Relationship between serum cardiac troponin T level and cardiopulmonary function in stable chronic obstructive pulmonary disease

Abstract

Background

High-sensitivity cardiac troponin T (hs-cTnT) in serum is a useful marker of acute myocardial injury, yet information is limited in patients with chronic obstructive pulmonary disease. We aimed to explore the association between hs-cTnT levels and cardiac and pulmonary dysfunction in patients with stable chronic obstructive pulmonary disease and at-risk individuals.

Methods

We examined community-dwelling adults with/without chronic obstructive pulmonary disease, with a life-long smoking history, current symptoms of dyspnea during exertion, prolonged coughing, and/or sputum. Serum hs-cTnT concentrations were measured, and subjects underwent pulmonary function tests, high-resolution computed tomography of the chest, an echocardiogram, and a 6-minute walking test.

Results

Eighty-six stable patients were identified (mean age 65.5 years; predicted forced expiratory volume in 1 second [FEV₁% predicted] 75.0%). Their overall mean hs-cTnT level was 0.008 ng/mL. Logarithmically transformed hs-cTnT levels significantly and positively correlated with age, smoking index, serum high-sensitivity C-reactive protein levels, right ventricle systolic pressure, low attenuation area percentage, and brain natriuretic peptide levels (range r=0.231–0.534, P=0.000 to P=0.042). Further, logarithmically transformed hs-cTnT values significantly and negatively correlated with forced vital capacity, FEV₁% predicted, diffusion capacity, arterial oxygen tension, and 6-minute walking distance (range r= −0.482 to −0.377, P=0.000 to P=0.002). Multivariate analyses showed that hs-cTnT values varied independently according to the following three parameters: high-sensitivity C-reactive protein levels (B=0.157, β=0.450, t=3.571, P=0.001), age (B=0.008, β=0.352, t=2.789, P=0.009), and right ventricular systolic pressure (B=0.008, β=0.280, t=2.202, P=0.035).

Conclusion

Even in patients with stable chronic obstructive pulmonary disease, the serum troponin T concentration was controlled by at least three major factors, ie, systemic inflammation, advancing age, and right cardiac overload.

Keywords:

• chronic obstructive pulmonary disease
• troponin T
• C-reactive protein
• aging

Supplementary materials

Study design

The study design is shown in Figure S1. The subjects were recruited from March 2005 to December 2013 at the Respiratory Care Clinic, which is a secondary referral facility affiliated with the Nippon Medical School in Tokyo, Japan. From a total of 548 subjects, 86 who either had or were at risk of chronic obstructive pulmonary disease (COPD) were selected as the patient group, and any patients with cardiac and/or pulmonary comorbidities after various examinations were carefully excluded (details in the following section on Exclusion criteria).

Exclusion criteria

Subjects with only COPD were examined in this study, excluding any cardiac and pulmonary comorbidities. Subjects suffering from any one of these pulmonary and/or cardiovascular diseases were excluded: bronchial asthma, bronchiectasis, interstitial pneumonia, sinobronchial syndrome, active or old pulmonary tuberculosis, non-tuberculous mycobacteriosis, abnormal chest shadow suggestive of a lung tumor, resolved pneumothorax, lymphangioleiomyomatosis, lung cancer, diffuse panbronchiolitis, hypersensitivity pneumonitis, asbestosis, pulmonary hypertension, pneumonia, chronic eosinophilic pneumonia, chronic pulmonary thromboembolism, hypertension, ischemic heart disease, any type of arrhythmia, congestive heart failure, atrial septal aneurysm, ventricular septal aneurysm, hypertrophic cardiomyopathy, valvular disease, atrial septal defect, ventricular septal defect, tetralogy of Fallot, and genetic α1 anti-trypsin deficiency. Thus, careful attention was paid to exclude all these cases with cardiopulmonary comorbidities in order to focus on subjects with only COPD or those with a life-long smoking history who exhibited clinical symptoms similar to COPD, whom we considered at-risk subjects.

Pulmonary function tests

The tests were performed by well-trained technicians according to the American Thoracic Society guidelines¹ using specialized equipment for lung function testing with computer processing (Chestac 55; Chest Co., Tokyo, Japan). The standards of the Japanese Respiratory Society² were used as the reference values for post-bronchodilator forced expiratory volume in 1 second and forced vital capacity.

High-resolution computed tomography

We performed helical high-resolution computed tomography scans at 1.25 mm collimation, 0.8 second scan time (rotation time), 120 kV, and 100–600 mA using a Light Speed Pro16 CT Scanner (GE Co., Tokyo, Japan).

Echocardiography

The same experienced echocardiographer performed the procedure on all subjects. The examination was recorded in the standard parasternal and apical views during normal breathing at end-expiration. All measurements were obtained according to the standards of the American Society of Echocardiography.³ The left ventricular internal end-diastolic and end-systolic diameters were measured over five consecutive cycles. Systolic pulmonary artery pressure was calculated using the modified Bernoulli equation with an estimated right atrial pressure of 10 mmHg.

Multiple regression analysis for hs-cTnT levels (logged) in the COPD group and at-risk group

We determined whether this multivariate model for high-sensitivity cardiac troponin T (hs-cTnT) would be accurate for both a subgroup of COPD and at-risk subjects. High-sensitivity C-reactive protein and age, but not right ventricular systolic pressure, were associated with hs-cTnT using this model for these two subgroups (Tables S1 and S2).

Association between hs-cTnT levels (logged) and demographic and cardiopulmonary parameters in subjects with median or higher hs-TnT levels and in subjects with lower hs-TnT levels

The hs-cTnT level was low in the entire population. Thus, we also performed simple correlation analyses between hs-cTnT and clinical parameters (Table S3), and performed stepwise regression analysis on logged hs-cTnT values (Table S4) again in the subjects whose hs-cTnT was greater than the median (0.007). Although the population was relatively small in this analysis, we were still able to observe an association between hs-cTnT and C-reactive protein.

Figure S1 Study flow chart. Subjects (n=548) were recruited, and those with other pulmonary diseases (n=129; eg, bronchial asthma and bronchiectasis) and/or any cardiovascular diseases (n=232; eg, hypertension and ischemic heart disease) were all excluded. Some subjects had multiple comorbidities. A total of 86 subjects were enrolled in the study.

Table S1 Multiple regression analysis for hs-cTnT levels (logged) in the group with chronic obstructive pulmonary disease

Table S2 Multiple regression analysis for hs-cTnT levels (logged) in the at-risk group

Table S3 Association between hs-cTnT levels (logged) and demographic and cardiopulmonary parameters in subjects with median or higher level of hs-TnT and in subjects with lower levels of hs-TnT

Table S4 Multiple regression analysis for hs-cTnT levels (logged) in subjects with median or higher levels of hs-TnT (stepwise estimation model)

References

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Disclosure

The authors report no conflicts of interest in this work.