gender, peripheral edema, and cephalization of the lung veins were also independently associated with mortality. None of the interaction terms investigated proved statistically significant (p-values >0.05). Using the natural logarithm of the NT-proBNP concentration (lnBNP) as a continuous variable in the final model showed a hazard ratio of 1.5 (95% CI: 1.2–1.9, p=0.0005) per unit increase in lnBNP. By adhering to the model reduction described, BMI and CRP were eliminated from the model both when analyzed as continuous and dichotomized variables. Similarly, analyzing hs-cTnT continuously and categorized made no noteworthy change in the model. Patients with a history of heart failure had non-significantly higher NT-proBNP concentrations (median 1554 vs. 400 pg/mL, p=0.102), and when restricting the analysis to the 85 patients without history of heart failure, the associations with mortality remained practically unchanged (Table 3). At the index admission, patients with (n=35) and without (n=64) chest pain or ECG signs of acute ischemia had median NT-proBNP concentrations 655 (IQR 197–1311) and 345 (IQR 145–1312) pg/mL, respectively (p-value 0.219). When restricting the analysis to admissions without chest pain or ST-T changes, the association between cTnT and mortality increased markedly while the association between NT-proBNP and mortality was moderately attenuated and was no longer statically significant (Table 3).
None of the models violated the proportional hazards assumption.