Información del artículo
Los síndromes coronarios agudos (SCA) son la manifestación clínica final de un proceso inflamatorio crónico de la pared vascular puesto en marcha por diferentes agentes que causan daño en el endotelio. La rotura o la erosión de la placa aterosclerótica vulnerable provocan la trombosis y la aparición de los SCA. La respuesta inflamatoria local y sistémica desempeña un papel fundamental en la vulnerabilidad y la rotura de la placa. En el presente artículo revisaremos la fisiopatología, las técnicas disponibles para la detección de la placa vulnerable, el papel de las estatinas en el SCA (ensayos clínicos publicados) y las implicaciones terapéuticas para la prevención de las complicaciones trombóticas de la aterosclerosis.
Palabras clave:
Síndrome coronario agudo
Inflamación
Placa vulnerable
Aterosclerosis
Trombosis
Estatinas
Prevención
Acute coronary syndrome is the ultimate clinical manifestation of the chronic inflammation of the vascular wall that results from various processes which damage the endothelium. Rupture of atherosclerotic plaque causes thrombosis and leads to acute coronary syndromes. Both local and systemic inflammatory responses have important influences on plaque vulnerability and rupture. In the present article, we review disease pathophysiology, the techniques available for detecting vulnerable plaque, the role of statins in acute coronary syndromes (based on published clinical trials), and the therapeutic implications of preventing the thrombotic complications of atherosclerosis.
Key words:
Acute coronary syndrome
Inflammation
Vulnerable plaque
Atherosclerosis
Thrombosis
Statins
Prevention
El Texto completo está disponible en PDF
Bibliografía
[1.]
V. Fuster, Z.A. Fayad, J.J. Badimon.
Acute coronary syndromes: biology.
Lancet, 353 (1999), pp. S115-S119
[2.]
R. Ross.
Atherosclerosis-an inflammatory disease.
N Engl J Med, 340 (1999), pp. 115-126
[3.]
P. Libby.
Current concepts of the pathogenesis of the acute coronary syndromes.
Circulation, 104 (2001), pp. 365-372
[4.]
P.M. Vanhoutte, C.M. Boulanger.
Endothelium-dependent responses in hipertension.
Hipertens Res, 18 (1995), pp. 87-98
[5.]
A.M. Schmidt, S.D. Yan, J.L. Watier, D. Stern.
Activation of receptor for advance glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis.
Circ Res, 84 (1999), pp. 489-497
[6.]
R. Puranik, D.S. Celermajer.
Smoking and endotelial function.
Prog Cardiovasc Dis, 45 (2003), pp. 443-458
[7.]
J. Danesh, R. Collins, R. Peto.
Chronic infections and coronary artery disease: is there a link?.
Lancet, 350 (1997), pp. 430-436
[8.]
T.F. Luscher, F.C. Tanner, G. Noll.
Lipids and endothelial function:effects of lipid lowering and other therapeutic interventions.
Curr Opin Lipidol, 7 (1996), pp. 234-240
[9.]
D. Hackett, G. Davies, A. Maseri.
Pre-existing coronary stenoses in patients with first myocardial infarction are not necessarily severe.
Eur Heart J, 9 (1988), pp. 1317-1323
[10.]
E. Falk, P.K. Shah, V. Fuster.
Coronary plaque disruption.
Circulation, 92 (1995), pp. 657-671
[11.]
A. Fernández Ortiz, J.J. Badimon, E. Falk, V. Fuster, B. Meyer, A. Mailhac, et al.
Characterization of the relative trombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture.
J Am Coll Cardiol, 23 (1994), pp. 1562-1569
[12.]
M.J. Davies, P.D. Richardson, N. Woolf, D.R. Katz, J. Mann.
Risk of thrombosis in human atherosclerotic plaques: role of extracelular lipid, macrophage, and smooth muscular cell content.
Br Heart J, 69 (1993), pp. 377-381
[13.]
P.R. Moreno, V.H. Bernardi, J. López Cuellar, J.B. Newell, C. McMellon, H.K. Gold, et al.
Macrophages, smooth muscular cells, and tissue factor in unestable angina. Implication for cell-mediated thrombogenicity in acute coronary syndromes.
Circulation, 94 (1996), pp. 3090-3097
[14.]
C. Depre, X. Havaux, W. Wijns.
Neovascularization in human coronary atherosclerotic lesions.
Cathet Cardiovasc Diagn, 39 (1996), pp. 215-220
[15.]
A.N. Tenaglia, K.G. Peters, M.H. Sketch, B.H. Annex.
Neovascularization atherectomy specimens from patients with unestable angina: implications for pathogenesis os unestable angina.
Am Heart J, 135 (1998), pp. 10-14
[16.]
A. Farb, A.P. Burke, A.l. Tang, T.V. Liang, P. Mannan, J. Amialek, et al.
Coronary plaque erosion without into a lipid core: a frequent cause of coronary thrombosis in sudden cardiac death.
Circulation, 93 (1996), pp. 1354-1363
[17.]
A.P. Burke, A. Farb, G.T. Malcom, Y.H. Liang, J. Smialek, R. Virmani.
Coronary risk factors ans plaque morphology in men with coronary disease who died suddenly.
N Engl J Med, 336 (1997), pp. 1276-1282
[18.]
A. Fernández Ortiz.
Fisiopatología de la angina instable. Papel de la rotura y trombosis de la placa aterosclerótica.
Rev Esp Cardiol, 52 (1999), pp. S3-S12
[19.]
V. Toschi, R. Gallo, M. Lettino, J.T. Fallon, S.D. Gertz, A. Fernández Ortiz, et al.
Tissue factor modilates the thrombogenicity of human atherosclerotic plaques.
Circulation, 95 (1997), pp. 594-599
[20.]
Z. Mallat, B. Hugel, J. Ohan, G. Leseche, J.M. Freyssinet, A. Tedgui.
Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thromobogenicity.
Circulation, 99 (1999), pp. 348-353
[21.]
F. Miranda Guardiola, X. Bosch.
Papel de la inflamación en la patogenia y pronóstico de la angina inestable.
Rev Esp Cardiol, 52 (1999), pp. S13-S22
[22.]
A.M. Zeiher, H. Goebel, V. Schachinger, C. Ihling.
Tissue endothelin-1 immunoractivity in the active coronary atherosclerotic plaque. A clue to the mechanism of the increased vasoreactivity of the culprit lesion in unstable angina.
Ciculation, 91 (1995), pp. 941-947
[23.]
P. Constantinides.
Plaque fissuring in human coronary thrombosis.
J Atheroscler Res, 6 (1966), pp. 1-17
[24.]
M. Friedman, G.J. Van der Bovenkamp.
The pathogenesis of a coronary thrombus.
Am J Pathol, 48 (1966), pp. 19-44
[25.]
M. Kaartinen, A.C. Van der Wal, C.M. Van der Loos, J.J. Piek, K.T. Koch, A.E. Becker, et al.
Mast cell infiltration in acute coronary síndromes: implications for plaque rupture.
J Am Coll Cardiol, 32 (1998), pp. 606-612
[26.]
P. Laine, M. Karartinen, A. Penttila, P. Panula, T. Paavonen, P.T. Kovanen.
Association between myocardial infarction and the mast cells in the adventicia of the infarct-relative artery.
Circulation, 99 (1999), pp. 361-369
[27.]
T.B. Rajavashisth, X.P. Xu, S. Jovinge, S. Meisel, X.O. Xu, N.N. Chai, et al.
Membrane type I matrix metalloproteinase expression in human atherosclerotic plaques: evidence ogf activation by proinflammatory mediators.
Circulation, 99 (1999), pp. 3103-3109
[28.]
M.P. Herman, G.K. Sukhova, P. Libby, N. Gerdes, N. Tang, D.B. Horton, et al.
Expression of neutrophil collagenase (matrix metalloproteinase-8) in human atheroma: a novel collagenolytic pathway suggested by trabscriptional profiling.
Circulation, 104 (2001), pp. 1899-1904
[29.]
G.K. Sukhova, U. Schonbeck, E. Rabkin, F.J. Schoen, A.R. Poole, R.C. Billinghurst, et al.
Evidence for increased collagenolysis by interstitial collagenases-1 and-3 in vulnerable human atherosclerotic plaques.
Circulation, 99 (1999), pp. 2503-2509
[30.]
P.K. Shah.
Role of inflammation and metalloproteinases in plaque disruption and thrombosis.
Vasc Med, 3 (1998), pp. 199-206
[31.]
A. Kol, G.K. Sukhova, A.H. Lichtman, P. Libby.
Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-alpha and matrix metalloproteinase expression.
Circulation, 98 (1998), pp. 300-307
[32.]
F. Mach, U. Schobenck, R.P. Fabunmi, C. Murphy, E. Atkinson, J.Y. Bonnefoy, et al.
T lymphocytes induce endothelial cell matrix metalloproteinase expression by a CD40L dependent mechanism:implication for tubule formation.
Am J Pathol, 154 (1999), pp. 229-238
[33.]
K. Wallner, C. Li, P.K. Shah, M.C. Fishbein, J.S. Forrester, S. Kaul, et al.
Tenascina C is expressed in macrophage-rich human coronary atherosclerotic plaque.
Circulation, 99 (1999), pp. 1284-1289
[34.]
Z. Malat, A. Tedgui.
Apoptosis In the vasculature: mechanism and functional importance.
Br J Pharmacol, 130 (2000), pp. 947-962
[35.]
J.l. Torre, P.M. Ridker.
Clinical use of high sensitive C-reactive protein for the prediction of adverse cardiovascular events.
Curr Opin Cardiol, 18 (2003), pp. 471-478
[36.]
M.E. Ritchie.
Nuclear factor- B is selectively and markedly activated in humans with unestable angina pectoris.
Circulation, 98 (1998), pp. 1707-1713
[37.]
J.A. De Lemos, D.A. Morrow, M.S. Sabatine, S.A. Murphy, L.A. Demopoulos, P.M. DiBattiste, et al.
Association between plasma levels of monocyte chemo-attractant protein-1 and long term clinical outcomes in patients with acute coronary syndromes.
Circulation, 107 (2003), pp. 690-695
[38.]
C. Heeschen, S. Dimmeler, C.W. Hamm, M.J. Van der Brand, E. Boersma, A.M. Zeiher, et al.
Soluble CD40 ligand in acute coronary syndromes.
N Engl J Med, 348 (2003), pp. 1104-1111
[39.]
B. MacNeill, H. Lowe, M. Takano, V. Fuster, I. Kyung Jang.
Intravascular modalities for detection of vulnerable plaque. Current status.
Arterioscler Thromb Vasc Biol, 23 (2003), pp. 1333-1342
[40.]
R.A. Nishimura, W.D. Edwards, C.A. Warnes, G.S. Reeder, D.R. Holmes, A.J. Tajik, et al.
Intravascular ultrasound imaging: in vitro validation and pathologic correlation.
J Am Coll Cardiol, 16 (1990), pp. 145-154
[41.]
B.N. Potkin, A.L. Bartonerelli, J.M. Gessert, R.F. Neville, Y. Almangor, W.C. Roberts, et al.
Coronary artery imaging with intravascular high-frequency ultrasound.
Circulation, 81 (1990), pp. 1575-1585
[42.]
Y. Ueda, N. Kondo, A. Hirayama, K. Kodama.
Assesment of plaque vulnerability by angioscopic classification of plaque color.
Circulation, 104 (2001),
[43.]
P. Hrynchak, T. Simpson.
Optical coherence tomography: an introduction to the technique and its use.
Optom Vis Sci, 77 (2000), pp. 347-356
[44.]
C. Stefanadis, L. Diamantopoulos, C. Vlachopoulos, E. Tsiamis, J. Dernellis, K. Toutouzas, et al.
Termal heterogenicity withim human atherosclerotic coronary arteries detected in vivo: anew method of detection by aplication of a special termography caheter.
Circulation, 99 (1999), pp. 1965-1971
[45.]
C. Stefanadis, K. Toutouzas, E. Tsiamis, C. Stratos, M. Vavuranakis, I. Kallikazoros, et al.
Increased local temperatura in human coronary atheroscleriotic plaques: an independent predictor of clinical outcome in patients undergoing a percutaneous coronary intervention.
J Am Coll Cardiol, 37 (2001), pp. 1277-1283
[46.]
T.J. Romer, J.F. Brennan, M. Fitzmaurice, M.L. Feldstein, G. Deinum, J.L. Myles.
Histopathology of human coronary atherosclerosis by quantifying its chemical composition witn Raman sprectoscopy.
Circulation, 97 (1998), pp. 878-885
[47.]
J.A. Schaar, C.L. De Korte, F. Mastik, C. Strijder, G. Pasterkamp, E. Boresma, et al.
Characterizing vulnerable plaque features with intravascular elastography.
Circulation, 108 (2003), pp. 2636-2641
[48.]
J.A. Schaar, E. Regar, F. Mastik, E.P. McFadden, F. Saia, C. Disco, et al.
incidence of high-strain patterns in human coronary areteries assessment with three-dimensional intravascular palpography and correlation with clinical presentation.
Circulation, 109 (2004), pp. 2716-2719
[49.]
J.W.R. Schneiderman, A. Weiss, E. Smouha, L. Muchnik, G. Alexandrowicz, M. Chen-Zion, et al.
Vulnerable plaque diagnosis by a self-contained intravascular magnetic resonance imaging probe in ex-vivo human in-situ coronary arteries.
J Am Coll Cardiol, 41 (2003), pp. A59
[50.]
V. Fuster, A. Sahi, Ph. Fayad, P.R. Moreno, M. Poon, R. Corti, et al.
Atherotrombosis and high risk plaque. Part II: Approaches by non-invasive computed tomographic/magnetic resonance imaging.
J Am Coll Cardiol, 46 (2005), pp. 1209-1215
[51.]
R. Corti, Z.A. Fayad, V. Fuster, S.G. Worthley, G. Helft, J. Chesebro, et al.
Effects of lipid-lowering by simvastatin on human atherosclerotic lesions: a longitudinal study by high resolution, non invasive magnetic resonance imaging.
Circulation, 104 (2001), pp. 249-252
[52.]
R. Corti, Z.A. Fayad, V. Fuster, S.G. Worthley, G. Helft, W.G. Chaplin, et al.
Effects of aggressive versus conventional lipid lowering therapy by simvastatin on human atherosclerotic lesions: a prospective, randomized, double-blind trial with high resolution magnetic resonance imaging.
J Am Coll Cardiol, 46 (2005), pp. 106-112
[53.]
J.A. Goldstein, D. Demetriou, C.L. Grines, M. Pica, M. Shoukfeh, W.W. ONeill.
Multiple complex coronary plaques in patients with acute myocardial infarction.
N Engl J Med, 343 (2000), pp. 915-922
[54.]
M. Asakura, Y. Ueda, O. Yamaguchi, T. Adachi, A. Hirayama, M. Hori, et al.
Extensive development of vulnerable plaques as a pancoronary process in patient with myocardial infraction: an angioscopy study.
J Am Coll Cardiol, 37 (2001), pp. 1284-1288
[55.]
G. Rioufol, G. Finet, I. Ginon, X. Andre-Fouet, R. Rossi, E. Vialle, et al.
Multiple atherosclerotic plaque rupture in acute coronary syndromes: a three-vessel intravascular intrasound study.
Circulation, 106 (2002), pp. 804-808
[56.]
G. Schwartz, A. Olsson, M. Ezekowittz, P. Ganz, M. Oliver, D. Waters, et al.
Effects of atrorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL Study: a randomized controlled trial.
JAMA, 285 (2001), pp. 1711-1718
[57.]
Scandinavian Simvastatin Survival Study Group.
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).
Lancet, 334 (1994), pp. 1383-1389
[58.]
F.M. Sacks, M.A. Pfeffer, L.A. Moye, J.L. Rouleau, J.D. Rutherford, T.G. Coles, et al.
The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterols levels.
N Engl J Med, 335 (1996), pp. 1001-1009
[59.]
Long-term intervention with pravastatin in ischaemic disease (LIPID) study group.
Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels.
N Engl J Med, 339 (1998), pp. 1349-1357
[60.]
C.P. Cannon, E. Braunwald, C. McCabe, D. Rader, J. Rouleau, R. Belder, et al.
Intensive versus moderate lipids lowering with statins after acute coronary syndromes.
N Engl J Med, 350 (2004), pp. 1495-1504
[61.]
S.M. Grundy, J. Cleeman, C.N. Merz, H.B. Brewer, L.T. Clark, D.B. Hunninghake, et al.
Implications of recents trials for the National Education Program adult Treatment Panel III guidelines.
Circulation, 110 (2004), pp. 227-239
[62.]
J.A. De Lemos, M.A. Blazing, S. Wiviott, E. Lewis, K.A. Fox, H.D. White, et al.
Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes. Phase Z of the A to Z Trial.
JAMA, 292 (2004), pp. 1307-1316
[63.]
M. Aikawa, E. Rabkin, Y. Okada, S.J. Voglic, S.K. Clinton, C.E. Brinckerhoff, et al.
Lipid lowering by diet reduces matriz metalloproteinase activity and increases collagen content of rabbit atheroma:a potencial mechanicsm of lesion stabilization.
Circulation, 97 (1998), pp. 2433-2444
[64.]
P.K. Shah, J. Yano, O. Reyes, K.Y. Chyu, S. Kaul, C.L. Bisgaier, et al.
High dosis recombinant apolipoprotein A-I (Milano) mobilizes tissue cholesterol and rapidly reduces plaque lipid and macrophage content in apolipoprotein c deficient mice: potencial implications for acute plaque stabilization.
Circulation, 103 (2001), pp. 3047-3050
[65.]
M. Crisby, G. Nordin-Fredriksson, P.K. Shah, J. Yano, J. Zhu, J. Nilsson.
Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for acute plaque stabilization.
Circulation, 103 (2001), pp. 926-933
[66.]
I. Jialal, D. Stein, D. Balis, S.M. Grundy, B. Adams-Huet, Sl. Devaraj.
Effect of hydroxymethyl glutaryl coenzyme A reductasa inhibitor therapy on high sensitive C-reactive protein levels.
Circulation, 103 (2001), pp. 1933-1935
[67.]
P.M. Ridker, N. Rifai, M. Clearfield, J.R. Downs, S.E. Weiss, J.S. Miles, et al.
Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events.
N Engl J Med, 344 (2001), pp. 1959-1965
[68.]
L.M. Biasucci, G. Liuzzo, R.L. Grillo, G. Caligiuri, A.G. Rebuzzi, A. Buffon, et al.
Elevated levels of C-reactive protein at discharge in patients with unstable angina predict instability.
Circulation, 99 (1999), pp. 855-860
[69.]
P.M. Ridker, N. Rifai, M.A. Pfeffer, F.M. Sacks, L.A. Moye, S. Goldman, et al.
Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels.
Circulation, 98 (1998), pp. 839-844
[70.]
P.M. Ridker, D. Molrrow, L. Rose, N. Rifai, C.P. Cannon, E. Braunwald.
Relative efficacy of atorvastatin 80 mg and pravastatin 40 mg in achieving the dual goals of low-density protein cholesterol < 70mg/dl and C-reative protein < 2mg/l. An analysis of the PROVE- IT TIMI-22 Trial.
J Am Coll Cardiol, 45 (2005), pp. 1644-1648
[71.]
S.E. Nissen, E.M. Tuzcu, P. Schoenhagen, B.G. Brown, P. Ganz, R.A. Vogel, et al.
Effect of intensive compared with moderate lipidlowering therapy on progression of coronary atherosclerosis: a randomised controlled trial.
JAMA, 291 (2004), pp. 1071-1080
[72.]
S. Okazaki, T. Yokoyama, K. Miyauchi, K. Shimada, T. Kurata, H. Sato, et al.
Demostration of the beneficial effect on atherosclerotic by serial volumetric intravascular iltrasound analysis during half a year after coronary event: the ESTABLISH study.
Circulation, 110 (2004), pp. 1061-1068
[73.]
A. Hackman, Y. Abe, W. Insull, H. Pownall, L. Smith, K. Duna, et al.
Levels of soluble cell adhesion in patients with dyslipidemia.
Circulation, 93 (1996), pp. 1334-1338
[74.]
A. Kalela, R. Laaksonen, T. Lehtimaki, K.A. Koivu, M. Hoythya, T. Janatuinen, et al.
Effect of pravastatin in midly hypercholesterolemic young men on serum matriz metalloproteinases.
Am J Cardiol, 88 (2001), pp. 173-175
[75.]
P.M. Ridker, M. Cushman, M.J. Stampfer, R.P. Tracy, C.H. Hennekens.
Inflammation, aspirin, and the rIsk of cardiovascular disease in apparently healthy men.
N Engl J Med, 326 (1997), pp. 973-979
Copyright © 2006. Sociedad Española de Cardiología
