Chronic Obstructive Pulmonary Disease Exacerbations Increase the Risk of Subsequent Cardiovascular Events: A Longitudinal Analysis of the COPDGene Study
Authors: Yang Han‐Mo , Ryu Min Hyung , Carey Vincent J. , Kinney Gregory L. , Hokanson John E. , Dransfield Mark T. , Hersh Craig P. , Silverman Edwin K. , Crapo James D. , Silverman Edwin K. , Make Barry J. , Regan Elizabeth A. , Beaty Terri H. , Castaldi Peter J. , Cho Michael H. , DeMeo Dawn L. , El Boueiz Adel , Foreman Marilyn G. , Ghosh Auyon , Hayden Lystra P. , Hersh Craig P. , Hetmanski Jacqueline , Hobbs Brian D. , Hokanson John E. , Kim Wonji , Laird Nan , Lange Christoph , Lutz Sharon M. , McDonald Merry‐Lynn , Prokopenko Dmitry , Moll Matthew , Morrow Jarrett , Qiao Dandi , Regan Elizabeth A. , Saferali Aabida , Sakornsakolpat Phuwanat , Silverman Edwin K. , Wan Emily S. , Yun Jeong , Centeno Juan Pablo , Charbonnier Jean‐Paul , Coxson Harvey O. , Galban Craig J. , Han MeiLan K. , Hoffman Eric A. , Humphries Stephen , Jacobson Francine L. , Judy Philip F. , Kazerooni Ella A. , Kluiber Alex , Lynch David A. , Nardelli Pietro , Newell John D. , Notary Aleena , Oh Andrea , Regan Elizabeth A. , Ross James C. , Estepar Raul San Jose , Schroeder Joyce , Sieren Jered , Stoel Berend C. , Tschirren Juerg , Van Beek Edwin , van Ginneken Bram , van Rikxoort Eva , Sanchez‐Ferrero Gonzalo Vegas , Veitel Lucas , Washko George R. , Wilson Carla G. , Jensen Robert , Everett Douglas , Crooks Jim , Pratte Katherine , Strand Matt , Wilson Carla G. , Hokanson John E. , Austin Erin , Kinney Gregory , Lutz Sharon M. , Young Kendra A. , Bhatt Surya P. , Bon Jessica , Diaz Alejandro A. , Han MeiLan K. , Make Barry , Murray Susan , Regan Elizabeth , Soler Xavier , Wilson Carla G. , Bowler Russell P. , Kechris Katerina , Banaei‐Kashani Farnoush , Curtis Jeffrey L. , Pernicano Perry G. , Hanania Nicola , Atik Mustafa , Boriek Aladin , Guntupalli Kalpatha , Guy Elizabeth , Parulekar Amit , DeMeo Dawn L. , Hersh Craig , Jacobson Francine L. , Washko George , Barr R. Graham , Austin John , D’Souza Belinda , Thomashow Byron , MacIntyre Neil , McAdams H. Page , Washington Lacey , McEvoy Charlene , Tashjian Joseph , Wise Robert , Brown Robert , Hansel Nadia N. , Horton Karen , Lambert Allison , Putcha Nirupama , Casaburi Richard , Adami Alessandra , Budoff Matthew , Fischer Hans , Porszasz Janos , Rossiter Harry , Stringer William , Sharafkhaneh Amir , Lan Charlie , Wendt Christine , Bell Brian , Kunisaki Ken M. , Flenaugh Eric L. , Gebrekristos Hirut , Ponce Mario , Terpenning Silanath , Westney Gloria , Bowler Russell , Lynch David A. , Rosiello Richard , Pace David , Criner Gerard , Ciccolella David , Cordova Francis , Dass Chandra , D’Alonzo Gilbert , Desai Parag , Jacobs Michael , Kelsen Steven , Kim Victor , Mamary A. James , Marchetti Nathaniel , Satti Aditi , Shenoy Kartik , Steiner Robert M. , Swift Alex , Swift Irene , Vega‐Sanchez Maria Elena , Dransfield Mark , Bailey William , Bhatt Surya P. , Iyer Anand , Nath Hrudaya , Wells J. Michael , Conrad Douglas , Soler Xavier , Yen Andrew , Comellas Alejandro P. , Hoth Karin F. , Newell John , Thompson Brad , Han MeiLan K. , Kazerooni Ella , Labaki Wassim , Galban Craig , Vummidi Dharshan , Billings Joanne , Begnaud Abbie , Allen Tadashi , Sciurba Frank , Bon Jessica , Chandra Divay , Weissfeld Joel , Anzueto Antonio , Adams Sandra , Ruiz Mario E. , Singh Harjinder 
Published: May 2024

Background
Cardiovascular disease (CVD) is the most important comorbidity in patients with chronic obstructive pulmonary disease (COPD). COPD exacerbations not only contribute to COPD progression but may also elevate the risk of CVD. This study aimed to determine whether COPD exacerbations increase the risk of subsequent CVD events using up to 15 years of prospective longitudinal follow‐up data from the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study.

Methods and Results
The COPDGene study is a large, multicenter, longitudinal investigation of COPD, including subjects at enrollment aged 45 to 80 years with a minimum of 10 pack‐years of smoking history. Cox proportional hazards models and Kaplan‐Meier survival curves were used to assess the risk of a composite end point of CVD based on the COPD exacerbation rate. Frequent exacerbators exhibited a higher cumulative incidence of composite CVD end points than infrequent exacerbators, irrespective of the presence of CVD at baseline. After adjusting for covariates, frequent exacerbators still maintained higher hazard ratios (HRs) than the infrequent exacerbator group (without CVD: HR, 1.81 [95% CI, 1.47–2.22]; with CVD: HR, 1.92 [95% CI, 1.51–2.44]). This observation remained consistently significant in moderate to severe COPD subjects and the preserved ratio impaired spirometry population. In the mild COPD population, frequent exacerbators showed a trend toward more CVD events.

Conclusions
COPD exacerbations are associated with an increased risk of subsequent cardiovascular events in subjects with and without preexisting CVD. Patients with COPD experiencing frequent exacerbations may necessitate careful monitoring and additional management for subsequent potential CVD.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00608764.