Lewis A. Conner Memorial Lecture. Mechanisms leading to myocardial infarction: insights from studies of vascular biology.
Abstract
Myocardial infarction is the most frequent cause of mortality in the United States as well as in most western countries. In this review, the processes leading to myocardial infarction are described based on the most recent studies of vascular biology; in addition, evolving strategies for prevention are outlined. The following was specifically discussed. (1) Five phases of the progression of coronary atherosclerosis (phases 1 to 5) and eight morphologically different lesions (types I, II, III, IV, Va, Vb, Vc, and VI) in the various phases are defined. (2) The present understanding of the pathogenesis of each of the phases of progression and of the various lesion types preceding myocardial infarction is described; particular emphasis is placed on the physical, structural, cellular, and chemical characteristics of the "vulnerable or unstable plaques" prone to disruption (types IV and Va lesions). (3) The fate of plaque disruption (type VI lesion) in the genesis of the various coronary syndromes and especially acute myocardial infarction is defined; particular emphasis is placed on the combination of plaque disruption and a high thrombogenic risk profile--local factors (ie, degree of plaque disruption, exposure of lipid-macrophage-rich plaque, etc) and systemic factors (ie, catecholamines, RAS, fibrinogen, etc)--in the genesis of myocardial infarction. (4) Strategies of regression or stabilization of "vulnerable or unstable plaques" for prevention of myocardial infarction are presented within the context of recent favorable experience with risk factor modification and lipid-modifying angiographic trials, beta-blockade and angiotensin-converting enzyme inhibition, antithrombotic strategies, and the possible role of estrogens. The recent past has been very fruitful in yielding a better understanding of the processes leading to myocardial infarction, and the near future appears very promising in terms of preventing the number 1 killer in the western world.
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Therapies for lowering the concentration of homocysteine through vitamin supplementation did not result in the suppression of events.
“However, therapies for lowering the concentration of homocysteine through vitamin supplementation did not result in the suppression of events292, 293).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [293]
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Atherosclerosis--an inflammatory disease
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Falk, E., Shah, P. K., & Fuster, V. (1995) · Circulation · doi:10.1161/01.cir.92.3.657 · Cited by 3,536 · see citing works
Self-citationMolecular Bases of the Acute Coronary Syndromes
Libby, P. (1995) · Circulation · doi:10.1161/01.cir.91.11.2844 · Cited by 2,029 · see citing works
Plasma Homocysteine Levels and Mortality in Patients with Coronary Artery Disease
Nygard, O. K., Nordrehaug, J. E., Refsum, H., Ueland, P. M., Farstad, M., & Vollset, S. E. (1997) · New England Journal of Medicine · doi:10.1056/nejm199707243370403 · Cited by 1,746 · see citing works
Atherosclerosis: Basic Mechanisms
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Inflammation as a Cardiovascular Risk Factor
Willerson, J. T., & Ridker, P. M. (2004) · Circulation · doi:10.1161/01.cir.0000129535.04194.38 · Cited by 1,304 · see citing works
Barua, S., & Mitragotri, S. (2014) · Nano Today · doi:10.1016/j.nantod.2014.04.008 · Cited by 1,270 · see citing works
Our Preoccupation With Coronary Luminology
Topol, E. J., & Nissen, S. E. (1995) · Circulation · doi:10.1161/01.cir.92.8.2333 · Cited by 1,112 · see citing works
Wexler, L., Brundage, B. H., Crouse, J. R., Detrano, R., Fuster, V., Maddahi, J., Rumberger, J. A., Stanford, W. L., White, R. D., & Taubert, K. A. (1996) · Circulation · doi:10.1161/01.cir.94.5.1175 · Cited by 1,067 · see citing works
Self-citationWhich White Blood Cell Subtypes Predict Increased Cardiovascular Risk?
Horne, B. D., Anderson, J. L., John, J. M., Weaver, A. N., Bair, T. L., Jensen, K. R., Renlund, D. G., & Muhlestein, J. B. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.02.054 · Cited by 967 · see citing works
Greenland, P., Bonow, R. O., Brundage, B. H., Budoff, M. J., Eisenberg, M. J., Grundy, S. M., Lauer, M. S., Post, W. S., Raggi, P., Redberg, R. F., et al. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.10.001 · Cited by 959 · see citing works
Reduction of atherosclerosis in mice by inhibition of CD40 signalling
Mach, F., Schönbeck, U., Sukhova, G. K., Atkinson, E., & Libby, P. (1998) · Nature · doi:10.1038/28204 · Cited by 910 · see citing works
Bertrand, M. E. (2002) · European Heart Journal · doi:10.1053/euhj.2002.3385 · Cited by 896 · see citing works
Shaw, L. J., Raggi, P., Schisterman, E. F., Berman, D. S., & Callister, T. Q. (2003) · Radiology · doi:10.1148/radiol.2283021006 · Cited by 884 · see citing works
Kornowski, R., Hong, M. K., Tio, F. O., Bramwell, O., Wu, H., & Leon, M. B. (1998) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(97)00450-6 · Cited by 842 · see citing works
Vascular proliferation and atherosclerosis: New perspectives and therapeutic strategies
Dzau, V. J., Braun-Dullaeus, R. C., & Sedding, D. (2002) · Nature Medicine · doi:10.1038/nm1102-1249 · Cited by 825 · see citing works
Kinoshita, M., Yokote, K., Arai, H., Iida, M., Ishigaki, Y., Ishibashi, S., Umemoto, S., Egusa, G., Ohmura, H., Okamura, T., et al. (2018) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.gl2017 · Cited by 813 · see citing works
O’Rourke, R. A., Brundage, B. H., Froelicher, V. F., Greenland, P., Grundy, S. M., Hachamovitch, R., Pohost, G. M., Shaw, L. J., Weintraub, W. S., Winters, W. L., et al. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)00831-7 · Cited by 790 · see citing works
Triggering Myocardial Infarction by Marijuana
Mittleman, M. A., Lewis, R. A., Maclure, M., Sherwood, J. B., & Muller, J. E. (2001) · Circulation · doi:10.1161/01.cir.103.23.2805 · Cited by 769 · see citing works
Prediction of coronary events with electron beam computed tomography
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Atherothrombosis and High-Risk Plaque
Fuster, V., Moreno, P., Fayad, Z. A., Corti, R., & Badimón, J. J. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.03.074 · Cited by 736 · see citing works
Self-citationSimoons, M. L. (1996) · RePub (Erasmus University Rotterdam) · Cited by 706 · see citing works
Quantification of Macrophage Content in Atherosclerotic Plaques by Optical Coherence Tomography
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Low-molecular-weight heparin during instability in coronary artery disease
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Toussaint, J., LaMuraglia, G. M., Southern, J. F., Fuster, V., & Kantor, H. L. (1996) · Circulation · doi:10.1161/01.cir.94.5.932 · Cited by 669 · see citing works
Self-citationA Comparison of Recombinant Hirudin with Heparin for the Treatment of Acute Coronary Syndromes
The GUSTO-I Investigators (1996) · New England Journal of Medicine · doi:10.1056/nejm199609123351103 · Cited by 655 · see citing works
Androgens and Coronary Artery Disease
Wu, F. C. W., & von Eckardstein, A. (2003) · Endocrine Reviews · doi:10.1210/er.2001-0025 · Cited by 592 · see citing works
Nonobstructive Coronary Artery Disease and Risk of Myocardial Infarction
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Pathophysiology of native coronary, vein graft, and in-stent atherosclerosis
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Meta-Analysis of the Morning Excess of Acute Myocardial Infarction and Sudden Cardiac Death
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Clinical Imaging of the High-Risk or Vulnerable Atherosclerotic Plaque
Fayad, Z. A., & Fuster, V. (2001) · Circulation Research · doi:10.1161/hh1601.095596 · Cited by 519 · see citing works
Self-citationMiettinen, T. A., Pyörälä, K., Olsson, A. G., Musliner, T. A., Cook, T. J., Faergeman, O., Berg, K., Pedersen, T., Kjekshus, J., & Group, F. T. S. S. S. (1997) · Circulation · doi:10.1161/01.cir.96.12.4211 · Cited by 508 · see citing works
Mach, F., Schönbeck, U., Bonnefoy, J., Pober, J. S., & Libby, P. (1997) · Circulation · doi:10.1161/01.cir.96.2.396 · Cited by 493 · see citing works
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Increased Accumulation of Tissue ACE in Human Atherosclerotic Coronary Artery Disease
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von Känel, R., Mills, P. J., Fainman, C., & Dimsdale, J. E. (2001) · Psychosomatic Medicine · doi:10.1097/00006842-200107000-00003 · Cited by 422 · see citing works
Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease
Austin, R. C., Lentz, S. R., & Werstuck, G. H. (2004) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401451 · Cited by 414 · see citing works
Ömürlü, İ. K., Türe, M., & Kurum, A. T. (2006) · Expert Systems with Applications · doi:10.1016/j.eswa.2006.09.004 · Cited by 406 · see citing works
Bertrand, M. E. (2000) · European Heart Journal · doi:10.1053/euhj.2000.2301 · Cited by 402 · see citing works
The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease
Kjekshus, J., Pedersen, T. R., Olsson, A. G., Færgeman, O., & Pyörälä, K. (1997) · Journal of Cardiac Failure · doi:10.1016/s1071-9164(97)90022-1 · Cited by 386 · see citing works
The role of vascular smooth muscle cells on the pathogenesis of atherosclerosis.
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Rasmussen, S. E., Frederiksen, H. W., Krogholm, K. S., & Bredsdorff, L. (2005) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200400082 · Cited by 373 · see citing works
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Circulating markers of inflammation and atherosclerosis
Lind, L. (2003) · Atherosclerosis · doi:10.1016/s0021-9150(03)00012-1 · Cited by 369 · see citing works
Théroux, P., & Fuster, V. (1998) · Circulation · doi:10.1161/01.cir.97.12.1195 · Cited by 355 · see citing works
Self-citationMacrophages, Smooth Muscle Cells, and Tissue Factor in Unstable Angina
Moreno, P., Bernardi, V., López-Cuellar, J., Murcia, A. M., Palacios, I. F., Gold, H. K., Mehran, R., Sharma, S. K., Nemerson, Y., Fuster, V., et al. (1996) · Circulation · doi:10.1161/01.cir.94.12.3090 · Cited by 355 · see citing works
Self-citationCoronary Artery Spatial Distribution of Acute Myocardial Infarction Occlusions
Wang, J. C., Normand, S. T., Mauri, L., & Kuntz, R. E. (2004) · Circulation · doi:10.1161/01.cir.0000135468.67850.f4 · Cited by 351 · see citing works
Lee, C.-D. (2001) · American Journal of Epidemiology · doi:10.1093/aje/154.8.758 · Cited by 346 · see citing works
Allograft Vasculopathy Versus Atherosclerosis
Rahmani, M., Cruz, R. P., Granville, D. J., & McManus, B. M. (2006) · Circulation Research · doi:10.1161/01.res.0000246086.93555.f3 · Cited by 344 · see citing works
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Inflammation in Peripheral Artery Disease
Brevetti, G., Giugliano, G., Brevetti, L., & Hiatt, W. R. (2010) · Circulation · doi:10.1161/circulationaha.109.918417 · Cited by 317 · see citing works
Okamura, T., Tsukamoto, K., Arai, H., Fujioka, Y., Ishigaki, Y., Koba, S., Ohmura, H., Shoji, T., Yokote, K., Yoshida, H., et al. (2023) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.gl2022 · Cited by 317 · see citing works
Feasibility of FDG Imaging of the Coronary Arteries
Rogers, I. S., Nasir, K., Figueroa, A. L., Cury, R. C., Hoffmann, U., Vermylen, D., Brady, T. J., & Tawakol, A. A. (2010) · JACC. Cardiovascular imaging · doi:10.1016/j.jcmg.2010.01.004 · Cited by 304 · see citing works
Thrombus Formation on Atherosclerotic Plaques: Pathogenesis and Clinical Consequences
Rauch, U., Osende, J. I., Fuster, V., Badimón, J. J., Fayad, Z. A., & Chesebro, J. H. (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-134-3-200102060-00014 · Cited by 297 · see citing works
Self-citationZhou, J., Lhoták, Š., Hilditch, B. A., & Austin, R. C. (2005) · Circulation · doi:10.1161/01.cir.0000160864.31351.c1 · Cited by 290 · see citing works
Sinha, M. K. (2004) · Emergency Medicine Journal · doi:10.1136/emj.2003.006007 · Cited by 285 · see citing works
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Acute coronary syndromes: biology
Fuster, V., Fayad, Z. A., & Badimon, J. J. (1999) · The Lancet · doi:10.1016/s0140-6736(99)90234-9 · Cited by 282 · see citing works
Self-citationMann, J. M., & Davies, M. J. (1996) · Circulation · doi:10.1161/01.cir.94.5.928 · Cited by 281 · see citing works
The role of plaque rupture and thrombosis in coronary artery disease
Zaman, A., Helft, G., Worthley, S. G., & Badimón, J. J. (2000) · Atherosclerosis · doi:10.1016/s0021-9150(99)00479-7 · Cited by 279 · see citing works
Circumferential Stress and Matrix Metalloproteinase 1 in Human Coronary Atherosclerosis
Lee, R. T., Schöen, F. J., Loree, H. M., Lark, M. W., & Libby, P. (1996) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.16.8.1070 · Cited by 278 · see citing works
Tea flavonoids and cardiovascular diseases: A review
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Feasibility of 18F-Sodium Fluoride PET/CT for Imaging of Atherosclerotic Plaque
Derlin, T., Richter, U., Bannas, P., Begemann, P. G. C., Buchert, R., Mester, J., & Klutmann, S. (2010) · Journal of Nuclear Medicine · doi:10.2967/jnumed.110.076471 · Cited by 260 · see citing works
Yeghiazarians, Y., Braunstein, J. B., Askari, A. T., & Stone, P. H. (2000) · New England Journal of Medicine · doi:10.1056/nejm200001133420207 · Cited by 256 · see citing works
Toward a New Frontier in Myocardial Reperfusion Therapy
Topol, E. J. (1998) · Circulation · doi:10.1161/01.cir.97.2.211 · Cited by 251 · see citing works
Clinical Pharmacology of Eptifibatide
Phillips, D. R., & Scarborough, R. M. (1997) · The American Journal of Cardiology · doi:10.1016/s0002-9149(97)00572-9 · Cited by 250 · see citing works
Platelet Glycoprotein IIb/IIIa Antagonists
Scarborough, R. M., Kleiman, N. S., & Phillips, D. R. (1999) · Circulation · doi:10.1161/01.cir.100.4.437 · Cited by 246 · see citing works
THE VASCULAR BIOLOGY OF NITRIC OXIDE AND ITS ROLE IN ATHEROGENESIS
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White blood cells as a novel mortality predictor in haemodialysis patients
Reddan, D. N., Klassen, P., Szczech, L. A. M., Coladonato, J. A., O’Shea, S., Owen, W. F., & Lowrie, E. G. (2003) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfg066 · Cited by 214 · see citing works
Madamanchi, N. R., Hakim, Z. S., & Runge, M. S. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2004.01085.x · Cited by 212 · see citing works
Greniér, P., & Beigelman‐Aubry, C. (1998) · Thorax · doi:10.1136/thx.53.2008.s25 · Cited by 212 · see citing works
Risk Factors for Ischaemic Stroke
Allen, C., & Bayraktutan, U. (2008) · International Journal of Stroke · doi:10.1111/j.1747-4949.2008.00187.x · Cited by 212 · see citing works
C-REACTIVE PROTEIN, INFLAMMATION, AND CORONARY RISK
Morrow, D. A., & Ridker, P. M. (2000) · Medical Clinics of North America · doi:10.1016/s0025-7125(05)70211-x · Cited by 212 · see citing works
Hossain, G. S., van Thienen, J. V., Werstuck, G. H., Zhou, J., Sood, S. K., Dickhout, J. G., de Koning, A. B. L., Tang, D., Wu, D., Falk, E., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212897200 · Cited by 207 · see citing works
Platelets synthesize large amounts of active plasminogen activator inhibitor 1
Brogren, H., Karlsson, L., Andersson, M., Wang, L., Erlinge, D., & Jern, S. (2004) · Blood · doi:10.1182/blood-2004-04-1439 · Cited by 210 · see citing works
Plasminogen activator inhibitor-1 and vitronectin promote vascular thrombosis in mice
Eitzman, D. T., Westrick, R. J., Nabel, E. G., & Ginsburg, D. (2000) · Blood · doi:10.1182/blood.v95.2.577 · Cited by 202 · see citing works
Regulation of Arterial Thrombolysis by Plasminogen Activator Inhibitor-1 in Mice
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Unanswered Questions for Management of Acute Coronary Syndrome
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Coronary angioplasty, atherectomy and bypass surgery in cardiac transplant recipients
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Computation of hemodynamics in the left coronary artery with variable angulations
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Coronary Artery Calcium in Acute Coronary Syndromes
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Ultrasound and Lipoproteins as Predictors of Lipid-Rich, Rupture-Prone Plaques in the Carotid Artery
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Subclinical atherosclerosis: what it is, what it means and what we can do about it
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C-reactive protein, inflammation, and coronary risk
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Task force 1. Pathogenesis of coronary disease: The biologic role of risk factors
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White Blood Cell Count and the Risk of Coronary Heart Disease and All-Cause Mortality in Elderly Men
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Development and Disease in Proteinase-Deficient Mice
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Pathogenetic concepts of acute coronary syndromes
Corti, R., Fuster, V., & Badimón, J. J. (2003) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)02833-4 · Cited by 168 · see citing works
Self-citationChen, X. Y., Wong, K. S., Lam, W. W. M., Zhao, H.-L., & Ng, H. (2007) · Cerebrovascular Diseases · doi:10.1159/000111525 · Cited by 167 · see citing works
- Authors
- Fuster, V
- Affiliations
- Mount Sinai Hospital (US)
- Corresponding author
- Fuster, V
- ORCID
- Fuster, V
- Venue
- Circulation
- Published
- 1994-10
- Volume
- 90
- Issue
- 4
- Pages
- 2126-2146
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2110185147
- Cited by
- 848
- References
- 240
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 7 · 2023: 11 · 2022: 9 · 2021: 4 · 2020: 14 · 2019: 6 · 2018: 5 · 2017: 12 · 2016: 19 · 2015: 16 · 2014: 19 · 2013: 24 · 2012: 18
- FWCI
- 16.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Coronary Interventions and Diagnostics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- myocardial infarction, coronary artery disease, vulnerable plaque, plaque disruption, lesion type, plaque regression, thrombosis, coronary syndrome, risk factor control, lipid therapy, beta-adrenergic blockade, angiotensin-converting enzyme inhibition, antithrombotic therapy, estrogen, vascular biology
- MeSH terms
- Coronary Artery Disease, Coronary Thrombosis, Coronary Vessels, Humans, Myocardial Infarction, Lipid Metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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