on March 10, 2003
Circulation. 2003
Published online before print March 10, 2003, doi: 10.1161/01.CIR.0000056767.69054.B3
Published online before print March 10, 2003, doi: 10.1161/01.CIR.0000056767.69054.B3
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on November 21, 2002
From the Department of Medicine, Pulmonary Division (D.D.S., S.F.P.M.), University of Alberta, Edmonton, Alberta, Canada, and The Institute of Health Economics (D.D.S.), Edmonton, Alberta, Canada. * To whom correspondence should be addressed. E-mail: don.sin{at}ualberta.ca.
Background--Chronic obstructive pulmonary disease (COPD) increases the risk of cardiovascular disease 2- to 3- fold. The factors responsible for this association remain largely unknown. Methods and Results--We analyzed data from participants, Conclusion--Low-grade systemic inflammation was present in participants with moderate to severe airflow obstruction and was associated with increased risk of cardiac injury. This may in part explain the high rates of cardiovascular complications in COPD.
Accepted on December 5, 2002
Why Are Patients With Chronic Obstructive Pulmonary Disease at Increased Risk of Cardiovascular Diseases?. The Potential Role of Systemic Inflammation in Chronic Obstructive Pulmonary Disease
Don D. Sin MD, MPH* and S.F. Paul Man MD
50 years of age, of the Third National Health and Nutrition Examination Survey (n=6629) to determine whether C-reactive protein (CRP) and other systemic inflammatory markers are present in participants with chronic airflow obstruction and are associated with cardiac injury. Participants with severe airflow obstruction had circulating leukocyte, platelet, and fibrinogen levels that were 460/µL (95% confidence interval [CI], 30 to 890/µL), 39 510/µL (95% CI, 21 730 to 57 290/µL), and 41.63 mg/dL (95% CI, 19.87 to 63.39 mg/dL) higher, respectively, than in those without airflow obstruction. They were also 2.18 times (95% CI, 1.46 to 3.27) more likely to have an elevated circulating CRP level. Moderate airflow obstruction was associated with smaller but still significant increases in these levels. Moderate and severe airflow obstruction was associated with increased occurrence of ischemic changes on electrocardiograms of participants. In the presence of both highly elevated CRP and moderate or severe airflow obstruction, the Cardiac Infarction Injury Score was 2.68 and 5.88 U higher, respectively, than in those without airflow obstruction and with low CRP, which suggests an additive effect of CRP and COPD on the risk of cardiac injury.
Key words: chronic obstructive pulmonary disease • inflammation, systemic • C-reactive protein • epidemiology
This article has been cited by other articles:
 |
|
 |
|
  S. Singh, Y. K. Loke, and C. D. Furberg Inhaled Anticholinergics and Risk of Major Adverse Cardiovascular Events in Patients With Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis JAMA, September 24, 2008; 300(12): 1439 - 1450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sunyer, R. Pistelli, E. Plana, M. Andreani, F. Baldari, M. Kolz, W. Koenig, J. Pekkanen, A. Peters, and F. Forastiere Systemic inflammation, genetic susceptibility and lung function Eur. Respir. J., July 1, 2008; 32(1): 92 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Moro, C. Pedone, S. Scarlata, V. Malafarina, F. Fimognari, and R. Antonelli-Incalzi Endothelial Dysfunction in Chronic Obstructive Pulmonary Disease Angiology, July 1, 2008; 59(3): 357 - 364. [Abstract] [PDF]
|
|
|
|
 |
|
 A K Johnston, D M Mannino, G W Hagan, K J Davis, and V A Kiri Relationship between lung function impairment and incidence or recurrence of cardiovascular events in a middle-aged cohort Thorax, July 1, 2008; 63(7): 599 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Todd, R. A. McIvor, S. O. Pugsley, and G. Cox Approach to chronic obstructive pulmonary disease in primary care Can Fam Physician, May 1, 2008; 54(5): 706 - 711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Falk, S. Kadiev, G. J. Criner, S. M. Scharf, O. A. Minai, and P. Diaz Cardiac Disease in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, May 1, 2008; 5(4): 543 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N L Mills, J J Miller, A Anand, S D Robinson, G A Frazer, D Anderson, L Breen, I B Wilkinson, C M McEniery, K Donaldson, et al. Increased arterial stiffness in patients with chronic obstructive pulmonary disease: a mechanism for increased cardiovascular risk Thorax, April 1, 2008; 63(4): 306 - 311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Brekke, T. Omland, S. H. Holmedal, P. Smith, and V. Soyseth Troponin T elevation and long-term mortality after chronic obstructive pulmonary disease exacerbation Eur. Respir. J., March 1, 2008; 31(3): 563 - 570. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cazzola, W. MacNee, F. J. Martinez, K. F. Rabe, L. G. Franciosi, P. J. Barnes, V. Brusasco, P. S. Burge, P. M. A. Calverley, B. R. Celli, et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers Eur. Respir. J., February 1, 2008; 31(2): 416 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Poulain, M. Doucet, V. Drapeau, G. Fournier, A. Tremblay, P. Poirier, and F. Maltais Metabolic and inflammatory profile in obese patients with chronic obstructive pulmonary disease Chronic Respiratory Disease, February 1, 2008; 5(1): 35 - 41. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Bozinovski, A. Hutchinson, M. Thompson, L. MacGregor, J. Black, E. Giannakis, A.-S. Karlsson, R. Silvestrini, D. Smallwood, R. Vlahos, et al. Serum Amyloid A Is a Biomarker of Acute Exacerbations of Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., February 1, 2008; 177(3): 269 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Sin and S. F. P. Man Interleukin-6: A Red Herring or a Real Catch in COPD? Chest, January 1, 2008; 133(1): 4 - 6. [Full Text] [PDF]
|
|
|
|
|
|
R. E. Walter, J. B. Wilk, M. G. Larson, R. S. Vasan, J. F. Keaney Jr, I. Lipinska, G. T. O'Connor, and E. J. Benjamin Systemic Inflammation and COPD: The Framingham Heart Study Chest, January 1, 2008; 133(1): 19 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Han, V. V. McLaughlin, G. J. Criner, and F. J. Martinez Pulmonary Diseases and the Heart Circulation, December 18, 2007; 116(25): 2992 - 3005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. McAllister, J. D. Maclay, N. L. Mills, G. Mair, J. Miller, D. Anderson, D. E. Newby, J. T. Murchison, and W. MacNee Arterial Stiffness Is Independently Associated with Emphysema Severity in Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., December 15, 2007; 176(12): 1208 - 1214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Tamisier, B. E. Hunt, G. S. Gilmartin, M. Curley, A. Anand, and J. W. Weiss Hemodynamics and muscle sympathetic nerve activity after 8 h of sustained hypoxia in healthy humans Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H3027 - H3035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tkac, S. F. P. Man, and D. D. Sin Review: Systemic consequences of COPD Therapeutic Advances in Respiratory Disease, October 1, 2007; 1(1): 47 - 59. [Abstract] [PDF]
|
|
|
|
|
|
A. Agusti Systemic Effects of Chronic Obstructive Pulmonary Disease: What We Know and What We Don't Know (but Should) Proceedings of the ATS, October 1, 2007; 4(7): 522 - 525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. Rennard Inflammation in COPD: a link to systemic comorbidities Eur. Respir. Rev., September 1, 2007; 16(105): 91 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Brusasco, E. Crimi, and R. Pellegrino Airway Inflammation in COPD: Friend or Foe? Am. J. Respir. Crit. Care Med., September 1, 2007; 176(5): 425 - 426. [Full Text] [PDF]
|
|
|
|
 |
|
 F. L. Fimognari, P. Pasqualetti, L. Moro, A. Franco, G. Piccirillo, R. Pastorelli, P. M. Rossini, and R. A. Incalzi The Association Between Metabolic Syndrome and Restrictive Ventilatory Dysfunction in Older Persons J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2007; 62(7): 760 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tomoda, M. Yoshikawa, T. Itoh, S. Tamaki, A. Fukuoka, K. Komeda, and H. Kimura Elevated Circulating Plasma Adiponectin in Underweight Patients With COPD Chest, July 1, 2007; 132(1): 135 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Vestbo Systemic inflammation and progression of COPD Thorax, June 1, 2007; 62(6): 469 - 470. [Full Text] [PDF]
|
|
|
|
|
|
D. Stolz, M. Christ-Crain, N. G. Morgenthaler, J. Leuppi, D. Miedinger, R. Bingisser, C. Muller, J. Struck, B. Muller, and M. Tamm Copeptin, C-Reactive Protein, and Procalcitonin as Prognostic Biomarkers in Acute Exacerbation of COPD Chest, April 1, 2007; 131(4): 1058 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Agusti and J. B. Soriano Dynamic hyperinflation and pulmonary inflammation: a potentially relevant relationship? Eur. Respir. Rev., December 1, 2006; 15(100): 68 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D D Sin Inhaled corticosteroids and mortality in COPD. Thorax, October 1, 2006; 61(10): 918 - 918. [Full Text] [PDF]
|
|
|
|
|
|
S F P Man, J E Connett, N R Anthonisen, R A Wise, D P Tashkin, and D D Sin C-reactive protein and mortality in mild to moderate chronic obstructive pulmonary disease Thorax, October 1, 2006; 61(10): 849 - 853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Aronson, I. Roterman, M. Yigla, A. Kerner, O. Avizohar, R. Sella, P. Bartha, Y. Levy, and W. Markiewicz Inverse Association between Pulmonary Function and C-Reactive Protein in Apparently Healthy Subjects Am. J. Respir. Crit. Care Med., September 15, 2006; 174(6): 626 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Sin and S.F. P. Man Cooling the Fire Within: Inhaled Corticosteroids and Cardiovascular Mortality in COPD. Chest, September 1, 2006; 130(3): 629 - 631. [Full Text] [PDF]
|
|
|
|
|
|
D. D. Sin and S. F. P. Man Pharmacotherapy for Mortality Reduction in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, September 1, 2006; 3(7): 624 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Agusti Thomas A. Neff Lecture. Chronic Obstructive Pulmonary Disease: A Systemic Disease Proceedings of the ATS, August 1, 2006; 3(6): 478 - 481. [Full Text] [PDF]
|
|
|
|
|
|
W. MacNee Conference Summary Proceedings of the ATS, August 1, 2006; 3(6): 539 - 542. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Thyagarajan, D. R Jacobs, G. G Apostol, L. J Smith, C. E Lewis, and O D. Williams Plasma fibrinogen and lung function: the CARDIA Study Int. J. Epidemiol., August 1, 2006; 35(4): 1001 - 1008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D Sin and S. P. Man Commentary: Fuelling the fire--systemic inflammation and development of lung disease in the general community Int. J. Epidemiol., August 1, 2006; 35(4): 1008 - 1010. [Full Text] [PDF]
|
|
|
|
 |
|
 G.B. J. Mancini, M. Etminan, B. Zhang, L. E. Levesque, J. M. FitzGerald, and J. M. Brophy Reduction of Morbidity and Mortality by Statins, Angiotensin-Converting Enzyme Inhibitors, and Angiotensin Receptor Blockers in Patients With Chronic Obstructive Pulmonary Disease J. Am. Coll. Cardiol., June 20, 2006; 47(12): 2554 - 2560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. F. M. Wouters The systemic face of airway diseases: the role of C-reactive protein. Eur. Respir. J., May 1, 2006; 27(5): 877 - 879. [Full Text] [PDF]
|
|
|
|
|
|
E. F. M. Wouters Approaches to Improving Health Status in Chronic Obstructive Pulmonary Disease: One or Several? Proceedings of the ATS, May 1, 2006; 3(3): 262 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. I. Rennard Chronic Obstructive Pulmonary Disease: Linking Outcomes and Pathobiology of Disease Modification Proceedings of the ATS, May 1, 2006; 3(3): 276 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. de Torres, E. Cordoba-Lanus, C. Lopez-Aguilar, M. Muros de Fuentes, A. Montejo de Garcini, A. Aguirre-Jaime, B. R. Celli, and C. Casanova C-reactive protein levels and clinically important predictive outcomes in stable COPD patients Eur. Respir. J., May 1, 2006; 27(5): 902 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Poulain, M. Doucet, G. C. Major, V. Drapeau, F. Series, L.-P. Boulet, A. Tremblay, and F. Maltais The effect of obesity on chronic respiratory diseases: pathophysiology and therapeutic strategies. Can. Med. Assoc. J., April 25, 2006; 174(9): 1293 - 1299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Ochs-Balcom, B. J.B. Grant, P. Muti, C. T. Sempos, J. L. Freudenheim, M. Trevisan, P. A. Cassano, L. Iacoviello, and H. J. Schunemann Pulmonary function and abdominal adiposity in the general population. Chest, April 1, 2006; 129(4): 853 - 862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Mannino, G. Watt, D. Hole, C. Gillis, C. Hart, A. McConnachie, G. Davey Smith, M. Upton, V. Hawthorne, D. D. Sin, et al. The natural history of chronic obstructive pulmonary disease. Eur. Respir. J., March 1, 2006; 27(3): 627 - 643. [Full Text] [PDF]
|
|
|
|
|
|
R Broekhuizen, E F M Wouters, E C Creutzberg, and A M W J Schols Raised CRP levels mark metabolic and functional impairment in advanced COPD Thorax, January 1, 2006; 61(1): 17 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V M Pinto-Plata, H Mullerova, J F Toso, M Feudjo-Tepie, J B Soriano, R S Vessey, and B R Celli C-reactive protein in patients with COPD, control smokers and non-smokers Thorax, January 1, 2006; 61(1): 23 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. N. Agusti Systemic Effects of Chronic Obstructive Pulmonary Disease Proceedings of the ATS, November 1, 2005; 2(4): 367 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. I. Rennard and J. A. Stoner Challenges and Opportunities for Combination Therapy in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, November 1, 2005; 2(4): 391 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Andreas, S. D. Anker, P. D. Scanlon, and V. K. Somers Neurohumoral Activation as a Link to Systemic Manifestations of Chronic Lung Disease Chest, November 1, 2005; 128(5): 3618 - 3624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. Donaldson, T. A. R. Seemungal, I. S. Patel, A. Bhowmik, T. M. A. Wilkinson, J. R. Hurst, P. K. MacCallum, and J. A. Wedzicha Airway and Systemic Inflammation and Decline in Lung Function in Patients With COPD Chest, October 1, 2005; 128(4): 1995 - 2004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F L Fimognari, L Moro, R Antonelli Incalzi, D D Sin, W Q Gan, S F P Man, and A Senthilselvan COPD, restrictive syndrome and inflammation Thorax, July 1, 2005; 60(7): 612 - 613. [Full Text] [PDF]
|
|
|
|
|
|
D. D. Sin, L. Wu, and S. F. P. Man The Relationship Between Reduced Lung Function and Cardiovascular Mortality: A Population-Based Study and a Systematic Review of the Literature Chest, June 1, 2005; 127(6): 1952 - 1959. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sunyer and C. S. Ulrik Level of FEV1 as a predictor of all-cause and cardiovascular mortality: an effect beyond smoking and physical fitness? Eur. Respir. J., April 1, 2005; 25(4): 587 - 588. [Full Text] [PDF]
|
|
|
|
|
|
D. D. Sin and S. F. P. Man Chronic Obstructive Pulmonary Disease as a Risk Factor for Cardiovascular Morbidity and Mortality Proceedings of the ATS, April 1, 2005; 2(1): 8 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Hunninghake Cardiovascular Disease in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 44 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. MacNee Pulmonary and Systemic Oxidant/Antioxidant Imbalance in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 50 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. F. P. Man and D. D. Sin Effects of Corticosteroids on Systemic Inflammation in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 78 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Buhl and S. G. Farmer Future Directions in the Pharmacologic Therapy of Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 83 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. I. Rennard Clinical Approach to Patients with Chronic Obstructive Pulmonary Disease and Cardiovascular Disease Proceedings of the ATS, April 1, 2005; 2(1): 94 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Q. Gan, S.F. P. Man, and D. D. Sin The Interactions Between Cigarette Smoking and Reduced Lung Function on Systemic Inflammation Chest, February 1, 2005; 127(2): 558 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Sin, P. Lacy, E. York, and S. F. P. Man Effects of Fluticasone on Systemic Markers of Inflammation in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., October 1, 2004; 170(7): 760 - 765. [Abstract] [Full Text] [PDF] |