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

Surya P. Bhatt; Hrudaya P. Nath; Young Il Kim; Rekha Ramachandran; Jubal R. Watts; Nina L.J. Terry; Sushil Sonavane; Swati P. Deshmane; Prescott G. Woodruff; Elizabeth C. Oelsner; Sandeep Bodduluri; Meilan K. Han; Wassim W. Labaki; J. Michael Wells; Fernando J. Martinez; R. Graham Barr; Mark T. Dransfield; Neil E. Alexis; Wayne H. Anderson; Eugene R. Bleecker; Richard C. Boucher; Russell P. Bowler; Elizabeth E. Carretta; Stephanie A. Christenson; Alejandro P. Comellas; Christopher B. Cooper; David J. Couper; Gerard J. Criner; Ronald G. Crystal; Jeffrey L. Curtis; Claire M. Doerschuk; Christine M. Freeman; Nadia N. Hansel; Annette T. Hastie; Eric A. Hoffman; Robert J. Kaner; Richard E. Kanner; Eric C. Kleerup; Jerry A. Krishnan; Lisa M. Lavange; Stephen C. Lazarus; Deborah A. Meyers; Wendy C. Moore; John D. Newell; Laura Paulin; Stephen Peters; Wanda K. O'Neal; Victor E. Ortega; Robert Paine; Nirupama Putcha; Stephen I. Rennard; Donald P. Tashkin; Mary Beth Scholand; J. Michael Wells; Robert A. Wise

doi:10.1186/s12931-018-0946-1

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

Surya P. Bhatt, Hrudaya P. Nath, Young Il Kim, Rekha Ramachandran, Jubal R. Watts, Nina L.J. Terry, Sushil Sonavane, Swati P. Deshmane, Prescott G. Woodruff, Elizabeth C. Oelsner, Sandeep Bodduluri, Meilan K. Han, Wassim W. Labaki, J. Michael Wells, Fernando J. Martinez, R. Graham Barr, Mark T. Dransfield, Neil E. Alexis, Wayne H. Anderson, Eugene R. BleeckerRichard C. Boucher, Russell P. Bowler, Elizabeth E. Carretta, Stephanie A. Christenson, Alejandro P. Comellas, Christopher B. Cooper, David J. Couper, Gerard J. Criner, Ronald G. Crystal, Jeffrey L. Curtis, Claire M. Doerschuk, Christine M. Freeman, Nadia N. Hansel, Annette T. Hastie, Eric A. Hoffman, Robert J. Kaner, Richard E. Kanner, Eric C. Kleerup, Jerry A. Krishnan, Lisa M. Lavange, Stephen C. Lazarus, Deborah A. Meyers, Wendy C. Moore, John D. Newell, Laura Paulin, Stephen Peters, Wanda K. O'Neal, Victor E. Ortega, Robert Paine, Nirupama Putcha, Stephen I. Rennard, Donald P. Tashkin, Mary Beth Scholand, J. Michael Wells, Robert A. Wise

Medicine

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

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.

Original language	English (US)
Article number	257
Journal	Respiratory Research
Volume	19
Issue number	1
DOIs	https://doi.org/10.1186/s12931-018-0946-1
State	Published - Dec 18 2018

Keywords

COPD
Cardiovascular disease
Coronary artery calcification
Emphysema
Mediators

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

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10.1186/s12931-018-0946-1

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Bhatt, S. P., Nath, H. P., Kim, Y. I., Ramachandran, R., Watts, J. R., Terry, N. L. J., Sonavane, S., Deshmane, S. P., Woodruff, P. G., Oelsner, E. C., Bodduluri, S., Han, M. K., Labaki, W. W., Michael Wells, J., Martinez, F. J., Barr, R. G., Dransfield, M. T., Alexis, N. E., Anderson, W. H., ... Wise, R. A. (2018). Centrilobular emphysema and coronary artery calcification: Mediation analysis in the SPIROMICS cohort. Respiratory Research, 19(1), Article 257. https://doi.org/10.1186/s12931-018-0946-1

Bhatt, SP, Nath, HP, Kim, YI, Ramachandran, R, Watts, JR, Terry, NLJ, Sonavane, S, Deshmane, SP, Woodruff, PG, Oelsner, EC, Bodduluri, S, Han, MK, Labaki, WW, Michael Wells, J, Martinez, FJ, Barr, RG, Dransfield, MT, Alexis, NE, Anderson, WH, Bleecker, ER, Boucher, RC, Bowler, RP, Carretta, EE, Christenson, SA, Comellas, AP, Cooper, CB, Couper, DJ, Criner, GJ, Crystal, RG, Curtis, JL, Doerschuk, CM, Freeman, CM, Hansel, NN, Hastie, AT, Hoffman, EA, Kaner, RJ, Kanner, RE, Kleerup, EC, Krishnan, JA, Lavange, LM, Lazarus, SC, Meyers, DA, Moore, WC, Newell, JD, Paulin, L, Peters, S, O'Neal, WK, Ortega, VE, Paine, R, Putcha, N, Rennard, SI, Tashkin, DP, Scholand, MB, Michael Wells, J & Wise, RA 2018, 'Centrilobular emphysema and coronary artery calcification: Mediation analysis in the SPIROMICS cohort', Respiratory Research, vol. 19, no. 1, 257. https://doi.org/10.1186/s12931-018-0946-1

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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 = "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",

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TY - JOUR

T1 - Centrilobular emphysema and coronary artery calcification

T2 - Mediation analysis in the SPIROMICS cohort

AU - Bhatt, Surya P.

AU - Nath, Hrudaya P.

AU - Kim, Young Il

AU - Ramachandran, Rekha

AU - Watts, Jubal R.

AU - Terry, Nina L.J.

AU - Sonavane, Sushil

AU - Deshmane, Swati P.

AU - Woodruff, Prescott G.

AU - Oelsner, Elizabeth C.

AU - Bodduluri, Sandeep

AU - Han, Meilan K.

AU - Labaki, Wassim W.

AU - Michael Wells, J.

AU - Martinez, Fernando J.

AU - Barr, R. Graham

AU - Dransfield, Mark T.

AU - Alexis, Neil E.

AU - Anderson, Wayne H.

AU - Bleecker, Eugene R.

AU - Boucher, Richard C.

AU - Bowler, Russell P.

AU - Carretta, Elizabeth E.

AU - Christenson, Stephanie A.

AU - Comellas, Alejandro P.

AU - Cooper, Christopher B.

AU - Couper, David J.

AU - Criner, Gerard J.

AU - Crystal, Ronald G.

AU - Curtis, Jeffrey L.

AU - Doerschuk, Claire M.

AU - Freeman, Christine M.

AU - Hansel, Nadia N.

AU - Hastie, Annette T.

AU - Hoffman, Eric A.

AU - Kaner, Robert J.

AU - Kanner, Richard E.

AU - Kleerup, Eric C.

AU - Krishnan, Jerry A.

AU - Lavange, Lisa M.

AU - Lazarus, Stephen C.

AU - Meyers, Deborah A.

AU - Moore, Wendy C.

AU - Newell, John D.

AU - Paulin, Laura

AU - Peters, Stephen

AU - O'Neal, Wanda K.

AU - Ortega, Victor E.

AU - Paine, Robert

AU - Putcha, Nirupama

AU - Rennard, Stephen I.

AU - Tashkin, Donald P.

AU - Scholand, Mary Beth

AU - Michael Wells, J.

AU - Wise, Robert A.

PY - 2018/12/18

Y1 - 2018/12/18

N2 - 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.

AB - 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.

KW - COPD

KW - Cardiovascular disease

KW - Coronary artery calcification

KW - Emphysema

KW - Mediators

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U2 - 10.1186/s12931-018-0946-1

DO - 10.1186/s12931-018-0946-1

M3 - Article

C2 - 30563576

AN - SCOPUS:85058800500

SN - 1465-9921

VL - 19

JO - Respiratory Research

JF - Respiratory Research

IS - 1

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ER -

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

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