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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 13
| Issue : 3 | Page : 161-165 |
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Role of cardiac biomarkers in patients of chronic obstructive pulmonary disease with acute exacerbation
RV Raghu1, Govind Mawari2, Naresh Kumar1, Mradul Kumar Daga3, Sachin Gautam1, J Aarthi1, Siddharth Chand1, Nupur Ritchie1, Gunjan Rana1, Shubho Acharya1, Parikshit Sen1, Divyansh Chaudhary1, Pratischtha Kain1, Nishant Garg1, Dhruv Bhoria1
1 Department of Internal Medicine, Maulana Azad Medical College, New Delhi, India
2 Centre for Occupational and Environment Health, Maulana Azad Medical College, New Delhi, India
3 Department of Internal Medicine and Infectious Disease, Institute of Liver and Biliary Sciences, New Delhi, India
| Date of Submission | 09-Jan-2022 |
| Date of Decision | 17-Feb-2022 |
| Date of Acceptance | 19-Feb-2022 |
| Date of Web Publication | 16-Jul-2022 |
Correspondence Address:
Dr. Mradul Kumar Daga
Internal Medicine and Infectious Disease, Institute of Liver and Biliary Sciences, New Delhi
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/injms.injms_4_22
Background: Patients with chronic obstructive pulmonary disease (COPD) often have cardiovascular comorbidities. Patients of COPD with cardiovascular complications tend to have more symptoms and a higher mortality than do patients with COPD alone. There are several cardiac biomarkers such as Troponin-T, creatine phosphokinase-MB (CPK-MB), and N-terminal pro-brain natriuretic peptide (NT-proBNP) which can be used to detect cardiac dysfunction in patients of COPD. Retrospective studies suggest that plasma levels of NT-proBNP and cardiac Troponin-T are often elevated in patients with acute exacerbations of COPD and are associated with increased mortality. Aims and objectives: In this study, we assessed the presence of cardiac dysfunction in patients presenting with acute exacerbation of COPD (AECOPD) by using cardiac biomarkers proBNP, Troponin-T, and CPK-MB. Patients were followed up for 30 days to know the relationship between cardiac dysfunction and outcome in terms of repeated admissions, intensive care units (ICU) admissions, and/or mortality. Methodology: Ninety patients of AECOPD were enrolled in our study. A detailed history was taken and physical examination performed in these patients. All patients in the study were subjected to hematological and biochemical investigations. ProBNP, Troponin-T, and CPK-MB were measured within 48 h of admission as measure of cardiac dysfunction; and outcome was assessed in terms of mortality, ICU admission, and repeated admissions within 30 days of admission. Results: Among the study population, 77.77% had at least one deranged cardiac biomarker, and 18.88% of populations had all the three biomarkers of cardiac dysfunction deranged. 24 out of the 90 participants required ventilatory support in the form of noninvasive or invasive ventilation. 7.14% of the study population had repeated admissions, 24.28% had ICU admissions and 11.43% had mortality. All of them had deranged cardiac biomarkers. There was a significant association between deranged proBNP and ICU admission and mortality (P = 0.0151 and 0.0217, respectively). COPD was more prevalent in the age group of 50–70 years and in males. ProBNP levels were significantly elevated in patients who required ventilatory support (P = 0.003). Conclusions: Cardiac dysfunction is common during exacerbations of COPD and portends a poor prognosis. Cardiac dysfunction was more prevalent in the elderly. Patients with deranged cardiac biomarkers had a greater number of ICU admissions, repeated hospital admissions, and a higher mortality. In the follow-up, elevated proBNP was found to be a strong marker for predicting ICU admission, mortality, and repeated admissions.
Keywords: Cardiac biomarkers, cardiac dysfunction, chronic obstructive pulmonary disease, creatine phosphokinase-MB, pro-brain natriuretic peptide, troponin-T
How to cite this article:
Raghu R V, Mawari G, Kumar N, Daga MK, Gautam S, Aarthi J, Chand S, Ritchie N, Rana G, Acharya S, Sen P, Chaudhary D, Kain P, Garg N, Bhoria D. Role of cardiac biomarkers in patients of chronic obstructive pulmonary disease with acute exacerbation. Indian J Med Spec 2022;13:161-5 |
How to cite this URL:
Raghu R V, Mawari G, Kumar N, Daga MK, Gautam S, Aarthi J, Chand S, Ritchie N, Rana G, Acharya S, Sen P, Chaudhary D, Kain P, Garg N, Bhoria D. Role of cardiac biomarkers in patients of chronic obstructive pulmonary disease with acute exacerbation. Indian J Med Spec [serial online] 2022 [cited 2023 Jun 7];13:161-5. Available from: http://www.ijms.in/text.asp?2022/13/3/161/351061 |
| Introduction | |  |
Chronic obstructive pulmonary disease (COPD), a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and is associated with an enhanced chronic inflammatory response in the airways and lungs to noxious particles or gases, which is influenced by host factors including abnormal lung development.
Patients with COPD often have cardiovascular comorbidities.[1] Patients with cardiovascular complications tend to have more symptoms and higher mortality than do patients with COPD alone.[2] It can be difficult to distinguish the symptoms of the cardiac disease from those of COPD, and cardiac disease often goes unrecognized in acute exacerbation of COPD (AECOPD).[3],[4] Decompensated cardiac failure could be mistaken for COPD exacerbation.[4],[5] Biochemical evidence of cardiac dysfunction is often present even without the clinical signs of cardiac involvement.[6]
There are several cardiac biomarkers such as Troponin-T, creatine phosphokinase-MB (CPK-MB), and N-terminal pro-brain natriuretic peptide (NT-proBNP) which can be used to detect cardiac dysfunction in patients of COPD. Troponins are globular protein complexes bound to the actin filaments of myocytes that regulate the contraction of skeletal and cardiac muscle. These proteins are released into the peripheral blood from cardiomyocytes after myocardial injury. Troponin measurements are mainly used to diagnose acute myocardial infarction. Although specific for myocardial necrosis, they are not specific for ischemic injury-cardiac troponins can also be raised in heart failure, renal dysfunction, pulmonary embolism, pulmonary hypertension, tachyarrhythmias, and sepsis.
B-type natriuretic peptides (BNPs) are secreted from ventricular cardiomyocytes in response to stretching of the cardiac wall as a result of either volume or pressure overload under sympathetic drive. BNPs downregulate the sympathetic nervous system and the renin-angiotensin-aldosterone system, enable natriuresis, decrease peripheral vascular resistance, increase smooth-muscle relaxation, stimulate myocardial relaxation, and inhibit cardiac remodelling.[7]
Biochemical evidence of cardiac injury during COPD exacerbations is common and predicts both short-term and long-term mortality. Biochemical evidence of myocardial stretch (BNPs) and myocardial injury (troponins and CPK-MB) is often noted in exacerbations of COPD and is associated with increased mortality.[6]
In this study, we planned to assess the presence of cardiac dysfunction in patients presenting with AECOPD by using cardiac biomarkers proBNP, Troponin-T, and CPK-MB. We followed up the patients for 30 days to know the relationship between cardiac biomarkers and outcome in terms of intensive care units (ICU) admissions, repeated admissions and mortality.
| Materials and Methods | | |
Study design
This was a longitudinal observational study carried out over a period of 1 year in the Department of Medicine, Maulana Azad Medical College, and associated Lok Nayak Hospital, New Delhi, India, after obtaining clearance from the Institutional Ethics Committee.
Inclusion criteria
Patients of COPD with acute exacerbation (as defined by GOLD criteria),[1] aged ≥35 years AECOPD is defined as an acute event characterized by worsening of the patient's respiratory symptoms that is beyond the normal day to day variations and requires a change in the medication of patients.
Exclusion criteria
Known cases of cardiovascular disease, other chronic respiratory diseases such as asthma, interstitial lung disease and other chronic diseases like chronic kidney or liver diseases were excluded from the study.
Methodology
Ninety patients of AECOPD fulfilling the above-mentioned inclusion criteria were enrolled in the study after taking informed consent. A detailed history was taken and physical examination was performed on each patient. All the patients in the study were subjected to hematological and biochemical investigations such as hemogram, kidney function test, liver function tests, serum electrolytes along with electrocardiography, chest X-ray, and arterial blood gas analysis. Data on demographics, smoking status, history of chronic disease, comorbid conditions, and pharmacological therapy were collected from the patients or obtained from the medical records at baseline. NT-proBNP, troponin-T, and CPK-MB were measured within 48 h of admission. We took the reference cutoff values of proBNP, Troponin-T, and CPK-MB were taken as 500 pg/ml, 0.1 ng/ml, and 20 IU/l, respectively. Patients with values above the reference value were considered to be having cardiac dysfunction.
Statistical analysis
The data were analyzed using SPSS 25 software by IBM. The description of quantitative variables was performed using the mean, standard deviation, median, and quartiles. The association between two qualitative variables was done using the Chi-square test while that between two quantitative variables was done using the Pearson correlation test. P < 0.05 is considered statistically significant.
Ethical consideration
The study was conducted after obtaining clearance from the Institutional Ethics Committee, Maulana Azad Medical College and associated Lok Nayak Hospital, Delhi, India. An informed consent was taken from all the individuals who were also explained the purpose of the study and their right to exit at any time. Patient's information was dealt with utmost confidentiality. Any abnormality detected incidentally during screening of individuals was appropriately managed.
| Results | | |
Baseline characteristics of cases
All the patients included in the study were above 35 years of age. The study population includes 92.22% of males and 7.78% of females. The average age of the patients was 63.53 ± 9.98 years. The mean age of the males was 63.18 while that of females was 67.71. 91.11% of the patients had a history of smoking and 63.33% were already undergoing treatment for COPD [Figure 1].
Cardiac biomarkers
Among the study population, 77.77% had at least one deranged cardiac biomarker out of three biomarkers assessed namely proBNP, Troponin T, and CPK MB. 18.88% of the population had all these three biomarkers deranged. The mean age of patients with cardiac dysfunction was 65.07 years while that with normal cardiac function was 57.82 years (P < 0.001). [Table 1] shows the number of patients with deranged parameters.
Outcome at 30 days
7.14% of the study population had repeated admissions, 24.28% had ICU admission. The mortality rate was 11.43% with all of them having deranged levels of at least one cardiac biomarker [Figure 2]. Significant association was seen between deranged proBNP and ICU admission and mortality (P = 0.0151 and 0.0217, respectively).
Ventilatory support
Twenty-four patients out of the study population of 90 (27.4%) required ventilatory support in the form of noninvasive or invasive ventilation. Mann–Whitney's test was used to determine the association, and no significant association was found between ventilatory requirement and cardiac dysfunction (P > 0.05). 14 out of 24 (46.16%) and 6 out of 24 (25%) had elevated Trop T and CPK MB, respectively. However, there was no statistical significance. 22 out 24 (91.17%) who required ventilatory support were having elevated ProBNP with significant association (P = 0.003) [Figure 3] and [Figure 4]. | Figure 4: Showing requirement of ventilatory support with individual biomarker
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| Discussion | | |
Baseline characteristics
In the study group, 92.22% were male, whereas 7.78% were female. This revealed that males were dominant in the study. This may be due to the smoking habit, being more common in male. Recent epidemiological data have shown that there is increasing trend in the prevalence of COPD in females probably reflecting the changing pattern of tobacco smoking. Further study into gender differences in COPD should be investigated as some studies have even suggested that women are more susceptible to the effect of tobacco smoke than men.
The mean age of our study group, 63.5 (53.5–73.5) years was consistent with previous studies that consisted of a predominantly elderly population.[8],[9],[10] This is unsurprising as a correlation between advancing age and cardiovascular complications in COPD patients is suggested by the current literature, such as the multicentric PLATINO study which reported highest prevalence over the age of 60 years.[11] The presenting chief complaints of the patients in this study, which included shortness of breath (94.4%), fever (77.8%), and cough with expectoration (64.4%) were again, consistent with previous studies. The study by Li et al., for example, revealed dyspnea and cough to be the most common presentations.[12]
Cardiac dysfunction and acute exacerbation of chronic obstructive pulmonary disease
Our study found that among the patients with COPD exacerbation, more than three fourths (77.77%) had at least one cardiac biomarker deranged, while a considerable percentage (18.88%) had all the three biomarkers, proBNP, troponin-T, and CPK-MB, deranged. Similar results were seen in previous studies where laboratory tests revealed an elevation of these cardiac biomarkers in patients presenting with acute COPD exacerbation have often been followed by a diagnosis of underlying cardiac dysfunction.[13],[14],[15] Gariani et al. reported an elevation of proBNP in 81% of patients presenting with COPD exacerbation with underlying cardiac dysfunction, which was significantly higher percentage than our study. This may be attributed to the fact that a demarcating limit of >100 pg/ml had been considered in that study, which was lower than the cutoff in our study.[16] Conversely, a lower incidence of elevated biomarkers (27.5% with elevated proBNP and 16.6% with elevated troponin-T) in COPD patients with acute exacerbation was reported by Chang et al., although this might be due to the exclusion of patients with evidence of concomitant respiratory illness in that study.[17] The positive correlation between elevated cardiac biomarkers and cardiac dysfunction may be of a possible diagnostic utility of these biomarkers, especially proBNP in identifying underlying cardiovascular dysfunction in patients with acute exacerbation of COPD. This has been previously explored prospectively by Wang et al., who found comparable results to our study, with significantly elevated NT-proBNP levels in patients with LVSD and AECOPD.[18] Early diagnosis of cardiac dysfunction is instrumental in guiding early treatment interventions to reduce mortality in patients with acute COPD exacerbation, severe cardiovascular adverse events being a relatively common entity in these patients, often associated with poor prognosis and high mortality.[19],[20],[21] Thus, further studies are required to evaluate the diagnostic utility of proBNP and other biomarkers in detecting underlying cardiac dysfunction in patients with AECOPD.
Ventilatory support and cardiac dysfunction
While a sizable number of patients in our study requiring ventilatory support (noninvasive ventilation [NIV] or invasive ventilation) had underlying cardiac dysfunction, no statistically significant correlation was found between cardiac dysfunction during the study period. However, a correlation between the requirement of ventilatory support and elevation of the cardiac biomarker proBNP was found. This is consistent with previous studies that have found proBNP to be elevated in patients with AECOPD requiring ventilation.[22] A study by Adrish et al. did not show any relationship between proBNP and the need for NIV or mechanical ventilation, this might be attributed to the exclusion of all patients with left ventricular dysfunction detected on echocardiography in that study.[8] Thus, proBNP levels may be of significance in prioritizing patients for ventilation in resource-limited settings.
Outcome and cardiac biomarkers
All the patients in our study requiring repeated admission or intensive care and patients who had died, had at least one of the three cardiac biomarkers deranged. However, no significant statistical association was found on comparing the patients who were having all the three cardiac biomarkers deranged with the rest of the study population. When we compared individual cardiac biomarkers with the outcome, even though there were a greater number of mortalities, ICU admission, and repeated admissions for patients with elevated troponin-T and CPK-MB, there was no statistical significance. On the other hand, all the patients with repeated admissions, all those who had died, and 16 out of 17 patients who had ICU admissions had elevated BNP with a P = 0.0151. A study conducted by Stolz et al. showed that BNP accurately predicted the need for ICU care, which is consistent with our study.[23] This has been validated by other previous studies.[17],[24] However, in contrast to our study, Stolz et al. were not able to prove any association between in-hospital mortality and 6 month mortality and proBNP. 5 out of the 90 patients in our study had repeated admission within 30 days of first admissions. All had at least one cardiac biomarker deranged. There was no significant association between troponin-T and CPK-MB, but proBNP was significantly associated with repeat admission.
| Conclusions and Recommendations | | |
Seventy-seven percent of the patients of COPD with acute exacerbation had cardiac dysfunction which was more prevalent in the elderly age group. ProBNP levels were significantly elevated in patients who required ventilatory support and was found to be a strong marker for predicting ICU admission, mortality, and repeated admission. Hence, cardiac dysfunction during exacerbations of COPD is common and portends a poor prognosis.
Limitations
The sample size in the present study was small; therefore, the statistical power of the study was low. As only serious patients were enrolled in the study, thus the study population included patients with severe exacerbation and missed the subset of patients with mild exacerbation. Apart from this, confounders of elevated NT-proBNP levels including sepsis and pneumonia were not excluded.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Müllerova H, Agusti A, Erqou S, Mapel DW. Cardiovascular comorbidity in COPD: Systematic literature review. Chest 2013;144:1163-78.  |
| 2. | Patel AR, Donaldson GC, Mackay AJ, Wedzicha JA, Hurst JR. The impact of ischemic heart disease on symptoms, health status, and exacerbations in patients with COPD. Chest 2012;141:851-7. |
| 3. | Brekke PH, Omland T, Smith P, Søyseth V. Underdiagnosis of myocardial infarction in COPD – Cardiac Infarction Injury Score (CIIS) in patients hospitalised for COPD exacerbation. Respir Med 2008;102:1243-7. |
| 4. | Wang CS, FitzGerald JM, Schulzer M, Mak E, Ayas NT. Does this dyspneic patient in the emergency department have congestive heart failure? JAMA 2005;294:1944-56. |
| 5. | Connors AF Jr., Dawson NV, Thomas C, Harrell FE Jr., Desbiens N, Fulkerson WJ, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments) Am J Respir Crit Care Med 1996;154:959-67. |
| 6. | Pavasini R, d'Ascenzo F, Campo G, Biscaglia S, Ferri A, Contoli M, et al. Cardiac troponin elevation predicts all-cause mortality in patients with acute exacerbation of chronic obstructive pulmonary disease: Systematic review and meta-analysis. Int J Cardiol 2015;191:187-93. |
| 7. | Daniels LB, Maisel AS. Natriuretic peptides. J Am Coll Cardiol 2007;50:2357-68. |
| 8. | Adrish M, Nannaka VB, Cano EJ, Bajantri B, Diaz-Fuentes G. Significance of NT-pro-BNP in acute exacerbation of COPD patients without underlying left ventricular dysfunction. Int J Chron Obstruct Pulmon Dis 2017;12:1183-9. |
| 9. | Rolink M, van Dijk W, van den Haak-Rongen S, Pieters W, Schermer T, van den Bemt L. Using the DOSE index to predict changes in health status of patients with COPD: A prospective cohort study. Prim Care Respir J 2013;22:169-74. |
| 10. | Jones RC, Donaldson GC, Chavannes NH, Kida K, Dickson-Spillmann M, Harding S, et al. Derivation and validation of a composite index of severity in chronic obstructive pulmonary disease: The DOSE index. Am J Respir Crit Care Med 2009;180:1189-95. |
| 11. | Menezes AM, Perez-Padilla R, Jardim JR, Muiño A, Lopez MV, Valdivia G, et al. Chronic obstructive pulmonary disease in five Latin American cities (the PLATINO study): A prevalence study. Lancet 2005;366:1875-81. |
| 12. | Li X, Wu Z, Xue M, Du W. Smoking status affects clinical characteristics and disease course of acute exacerbation of chronic obstructive pulmonary disease: A prospectively observational study. Chron Respir Dis 2020;17:1479973120916184. doi:10.1177/1479973120916184. |
| 13. | Søyseth V, Bhatnagar R, Holmedahl NH, Neukamm A, Høiseth AD, Hagve TA, et al. Acute exacerbation of COPD is associated with fourfold elevation of cardiac troponin T. Heart 2013;99:122-6. |
| 14. | Abroug F, Ouanes-Besbes L, Nciri N, Sellami N, Addad F, Hamda KB, et al. 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;174:990-6. |
| 15. | Marcun R, Sustic A, Brguljan PM, Kadivec S, Farkas J, Kosnik M, et al. Cardiac biomarkers predict outcome after hospitalisation for an acute exacerbation of chronic obstructive pulmonary disease. Int J Cardiol 2012;161:156-9. |
| 16. | 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 Med Wkly 2011;141:w13298. |
| 17. | Chang CL, Robinson SC, Mills GD, Sullivan GD, Karalus NC, McLachlan JD, et al. Biochemical markers of cardiac dysfunction predict mortality in acute exacerbations of COPD. Thorax 2011;66:764-8. |
| 18. | Wang QP, Cao XZ, Wang XD, Gu J, Wen LM, Mao LM, et al. Utility of NT-proBNP for identifying LV failure in patients with acute exacerbation of chronic bronchitis. PLoS One 2013;8:e52553. |
| 19. | Kunisaki KM, Dransfield MT, Anderson JA, Brook RD, Calverley PM, Celli BR, et al. Exacerbations of chronic obstructive pulmonary disease and cardiac events. A Post hoc cohort analysis from the SUMMIT randomized clinical trial. Am J Respir Crit Care Med 2018;198:51-7. |
| 20. | Halpin DM, Decramer M, Celli B, Kesten S, Leimer I, Tashkin DP. Risk of nonlower respiratory serious adverse events following COPD exacerbations in the 4-year UPLIFT® trial. Lung 2011;189:261-8. |
| 21. | MacDonald MI, Shafuddin E, King PT, Chang CL, Bardin PG, Hancox RJ. Cardiac dysfunction during exacerbations of chronic obstructive pulmonary disease. Lancet Respir Med 2016;4:138-48. |
| 22. | Grasso S, Leone A, De Michele M, Anaclerio R, Cafarelli A, Ancona G, et al. Use of N-terminal pro-brain natriuretic peptide to detect acute cardiac dysfunction during weaning failure in difficult-to-wean patients with chronic obstructive pulmonary disease. Crit Care Med 2007;35:96-105. |
| 23. | Stolz D, Breidthardt T, Christ-Crain M, Bingisser R, Miedinger D, Leuppi J, et al. Use of B-type natriuretic peptide in the risk stratification of acute exacerbations of COPD. Chest 2008;133:1088-94. |
| 24. | Campo G, Pavasini R, Malagù M, Punzetti S, Napoli N, Guerzoni F, et al. Relationship between troponin elevation, cardiovascular history and adverse events in patients with acute exacerbation of COPD. COPD 2015;12:560-7. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1]
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