Common physiologic and proteomic biomarkers in pulmonary and coronary artery disease

Abstract

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.

Association of plasma proteomics with incident coronary heart disease in individuals with and without type 2 diabetes: results from the population-based KORA study

“…In line with our findings, cathepsin L1, gal-9, spondin-2, and TNFRSF11A measured using PEA technology were significantly altered in patients with prevalent CHD compared to participants without CHD [ 51 ]. Additionally, other proteins including HB-EGF, IL-27, sortilin, matrix metalloproteinase-1, OSM, ST2, TNFRSF9, and HOSCAR were reported to show higher concentrations in blood samples from individuals with CHD compared with healthy controls or non-CHD participants [ 52 – 59 ].…”

An investigation of the risk factors of chronic obstructive pulmonary disease in natural population-based cohorts in China – a nested case-control study

“…However, there is now little direct evidence of mechanism linking one disease to the other's advancement (41,42). In a similar vein, it's well accepted that COPD and cardiovascular illness are tightly associated (43). Common risk factors for cardiovascular disease and COPD include smoking and tobacco use (44).…”

“…On the other hand, the aforementioned variables could cause cardiovascular and pulmonary illnesses to appear simultaneously. It is still up to us to discover and verify the mechanism (43,45).…”

Proteomics discovery in children and young adults with HIV identifies fibrosis, inflammatory, and immune biomarkers associated with myocardial impairment

“…To our knowledge, this is the first study showing a link between higher EN-RAGE concentrations and abnormal cardiac function. Higher concentrations of VSIG2, a protein involved in lipid metabolism, have previously been associated with coronary artery disease in patients with rheumatoid arthritis and obstructive pulmonary disease [ 28 – 30 ]. Interestingly, VSIG2 was the only of the four proteins that appeared to be inversely associated with an abnormal MPI, such that higher concentrations of VSIG2 were observed in individuals with a normal vs. abnormal MPI.…”