NT-proBNP independently predicts long term mortality after acute exacerbation of COPD – a prospective cohort study

Respiratory Research

Vidar Søyseth¹  Pål H Brekke¹  Tor-Arne Hagve³  Torbjørn Omland¹  Arne Didrik Høiseth² 

[1] Division of Medicine, Akershus University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway;Akershus University Hospital, 1478, Lørenskog, Norway;Unit of Medical Biochemistry, Division of Diagnostics and Technology, Akershus University Hospital and University of Oslo, Oslo, Norway

关键词: Mortality;    NT-proBNP;    Heart failure;    Chronic obstructive pulmonary disease;   

Others  :  796617
DOI  :  10.1186/1465-9921-13-97

 received in 2012-08-17, accepted in 2012-10-26,  发布年份 2012

【 摘 要 】

Background

Cardiovascular disease is prevalent and frequently unrecognized in patients with chronic obstructive pulmonary disease (COPD). NT-proBNP is an established risk factor in patients with heart failure. NT-proBNP may also be released from the right ventricle. Thus serum NT-proBNP may be elevated during acute exacerbations of COPD (AECOPD). The prognostic value of NT-proBNP in patients hospitalized with AECOPD is sparsely studied. Our objective was to test the hypothesis that NT-proBNP independently predicts long term mortality following AECOPD.

Methods

A prospective cohort study of 99 patients with 217 admissions with AECOPD. Clinical, electrocardiographic, radiological and biochemical data were collected at index and repeat admissions and analyzed in an extended survival analysis with time-dependent covariables.

Results

Median follow-up time was 1.9 years, and 57 patients died during follow-up. NT-proBNP tertile limits were 264.4 and 909 pg/mL, and NT-proBNP in tertiles 1 through 3 was associated with mortality rates of 8.6, 35 and 62 per 100 patient-years, respectively (age-adjusted log-rank p<0.0001). After adjustment for age, gender, peripheral edema, cephalization and cTnT in a multivariable survival model, the corresponding hazard ratios for dying were 2.4 (0.95-6.0) and 3.2 (1.3-8.1) (with 95% confidence intervals in parentheses, p-value for trend 0.013).

Conclusions

NT-proBNP is a strong and independent determinant of mortality after AECOPD.

【 授权许可】

   
2012 Høiseth et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Patel AR, Hurst JR: Extrapulmonary comorbidities in chronic obstructive pulmonary disease: state of the art. Expert review of respiratory medicine 2011, 5(5):647-662.
• [2]Sidney S, Sorel M, Quesenberry CP Jr, DeLuise C, Lanes S, Eisner MD: COPD and incident cardiovascular disease hospitalizations and mortality: Kaiser permanente medical care program. Chest 2005, 128(4):2068-2075.
• [3]Huiart L, Ernst P, Suissa S: Cardiovascular morbidity and mortality in COPD. Chest 2005, 128(4):2640-2646.
• [4]Curkendall SM, DeLuise C, Jones JK, Lanes S, Stang MR, Goehring E Jr, She D: Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. Ann Epidemiol 2006, 16(1):63-70.
• [5]Sin DD, Anthonisen NR, Soriano JB, Agusti AG: Mortality in COPD: role of comorbidities. Eur Respir J 2006, 28(6):1245-1257.
• [6]Feary JR, Rodrigues LC, Smith CJ, Hubbard RB, Gibson JE: Prevalence of major comorbidities in subjects with COPD and incidence of myocardial infarction and stroke: a comprehensive analysis using data from primary care. Thorax 2010, 65:956-962.
• [7]Brekke PH, Omland T, Smith P, Soyseth V: Underdiagnosis of myocardial infarction in C. Respir Med 2008, 102(9):1243-1247.
• [8]Buajordet I, Ebbesen J, Erikssen J, Brors O, Hilberg T: Fatal adverse drug events: the paradox of drug treatment. J Intern Med 2001, 250(4):327-341.
• [9]McCullough PA, Hollander JE, Nowak RM, Storrow AB, Duc P, Omland T, McCord J, Herrmann HC, Steg PG, Westheim A, et al.: Uncovering heart failure in patients with a history of pulmonary disease: rationale for the early use of B-type natriuretic peptide in the emergency department. Acad Emerg Med 2003, 10(3):198-204.
• [10]Rutten FH, Moons KG, Cramer MJ, Grobbee DE, Zuithoff NP, Lammers JW, Hoes AW: Recognising heart failure in elderly patients with stable chronic obstructive pulmonary disease in primary care: cross sectional diagnostic study. BMJ 2005, 331(7529):1379.
• [11]Brekke PH, Omland T, Holmedal SH, Smith P, Soyseth V: Determinants of cardiac troponin T elevation in COPD exacerbation - a cross-sectional study. BMC Pulm Med 2009, 9:35. BioMed Central Full Text
• [12]McAllister DA, Maclay JD, Mills NL, Leitch A, Reid P, Carruthers R, O'Connor J, McAlpine L, Chalmers G, Newby DE, et al.: Diagnosis of myocardial infarction following hospitalisation for exacerbation of COPD. Eur RespirJ 2012, 39(5):1097-1103.
• [13]Hoiseth AD, Omland T, Hagve TA, Brekke PH, Soyseth V: Determinants of high-sensitivity cardiac troponin T during acute exacerbation of chronic obstructive pulmonary disease: a prospective cohort study. BMC pulmonary medicine 2012, 12(1):22. BioMed Central Full Text
• [14]Hoiseth AD, Neukamm A, Karlsson BD, Omland T, Brekke PH, Soyseth V: Elevated high-sensitivity cardiac troponin T is associated with increased mortality after acute exacerbation of chronic obstructive pulmonary disease. Thorax 2011, 66(9):775-781.
• [15]Chang CL, Robinson SC, Mills GD, Sullivan GD, Karalus NC, McLachlan JD, Hancox RJ: Biochemical markers of cardiac dysfunction predict mortality in acute exacerbations of COPD. Thorax 2011.
• [16]Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Stromberg A, van Veldhuisen DJ, Atar D, Hoes AW, et al.: ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008, 29(19):2388-2442.
• [17]Medina AM, Marteles MS, Saiz EB, Martinez SS, Laiglesia FR, Rodriguez JA, Perez-Calvo JI: Prognostic utility of NT-proBNP in acute exacerbations of chronic pulmonary diseases. Eur J Intern Med 2011, 22(2):167-171.
• [18]Stolz D, Breidthardt T, Christ-Crain M, Bingisser R, Miedinger D, Leuppi J, Mueller B, Tamm M, Mueller C: Use of B-type natriuretic peptide in the risk stratification of acute exacerbations of COPD. Chest 2008, 133(5):1088-1094.
• [19]Leuchte HH, Baumgartner RA, Nounou ME, Vogeser M, Neurohr C, Trautnitz M, Behr J: Brain natriuretic peptide is a prognostic parameter in chronic lung disease. Am J Respir Crit Care Med 2006, 173(7):744-750.
• [20]van Gestel YR, Goei D, Hoeks SE, Sin DD, Flu WJ, Stam H, Mertens FW, Bax JJ, van Domburg RT, Poldermans D: Predictive value of NT-proBNP in vascular surgery patients with COPD and normal left ventricular systolic function. Copd 2010, 7(1):70-75.
• [21]Gale CP, White JE, Hunter A, Owen J, Allen J, Watson J, Holbrook I, Durham NP, Pye MP: Predicting mortality and hospital admission in patients with COPD: significance of NT pro-BNP, clinical and echocardiographic assessment. J Cardiovasc Med (Hagerstown) 2011, 12(9):613-618.
• [22]Stamm JA, Belloli EA, Zhang Y, Bon J, Sciurba FC, Gladwin MT: Elevated N-terminal pro-brain natriuretic peptide is associated with mortality in tobacco smokers independent of airflow obstruction. PLoS One 2011, 6(11):e27416.
• [23]Inoue Y, Kawayama T, Iwanaga T, Aizawa H: High plasma brain natriuretic peptide levels in stable COPD without pulmonary hypertension or cor pulmonale. Intern Med 2009, 48(7):503-512.
• [24]Gemici G, Erdim R, Celiker A, Tokay S, Ones T, Inanir S, Oktay A: B-type natriuretic peptide levels in patients with COPD and normal right ventricular function. Adv Ther 2008, 25(7):674-680.
• [25]Martins CS, Rodrigues MJ, Miranda VP, Nunes JP: Prognostic value of cardiac troponin I in patients with COPD acute exacerbation. Neth J Med 2009, 67(10):341-349.
• [26]Rautaharju PM, Warren JW, Jain U, Wolf HK, Nielsen CL: Cardiac infarction injury score: an electrocardiographic coding scheme for ischemic heart disease. Circulation 1981, 64(2):249-256.
• [27]Hurst JR, Vestbo J, Anzueto A, Locantore N, Mullerova H, Tal-Singer R, Miller B, Lomas DA, Agusti A, Macnee W, et al.: Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 2010, 363(12):1128-1138.
• [28]Mantel N: Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer chemotherapy reports Part 1 1966, 50(3):163-170.
• [29]Kleinbaum DG, Klein M: Survival Analysis. A Self-Learning Text. New York: Springer; 2005.
• [30]Abroug F, Ouanes-Besbes L, Nciri N, Sellami N, Addad F, Hamda KB, Amor AB, Najjar MF, Knani J: Association of left-heart dysfunction with severe exacerbation of chronic obstructive pulmonary disease: diagnostic performance of cardiac biomarkers. Am J Respir Crit Care Med 2006, 174(9):990-996.
• [31]Omland T, Hagve TA: Natriuretic peptides: physiologic and analytic considerations. Heart Fail Clin 2009, 5(4):471-487.
• [32]Hall C: NT-ProBNP: the mechanism behind the marker. J Card Fail 2005, 11(5 Suppl):S81-83.
• [33]Arjamaa O, Nikinmaa M: Hypoxia regulates the natriuretic peptide system. Int J Physiol Pathophysiol Pharmacol 2011, 3(3):191-201.
• [34]Renzetti AD Jr, McClement JH, Litt BD: The Veterans Administration cooperative study of pulmonary function. 3. Mortality in relation to respiratory function in chronic obstructive pulmonary disease. Am J Med 1966, 41(1):115-129.
• [35]Mascarenhas J, Azevedo A, Bettencourt P: Coexisting chronic obstructive pulmonary disease and heart failure: implications for treatment, course and mortality. Curr Opin Pulm Med 2010, 16(2):106-111.
• [36]Gariani K, Delabays A, Perneger TV, Agoritsas T: Use of brain natriuretic peptide to detect previously unknown left ventricular dysfunction in patients with acute exacerbation of chronic obstructive pulmonary disease. Swiss medical weekly 2011, 141:w13298.
• [37]Baggish AL, Siebert U, Lainchbury JG, Cameron R, Anwaruddin S, Chen A, Krauser DG, Tung R, Brown DF, Richards AM, et al.: A validated clinical and biochemical score for the diagnosis of acute heart failure: the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Acute Heart Failure Score. Am Hear J 2006, 151(1):48-54.
• [38]Ouanes I, Jalloul F, Ayed S, Dachraoui F, Ouanes-Besbes L, Fekih Hassen M, Elatrous S, Abroug F: N-terminal proB-type natriuretic peptide levels aid the diagnosis of left ventricular dysfunction in patients with severe acute exacerbations of chronic obstructive pulmonary disease and renal dysfunction. Respirology 2012, 17(4):660-666.
• [39]White HD: Pathobiology of troponin elevations: do elevations occur with myocardial ischemia as well as necrosis? J Am Coll Cardiol 2011, 57(24):2406-2408.
• [40]Latini R, Masson S, Anand IS, Missov E, Carlson M, Vago T, Angelici L, Barlera S, Parrinello G, Maggioni AP, et al.: Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure. Circulation 2007, 116(11):1242-1249.
• [41]Omland T, de Lemos JA, Sabatine MS, Christophi CA, Rice MM, Jablonski KA, Tjora S, Domanski MJ, Gersh BJ, Rouleau JL, et al.: A sensitive cardiac troponin T assay in stable coronary artery disease. N Engl J Med 2009, 361(26):2538-2547.
• [42]de Lemos JA, Drazner MH, Omland T, Ayers CR, Khera A, Rohatgi A, Hashim I, Berry JD, Das SR, Morrow DA, et al.: Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA : the journal of the American Medical Association 2010, 304(22):2503-2512.
• [43]deFilippi CR, de Lemos JA, Christenson RH, Gottdiener JS, Kop WJ, Zhan M, Seliger SL: Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults. JAMA: the journal of the American Medical Association 2010, 304(22):2494-2502.
• [44]Seemungal TA, Hurst JR, Wedzicha JA: Exacerbation rate, health status and mortality in COPD–a review of potential interventions. Int J Chron Obstruct Pulmon Dis 2009, 4:203-223.
• [45]Hosmer DW, Lemeshow S, May S: Applied survival analysis: regression modeling of time-to-event data. 2nd edition. Hoboken, N.J.: Wiley-Interscience; 2008.
• [46]Brekke PH, Omland T, Holmedal SH, Smith P, Soyseth V: Troponin T elevation and long-term mortality after chronic obstructive pulmonary disease exacerbation. Eur Res pir J 2008, 31(3):563-570.
• [47]Fruchter O, Yigla M: Cardiac Troponin-I predicts long-term mortality in chronic obstructive pulmonary disease. COPD: Journal of Chronic Obstructive Pulmonary Disease 2009, 6(3):155-161.