Ventricular Dysfunction and the Risk of Stroke after Myocardial Infarction
Evan Loh, M.D., Martin St. John Sutton, M.D., Chuan-Chuan C. Wun, Ph.D., Jean L. Rouleau, M.D., Greg C. Flaker, M.D., Stephen S. Gottlieb, M.D., Gervasio A. Lamas, M.D., Lemuel A. Moyé, Ph.D., Samuel Z. Goldhaber, M.D., and Marc A. Pfeffer, M.D., Ph.D.
Background In patients who have had a myocardial infarction,the long-term risk of stroke and its relation to the extentof left ventricular dysfunction have not been determined. Westudied whether a reduced left ventricular ejection fractionis associated with an increased risk of stroke after myocardialinfarction and whether other factors such as older age and therapywith anticoagulants, thrombolytic agents, or captopril affectlong-term rates of stroke.
Methods We performed an observational analysis of prospectivelycollected data on 2231 patients who had left ventricular dysfunctionafter acute myocardial infarction who were enrolled in the Survivaland Ventricular Enlargement trial. The mean follow-up was 42months. Risk factors for stroke were assessed by both univariateand multivariate Cox proportional-hazards analysis.
Results Among these patients, 103 (4.6 percent) had fatal ornonfatal strokes during the study (rate of stroke per year offollow-up, 1.5 percent). The estimated five-year rate of strokein all the patients was 8.1 percent. As compared with patientswithout stroke, patients with stroke were older (mean [±SD]age, 63±9 years vs. 59±11 years; P<0.001) andhad lower ejection fractions (29±7 percent vs. 31±7percent, P = 0.01). Independent risk factors for stroke includeda lower ejection fraction (for every decrease of 5 percentagepoints in the ejection fraction there was an 18 percent increasein the risk of stroke), older age, and the absence of aspirinor anticoagulant therapy. Patients with ejection fractions of<28 percent after myocardial infarction had a relative riskof stroke of 1.86, as compared with patients with ejection fractionsof >35 percent (P = 0.01). The use of thrombolytic agentsand captopril had no significant effect on the risk of stroke.
Conclusions During the five years after myocardial infarction,patients have a substantial risk of stroke. A decreased ejectionfraction and older age are both independent predictors of anincreased risk of stroke. Anticoagulant therapy appears to havea protective effect against stroke after myocardial infarction.
Source Information
From the Hospital of the University of Pennsylvania, Philadelphia (E.L., M.S.S.); the University of Texas Health Science Center, Houston (C.-C.C.W., L.A.M.); Montreal Heart Institute, Montreal (J.L.R.); the University of Missouri Hospital and Clinics, Columbia (G.C.F.); the University of Maryland Hospital, Baltimore (S.S.G.); Mt. Sinai Medical Center, Miami Beach, Fla. (G.A.L.); and Brigham and Women's Hospital, Boston (S.Z.G., M.A.P.).
Address reprint requests to Dr. Loh at the Hospital of the University of Pennsylvania, 9 Founders Pavilion, 3400 Spruce St., Philadelphia, PA 19104.
Schafer, A., Fraccarollo, D., Widder, J., Eigenthaler, M., Ertl, G., Bauersachs, J.
(2009). Inhibition of platelet activation in rats with severe congestive heart failure by a novel endothelial nitric oxide synthase transcription enhancer. Eur J Heart Fail
11: 336-341
[Abstract][Full Text]
Ripley, T. L., Nutescu, E.
(2009). Anticoagulation in patients with heart failure and normal sinus rhythm. Am J Health Syst Pharm
66: 134-141
[Abstract][Full Text]
Diener, H.-C., Mattle, H., Böhm, M., Ruschitzka, F.
(2009). CHAPTER 15a The Heart and the Brain. ESC Textbook of Cardiovascular Medicine
2: med-9780199566990-chapter-med-9780199566990-chapter
[Abstract][Full Text]
Weinsaft, J. W., Kim, H. W., Shah, D. J., Klem, I., Crowley, A. L., Brosnan, R., James, O. G., Patel, M. R., Heitner, J., Parker, M., Velazquez, E. J., Steenbergen, C., Judd, R. M., Kim, R. J.
(2008). Detection of Left Ventricular Thrombus by Delayed-Enhancement Cardiovascular Magnetic Resonance: Prevalence and Markers in Patients With Systolic Dysfunction. J Am Coll Cardiol
52: 148-157
[Abstract][Full Text]
Becker, R. C., Meade, T. W., Berger, P. B., Ezekowitz, M., O'Connor, C. M., Vorchheimer, D. A., Guyatt, G. H., Mark, D. B., Harrington, R. A.
(2008). The Primary and Secondary Prevention of Coronary Artery Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest
133: 776S-814S
[Abstract][Full Text]
Aull-Watschinger, S., Konstantin, H., Demetriou, D., Schillinger, M., Habicht, A., Horl, W. H., Watschinger, B.
(2008). Pre-transplant predictors of cerebrovascular events after kidney transplantation. Nephrol Dial Transplant
23: 1429-1435
[Abstract][Full Text]
Doufekias, E., Segal, A. Z., Kizer, J. R.
(2008). Cardiogenic and aortogenic brain embolism.. J Am Coll Cardiol
51: 1049-1059
[Abstract][Full Text]
Weir, N U
(2008). An update on cardioembolic stroke. Postgrad. Med. J.
84: 133-142
[Abstract][Full Text]
Coca, A., Messerli, F. H., Benetos, A., Zhou, Q., Champion, A., Cooper-DeHoff, R. M., Pepine, C. J.
(2008). Predicting Stroke Risk in Hypertensive Patients With Coronary Artery Disease: A Report From the INVEST. Stroke
39: 343-348
[Abstract][Full Text]
de Boer, R. A., van Veldhuisen, D. J.
(2008). Letter by de Boer and van Veldhuisen Regarding Article, "Risk of Thromboembolism in Heart Failure: An Analysis from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)". Circulation
117: e7-e7
[Full Text]
Schneider, D. J., Sobel, B. E.
(2007). Conundrums in the Combined Use of Anticoagulants and Antiplatelet Drugs. Circulation
116: 305-315
[Full Text]
Freudenberger, R. S., Hellkamp, A. S., Halperin, J. L., Poole, J., Anderson, J., Johnson, G., Mark, D. B., Lee, K. L., Bardy, G. H., for the SCD-HeFT Investigators,
(2007). Risk of Thromboembolism in Heart Failure: An Analysis From the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Circulation
115: 2637-2641
[Abstract][Full Text]
Sampson, U. K., Pfeffer, M. A., McMurray, J. J.V., Lokhnygina, Y., White, H. D., Solomon, S. D., for the Valsartan in Acute Myocardial iNfarcTion (,
(2007). Predictors of stroke in high-risk patients after acute myocardial infarction: insights from the VALIANT trial. Eur Heart J
28: 685-691
[Abstract][Full Text]
Chong, A.-Y., Lip, G. Y.H.
(2007). Viewpoint: The prothrombotic state in heart failure: A maladaptive inflammatory response?. Eur J Heart Fail
9: 124-128
[Abstract][Full Text]
Van De Graaff, E., Dutta, M., Das, P., Shry, E. A., Frederick, P. D., Blaney, M., Pasta, D. J., Steinhubl, S. R.
(2006). Early Coronary Revascularization Diminishes the Risk of Ischemic Stroke With Acute Myocardial Infarction. Stroke
37: 2546-2551
[Abstract][Full Text]
Suarez, J. I.
(2006). Acute Myocardial Infarction, Ischemic Stroke, Sympathetic Stress, and Inflammation: Birds of a Feather. Stroke
37: 2449-2450
[Full Text]
Nair, A., Sealove, B., Halperin, J. L., Webber, G., Fuster, V.
(2006). Anticoagulation in patients with heart failure: who, when, and why?. Eur Heart J Suppl
8: E32-E38
[Abstract][Full Text]
Hankey, G. J.
(2006). Potential New Risk Factors for Ischemic Stroke: What Is Their Potential?. Stroke
37: 2181-2188
[Abstract][Full Text]
Hays, A. G., Sacco, R. L., Rundek, T., Sciacca, R. R., Jin, Z., Liu, R., Homma, S., Di Tullio, M. R.
(2006). Left Ventricular Systolic Dysfunction and the Risk of Ischemic Stroke in a Multiethnic Population. Stroke
37: 1715-1719
[Abstract][Full Text]
Appelros, P.
(2006). Heart Failure and Stroke. Stroke
37: 1637-1637
[Full Text]
Goldstein, L. B., Adams, R., Alberts, M. J., Appel, L. J., Brass, L. M., Bushnell, C. D., Culebras, A., DeGraba, T. J., Gorelick, P. B., Guyton, J. R., Hart, R. G., Howard, G., Kelly-Hayes, M., Nixon, J.V., Sacco, R. L.
(2006). Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline.. Circulation
113: e873-e923
[Abstract][Full Text]
Cokkinos, D. V., Haralabopoulos, G. C., Kostis, J. B., Toutouzas, P. K., for the HELAS investigators,
(2006). Efficacy of antithrombotic therapy in chronic heart failure: The HELAS study. Eur J Heart Fail
8: 428-432
[Abstract][Full Text]
Goldstein, L. B., Adams, R., Alberts, M. J., Appel, L. J., Brass, L. M., Bushnell, C. D., Culebras, A., DeGraba, T. J., Gorelick, P. B., Guyton, J. R., Hart, R. G., Howard, G., Kelly-Hayes, M., Nixon, J.V., Sacco, R. L.
(2006). Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline.. Stroke
37: 1583-1633
[Abstract][Full Text]
Sacco, R. L., Adams, R., Albers, G., Alberts, M. J., Benavente, O., Furie, K., Goldstein, L. B., Gorelick, P., Halperin, J., Harbaugh, R., Johnston, S. C., Katzan, I., Kelly-Hayes, M., Kenton, E. J., Marks, M., Schwamm, L. H., Tomsick, T.
(2006). Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline.. Circulation
113: e409-e449
[Abstract][Full Text]
Sinha, A.-M., Skobel, E. C., Breithardt, O.-A., Zheng, H., Zhan, H., Wilcox, I., Booth, V., Lattimore, J., Chhajed, P. N., Tamm, M., Strobel, W., Neuberger, H.-R., Bohm, M., Mewis, C., Bradley, T. D., Floras, J. S., Logan, A. G., Yaggi, H. K., Concato, J., Mohsenin, V.
(2006). Sleep apnea and heart disease.. NEJM
354: 1086-1089
[Full Text]
Blankfield, R. P.
(2006). Can Natriuretic Peptide Levels Predict the Cardiovascular Complications of COX-2 Inhibitors and Nonsteroidal Anti-inflammatory Drugs?. J Am Board Fam Med
19: 178-182
[Abstract][Full Text]
Sacco, R. L., Adams, R., Albers, G., Alberts, M. J., Benavente, O., Furie, K., Goldstein, L. B., Gorelick, P., Halperin, J., Harbaugh, R., Johnston, S. C., Katzan, I., Kelly-Hayes, M., Kenton, E. J., Marks, M., Schwamm, L. H., Tomsick, T.
(2006). Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline.. Stroke
37: 577-617
[Abstract][Full Text]
Szummer, K. E., Solomon, S. D., Velazquez, E. J., Kilaru, R., McMurray, J., Rouleau, J.-L., Mahaffey, K. W., Maggioni, A. P., Califf, R. M., Pfeffer, M. A., White, H. D., on behalf of the VALIANT registry,
(2005). Heart failure on admission and the risk of stroke following acute myocardial infarction: the VALIANT registry. Eur Heart J
26: 2114-2119
[Abstract][Full Text]
Schafer, A., Fraccarollo, D., Eigenthaler, M., Tas, P., Firnschild, A., Frantz, S., Ertl, G., Bauersachs, J.
(2005). Rosuvastatin Reduces Platelet Activation in Heart Failure: Role of NO Bioavailability. Arterioscler. Thromb. Vasc. Bio.
25: 1071-1077
[Abstract][Full Text]
Burger, P. C., Rocca, H. B.-L.
(2005). Pharmacotherapy of Congestive Heart Failure in Elderly Patients. J CARDIOVASC PHARMACOL THER
10: 85-94
[Abstract]
Yan, A. T., Yan, R. T., Liu, P. P.
(2005). Narrative Review: Pharmacotherapy for Chronic Heart Failure: Evidence from Recent Clinical Trials. ANN INTERN MED
142: 132-145
[Abstract][Full Text]
Flemming, K. D., Brown, R. D. Jr
(2004). Secondary Prevention Strategies in Ischemic Stroke: Identification and Optimal Management of Modifiable Risk Factors. Mayo Clin Proc.
79: 1330-1340
[Abstract]
Albers, G. W., Amarenco, P., Easton, J. D., Sacco, R. L., Teal, P.
(2004). Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest
126: 483S-512S
[Abstract][Full Text]
Harrington, R. A., Becker, R. C., Ezekowitz, M., Meade, T. W., O'Connor, C. M., Vorchheimer, D. A., Guyatt, G. H.
(2004). Antithrombotic Therapy for Coronary Artery Disease: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest
126: 513S-548S
[Abstract][Full Text]
Ho, J. E., Paultre, F., Mosca, L.
(2003). Is Diabetes Mellitus a Cardiovascular Disease Risk Equivalent for Fatal Stroke in Women?: Data From the Women's Pooling Project. Stroke
34: 2812-2816
[Abstract][Full Text]
Echemann, M., Alla, F., Briancon, S., Juilliere, Y., Virion, J.M., Mertes, P.M., Villemot, J.P., Zannad, F., EPICAL Investigators,
(2002). Antithrombotic therapy is associated with better survival in patients with severe heart failure and left ventricular systolic dysfunction (EPICAL study). Eur J Heart Fail
4: 647-654
[Abstract][Full Text]
Straus, S. E., Majumdar, S. R., McAlister, F. A.
(2002). New Evidence for Stroke Prevention: Scientific Review. JAMA
288: 1388-1395
[Abstract][Full Text]
Lip, G.Y.H., Gibbs, C.R.
(2002). Anticoagulation for heart failure in sinus rhythm: a Cochrane systematic review. QJM
95: 451-459
[Abstract][Full Text]
Lip, G.Y.H., Gibbs, C.R.
(2002). Antiplatelet agents versus control or anticoagulation for heart failure in sinus rhythm: a Cochrane systematic review. QJM
95: 461-468
[Abstract][Full Text]
Zannad, F
(2002). Evidence-based drug therapy for chronic heart failure. Eur Heart J Suppl
4: D66-D72
[Abstract]
Struthers, A D, Donnan, P T, Lindsay, P, McNaughton, D, Broomhall, J, MacDonald, T M
(2002). Effect of allopurinol on mortality and hospitalisations in chronic heart failure: a retrospective cohort study. Heart
87: 229-234
[Abstract][Full Text]
Tanne, D., Shotan, A., Goldbourt, U., Haim, M., Boyko, V., Adler, Y., Mandelzweig, L., Behar, S.
(2002). Severity of Angina Pectoris and Risk of Ischemic Stroke. Stroke
33: 245-250
[Abstract][Full Text]
Pullicino, P. M., Hart, J.
(2001). Cognitive impairment in congestive heart failure?: Embolism vs hypoperfusion. Neurology
57: 1945-1946
[Full Text]
Task Force for the Diagnosis and Treatment of Chro, , Remme, W. J., Swedberg, K.
(2001). Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J
22: 1527-1560
Cleland, J.G.F., Thygesen, K., Uretsky, B.F., Armstrong, P., Horowitz, J.D., Massie, B., Packer, M., Poole-Wilson, P.A., Ryden, L., on behalf of the ATLAS investigators,
(2001). Cardiovascular critical event pathways for the progression of heart failure; a report from the ATLAS study. Eur Heart J
22: 1601-1612
[Abstract]
Isnard, R., Komajda, M.
(2001). Thromboembolism in heart failure, old ideas and new challenges. Eur J Heart Fail
3: 265-269
[Abstract][Full Text]
Gibbs, C. R., Blann, A. D., Watson, R. D. S., Lip, G. Y. H.
(2001). Abnormalities of Hemorheological, Endothelial, and Platelet Function in Patients With Chronic Heart Failure in Sinus Rhythm : Effects of Angiotensin-Converting Enzyme Inhibitor and {beta}-Blocker Therapy. Circulation
103: 1746-1751
[Abstract][Full Text]
Cairns, J. A., Theroux, P., Lewis, H. D. Jr., Ezekowitz, M., Meade, T. W.
(2001). Antithrombotic Agents in Coronary Artery Disease. Chest
119
: 228S-252S
[Full Text]
Albers, G. W., Amarenco, P., Easton, J. D., Sacco, R. L., Teal, P.
(2001). Antithrombotic and Thrombolytic Therapy for Ischemic Stroke. Chest
119
: 300S-320S
[Full Text]
Brett, A. S., Meilof, J. F., Uitdehaag, B. M.I., Fruchter, O., White, H. D., Simes, R. J., Tonkin, A. M., The LIPID Study Group,
(2000). Pravastatin Therapy and the Risk of Stroke. NEJM
343: 1894-1896
[Full Text]
Diet, F., Erdmann, E.
(2000). Thromboembolism in heart failure: who should be treated?. Eur J Heart Fail
2: 355-363
[Abstract][Full Text]
Lip, G. Y. H.
(2000). Target Organ Damage and the Prothrombotic State in Hypertension. Hypertension
36: 975-977
[Full Text]
WIEGERS, S. E, SUTTON, M. S. J.
(2000). When should ACE inhibitors or warfarin be discontinued after myocardial infarction?. Heart
84: 361-362
[Full Text]
Holloway, R. G., Benesch, C., Rush, S. R.
(2000). Stroke prevention: Narrowing the evidence-practice gap. Neurology
54: 1899-1906
[Abstract][Full Text]
Sharma, N. D., McCullough, P. A., Philbin, E. F., Weaver, W. D.
(2000). Left Ventricular Thrombus and Subsequent Thromboembolism in Patients With Severe Systolic Dysfunction. Chest
117: 314-320
[Abstract][Full Text]
Pullicino, P. M., Halperin, J. L., Thompson, J. L. P.
(2000). Stroke in patients with heart failure and reduced left ventricular ejection fraction. Neurology
54: 288-288
[Abstract][Full Text]
Cokkinos, D. V., Toutouzas, P. K.
(1999). Antithrombotic therapy in heart failure: a randomized comparison of warfarin vs. aspirin (HELAS). Eur J Heart Fail
1: 419-423
[Abstract][Full Text]
Nadareishvili, Z. G., Choudary, Z., Joyner, C., Brodie, D., Norris, J. W.
(1999). Cerebral Microembolism in Acute Myocardial Infarction. Stroke
30: 2679-2682
[Abstract][Full Text]
Kapral, M. K., Silver, F. L.
(1999). Preventive health care, 1999 update: 2. Echocardiography for the detection of a cardiac source of embolus in patients with stroke. CMAJ
161: 989-996
[Abstract][Full Text]
Kelly, R., Struthers, A.D.
(1999). Screening for left ventricular systolic dysfunction in patients with stroke, transient ischaemic attacks, and peripheral vascular disease. QJM
92: 295-297
[Full Text]
Davis, T. M. E., Millns, H., Stratton, I. M., Holman, R. R., Turner, R. C., for the UK Prospective Diabetes Study Group,
(1999). Risk Factors for Stroke in Type 2 Diabetes Mellitus: United Kingdom Prospective Diabetes Study (UKPDS) 29. Arch Intern Med
159: 1097-1103
[Abstract][Full Text]
Mooe, T., Olofsson, B.-O., Stegmayr, B., Eriksson, P.
(1999). Ischemic Stroke : Impact of a Recent Myocardial Infarction. Stroke
30: 997-1001
[Abstract][Full Text]
Gorelick, P. B., Sacco, R. L., Smith, D. B., Alberts, M., Mustone-Alexander, L., Rader, D., Ross, J. L., Raps, E., Ozer, M. N., Brass, L. M., Malone, M. E., Goldberg, S., Booss, J., Hanley, D. F., Toole, J. F., Greengold, N. L., Rhew, D. C.
(1999). Prevention of a First Stroke: A Review of Guidelines and a Multidisciplinary Consensus Statement From the National Stroke Association. JAMA
281: 1112-1120
[Abstract][Full Text]
Plehn, J. F., Davis, B. R., Sacks, F. M., Rouleau, J. L., Pfeffer, M. A., Bernstein, V., Cuddy, T. E., Moye, L. A., Piller, L. B., Rutherford, J., Simpson, L. M., Braunwald, E.
(1999). Reduction of Stroke Incidence After Myocardial Infarction With Pravastatin : The Cholesterol and Recurrent Events (CARE) Study. Circulation
99: 216-223
[Abstract][Full Text]
Chen, C.-H., Nakayama, M., Nevo, E., Fetics, B. J., Maughan, W. L., Kass, D. A.
(1998). Coupled systolic-ventricular and vascular stiffening with age: Implications for pressure regulation and cardiac reserve in the elderly. J Am Coll Cardiol
32: 1221-1227
[Abstract][Full Text]
Wu, K. C., Zerhouni, E. A., Judd, R. M., Lugo-Olivieri, C. H., Barouch, L. A., Schulman, S. P., Blumenthal, R. S., Lima, J. A. C.
(1998). Prognostic Significance of Microvascular Obstruction by Magnetic Resonance Imaging in Patients With Acute Myocardial Infarction. Circulation
97: 765-772
[Abstract][Full Text]
Oppenheimer, S. M, Lima, J.
(1998). Neurology and the heart. J. Neurol. Neurosurg. Psychiatry
64: 289-297
[Full Text]
Delanty, N., Vaughan, C. J.
(1997). Vascular Effects of Statins in Stroke. Stroke
28: 2315-2320
[Abstract][Full Text]
Michaels, A. D., Gambassi, G., Carbonin, P., Bernabei, R., Loh, E., Moye, L. A., Pfeffer, M. A.
(1997). Risk of Stroke after Myocardial Infarction. NEJM
336: 1916-1917
[Full Text]
(1997). STROKE AFTER MYOCARDIAL INFARCTION. JWatch General
1997: 1-1
[Full Text]
Lichtman, J. H., Krumholz, H. M., Wang, Y., Radford, M. J., Brass, L. M.
(2002). Risk and Predictors of Stroke After Myocardial Infarction Among the Elderly: Results From the Cooperative Cardiovascular Project. Circulation
105: 1082-1087
[Abstract][Full Text]