Cardiac biomarkers predict outcome after hospitalisation for an acute exacerbation of chronic obstructive pulmonary disease

doi:10.1016/j.ijcard.2012.05.044

International Journal of Cardiology

Volume 161, Issue 3, 29 November 2012, Pages 156-159

https://doi.org/10.1016/j.ijcard.2012.05.044 Get rights and content

Abstract

Purpose

In chronic obstructive pulmonary disease (COPD), cardiovascular system is involved but less is known about role of specific cardiac biomarkers. We aimed to investigate associations between N-terminal pro B-type natriuretic peptide (NT-proBNP) and troponin T during hospitalisation with 6-month outcome.

Methods

This was a prospective study conducted in consecutive patients hospitalized for an acute exacerbation of COPD. On admission, and at discharge, NT-proBNP and troponin T were measured, and echocardiography was performed. Hospitalisations and mortality were recorded for 6 months after discharge.

Results

We included 127 patients (70 ± 10 years, 70% men, GOLD III/IV 87%). Left ventricular dysfunction was detected in 70 (55%) patients and diastolic dysfunction was the most common type (53 patients–42%). NT-proBNP and troponin T were elevated on admission in 60% and 36%, and at discharge in 28% and 19% of patients. During follow-up, 53 (42%) patients were hospitalized and 17 (13%) patients died. In Kaplan Meier analysis of survival curves, NT-proBNP on admission distinguished between deceased and surviving patients (p = 0.011) whilst troponin T at discharge separated hospitalized and non-hospitalized patients (p = 0.017). The adjusted Cox proportional hazard model confirmed these findings: discharge troponin T predicted hospitalisations (hazard ratio 2.89, 95% confidence interval 1.13–7.36) and admission NT-proBNP predicted mortality (hazard ratio 4.20, 95% confidence interval 1.07–14.01).

Conclusions

Elevated NT-proBNP at discharge and troponin T on admission predict outcome in patients hospitalized for an acute exacerbation of COPD.

Introduction

Clinical management of chronic obstructive pulmonary disease (COPD) focuses primarily on symptom control and prevention of exacerbations. As a result repeat hospitalisation should be regarded as a relevant end-point in patients with COPD [1]. This is particularly true in hospitalized patients as about 30–50% will be rehospitalized within 6 months after discharge [1], [2]. The identification of risk predictors others than those previously reported would therefore be both of considerable importance in planning strategies to reduce disease burden and have significant financial implications. With growing awareness of and scientific interest in comorbidities associated with COPD, cardiac biomarkers are an attractive option to investigate [3], [4].

Several studies have demonstrated an association between cardiac laboratory biomarkers and survival in patients managed for an acute exacerbation of COPD [5], [6], [7], [8], [9], [10], [11], [12]. Much more limited information is available, however, for the prediction of rehospitalisations. There remains some uncertainty about the applicability and clinical implications of the published results as some studies were retrospective, did not control for left ventricular function, and have focused on all-cause mortality. In addition, most of the studies analysed cardiac biomarkers only once during deterioration and the timing of the blood sampling was different across the reported studies.

We have thus designed this study to address the relationship between cardiac biomarkers and short-term outcome in patients hospitalized for acute exacerbation of COPD. Our specific aim was to investigate whether different time-points of biomarker evaluation affects short-term patient outcome.

Section snippets

Study design and patients

We conducted a prospective observational study in patients admitted for an acute exacerbation of COPD. Study design, patient inclusion and exclusion criteria were as detailed previously [13]. For this analysis, all admitted patients to our hospital were assessed for study eligibility. Patients with a clinical diagnosis of acute exacerbation of COPD on admission were approached for study participation if they were in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages II–IV [1]

Results

Table 1 summarizes the baseline characteristics of the final sample of 127 patients. They were predominantly males with advanced COPD, a significant smoking history, with various comorbidities, and receiving COPD specific therapy according to guidelines. Left ventricular dysfunction was detected in 70 (55%) patients and diastolic dysfunction was the most common finding (53 patients — 42%). NT-proBNP and TnT were measured at admission and discharge; elevated values were recorded in 60%, 36%,

Discussion

This is the most comprehensive prospective study to report associations between cardiac biomarkers determined at different time-points during hospitalisation for acute exacerbation of COPD and short term prognosis. We were able to confirm previous findings that NT-proBNP and TnT predict patient outcome. In addition to that, we report specifically about differences in timing and the type of event: NT-proBNP on admission predicted mortality whilst TnT at discharge predicted re-hospitalisation.

Clinical implications and conclusions

An abundant literature supports an important involvement of abnormalities in the cardiovascular system in the prognosis of patients with COPD [28], [29], [30]. Our results support more detailed cardiovascular evaluation in patients with an acute exacerbation of COPD. Elevated NT-proBNP on admission and TnT at discharge should perhaps trigger further patient investigation to identify causative factors and to risk-stratify the patients for the risk of adverse short-term outcome. As cardiovascular

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2022, IJC Heart and Vasculature
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Cardiac and inflammatory biomarkers have been reported to be elevated in acute COVID-19 infection, especially among individuals requiring hospitalization and intensive care unit [5,6]. Elevations in cardiac troponins and NT-pro-B-type natriuretic peptide (BNP) are associated with increased risks of re-hospitalization, CV complications and death after COVID-19 infection [7]. However, most studies of COVID-19 serum biomarkers, particularly cardiac biomarkers, have been reported in hospitalized COVID-19 patients [8].
Coronavirus-2019 (COVID-19) is known to affect the heart and is associated with a pro-inflammatory state. Most studies to date have focused on clinically sick subjects. Here, we report cardiac and proinflammatory biomarkers levels in ambulatory young adults with asymptomatic or mild COVID-19 infection compared to those without infection 4–8 weeks after severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) testing.
131 asymptomatic or mildly symptomatic subjects were enrolled following testing for SARS-COV-2. Fifty subjects tested negative, and 81 subjects tested positive. Serum samples were collected for measurement of C-reactive protein, ferritin, interleukin-6, NT-pro-B-type natriuretic peptide, and cardiac troponin 28–55 days after SARS-COV-2 RT-PCR testing.
Biomarker levels trended higher in SARS-COV-2-positive vs negative subjects, but differences in biomarker levels or proportion of subjects with elevated biomarkers were not statistically significant with respect to SARS-COV-2 status. Among individuals with ≥ 1 comorbidity, odds of elevated CRP were greater compared to individuals without any comorbidities (odds ratio [OR] = 2.90); this effect size was increased 1.4-fold among SARS-COV-2-positive subjects (OR = 4.03). Similarly, NT-pro-BNP was associated with CVD, with the strongest association in COVID-positive individuals (OR = 16.9).
In a relatively young, healthy adult population, mild COVID-19 infection was associated with mild elevations in cardiac and proinflammatory biomarkers within 4–8 weeks of mild or asymptomatic COVID-19 infection in individuals with preexisting comorbidities, but not among individuals without comorbidities. For the general population of young adults, we did not find evidence of elevation of cardiac or proinflammatory biomarkers 4–8 weeks after COVID-19 infection.
Clinical Perspective: This is a characterization of cardiac and proinflammatory biomarkers in ambulatory subjects following asymptomatic or mild COVID-19 infection. Young, ambulatory individuals did not have cardiac and proinflammatory biomarker elevation 4–8 weeks after mild COVID-19 infection. However, COVID-19 infection was associated with biomarker elevations in select individuals with comorbidities.
Clinical study number: H-47423.
Heart failure in patients with COPD exacerbations: Looking below the tip of the iceberg
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Patients surviving hospitalization for exacerbations of chronic obstructive pulmonary disease (ECOPD) are at heightened risk of cardiovascular events. Heart failure is often underdiagnosed and undertreated in COPD; better care could improve outcome. We aimed to capture contemporary investigation and management of heart failure (HF) in patients hospitalized with ECOPD.
In two UK hospitals, patients admitted with ECOPD between 2017 and 2020 were retrospectively identified. Baseline characteristics between known, newly diagnosed and no HF were compared using analysis of variance and chi-squared test. Impact of HF on mortality was assessed by Kaplan-Meier analysis and Cox proportional-hazards regression. Sensitivity and specificity of NT-proBNP for diagnosing HF at recognized thresholds were reported.
On admission, 94/476 (19.7%) patients had known HF. Among remaining patients, 89/382 (23.3%) were investigated within 100 days of admission, confirming HF in 38. Of 33 patients with heart failure with reduced ejection fraction (HFrEF), 18 (54.5%) were prescribed ACE-inhibitor and B-blocker. 77/132 patients (58.3%) with HF and 108/344 patients (31.4%) without HF died (adjusted HR 2.03, 95% CI 1.46–2.82, p < 0.001) during follow up (median 11.7 months). At ≥400 pg/mL, NPV and PPV of NT-proBNP for the diagnosis of HF were 77.8% and 82.8%.
A new diagnosis of HF was made in over 40% investigated. In patients with coexistent HF, undertreatment was common and 1-year mortality exceeded 50%. NT-proBNP may help identify patients who need cardiovascular functional imaging. Research to improve HF diagnosis and treatment in hospitalized ECOPD is urgently needed.
Role of Cardiac Biomarkers in COVID-19: What Recent Investigations Tell Us?
2021, Current Problems in Cardiology
Purpose of review: Although the respiratory system is the main target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is evident from recent data that other systems, especially cardiovascular and hematological, are also significantly affected. In fact, in severe form, COVID-19 causes a systemic illness with widespread inflammation and cytokine flood, resulting in severe cardiovascular injury. Therefore, we reviewed cardiac injury biomarkers' role in various cardiovascular complications of COVID 19 in recent studies. Recent findings: Cardiac injury biomarkers were elevated in most of the complicated cases of COVID-19, and their elevation is directly proportional to the worst outcome. Evaluation of cardiac biomarkers with markers of other organ damage gives a more reliable tool for case fatalities and future outcome. Summary: Significant association of cardiac biomarkers in COVID-19 cases helps disease management and prognosis, especially in severely ill patients.
An emergency medicine approach to troponin elevation due to causes other than occlusion myocardial infarction
2020, American Journal of Emergency Medicine
Troponin is an integral component of the evaluation for acute coronary syndrome (ACS) and occlusion myocardial infarction (OMI). However, troponin may be elevated in conditions other than OMI.
This narrative review provides emergency clinicians with a focused evaluation of troponin elevation in patients with myocardial injury due to conditions other than OMI.
ACS includes the diagnosis of myocardial infarction (MI), which incorporates assessment for elevated troponin. Troponin I and T are the most common biomarkers used in assessment of myocardial injury and may be released with myocyte injury and necrosis, myocyte apoptosis and cell turnover, and oxygen supply demand mismatch. Troponin elevation is a reflection of myocardial injury, and many conditions associated with critical illness may result in troponin elevation. These include cardiac and non-cardiac conditions. Cardiac conditions include heart failure, dysrhythmia, and dissection, while non-cardiac causes include pulmonary embolism, sepsis, stroke, and many others. Clinicians should consider the clinical context, patient symptoms, electrocardiogram, and ultrasound in their assessment of the patient with troponin elevation. In most cases, elevated troponin is a marker for poor outcomes including increased rates of mortality.
Troponin can be elevated in many critical settings. The causes of troponin elevation include cardiac and non-cardiac conditions. Clinicians must consider the clinical context and other factors, as an inappropriate diagnosis of OMI may result in patient harm and misdiagnosis of another condition.
Changes in biomarkers of cardiac dysfunction during exacerbations of chronic obstructive pulmonary disease
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Citation Excerpt :
The time-course of cardiac biomarkers during acute exacerbations of COPD has not been carefully documented and previous studies report conflicting results [11,15–22]. Patel et al. reported that NT-proBNP and troponin T remained high for up to five weeks after the exacerbation [11], while other studies reported that the levels of cardiac biomarkers gradually declined within days to a few weeks after an exacerbation [15,17,19,21,22]. However, none of these studies investigated the changes in cardiac biomarkers during the first few days of the acute exacerbation.
Cardiac dysfunction is associated with a higher mortality in exacerbations of chronic obstructive pulmonary disease (COPD). It is unknown how the heart responds to treatment of COPD exacerbations. We followed cardiac biomarker levels during hospital admissions for exacerbations of COPD and hypothesised that these biochemical markers of cardiac dysfunction might be affected the severity and treatment of exacerbations of COPD.
N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin T were measured at admission, 12 h, 72 h, and clinical stability in 176 patients. In a second cohort (n = 93), associations between blood salbutamol concentrations and biomarker changes at 12 h were analysed.
NT-proBNP increased from a geometric mean of 43 pmol/L at admission to 56 pmol/L at 12 h (p < 0.001), 53 pmol/L at 72 h (p = 0.045), and decreased to 25 pmol/L (p < 0.001) at stability. Troponin T levels decreased at 12 h (p < 0.001), but 15/174 (9%) patients had a clinically significant rise. Nebulised bronchodilator treatment and blood salbutamol concentrations were associated with greater increases in NT-proBNP rise at 12 h independently of baseline COPD or exacerbation severity and other treatments (p < 0.05). Nebulised bronchodilator and blood salbutamol concentrations also predicted rises in troponin T in univariate analyses (p < 0.05).
NT-proBNP continues to rise after admission to hospital for COPD exacerbations and a minority of patients have clinically significant rises in cardiac troponins. These rises were associated with nebulised beta₂-agonist treatment. These findings suggest that high doses of beta₂-agonists may exacerbate cardiac dysfunction in COPD.
NT-proBNP in stable COPD and future exacerbation risk: Analysis of the SPIROMICS cohort
2018, Respiratory Medicine
Citation Excerpt :
Natriuretic peptide levels increase during acute exacerbations of COPD and return to baseline after successful treatment [13,14]. Higher NT-proBNP levels measured at the time of a COPD exacerbation have been associated with increased need for intensive care [15] and higher mortality [16–19]. However, the role of NT-proBNP as a prognostic biomarker in stable COPD has not been fully investigated.
High N-terminal pro-brain natriuretic peptide (NT-proBNP) during COPD exacerbations is associated with worse clinical outcomes. The prognostic value of NT-proBNP measured during clinical stability has not been well characterized.
We studied SPIROMICS participants 40–80 years of age with COPD GOLD spirometric stages 1–4. The association between baseline NT-proBNP and incident COPD exacerbations within one year of follow-up was tested using zero-inflated Poisson regression models adjusted for age, gender, race, body mass index, current smoking status, smoking history, FEV₁ percent predicted, COPD Assessment Test score, exacerbation history, total lung capacity on chest CT and cardiovascular disease (any of coronary artery disease, myocardial infarction or congestive heart failure).
Among 1051 participants (mean age 66.1 years, 41.4% women), mean NT-proBNP was 608.9 pg/ml. Subjects in GOLD stage D had the highest mean NT-proBNP. After one year of follow-up, 268 participants experienced one or more COPD exacerbations. One standard deviation increase in baseline NT-proBNP was associated with a 13% increase in the risk of incident exacerbations (incident risk ratio 1.13; 95% CI 1.06–1.19; p < 0.0001). This association was maintained in participants with and without cardiovascular disease.
Baseline NT-proBNP in COPD is an independent predictor of respiratory exacerbations, even in individuals without overt cardiac disease. The impact of detection and treatment of early cardiovascular dysfunction on COPD exacerbation frequency warrants further investigation.

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Cardiac biomarkers predict outcome after hospitalisation for an acute exacerbation of chronic obstructive pulmonary disease

Abstract

Purpose

Methods

Results

Conclusions

Introduction

Section snippets

Study design and patients

Results

Discussion

Clinical implications and conclusions

Chest

Eur J Intern Med

Chest

Respir Med

Int J Cardiol

Int J Cardiol

Clin Chim Acta

J Am Coll Cardiol

Chest

Global strategy for the diagnosis, management and prevention of COPD — 2006 update

Am J Respir Crit Care Med

Chronic obstructive pulmonary disease: current burden and future projections

Eur Respir J

Systemic manifestations and comorbidities of COPD

Eur Respir J

Neurohormonal activation and inflammation in chronic cardiopulmonary disease: a brief systematic review

Wien Klin Wochenschr

Troponin T elevation and long-term mortality after chronic obstructive pulmonary disease exacerbation

Eur Respir J

Cardiac troponin-I predicts long-term mortality in chronic obstructive pulmonary disease

COPD

Prognostic value of cardiac troponin I in patients with COPD acute exacerbation

Neth J Med