@article{656f83312f1948b69ae85993c113191d,
title = "Centrilobular emphysema and coronary artery calcification: Mediation analysis in the SPIROMICS cohort",
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: FEV 1 /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 FEV 1 /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",
author = "Bhatt, {Surya P.} and Nath, {Hrudaya P.} and Kim, {Young Il} and Rekha Ramachandran and Watts, {Jubal R.} and Terry, {Nina L.J.} and Sushil Sonavane and Deshmane, {Swati P.} and Woodruff, {Prescott G.} and Oelsner, {Elizabeth C.} and Sandeep Bodduluri and Han, {Meilan K.} and Labaki, {Wassim W.} and {Michael Wells}, J. and Martinez, {Fernando J.} and Barr, {R. Graham} and Dransfield, {Mark T.} and Alexis, {Neil E.} and Anderson, {Wayne H.} and Bleecker, {Eugene R.} and Boucher, {Richard C.} and Bowler, {Russell P.} and Carretta, {Elizabeth E.} and Christenson, {Stephanie A.} and Comellas, {Alejandro P.} and Cooper, {Christopher B.} and Couper, {David J.} and Criner, {Gerard J.} and Crystal, {Ronald G.} and Curtis, {Jeffrey L.} and Doerschuk, {Claire M.} and Freeman, {Christine M.} and Hansel, {Nadia N.} and Hastie, {Annette T.} and Hoffman, {Eric A.} and Kaner, {Robert J.} and Kanner, {Richard E.} and Kleerup, {Eric C.} and Krishnan, {Jerry A.} and Lavange, {Lisa M.} and Lazarus, {Stephen C.} and Meyers, {Deborah A.} and Moore, {Wendy C.} and Newell, {John D.} and Laura Paulin and Stephen Peters and O'Neal, {Wanda K.} and Ortega, {Victor E.} and Robert Paine and Nirupama Putcha and Rennard, {Stephen I.} and Tashkin, {Donald P.} and Scholand, {Mary Beth} and {Michael Wells}, J. and Wise, {Robert A.}",
note = "Funding Information: SPB received funding from the NIH (K23HL133438); MKH reports personal fees from GSK, personal fees from BI, personal fees from AstraZeneca, nonfinancial 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. Funding Information: The authors thank the SPIROMICS participants and participating physicians, investigators and staff for making this research possible. More information about the study and how to access SPIROMICS data is at www.spiromics.org. We would like to acknowledge the following current and former investigators of the SPIROMICS sites and reading centers: Neil E Alexis, PhD; Wayne H Anderson, PhD; R Graham Barr, MD, DrPH; Eugene R Bleecker, MD; Richard C Boucher, MD; Russell P Bowler, MD, PhD; Elizabeth E Carretta, MPH; Stephanie A Christenson, MD; Alejandro P Comellas, MD; Christopher B Cooper, MD, PhD; David J Couper, PhD; Gerard J Criner, MD; Ronald G Crystal, MD; Jeffrey L Curtis, MD; Claire M Doerschuk, MD; Mark T Dransfield, MD; Christine M Freeman, PhD; MeiLan K Han, MD, MS; Nadia N Hansel, MD, MPH; Annette T Hastie, PhD; Eric A Hoffman, PhD; Robert J Kaner, MD; Richard E Kanner, MD; Eric C Kleerup, MD; Jerry A Krishnan, MD, PhD; Lisa M LaVange, PhD; Stephen C Lazarus, MD; Fernando J Martinez, MD, MS; Deborah A Meyers, PhD; Wendy C Moore, MD; John D Newell Jr., MD; Laura Paulin, MD, MHS; Stephen Peters, MD, PhD; Elizabeth C Oelsner, MD, MPH; Wanda K O{\textquoteright}Neal, PhD; Victor E Ortega, MD, PhD; Robert Paine, III, MD; Nirupama Putcha, MD, MHS; Stephen I. Rennard, MD; Donald P Tashkin, MD; Mary Beth Scholand, MD; J Michael Wells, MD; Robert A Wise, MD; and Prescott G Woodruff, MD, MPH. The project officers from the Lung Division of the National Heart, Lung, and Blood Institute were Lisa Postow, PhD, and Thomas Croxton, PhD, MD. SPIROMICS was supported by contracts from the NIH/NHLBI (HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, HHSN268200900020C), and supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/MedImmune; Bayer; Bellerophon Therapeutics; Boehringer-Ingelheim Pharmaceuticals, Inc..; Chiesi Farmaceutici S.p.A.; Forest Research Institute, Inc.; GlaxoSmithKline; Grifols Therapeutics, Inc.; Ikaria, Inc.; Nycomed GmbH; Takeda Pharmaceutical Company; Novartis Pharmaceuticals Corporation; ProterixBio; Regeneron Pharmaceuticals, Inc.; Sanofi; and Sunovion. Funding Information: This study was supported by NHLBI grant K23HL133438 to SPB. SPIROMICS was supported by contracts from the NIH/NHLBI (HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, HHSN268200900020C), and supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/ MedImmune; Bayer; Bellerophon Therapeutics; Boehringer-Ingelheim Pharmaceuticals, Inc..; Chiesi Farmaceutici S.p.A.; Forest Research Institute, Inc.; GlaxoSmithKline; Grifols Therapeutics, Inc.; Ikaria, Inc.; Nycomed GmbH; Takeda Pharmaceutical Company; Novartis Pharmaceuticals Corporation; ProterixBio; Regeneron Pharmaceuticals, Inc.; Sanofi; and Sunovion. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "18",
doi = "10.1186/s12931-018-0946-1",
language = "English (US)",
volume = "19",
journal = "Respiratory Research",
issn = "1465-9921",
publisher = "BioMed Central",
number = "1",
}