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Systemic Inflammation Induced by Exacerbation of COPD Or Pneumonia in Patients with COPD Induces Cardiac Troponin Elevation

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Systemic Inflammation Induced by Exacerbation of COPD Or Pneumonia in Patients with COPD Induces Cardiac Troponin Elevation BMJ Open Resp Res: first published as 10.1136/bmjresp-2021-000997 on 27 August 2021. Downloaded from Chronic obstructive pulmonary disease Systemic inflammation induced by exacerbation of COPD or pneumonia in patients with COPD induces cardiac troponin elevation Vidar Søyseth,1,2 Natalia Kononova,3,4 Anke Neukamm,5 Nils Henrik Holmedahl,6 Tor- Arne Hagve,1 Torbjorn Omland,2,7 Gunnar Einvik3,4 To cite: Søyseth V, Kononova N, ABSTRACT Key messages Neukamm A, et al. Systemic Background Troponin is a biomarker of myocardial inflammation induced by injury. In chronic obstructive pulmonary disease (COPD), Cardiac troponin increases in chronic obstructive exacerbation of COPD or troponin is an important determinant of mortality after ► pulmonary disease (COPD) exacerbation. pneumonia in patients with acute exacerbation. Whether acute exacerbation of COPD COPD induces cardiac troponin Cardiac troponin is increased in exacerbation and (AECOPD) causes troponin elevation is not known. Here, ► elevation. BMJ Open Resp Res pneumonia in COPD. This increase is mediated by we investigated whether troponin is increased in AECOPD 2021;8:e000997. doi:10.1136/ systemic inflammation that accompanies exacerba- bmjresp-2021-000997 compared to stable COPD. Methods We included 320 patients with COPD in the tion and pneumonia in COPD. ► Additional supplemental stable state and 63 random individuals from Akershus ► Airways inflammation triggers a systemic inflamma- material is published online University hospital’s catchment area. All participants tion that damages the heart muscles. only. To view, please visit the were ≥40 years old (mean 65·1 years, SD 7·6) and journal online (http:// dx. doi. 176 (46%) were females. The geometric mean of high- org/ 10. 1136/ bmjresp- 2021- copyright. sensitivity cardiac troponin T (hs- cTnT) was 6·9 ng/L comorbidities that may represent major 000997). (geometric- SD 2·6). They were followed regarding hospital health problems for patients. In particular, admission for the subsequent 5 years. Received 28 May 2021 cardiovascular diseases are common and asso- Results During the 5- year follow- up, we noted 474 Accepted 19 August 2021 ciated with increased mortality in patients with hospitalisations: Totally, 150 and 80 admissions were due COPD.4–7 Previous studies have shown that a to AECOPD or pneumonia, respectively. The geometric circulatory marker of myocardial damage, mean ratio with geometric SE (GSE) between cTnT at cardiac troponin (cTn), is an independent admission and stable state in AECOPD and pneumonia was http://bmjopenrespres.bmj.com/ 1·27 (GSE=1.11, p=0·023) and 1·28 (GSE=1.14, p=0·054), prognostic marker of mortality in the general © Author(s) (or their respectively. After inclusion of blood leucocyte count and C population, in patients with stable COPD, employer(s)) 2021. Re- use 8–10 permitted under CC BY- NC. No reactive protein at hospitalisation, these ratios attenuated and after AECOPD. The level of cTn has commercial re- use. See rights to zero. However, we estimated an indirect of AECOPD and been shown to be inversely related to COPD and permissions. Published by pneumonia on the ratio between hs- cTnT at admission and severity as assessed by spirometry in the stable BMJ. the stable state to 1·16 (p=0·022) and 1·22 (p=0·008), 8 10–14 1 state. Moreover, the level of cTn has been Medical Division, Akershus representing 91% (95% CI 82% to 100%) and 95% (95% reported to be higher in patients hospitalised University Hospital, CI 83% to 100%) of the total effects, respectively. for AECOPD than in patients with COPD Lorenskog, Norway Conclusion AECOPD and pneumonia in patients 2 15 16 Campus Ahus, University with COPD is associated with higher cTnT levels. in the stable state. However, prospective of Oslo Faculty of Medicine, This association appears to be mediated by systemic studies that examine the trajectory of cTn Lorenskog, Norway on September 25, 2021 by guest. Protected 3 inflammation. during the course of COPD are lacking, and Institute for Clinical Medicine, whether myocardial damage, as indicated by University of Oslo, Oslo, Norway cTn, progresses during an exacerbated state 4Division of Medicine, of COPD has not been determined. Further- Akerhus University Hospital, INTRODUCTION more, the mechanisms that may contribute to Lørenskog, Norway 5 Chronic obstructive pulmonary disease elevations in cTn have not been established. Department of Cardiology, (COPD) is characterised by an irreversible We conducted a longitudinal study of cTn Akerhus University Hospital, Lørenskog, Norway limitation of airflow that is usually progres- in patients with COPD and healthy individ- 1 6Glittreklinikken, Hakadal, sive. A large proportion of patients expe- uals for 5 years. As our laboratory uses the Norway rience periods with acute exacerbation of T- isomere of cTn, we chose T-isomere of cTn 7 Lorenskog, Norway COPD symptoms (AECOPD) frequently trig- as our outcome parameter. Correspondence to gered by airway infections and characterised The primary aim of the present study was Dr Vidar Søyseth; by local airway and/or systemic inflamma- to test the hypothesis that the cTnT level 2 3 vidar. soyseth@ medisin.uio. no tion. COPD is also accompanied by several increases during incident severe AECOPD Søyseth V, et al. BMJ Open Resp Res 2021;8:e000997. doi:10.1136/bmjresp-2021-000997 1 BMJ Open Resp Res: first published as 10.1136/bmjresp-2021-000997 on 27 August 2021. Downloaded from Open access compared with stable COPD. We also aimed to assess the Statistical analysis effect of other hospitalisations on the cTnT level and Statistical analyses were performed in four levels. In the to elucidate possible mechanism(s) for any increase in first level, we compared the baseline values of relevant cTnT. variables in participants with incident hospitalisations to those of participants who were not hospitalised during the follow-up. Variables that were associated with hospi- MATERIAL AND METHODS talisation with a corresponding p<0.2 were retained for Study population and design further analysis in addition to established determinants of The study was conducted at Akershus University Hospital cTnT, such as gender, arterial oxygen tension and creati- and Glittre Rehabilitation Hospital. The population nine. Next, in the second level, we performed a multivar- consisted of five cohorts: (1) candidates for long-term iable linear regression analysis of the baseline data with oxygen therapy (LTOT), (2) patients with COPD partic- hs- cTnT as the dependent variable using ordinary least ipating in the rehabilitation course at the hospital’s square regression. In this analysis, we log- transformed outpatient clinic, (3) institutional COPD rehabilitation hs-cTnT at inclusion (ln_ctnt0) because hs-cTnT was patients, (4) patients with COPD referred to the hospi- highly skewed to the right (online supplemental figure tal’s outpatient clinic and (5) a presumably healthy 1). Selected covariates were included using forward reference group.17–19 All patients were in a stable state at selection procedure. These covariates were added to the inclusion, and none had AECOPD in the 6 weeks prior to model, ordered by increasing numbers of missing values. inclusion. The reference group was selected by random In the final analysis of the baseline data, we invoked a sampling from the general population in the hospital’s model using multiple imputation.21 recruitment area. Seven of these 62 participants (11%) In the third level, we analysed the association between had irreversible airflow limitation, but none of them had the level of hs- cTnT and the main diagnosis at each their COPD diagnosed by a doctor.17 hospitalisation. The diagnoses were categorised into The LTOT candidates and the outpatient rehabil- nine groups that were all inclusive and mutually exclu- itation group were re- examined in the stable state 3 sive. However, each participant could have several hospi- and 6 months after inclusion as a part of the routine talisations and different diagnoses during the follow-up. programme, respectively. All participants were followed In these analyses, we invoked a multivariable model using regarding acute hospitalisation until 5 years after inclu- log- transformed hs- cTnT (ln_ctnt) at follow- up as the copyright. sion. The main diagnosis at discharge was classified using outcome variable and diagnosis group at hospitalisation, the International Classification of Disease version 10. We baseline covariates (including baseline hs-cTnT) and included all diagnoses in order to compare changes in routine clinical data during follow-up as the explanatory troponin between stable state and any cause of hospital- variables. isation. All participants provided written consent. In the fourth level, we investigated whether the rela- tionship between hs- cTnT and diagnosis was mediated in the longitudinal analyses by any of the following clin- http://bmjopenrespres.bmj.com/ Measurements ical variables at hospitalisation: blood leucocytes, serum As our laboratory uses the T- isomere of cTn we chose CRP, arterial oxygen- tension, serum creatinine or heart T- isomere of cTn as our outcome parameter. High- rate. For details, see online supplemental figure 2. We sensitivity (hs)- cTnT at baseline was measured in venous performed these analyses using a multivariable mixed serum samples stored at −80°C using a cobas e 411 model with multiple imputations for missing values.21 If immuno- analyser (Roche Diagnostics). The lower limit the model did not converge, mixed
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