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Published on: January 28, 2020
Common physiologic and proteomic biomarkers in pulmonary and coronary artery disease
Andreas Casselbrant1,2, Artur Fedorowski1,3, Sophia Frantz4,5
1Department of Clinical Sciences, Lund University, Malmö, Sweden.
Insights
Coronary artery disease (CAD) is linked to reduced diffusing capacity in chronic obstructive pulmonary disease (COPD) patients, independent of other factors. Novel biomarkers may also indicate this complex comorbidity.
Area of Science:
- Cardiology
- Pulmonology
- Biomarker Research
Background:
- Chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) are leading global causes of death.
- The comorbidity between COPD and CAD is significant but not fully explained by shared risk factors like smoking.
Purpose of the Study:
- To investigate the relationship between COPD and CAD by analyzing myocardial perfusion, pulmonary function, and cardiovascular biomarkers.
- To identify novel biomarkers associated with the co-occurrence of CAD and pulmonary dysfunction.
Main Methods:
- Analysis of 396 patients from the Swedish Biomarkers and Genetics CardioPulmonary Physiology Study (BiG CaPPS) referred for myocardial perfusion imaging.
- Inclusion of pulmonary function tests (PFTs), myocardial perfusion imaging (MPI), and proteomic biomarker analysis (92 biomarkers).
- Linear regression models were used to assess associations between MPI, PFTs, and biomarkers, adjusting for covariates.
Main Results:
- Patients with CAD exhibited significantly lower diffusing capacity for carbon monoxide (DLCO) compared to those without CAD, even after adjusting for smoking, diabetes, and BNP.
- CAD was also associated with higher total airway resistance.
- Nine protein biomarkers were identified as significantly associated with the combined diagnosis of CAD and airflow obstruction.
Conclusions:
- Reduced DLCO in CAD patients is independent of FEV1, diabetes, and elevated BNP, suggesting complex underlying mechanisms.
- Specific cardiovascular biomarkers are linked to co-existent CAD and airflow obstruction, but not to airflow obstruction alone.
- The interaction between CAD and lung function is intricate, involving pathways beyond reduced ventilation.
Objective:
Chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) are leading causes of global morbidity and mortality. There is a well-known comorbidity between COPD and CAD, which is only partly explained by smoking and other known common risk factors. In order to better understand the relationship between COPD and CAD, we analyzed myocardial perfusion, pulmonary function and novel cardiovascular biomarkers in patients with symptoms suggesting myocardial ischemia.
Methods:
A total of 396 subjects from the Swedish Biomarkers and Genetics CardioPulmonary Physiology Study (BiG CaPPS) were included, all of whom had been referred to myocardial perfusion imaging due to suspected myocardial ischemia. Subjects performed myocardial perfusion imaging (MPI), pulmonary function tests (PFT) and analysis of 92 proteomic biomarkers, previously associated with cardiovascular disease. Linear regression was used to study the relationship between MPI and PFT results and proteomic biomarkers.
Results:
Subjects with CAD (n = 159) had lower diffusing capacity (DLCO) than patients without CAD (6.64 versus 7.17 mmol/(min*kPa*l); p = 0.004) in models adjusted for common covariates such as smoking, but also diabetes and brain natriuretic peptide (BNP). The association remained significant after additional adjustment for forced expiratory volume in one second (FEV1) (p = 0.009). Subjects with CAD, compared with subjects without CAD, had higher total airway resistance (0.37 vs 0.36 kPa/(l/s); p = 0.036). Among 92 protein biomarkers, nine were associated with a combined diagnosis of CAD and airflow obstruction: VSIG2, KIM1, FGF-23, REN, XCL1, GIF, ADM, TRAIL-R2 and PRSS8.
Significance:
Diffusing capacity for carbon monoxide is decreased in patients with CAD, independently of decreased FEV1, diabetes, and elevated BNP. Several cardiovascular biomarkers are associated with co-existent CAD and airflow obstruction, but none with airflow obstruction only. The current findings indicate that the interaction between CAD and lung function is complex, including mechanisms beyond the known association between CAD and reduced ventilation.
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