Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD

Abstract

Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality.pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic-femoral pulse wave velocity.pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=-0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05).In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.

Are COPD and cardiovascular disease fundamentally intertwined?

“…An increase in elastolysis may be due to either increases in elastolytic enzyme activity or reductions in inhibitors of these enzymes with subsequent replacement of elastin with collagen [24]. The findings of RABINOVICH et al [9] help us, as both scientists and clinicians, to understand further the possible mechanism of COPD and cardiovascular disease. They have shown that an increased level of elastolysis, by measuring plasma desmosine as a biomarker of elastin breakdown, exists in patients with COPD, in contrast to sex-and age-matched controls.…”

“…The lack of any association of plasma desmosine with emphysema or airflow obstruction is in contrast to that found previously [25], but is likely to reflect differences in the population studied, the size of the COPD population studied and possible differences in the definition of emphysema. Most significantly, the authors found an association with all-cause mortality and plasma desmosine levels in the COPD patient population [9]; however, without a control population with only cardiovascular disease it remains unclear if this is a COPD or cardiovascular phenomenon and warrants further investigation. This work [9] does further the hypothesis that the common factor in any association of COPD and cardiovascular risk is elastin loss.…”

“…Most significantly, the authors found an association with all-cause mortality and plasma desmosine levels in the COPD patient population [9]; however, without a control population with only cardiovascular disease it remains unclear if this is a COPD or cardiovascular phenomenon and warrants further investigation. This work [9] does further the hypothesis that the common factor in any association of COPD and cardiovascular risk is elastin loss. Elastin is highly conserved in our lifetime [26], with a half-life of 74 years [27]; thus, loss by accelerated breakdown, degradation or homeostatic imbalance is irreplaceable [28].…”

“…Elastin is highly conserved in our lifetime [26], with a half-life of 74 years [27]; thus, loss by accelerated breakdown, degradation or homeostatic imbalance is irreplaceable [28]. The study by RABINOVICH et al [9] finds that age is the factor with the strongest correlation to plasma desmosine levels, and it may prove in time that both COPD and cardiovascular disease represent accelerated ageing [29] with an (early) elastin-deficient process [30,31]. The authors acknowledge the study has limitations and we have to be cautious with its interpretation.…”

“…Finally, this paper [9] serves to remind us of the importance of comorbidities in COPD. We are reminded of the presence of shared causal factors leading to multiple pathological effects, and of the significance of measuring, monitoring and modifying risk.…”