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. 2018 Dec 18;19(1):257.
doi: 10.1186/s12931-018-0946-1.

Centrilobular emphysema and coronary artery calcification: mediation analysis in the SPIROMICS cohort

Surya P Bhatt  1   2 , Hrudaya P Nath  3   4 , Young-Il Kim  5   6 , Rekha Ramachandran  6 , Jubal R Watts  4 , Nina L J Terry  4 , Sushil Sonavane  4 , Swati P Deshmane  4 , Prescott G Woodruff  7 , Elizabeth C Oelsner  8 , Sandeep Bodduluri  5   3 , MeiLan K Han  9 , Wassim W Labaki  9 , J Michael Wells  5   3   10 , Fernando J Martinez  11 , R Graham Barr  8 , Mark T Dransfield  5   3   10 ; SPIROMICS investigators
Collaborators, Affiliations

Centrilobular emphysema and coronary artery calcification: mediation analysis in the SPIROMICS cohort

Surya P Bhatt et al. Respir Res. .

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is associated with a two-to-five fold increase in the risk of coronary artery disease independent of shared risk factors. This association is hypothesized to be mediated by systemic inflammation but this link has not been established.

Methods: We included 300 participants enrolled in the SPIROMICS cohort, 75 each of lifetime non-smokers, smokers without airflow obstruction, mild-moderate COPD, and severe-very severe COPD. We quantified emphysema and airway disease on computed tomography, characterized visual emphysema subtypes (centrilobular and paraseptal) and airway disease, and used the Weston visual score to quantify coronary artery calcification (CAC). We used the Sobel test to determine whether markers of systemic inflammation mediated a link between spirometric and radiographic features of COPD and CAC.

Results: FEV1/FVC but not quantitative emphysema or airway wall thickening was associated with CAC (p = 0.036), after adjustment for demographics, diabetes mellitus, hypertension, statin use, and CT scanner type. To explain this discordance, we examined visual subtypes of emphysema and airway disease, and found that centrilobular emphysema but not paraseptal emphysema or bronchial thickening was independently associated with CAC (p = 0.019). MMP3, VCAM1, CXCL5 and CXCL9 mediated 8, 8, 7 and 16% of the association between FEV1/FVC and CAC, respectively. Similar biomarkers partially mediated the association between centrilobular emphysema and CAC.

Conclusions: The association between airflow obstruction and coronary calcification is driven primarily by the centrilobular subtype of emphysema, and is linked through bioactive molecules implicated in the pathogenesis of atherosclerosis.

Trial registration: ClinicalTrials.gov: Identifier: NCT01969344 .

Keywords: COPD; Cardiovascular disease; Coronary artery calcification; Emphysema; Mediators.

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Conflict of interest statement

Ethics approval and consent to participate

All participants signed a written informed consent form, and the Institutional Review Boarsd of all participating centers approved the study.

Consent for publication

N/A

Competing interests

SPB received funding from the NIH (K23HL133438); MKH reports personal fees from GSK, personal fees from BI, personal fees from AstraZeneca, non-financial support from Novartis, non-financial support from Sunovion; MTD reports grants from NHLBI, during the conduct of the study; grants from Department of Defense, personal fees and other from Boehringer Ingeheim, personal fees and other from GlaxoSmithKline, other from Novartis, personal fees and other from AstraZeneca, other from Yungjin, other from PneumRx/BTG, other from Pulmonx, personal fees from Genentech, personal fees and other from Boston Scientific; NLJT reports stocks in GE, CVS Caremark Corp, Johnson and Johnson, Pfizer, and Kimberley-Clark; PGW reports personal fees from Astra Zeneca, grants from Medimmune, personal fees from Regeneron, personal fees from Sanofi, personal fees from Genentech, personal fees from Janssen; JMW reports grants from NIH/NHLBI, grants and other from GSK, grants from AstraZeneca, other from Quintiles, other from Mylan, other from Gilead, grants from Bayer, grants from Cystic Fibrosis Foundation, other from Mereo Biopharma; RGB reports grants from NIH, grants from Foundation for the NIH, grants from COPD Foundation, during the conduct of the study; grants from Alpha1 Foundation, personal fees from UpToDate; HN, YK, RR, JRW, SS, SPD, ECO, SB and WWL have no conflicts of interest to declare. Funding.

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