Pathophysiology of coronary artery disease
Abstract
During the past decade, our understanding of the pathophysiology of coronary artery disease (CAD) has undergone a remarkable evolution. We review here how these advances have altered our concepts of and clinical approaches to both the chronic and acute phases of CAD. Previously considered a cholesterol storage disease, we currently view atherosclerosis as an inflammatory disorder. The appreciation of arterial remodeling (compensatory enlargement) has expanded attention beyond stenoses evident by angiography to encompass the biology of nonstenotic plaques. Revascularization effectively relieves ischemia, but we now recognize the need to attend to nonobstructive lesions as well. Aggressive management of modifiable risk factors reduces cardiovascular events and should accompany appropriate revascularization. We now recognize that disruption of plaques that may not produce critical stenoses causes many acute coronary syndromes (ACS). The disrupted plaque represents a “solid-state” stimulus to thrombosis. Alterations in circulating prothrombotic or antifibrinolytic mediators in the “fluid phase” of the blood can also predispose toward ACS. Recent results have established the multiplicity of “high-risk” plaques and the widespread nature of inflammation in patients prone to develop ACS. These findings challenge our traditional view of coronary atherosclerosis as a segmental or localized disease. Thus, treatment of ACS should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid “stabilization” of other plaques that may produce recurrent events. The concept of “interventional cardiology” must expand beyond mechanical revascularization to embrace preventive interventions that forestall future events.
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Inflammation is a key pathogenic mechanism in many infectious, autoimmune, cardiovascular, and psychiatric diseases.
“However, with increasing recognition that inflammation is a key pathogenic mechanism in many infectious, autoimmune, cardiovascular, and psychiatric diseases (11–13), the adequacy of this explanation has been called into question (14–15).”
From A Functional Genomic Fingerprint of Chronic Stress in Humans: Blunted Glucocorticoid and Increased NF-κB Signaling (2008) · cites this paper as [11]
The profile suggests that long-term stress brings about functional resistance to glucocorticoid signal transduction in monocytes, reducing inhibition of NF-κB and EGR1 and fostering pro-inflammatory dynamics that promote chronic diseases.
“This profile suggests a scenario in which long-term stress brings about a functional resistance to glucocortioid signal transduction in monocytes, which reduces inhibition of NF-κB and EGR1, and thereby fosters the kind of pro-inflammatory dynamics that ultimately promote chronic diseases, including diabetes, coronary disease, autoimmune disorders, chronic infections, and some cancers (11–13).”
From A Functional Genomic Fingerprint of Chronic Stress in Humans: Blunted Glucocorticoid and Increased NF-κB Signaling (2008) · cites this paper as [11]
Cites
Inflammation and Atherosclerosis
Libby, P., Ridker, P. M., & Maseri, A. (2002) · Circulation · doi:10.1161/hc0902.104353 · Cited by 7,724 · see citing works
Self-citationGrundy, S. M., Cleeman, J. I., Merz, C. N. B., Brewer, H. B., Clark, L. T., Hunninghake, D. B., Pasternak, R. C., Smith, S. C., & Stone, N. J. (2004) · Circulation · doi:10.1161/01.cir.0000133317.49796.0e · Cited by 6,902 · see citing works
C-Reactive Protein Levels and Outcomes after Statin Therapy
Ridker, P. M., Cannon, C. P., Morrow, D., Rifai, N., Rose, L. M., McCabe, C. H., Pfeffer, M. A., & Braunwald, E. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa042378 · Cited by 2,292 · see citing works
Ridker, P. M., Rifai, N., Clearfield, M., Downs, J. R., Weis, S. E., Miles, J. S., & Gotto, A. M. (2001) · New England Journal of Medicine · doi:10.1056/nejm200106283442601 · Cited by 1,557 · see citing works
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The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442 · see citing works
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pacher, P., Bátkai, S., & Kunos, G. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.2 · Cited by 2,077 · see citing works
Genomewide Association Analysis of Coronary Artery Disease
Samani, N. J., Erdmann, J., Hall, A. S., Hengstenberg, C., Mangino, M., Mayer, B., Dixon, R. J., Meitinger, T., Braund, P., Wichmann, H.-E., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa072366 · Cited by 2,044 · see citing works
Ridker, P. M., Buring, J. E., Rifai, N., & Cook, N. R. (2007) · JAMA · doi:10.1001/jama.297.6.611 · Cited by 1,814 · see citing works
Miller, G. E., Chen, E., & Parker, K. J. (2011) · Psychological Bulletin · doi:10.1037/a0024768 · Cited by 1,785 · see citing works
Update on acute coronary syndromes: the pathologists' view
Falk, E., Nakano, M., Bentzon, J. F., Finn, A. V., & Virmani, R. (2013) · European Heart Journal · doi:10.1093/eurheartj/ehs411 · Cited by 1,047 · see citing works
Rosenfeld, M. G., Lunyak, V. V., & Glass, C. K. (2006) · Genes & Development · doi:10.1101/gad.1424806 · Cited by 952 · see citing works
Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction
Packard, R. R. S., & Libby, P. (2008) · Clinical Chemistry · doi:10.1373/clinchem.2007.097360 · Cited by 925 · see citing works
Self-citationDen Ruijter, H. M., Peters, S. A. E., Anderson, T. J., Britton, A. R., Dekker, J. M., Eijkemans, M. J., Engström, G., Evans, G. W., de Graaf, J., Grobbee, D. E., et al. (2012) · JAMA · doi:10.1001/jama.2012.9630 · Cited by 760 · see citing works
Miller, G., Chen, E., & Cole, S. W. (2009) · Annual Review of Psychology · doi:10.1146/annurev.psych.60.110707.163551 · Cited by 591 · see citing works
Santos, C. X. C., Tanaka, L. Y., Wosniak, J., & Laurindo, F. R. M. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2625 · Cited by 572 · see citing works
Miller, G. E., Chen, E., Sze, J., Marin, T., Arevalo, J. M. G., Doll, R., Ma, R., & Cole, S. W. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.03.017 · Cited by 552 · see citing works
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Mazur, A., Maier, J. A. M., Rock, E., Gueux, E., Nowacki, W., & Rayssiguier, Y. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2006.03.031 · Cited by 474 · see citing works
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Dokken, B. B. (2008) · Diabetes Spectrum · doi:10.2337/diaspect.21.3.160 · Cited by 299 · see citing works
Lansky, A. J., Ng, V. G., Maehara, A., Weisz, G., Lerman, A., Mintz, G. S., De Bruyne, B., Farhat, N., Niess, G., Jankovic, I., et al. (2012) · JACC: Cardiovascular Imaging · doi:10.1016/j.jcmg.2012.02.003 · Cited by 289 · see citing works
Bower, J. E., Greendale, G., Crosswell, A. D., Garet, D., Sternlieb, B., Ganz, P. A., Irwin, M. R., Olmstead, R., Arevalo, J., & Cole, S. W. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.01.019 · Cited by 283 · see citing works
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Spitzer, C., Barnow, S., Völzke, H., John, U., Freyberger, H. J., & Grabe, H. J. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181bc76b5 · Cited by 276 · see citing works
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Watanabe, Y., Kitamura, K., Nakamura, K., Sanpei, K., Wakasugi, M., Yokoseki, A., Onodera, O., Ikeuchi, T., Kuwano, R., Momotsu, T., et al. (2016) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000442585 · Cited by 65 · see citing works
Machha, A., & Schechter, A. N. (2012) · Nutrition Reviews · doi:10.1111/j.1753-4887.2012.00477.x · Cited by 51 · see citing works
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Simons, R. L., Lei, M.-K., Beach, S. R. H., Barr, A. B., Cutrona, C. E., Gibbons, F. X., & Philibert, R. A. (2017) · Social Science & Medicine · doi:10.1016/j.socscimed.2017.03.005 · Cited by 38 · see citing works
Velupillai, Y. N., Packard, C. J., Batty, G. D., Bezlyak, V., Burns, H., Cavanagh, J., Deans, K., Ford, I., McGinty, A., Millar, K., et al. (2008) · BMC Public Health · doi:10.1186/1471-2458-8-126 · Cited by 36 · see citing works
Pan, J.-A., Zhang, H., Yu, Q., Zhang, J.-F., Wang, C.-Q., Gu, J., & Chen, K. (2021) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2021.02.020 · Cited by 34 · see citing works
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Ehrlich, K. B., Miller, G. E., Rohleder, N., & Adam, E. K. (2016) · Development and Psychopathology · doi:10.1017/s0954579415000334 · Cited by 28 · see citing works
Gao, Z., Zhang, D., Yan, X., Shi, H., & Xian, X. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.904250 · Cited by 22 · see citing works
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Adebayo, J. O., Balogun, E. A., Malomo, S. O., Soladoye, A. O., Olatunji, L. A., Kolawole, O. M., Oguntoye, O. S., Babatunde, A. S., Akinola, O. B., Aguiar, A. C. C., et al. (2013) · Evidence-Based Complementary and Alternative Medicine · doi:10.1155/2013/742476 · Cited by 21 · see citing works
Roe, Y. L., Zeitz, C. J., & Fredericks, B. (2012) · BMC Health Services Research · doi:10.1186/1472-6963-12-397 · Cited by 17 · see citing works
Liu, Z., Xu, Y., Hao, H., Yin, C., Xu, J., Li, J., Wang, Y., & Xu, D. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.07.140 · Cited by 16 · see citing works
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- Authors
- Libby, P., & Theroux, P.
- Affiliations
- Brigham and Women's Hospital (US)
- From the Donald W. Reynolds Cardiovascular Clinical Research Center (P.L.), Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass, and the Department of Medicine (P.T.), Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada.
- ORCID
- Libby, Peter
- Venue
- Circulation
- Published
- 2005-06-28
- Volume
- 111
- Issue
- 25
- Pages
- 3481-3488
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2122450058
- Cited by
- 1,965
- References
- 4
- Citations by year
- 2026: 75 · 2025: 131 · 2024: 128 · 2023: 103 · 2022: 96 · 2021: 109 · 2020: 70 · 2019: 78 · 2018: 75 · 2017: 86 · 2016: 82 · 2015: 96 · 2014: 95 · 2013: 96 · 2012: 103
- FWCI
- 7.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Circulation
- Funders
- National Heart, Lung, and Blood Institute (P50HL056985, HL56985, HL-48743, HL-34636, P01HL048743)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Coronary Interventions and Diagnostics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Keywords
- coronary artery disease, atherosclerosis, inflammation, arterial remodeling, acute coronary syndrome, plaque rupture, thrombosis, vulnerable plaque, plaque stabilization, revascularization, cardiovascular risk factors, preventive cardiology
- MeSH terms
- Constriction, Pathologic, Coronary Artery Disease, Coronary Thrombosis, Humans, Inflammation, Secondary Prevention
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