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Raised troponin in COPD: clinical implications and possible mechanisms
  1. Ian S Stone1,2,
  2. Steffen E Petersen2,
  3. Neil C Barnes1
  1. 1Department of Respiratory Medicine, The London Chest Hospital, Barts Health NHS Trust, London, UK
  2. 2Centre for Advanced Cardiovascular Imaging, William Harvey Research Institute, NIHR Cardiovascular Biomedical Research Unit at Barts, The London Chest Hospital, London, UK
  1. Correspondence to Professor Neil C Barnes, Department of Respiratory Medicine, The London Chest Hospital, Barts Health NHS Trust, London E29JX, UK; neil.barnes{at}

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Chronic obstructive pulmonary disease (COPD) is predicted to become the sixth leading cause of disability and the third most common cause of death by 2020. Reduced forced expiratory volume in 1 s, a hallmark of COPD, is ranked second to smoking and above blood pressure and cholesterol as a predictor of all-cause and cardiovascular mortality. Even in mild to moderate COPD patients succumb to cardiovascular disease rather than respiratory failure although the causative mechanism is unknown.1

Over the past decade it has become apparent that during an exacerbation of COPD, classically defined by the combination of worsening dyspnoea with increased sputum volume and/or purulence, there is subclinical myocardial damage typified by an increase in troponin level and other biomarkers which predict mortality.2–4 The key question relates to the mechanisms behind this rise, since without an understanding of the mechanisms the ability to identify an appropriate intervention that will improve outcome is hindered.

Søyseth and colleagues5 seek to further the understanding of this relationship. Specifically they addressed the important issue as to whether the raised levels of troponin found at exacerbation are chronically raised or are a phenomenon related to the exacerbation itself, and found that the troponin levels were significantly higher in the exacerbator group compared with stable patients. The study compared those patients admitted to hospital for an exacerbation with those from a pulmonary rehabilitation clinic. It is however questionable whether these groups really represent similar populations in the stable and exacerbating state, with significantly different modes of referral, smoking histories and spirometry readings when measured during periods of stability. In an ideal world these exacerbating COPD patients would be compared against their own baseline measures, although this is clearly not always possible.

Various theories have been proposed to explain the rise in troponin during exacerbation, some of which have been addressed in the robust multiple linear regression model contained within table 3 in Soyseth et al5:

  1. Hypoxia

  2. Underlying coronary artery disease (CAD),

  3. Systemic inflammation

  4. The influence of left ventricular hypertrophy (LVH)

It has been argued the rise in troponin may be a consequence of hypoxic pulmonary vasoconstriction which causes increased afterload, right ventricular dysfunction, worsening ventilation-perfusion mismatch and resultant tachycardia,3 in a similar manner to pulmonary hypertension or an acute pulmonary embolus. Although no associations were found here with hypoxia the comments in the discussion regarding the use of supplementary oxygen en route to hospital in this and other papers are definitely valid and as a consequence the real contribution of hypoxia will always be difficult to establish.

It has also been postulated that the rise may be caused by stress to a circulation with pre-existing CAD, although no association was found here. Given the tachycardia associated with COPD exacerbations and the high prevalence of CAD in this population, a lower threshold for the investigation of CAD and a more aggressive approach to its management is warranted. Observational evidence that beta-blockers and statins have a protective effect during acute exacerbations of COPD goes some way to support this suggestion,6 ,7 however it is likely that other mechanisms also play a role since troponin rises in COPD exacerbations occur in the absence of CAD on invasive angiography.8

Other theories include increases in systemic inflammation caused by COPD contributing to cardiac risk. The authors found no association with leucocytes or C-reactive protein (CRP) in the regression model. It is unsurprising raised inflammatory markers were identified during an exacerbation given the likelihood of concomitant infection. The complex nature of inflammation within COPD has recently been elucidated, at least to some extent, as a result of data from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints)9 trial where it has been shown that in patients at risk of exacerbation, systemic inflammation defined according to a specific combination of several different inflammatory biomarkers persists during periods of stability. Given the size of the cohorts in this study it is therefore perhaps unsurprising that the limited number of biomarkers employed were unable to find an association with inflammation. Furthermore, the cross-sectional nature of this study requires adjustment for confounders and details have not been provided regarding concomitant medications, for example the use of statins, which are known to modulate inflammation. In other studies platelet dysfunction has been shown to exist in stable COPD which is worsened by exacerbations.10 This example may represent a genuine, affordable, therapeutic target and further research into the role for Aspirin or other antiplatelets during COPD exacerbations is warranted.

LVH was also considered as a contributory factor in stable and chronic disease. Limited information can be extrapolated from this study due to the few patients in this study with evidence of LVH on ECG combined with the low sensitivity (10–52%) of the ECG in identifying LVH using the traditional Sokolov criteria.11 The authors of this editorial agree with the notion that future studies should focus on more advanced imaging techniques such as cardiac magnetic resonance in order to better understand this association.

A number of alternative explanations exist for the raised troponin levels during COPD exacerbations:

Pulse wave velocity is an independent determinant of coronary flow reserve, is raised in COPD and further increases during excacerbations.13 ,14 Possible interventions to reduce pulse wave velocity during periods of stability, which may in turn limit the effects of incremental increases during exacerbations, include pulmonary rehabilitation and treatment of systemic inflammation through the use of inhaled corticosteroids,15 ,16 although at present no longitudinal outcome data exists.

In stable COPD lung hyperinflation is caused by the loss of elastic recoil in the lung combined with early airway collapse resulting in expiratory flow limitation and ‘air trapping’. This air trapping exerts its effects on the cardiovascular system via mechanical and neurohumoral mechanisms1 and is worsened during an exacerbation due to increased ventilatory demands, termed ‘dynamic lung hyperinflation’. It is quite feasible that the increased oxygen cost of breathing and increased LV afterload associated with dynamic lung hyperinflation further contributes to myocardial release of troponin, although its contribution to serum troponin levels has not been studied in the stable or exacerbating state. Furthermore, there is a scarcity of data on the ability of pharmacotherapies to reverse cardiac dysfunction through the treatment of lung hyperinflation in COPD, which warrants further attention.

The mechanisms surrounding increased cardiovascular morbidity and mortality in COPD are an important issue for cardiologists and respiratory physicians alike. Søyseth and colleagues have highlighted the need for further studies to better understand one of the key components of this association, in the hope of improving prognosis through targeted patient-centred therapeutic interventions.


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  • Contributors ISS and NCB were responsible for the conception of the manuscript. ISS was responsible for writing and editing of the manuscript while NCB and SEP contributed through the critical appraisal of the manuscript. All authors approved the final draft for publication (NCB is guarantor).

  • Funding ISS is an employee of Barts Health NHS trust who has received a research grant from GlaxoSmithKline. NCB is directly funded by Barts Health NHS trust. SEP was directly funded by the National Institute for Health Research Cardiovascular Biomedical Research Unit at Barts.

  • Competing interests None.

  • Provenance and peer review Commissioned; internally peer reviewed.

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