This Article Extract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Braunwald, E. Search for Related Content PubMed PubMed Citation Articles by Braunwald, E.

(Circulation. 1998;98:2219-2222.)
© 1998 American Heart Association, Inc.

Editorials

Unstable Angina

An Etiologic Approach to Management

Eugene Braunwald, MD

From the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.

Correspondence to Eugene Braunwald, MD, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.

Key Words: Editorials • angina

Nonocclusive Thrombus on Preexisting Plaques

Unstable angina results from an imbalance between myocardial oxygen supply and demand. Probably the most common cause is reduced myocardial perfusion resulting from a nonocclusive thrombus on a fissured or eroded atherosclerotic plaque that often had caused only mild to moderate obstruction previously.³ Nonocclusive thrombi in patients with unstable angina have been demonstrated by coronary angioscopy and arteriography.⁴ They occur most commonly on complex, irregular lesions.⁵ Plaques that have undergone disruption often have a core that is rich in cholesteryl esters and tissue factor. They have a thin fibrous cap; disruption is caused by shear forces acting on the shoulder of the plaque. In patients with unstable angina, products of aggregating platelets are released into the coronary circulation,⁶ and there appears to be continued thrombus formation, often for months, after the index event.⁷ Nonocclusive coronary thrombi often become organized and incorporated into the growing plaque.

Treatment with antithrombotic agents (unfractionated heparin⁸ and low-molecular-weight heparin⁹ ) and antiplatelet agents (aspirin,⁸ ticlopidine,¹⁰ and glycoprotein IIb/IIIa inhibitors² ) is beneficial in this form of angina. Perhaps tissue factor inhibitors will prove useful as well.

Dynamic Obstruction

A second form of unstable angina is caused by dynamic obstruction, ie, coronary vasoconstriction. Four subgroups are recognized. (1) The first is Prinzmetal's variant angina, with intense focal spasm of a segment of an epicardial coronary artery not involved by coronary atherosclerosis. (2) In the second, also called Prinzmetal's angina, the spasm occurs adjacent to a nonobstructive atheromatous plaque. Both of these forms of vasospastic angina appear to be due to hypercontractility of vascular smooth muscle and endothelial dysfunction occurring in the region of spasm. They are characterized by ST-segment elevation accompanying rest pain and can often be provoked by stimuli such as ergonovine, acetylcholine, or hyperventilation. Rarely, vasospastic angina is caused by allergic reactions, with mediators such as histamine or leukotrienes acting on coronary vascular smooth muscle. (3) The third subgroup results from nonfocal constriction of major coronary arteries containing atherosclerotic plaques.¹¹ Such coronary vasoconstriction may be caused by adrenergic stimuli, cold immersion, or cocaine. Most commonly, coronary vasoconstriction may also occur when shear stress and/or humoral stimuli such as thrombin and substances released from platelets, including serotonin and thromboxane A₂, act on dysfunctional coronary endothelium, with reduced production of relaxing factors and increased release of endothelin, causing contraction of coronary vascular smooth muscle. (4) The fourth is microcirculatory angina. In this condition, the ischemia is secondary to constriction of the small intramural coronary resistance vessels,^{11 12} which in some instances is also caused by endothelial dysfunction. The epicardial coronary arteries appear normal on coronary arteriography, but the clearance of contrast material from the myocardium may be prolonged.¹³

Dynamic obstruction often responds to coronary vasodilators: nitrates and calcium antagonists.

Progressive Mechanical Obstruction

The third form of unstable angina results from severe, organic luminal narrowing; perhaps its "purest" form is the restenosis after percutaneous transluminal coronary angioplasty and other forms of catheter-based revascularization. However, serial angiographic studies in many patients without previous intracoronary procedures have shown progressive luminal narrowing of the culprit vessel in the period just preceding the onset of unstable angina.¹⁴ In such cases, progressive coronary obstruction causes the severe imbalance between myocardial oxygen supply and demand that is responsible for this form of unstable angina.

Treatment of this cause of unstable angina consists of transcatheter or surgical revascularization. The benefit of mechanical revascularization is directly proportional to the contribution of the organic obstruction to the ischemia.

Inflammation and/or Infection

There is increasing evidence that arterial inflammation plays a role in atherogenesis and is responsible for thrombogenesis in some patients with unstable angina and other acute coronary syndromes. There may be an increase of circulating activated lymphocytes, as well as of neutrophil and monocyte adhesion molecules.¹⁵ Macrophages and T lymphocytes are present at the shoulder of atherosclerotic plaques.¹⁶ These cells may increase the expression of metalloproteinases and other enzymes that cause thinning of the fibrous cap, thereby predisposing to plaque rupture. Mononuclear cells exhibit enhanced secretion of cytokines, such as tumor necrosis factor (TNF)- and -interferon. Elevations of acute-phase reactants, such as C-reactive protein and serum amyloid A, portend a poor prognosis in patients with unstable angina.^{17 18} Taken together, these observations suggest that inflammation may precipitate unstable angina.¹⁹

There is serological evidence that infection with organisms such as Chlamydia pneumoniae, virulent strains of Helicobacter pylori,²⁰ herpes simplex virus, and cytomegalovirus are common in patients with chronic atherosclerosis and acute coronary syndromes¹⁵ ; C pneumoniae has been repeatedly identified in atherosclerotic plaques. It has been postulated that these organisms induce the production of cytokines, such as TNF- and several interleukins, which may unfavorably alter local lipid metabolism, destabilize coronary plaques, stimulate platelet activation, and enhance thrombus formation.

The ability to recognize an inflammatory or infectious origin of unstable angina is still primitive, but the inflammatory markers C-reactive protein and serum amyloid A, as well as antibodies to C pneumoniae, are becoming more widely available. These might form the basis for the management of patients with unstable angina in whom inflammation and/or infection plays an important role. It has been suggested that the increased leukocyte adhesiveness observed in some patients with unstable angina identifies those who will benefit from treatment with anti-inflammatory agents.²¹ Two small studies suggest that macrolide antibiotics reduce the incidence of recurrent events in patients with unstable angina²² and acute myocardial infarction.²³ Anti-inflammatory drugs, including the new COX II inhibitors; antibiotics that are effective against C pneumoniae and H pylori; and drugs that are effective against the other putative infectious organisms may prove useful in patients with unstable angina in whom an infectious and/or inflammatory component plays an important pathogenetic role.

Secondary Unstable Angina

This form of unstable angina is precipitated by conditions that are extrinsic to the coronary vascular bed. It can be caused by conditions that increase myocardial oxygen demand and those that impair oxygen supply, occurring against the background of coronary stenosis and chronic stable angina. Increases in myocardial oxygen demand may result from tachycardia, fever, thyrotoxicosis, endogenous and exogenous hyperadrenergic states, and elevations of left ventricular afterload—systemic hypertension and various forms of aortic stenosis. Unstable angina secondary to impaired oxygen delivery can result from anemia, hypoxemia, and hyperviscosity states. Hypotension can reduce coronary perfusion pressure and impair myocardial perfusion distal to an atherosclerotic obstruction, thereby causing severe ischemia.

In most cases, the cause of secondary unstable angina can be recognized and corrected. ß-Adrenergic receptor blockers are often effective in reducing excess myocardial oxygen demands.

Multiple Causes

Figure 2A represents the most common form of unstable angina, in which an atherosclerotic plaque causing 60% luminal stenosis forms the background for a very severe obstruction (90% luminal stenosis) caused by a superimposed thrombus. Figure 2B represents severe epicardial spasm occurring adjacent to a mild obstruction. Figure 3A represents the situation in a patient with stable angina due to moderately severe atherosclerotic obstruction in whom unstable angina is precipitated by a rise in myocardial oxygen demand during an intercurrent illness. In many patients with unstable angina, several causes are responsible; Figure 3B illustrates the situation in which a moderately severe atherosclerotic obstruction is complicated by local inflammation and thrombus formation.

View larger version (20K): [in this window] [in a new window]   Figure 2. A, Most common form of unstable angina, in which atherosclerotic plaque causes moderate (60% diameter) obstruction and acute thrombus overlying plaque causes very severe (90% diameter) narrowing. B, Common form of Prinzmetal's angina with mild (30% diameter) atherosclerotic obstruction, adjacent to which there is intense (90% diameter) vasoconstriction.

View larger version (21K): [in this window] [in a new window]   Figure 3. A, Moderately severe (70% diameter) obstruction with secondary unstable angina precipitated by an increase in myocardial oxygen demands due to an intercurrent illness. B, Complex form of unstable angina. Moderate organic obstruction (60% diameter stenosis). Severe inflammation in wall and small thrombus contribute to ultimate luminal narrowing.

Conclusions

The therapy of most illnesses is more successful when it is not empirical but rather is directed against a clearly defined etiology. It is therefore important to define more clearly the various established causes of unstable angina enumerated above and to seek additional causes. An assessment of the contributions of the various causes to the clinical syndrome should lead to therapy that is tailored to the individual patient. This approach to unstable angina is likely to be rewarded not only by more effective control of the acute syndrome but also by the prevention of recurrent events.

View larger version (18K): [in this window] [in a new window]   Figure 1. Framework for considering 5 major causes of unstable angina (UA).

View this table: [in this window] [in a new window]   Table 1. Causes of Unstable Angina

Footnotes

The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.

References

1. Braunwald E. Unstable angina: a classification. Circulation. 1989;80:410–414.[Free Full Text]

2. Braunwald E, Maseri A, Armstrong PW, Califf RM, Gibler WB, Hamm CW, Simoons ML, van de Werf F. Rationale and clinical evidence for the use of GP IIb/IIIa inhibitors in acute coronary syndromes. Am Heart J. 1998;135:S56–S66.[Medline] [Order article via Infotrieve]

3. Theroux P, Fuster V. Acute coronary syndromes: unstable angina and non–Q-wave myocardial infarction. Circulation. 1998;97:1195–1206.[Free Full Text]

4. Sherman CT, Litvack F, Grundfest W, Lee M, Hickey A, Chaux A, Kass R, Blanche C, Matloff J, Morgenstern L, Ganz W, Swan HJC, Forrester J. Coronary angioscopy in patients with unstable angina pectoris. N Engl J Med. 1986;315:913–919.[Abstract]

5. Ambrose JA, Winters SL, Arora R, Eng A, Riccio A, Gorlin R, Fuster V. Angiographic evolution of coronary artery morphology in unstable angina. J Am Coll Cardiol. 1986;7:472–478.[Abstract]

6. Hirsh PD, Hillis LD, Campbell WB, Firth BG, Willerson JT. Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease. N Engl J Med. 1981;304:685–691.[Abstract]

7. Merlini PA, Bauer KA, Oltrona L, Ardissino D, Cattaneo M, Belli C, Mannucci, PM, Rosenberg RD. Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation. 1994;90:61–68.[Abstract/Free Full Text]

8. Theroux P, Ouimet H, McCans J, Latour JG, Joly P, Levy G, Pelletier E, Juneau M, Stasiak J, de Guise P, Pelletier GB, Rinzler D, Waters DD. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med. 1988;319:1105–1111.[Abstract]

9. Cohen M, Demers C, Gurfinkel EP, Turpie AG, Fromell GJ, Goodman S, Langer A, Califf RM, Fox KA, Premmereur J, Bigonzi J. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease: the ESSENCE trial. N Engl J Med. 1997;337:447–452.[Abstract/Free Full Text]

10. Balsano F, Rizzon P, Violi F, Scrutinio D, Cimminiello C, Aguglia F, Pasotti C, Rudelli G, the Studio della Ticlopidina nell'Angina Instabile Group. Antiplatelet treatment with ticlopidine in unstable angina: a controlled, multicenter clinical trial. Circulation. 1990;82:17–26.[Abstract/Free Full Text]

11. Maseri A. Unstable angina. In: Ischemic Heart Disease. New York, NY: Churchill Livingstone; 1995:533–557.

12. Epstein SE, Cannon RO III. Site of increased resistance to coronary flow in patients with angina pectoris and normal epicardial coronary arteries. J Am Coll Cardiol. 1986;8:459–461.[Medline] [Order article via Infotrieve]

13. Diver DJ, Bier JD, Ferreira PE, Sharaf BL, McCabe C, Thompson B, Chaitman B, Williams DO, Braunwald E. Clinical and arteriographic characterization of patients with unstable angina without critical coronary arterial narrowing. Am J Cardiol. 1994;74:531–537.[Medline] [Order article via Infotrieve]

14. Kaski JC, Chester MR, Chen L, Katritsis D. Rapid angiographic progression of coronary artery disease in patients with angina pectoris: the role of complex stenosis morphology. Circulation. 1995;92:2058–2065.[Abstract/Free Full Text]

15. Mehta JL, Saldeen TGP, Rand K. Interactive role of infection, inflammation and traditional risk factors in atherosclerosis and coronary artery disease. J Am Coll Cardiol. 1998;31:1217–1225.[Abstract/Free Full Text]

16. van der Wal AC, Becker AE, van der Loos CM, Das PK. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation. 1994;89:36–44.[Abstract/Free Full Text]

17. Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med. 1994;331:417–424.[Abstract/Free Full Text]

18. Morrow DA, Rifai N, Antman EM, Weiner DL, McCabe CH, Cannon CP, Braunwald E. C-reactive protein is a potent predictor of mortality independently and in combination with troponin T in acute coronary syndromes. J Am Coll Cardiol. 1998;31:1460–1465.[Abstract/Free Full Text]

19. Ridker PM. Inflammation, infection, and cardiovascular risk: how good is the clinical evidence? Circulation. 1998;97:1671–1674.[Free Full Text]

20. Pasceri V, Cammarota G, Patti G, Cuoco L, Gasbarrani A, Grillo RL, Fedeli G, Gasbarrini G, Maseri A. Association of virulent Helicobacter pylori strains with ischemic heart disease. Circulation. 1998;97:1675–1679.[Abstract/Free Full Text]

21. Leibovitz E, Hertz Y, Liberman E, Sclarovsky S, Berliner S. Increased adhesiveness of white blood cells in patients with unstable angina: additional evidence for an involvement of the immune-inflammatory system. Clin Cardiol. 1997;20:1017–1019.[Medline] [Order article via Infotrieve]

22. Gurfinkel E, Bozovich G, Daroca A, Beck E, Mautner B. Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS Pilot Study. Lancet. 1997;350:404–407.[Medline] [Order article via Infotrieve]

23. Gupta S, Leatham EW, Carrington D, Mendall MA, Kaski JC, Camm AJ. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of acute myocardial infarction. Circulation. 1997;96:404–407.[Abstract/Free Full Text]

This article has been cited by other articles:

				U. Hoffmann and F. Bamberg Is Computed Tomography Coronary Angiography the Most Accurate and Effective Noninvasive Imaging Tool to Evaluate Patients With Acute Chest Pain in the Emergency Department?: CT Coronary Angiography Is the Most Accurate and Effective Noninvasive Imaging Tool for Evaluating Patients Presenting With Chest Pain to the Emergency Department Circ Cardiovasc Imaging, May 1, 2009; 2(3): 251 - 263. [Full Text] [PDF]

				J. L. Anderson, C. D. Adams, E. M. Antman, C. R. Bridges, R. M. Califf, D. E. Casey Jr, W. E. Chavey II, F. M. Fesmire, J. S. Hochman, T. N. Levin, et al. ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine J. Am. Coll. Cardiol., August 14, 2007; 50(7): e1 - e157. [Full Text] [PDF]

				J. L. Anderson, C. D. Adams, E. M. Antman, C. R. Bridges, R. M. Califf, D. E. Casey Jr, W. E. Chavey II, F. M. Fesmire, J. S. Hochman, T. N. Levin, et al. ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine J. Am. Coll. Cardiol., August 14, 2007; 50(7): 652 - 726. [Full Text] [PDF]

				D. A. Morrow, B. M. Scirica, E. Karwatowska-Prokopczuk, S. A. Murphy, A. Budaj, S. Varshavsky, A. A. Wolff, A. Skene, C. H. McCabe, E. Braunwald, et al. Effects of Ranolazine on Recurrent Cardiovascular Events in Patients With Non-ST-Elevation Acute Coronary Syndromes: The MERLIN-TIMI 36 Randomized Trial JAMA, April 25, 2007; 297(16): 1775 - 1783. [Abstract] [Full Text] [PDF]

				NACB WRITING GROUP MEMBERS, D. A. Morrow, C. P. Cannon, R. L. Jesse, L. K. Newby, J. Ravkilde, A. B. Storrow, A. H.B. Wu, and R. H. Christenson National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers in Acute Coronary Syndromes Circulation, April 3, 2007; 115(13): e356 - e375. [Full Text] [PDF]

				NACB WRITING GROUP MEMBERS, D. A. Morrow, C. P. Cannon, R. L. Jesse, L. K. Newby, J. Ravkilde, A. B. Storrow, A. H.B. Wu, R. H. Christenson, NACB COMMITTEE MEMBERS, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers in Acute Coronary Syndromes Clin. Chem., April 1, 2007; 53(4): 552 - 574. [Full Text] [PDF]

				M. de Chantal, J. G. Diodati, J. B. Nasmith, R. Amyot, A. R. LeBlanc, E. Schampaert, and C. Pharand Progressive epicardial coronary blood flow reduction fails to produce ST-segment depression at normal heart rates Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2889 - H2896. [Abstract] [Full Text] [PDF]

				E. J. Armstrong, D. A. Morrow, and M. S. Sabatine Inflammatory Biomarkers in Acute Coronary Syndromes: Part I: Introduction and Cytokines Circulation, February 14, 2006; 113(6): e72 - e75. [Full Text] [PDF]

				C. Heeschen, S. Dimmeler, C. W. Hamm, S. Fichtlscherer, M. L. Simoons, A. M. Zeiher, and CAPTURE Study Investigators Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes: Comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis J. Am. Coll. Cardiol., January 18, 2005; 45(2): 229 - 237. [Abstract] [Full Text] [PDF]

				G. G. Neri Serneri, M. Boddi, P. A. Modesti, M. Coppo, I. Cecioni, T. Toscano, M. L. Papa, M. Bandinelli, G. F. Lisi, and M. Chiavarelli Cardiac Angiotensin II Participates in Coronary Microvessel Inflammation of Unstable Angina and Strengthens the Immunomediated Component Circ. Res., June 25, 2004; 94(12): 1630 - 1637. [Abstract] [Full Text] [PDF]

				D. A. Morrow and E. Braunwald Future of Biomarkers in Acute Coronary Syndromes: Moving Toward a Multimarker Strategy Circulation, July 22, 2003; 108(3): 250 - 252. [Full Text] [PDF]

				G. G. Neri Serneri, M. Boddi, P. A. Modesti, I. Cecioni, M. Coppo, M. L. Papa, T. Toscano, A. Marullo, and M. Chiavarelli Immunomediated and Ischemia-Independent Inflammation of Coronary Microvessels in Unstable Angina Circ. Res., June 27, 2003; 92(12): 1359 - 1366. [Abstract] [Full Text] [PDF]

				W. E. Boden "Routine invasive" versus "selective invasive" approaches to non-ST-segment elevation acute coronary syndromes management in the post-stent/platelet inhibition era J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 113S - 122S. [Abstract] [Full Text] [PDF]

				A. Manhapra and S. Borzak Regular review: Treatment possibilities for unstable angina BMJ, November 18, 2000; 321(7271): 1269 - 1275. [Full Text]

				D. A. Morrow, E. M. Antman, M. Tanasijevic, N. Rifai, J. A. de Lemos, C. H. McCabe, C. P. Cannon, and E. Braunwald Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy J. Am. Coll. Cardiol., November 15, 2000; 36(6): 1812 - 1817. [Abstract] [Full Text] [PDF]

				E. Braunwald, E. M. Antman, J. W. Beasley, R. M. Califf, M. D. Cheitlin, J. S. Hochman, R. H. Jones, D. Kereiakes, J. Kupersmith, T. N. Levin, et al. ACC/AHA guidelines for the management of patients with unstable angina and non-st-segment elevation myocardial infarction: A report of the american college of cardiology/ american heart association task force on practice guidelines (committee on the management of patients with unstable angina) J. Am. Coll. Cardiol., September 1, 2000; 36(3): 970 - 1062. [Full Text] [PDF]

				P. A. Merlini, D. Ardissino, R. D. Rosenberg, E. Colombi, P. Agricola, L. Oltrona, F. Ottani, M. Galvani, K. A. Bauer, B. Bottasso, et al. In Vivo Thrombin Generation and Activity During and After Intravenous Infusion of Heparin or Recombinant Hirudin in Patients With Unstable Angina Pectoris Arterioscler. Thromb. Vasc. Biol., September 1, 2000; 20(9): 2162 - 2166. [Abstract] [Full Text] [PDF]

				C. W. Hamm and E. Braunwald A Classification of Unstable Angina Revisited Circulation, July 4, 2000; 102(1): 118 - 122. [Abstract] [Full Text] [PDF]

				M. J Davies CORONARY DISEASE: The pathophysiology of acute coronary syndromes Heart, March 1, 2000; 83(3): 361 - 366. [Full Text]

				N. G. Kounis, N. D. Grapsas, and J. A. Goudevenos Unstable Angina, Allergic Angina, and Allergic Myocardial Infarction Circulation, December 21, 1999; 100 (25): e156 - e156. [Full Text] [PDF]

				J.L Mehta and D.Y Li Inflammation in ischemic heart disease: Response to tissue injury or a pathogenetic villain? Cardiovasc Res, August 1, 1999; 43(2): 291 - 299. [Full Text] [PDF]

				M. S. Sabatine, D. A. Morrow, J. A. de Lemos, C. M. Gibson, S. A. Murphy, N. Rifai, C. McCabe, E. M. Antman, C. P. Cannon, and E. Braunwald Multimarker Approach to Risk Stratification in Non-ST Elevation Acute Coronary Syndromes: Simultaneous Assessment of Troponin I, C-Reactive Protein, and B-Type Natriuretic Peptide Circulation, April 16, 2002; 105(15): 1760 - 1763. [Abstract] [Full Text] [PDF]

This Article Extract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Braunwald, E. Search for Related Content PubMed PubMed Citation Articles by Braunwald, E.