This Article Abstract Full Text (PDF) All Versions of this Article: 110/12/1572    most recent 01.CIR.0000142047.28024.F2v1 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 patientINFORMation Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aguilar, D. Articles by Pfeffer, M. A. Search for Related Content PubMed PubMed Citation Articles by Aguilar, D. Articles by Pfeffer, M. A. Related Collections Type 2 diabetes Acute myocardial infarction

(Circulation. 2004;110:1572-1578.)
© 2004 American Heart Association, Inc.

Coronary Heart Disease

Newly Diagnosed and Previously Known Diabetes Mellitus and 1-Year Outcomes of Acute Myocardial Infarction

The Valsartan in Acute Myocardial Infarction (VALIANT) Trial

David Aguilar, MD; Scott D. Solomon, MD; Lars Køber, MD, DSc; Jean-Lucien Rouleau, MD; Hicham Skali, MD; John J.V. McMurray, MD; Gary S. Francis, MD; Marc Henis, MD; Christopher M. O’Connor, MD; Rafael Diaz, MD; Yuri N. Belenkov, MD, PhD; Sergei Varshavsky, MD; Jeffrey D. Leimberger, PhD; Eric J. Velazquez, MD; Robert M. Califf, MD; Marc A. Pfeffer, MD, PhD

From the University of Texas Health Science Center, Houston (D.A.); Brigham and Women’s Hospital, Boston, Mass (S.D.S., H.S., M.A.P.); Rigshospitalet, Copenhagen, Denmark (L.K.); Toronto Hospital, Toronto, Ontario, Canada (J.L.R.); University of Glasgow, Glasgow, United Kingdom (J.J.V.M.); The Cleveland Clinic Foundation, Cleveland, Ohio (G.S.F.); Medical Pharmaceutical Consultants, Randolph, NJ (M.H.); Duke Clinical Research Institute, Durham, NC (C.M.O., J.D.L., E.J.V, R.M.C.); Estudios Cardiologicos Latinoamerica, Santa Fe, Argentina (R.D.); Cardiology Research Institute, Moscow, Russia (Y.N.B.); and the CPR/Research Institute of Cardiology, St. Petersburg, Russia (S.V.).

Correspondence and reprint requests to Dr David Aguilar, Cardiovascular Division, University of Texas Health Science Center, 6431 Fannin, MSB 1.246, Houston, TX 77030. E-mail david.aguilar{at}uth.tmc.edu

Received January 29, 2004; revision received April 29, 2004; accepted May 18, 2004.

	Abstract

Top Abstract Introduction Methods Results Discussion Conclusion Disclosure References

 
Background— A prior diagnosis of diabetes mellitus is associated with adverse outcomes after acute myocardial infarction (MI), but the risk associated with a new diagnosis of diabetes in this setting has not been well defined.

Methods and Results— We assessed the risk of death and major cardiovascular events associated with previously known and newly diagnosed diabetes by studying 14 703 patients with acute MI enrolled in the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. Patients were grouped by diabetic status: previously known diabetes (insulin use or diagnosis of diabetes before MI, n=3400, 23%); newly diagnosed diabetes (use of diabetic therapy or diabetes diagnosed at randomization [median 4.9 d after infarction], but no known diabetes at presentation, n=580, 4%); or no diabetes (n=10 719). Patients with newly diagnosed diabetes were younger and had fewer comorbid conditions than did patients with previously known diabetes. At 1 year after enrollment, patients with previously known and newly diagnosed diabetes had similarly increased adjusted risks of mortality (hazard ratio [HR] 1.43; 95% confidence interval [CI], 1.29 to 1.59 and HR, 1.50; 95% CI, 1.21 to 1.85, respectively) and cardiovascular events (HR, 1.37; 95% CI, 1.27 to 1.48 and HR, 1.34; 95% CI, 1.14 to 1.56).

Conclusions— Diabetes mellitus, whether newly diagnosed or previously known, is associated with poorer long-term outcomes after MI in high-risk patients. The poor prognosis of patients with newly diagnosed diabetes, despite having baseline characteristics similar to those of patients without diabetes, supports the idea that metabolic abnormalities contribute to their adverse outcomes.

Key Words: myocardial infarction • prognosis • diabetes mellitus • heart failure

	Introduction

Top Abstract Introduction Methods Results Discussion Conclusion Disclosure References

 
The increasing prevalence of type 2 diabetes mellitus will have important cardiovascular consequences, given that diabetes is a major risk factor for the development of atherosclerotic disease.¹ Approximately 20% to 30% of patients with an acute myocardial infarction (MI) have a previous diagnosis of diabetes.^2–4 These patients are at increased risk of both short-term and long-term cardiovascular events after MI.^2–5

Most of the studies that have quantified the adverse outcomes of diabetic patients with MI have been limited to patients with a known diagnosis of diabetes at the time of infarction. During the early days after an MI, physicians often diagnose new cases of diabetes, although it is unclear whether this relates to "stress hyperglycemia" or to the discovery of previously unrecognized diabetes in the population. The characteristics and prognosis of these patients with a new diagnosis of diabetes at the time of MI have been less well defined.

We used the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial to characterize further the effect of previously known and newly diagnosed diabetes on 1-year mortality and major cardiovascular events in patients with heart failure and/or left ventricular systolic dysfunction after MI.

	Methods

Top Abstract Introduction Methods Results Discussion Conclusion Disclosure References

 
Patient Population
The VALIANT trial was a multinational, randomized trial comparing the effects of valsartan, captopril, or their combination in the treatment of acute MI complicated by either clinical or radiological signs of heart failure or evidence of left ventricular systolic dysfunction or both. Patients were at least 18 years old and demonstrated symptoms of MI for at least 12 h but not >10 d. The exclusion criteria included cardiogenic shock, a serum creatinine level >2.5 mg/dL, known intolerance of or a contraindication for angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, and other serious diseases that could severely limit life expectancy. Details of the protocol and results of the main trial have been published.^6,7

Diabetic status was assessed at presentation with MI and again at randomization into VALIANT (a median of 4.9 d after symptom onset). Investigators were asked whether patients had a known history of diabetes before the qualifying MI, referring to a recorded history of diabetes managed with diet, insulin, or oral medications. Patients with a history of diabetes or insulin use before the qualifying MI were defined as having previously known diabetes. At randomization, investigators were asked whether patients had developed diabetes from the time of MI to randomization and whether they had received insulin or oral hypoglycemic agents within 24 h before randomization. If the investigator answered yes to either of these questions and the patient did not have previously known diabetes at presentation, then the patient was considered to have newly diagnosed diabetes. The remaining participants in the study were considered not to have diabetes (Figure 1).

View larger version (34K): [in this window] [in a new window]   Figure 1. VALIANT study design.

Outcomes
The primary outcomes were the risks of death and major cardiovascular events within 1 year after MI. Suspected adverse cardiac events were identified by the primary investigator and were independently confirmed by the Clinical Endpoint Center. Reinfarction was confirmed in the presence of increased cardiac enzymes and typical clinical presentation or electrocardiographic changes that were consistent with MI. Heart failure was defined as an unplanned presentation for new or worsening heart failure requiring an overnight stay or admission to a healthcare facility in which the patient received intravenous inotropic, diuretic, or vasodilator therapy. Stroke was defined as a focal neurological deficit lasting >24 h or resulting in death that was presumed to be related to stroke. Resuscitated sudden cardiac arrest was defined as sudden death or cardiac arrest requiring cardioversion, defibrillation, or cardiopulmonary resuscitation. A composite cardiovascular outcome was defined as the occurrence of cardiovascular death, reinfarction, heart failure, resuscitated sudden death, and stroke.

Data Analysis
Continuous variables are presented as means with standard deviations unless otherwise specified. Differences in baseline demographics between groups were ascertained using Wilcoxon rank-sum tests for continuous variables and Pearson ² tests for categorical and ordinal data. Two-sided values of P<0.01 were considered significant.

Cox proportional-hazards models were used to assess the relations between diabetic status and the outcome of interest. Both unadjusted and multivariable adjusted hazard ratios are presented. From 70 candidate variables collected at randomization, both backward elimination and stepwise selection were used to identify independent predictors of the outcome. The multivariable model for mortality included the main effects of the following variables: age, heart rate, and systolic and diastolic blood pressures; Killip classification; anterior MI; new left bundle-branch block; thrombolytic therapy, primary percutaneous intervention, or ß-blocker use with qualifying MI; history of heart failure, previous MI, stroke, dyslipidemia, stable angina, hypertension, or alcohol abuse; previous unstable angina; trial enrollment in the United States; weight; current smoking; serum creatinine; atrial fibrillation, heart failure, hypertension, renal insufficiency, cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass graft surgery after the qualifying MI; and study treatment assignment. The multivariable model for the composite cardiovascular outcome included similar variables, with the exception of US enrollment and ß-blocker use with qualifying MI and the addition of gender, race, previous hospitalization, and history of peripheral vascular disease or transient cerebral ischemic event.

Log-rank tests were used to compare event curves for mortality, cardiovascular death, reinfarction, heart failure, stroke, and the composite outcome of cardiovascular death, heart failure, reinfarction, stroke, or cardiac arrest with resuscitation.

	Results

Top Abstract Introduction Methods Results Discussion Conclusion Disclosure References

 
VALIANT enrolled 14 703 patients with acute MI complicated by heart failure or left ventricular systolic dysfunction or both. Of these patients, 3400 had previously known diabetes at the time of MI (23%), 580 received a new diagnosis of diabetes between the time of MI and randomization (4%), 10 719 had no diabetes (73%), and 4 patients lacked the data necessary for classification.

Clinical Characteristics
Characteristics at baseline and at randomization are described in Table 1. Baseline demographics were similar between patients with newly diagnosed diabetes and patients without diabetes, except for body mass index. In contrast, patients with previously known diabetes were older and presented with more comorbid cardiovascular conditions than did either patients with newly diagnosed diabetes or patients without diabetes.

View this table: [in this window] [in a new window]   TABLE 1. Clinical Characteristics

Patients with previously known diabetes were more likely to have a non-Q-wave MI and had lower creatine kinase levels than both patients with newly diagnosed diabetes and patients without diabetes. The initial therapy for MI was similar between patients with newly diagnosed diabetes and those without diabetes. In contrast, patients with previously known diabetes were less likely to receive aspirin, ß-blockers, thrombolytic therapy, or primary percutaneous coronary intervention than were patients without diabetes. They also were less likely to receive ß-blockers and fibrinolytic therapy than were patients with newly diagnosed diabetes.

At randomization, patients with newly diagnosed or previously known diabetes had a faster heart rate and more often had a higher Killip classification than did patients without diabetes. Patients with previously known diabetes also had a slightly lower ejection fraction than did patients without diabetes and a higher systolic blood pressure than did patients with newly diagnosed diabetes and those without diabetes.

Medications, with the exception of diabetic therapy, did not differ between patients with newly diagnosed diabetes and those without diabetes. In contrast, patients with previously known diabetes were more likely to receive calcium channel blockers and HMG-CoA reductase inhibitors but were less likely to receive aspirin and ß-blockers than were patients without diabetes. Patients with previously known diabetes also were more likely to receive calcium channel blockers, insulin, and oral hypoglycemic therapy than those with newly diagnosed diabetes.

Mortality
By 1 year, 602 patients with previously known diabetes (17.7%), 94 patients with new diagnoses of diabetes (16.2%), and 1169 patients without diabetes (10.9%) had died. Despite similarities in characteristics between patients with newly diagnosed diabetes and those without diabetes, the rate of death was greater in patients with newly diagnosed diabetes and was similar to the rate in patients with previously known diabetes (Figure 2). The 1-year mortality rate for patients with newly diagnosed diabetes was similar whether they were or were not receiving diabetic therapy within 24 h of randomization (15.7% versus 16.8%, respectively; P=0.71). After adjustment for baseline differences, patients with either previously known or newly diagnosed diabetes maintained a higher risk of death as compared with patients without diabetes (Table 2).

View larger version (13K): [in this window] [in a new window]   Figure 2. Kaplan-Meier curves for mortality at 1 year by diabetic status. P=0.43 for previous vs new diabetes diagnosis, P<0.001 for previous vs no diabetes diagnosis, P<0.001 for new vs no diabetes diagnosis.

View this table: [in this window] [in a new window]   TABLE 2. Primary Outcomes

Nonfatal Events
The occurrences of nonfatal adverse cardiovascular events are described in Figure 3. Patients with previously known diabetes and those with newly diagnosed diabetes had higher rates of the composite cardiovascular outcome than those without diabetes (Figure 4). Similar to total mortality, the adjusted risk for the composite cardiovascular end point in patients with newly diagnosed diabetes was similar to the risk of patients with previously known diabetes (Table 2). The incidence of the composite cardiovascular outcome also was similar between patients with newly diagnosed diabetes who were or were not receiving diabetic therapy within 24 h of randomization (30% versus 28.2%, respectively; P=0.64).

View larger version (33K): [in this window] [in a new window]   Figure 3. Kaplan-Meier estimates of secondary outcomes at 1 year by diabetic status. *P<0.01 vs patients without diabetes, P<0.01 for previously known diabetes vs newly diagnosed diabetes patients.

View larger version (14K): [in this window] [in a new window]   Figure 4. Kaplan-Meier curves for composite outcome of cardiovascular mortality/morbidity at 1 year by diabetic status. P=0.005 for previous vs new diabetes diagnosis; P<0.001 for previous vs no diabetes diagnosis; P<0.001 for new vs no diabetes diagnosis. Composite cardiovascular outcome included cardiovascular death, reinfarction, heart failure, resuscitated sudden death, and stroke.

	Discussion

Top Abstract Introduction Methods Results Discussion Conclusion Disclosure References

 
In the large VALIANT cohort of high-risk patients with acute MI, 23% had a history of diabetes mellitus at the time of MI. Another 4% were newly diagnosed with diabetes in the early phase of the index infarction. The presence of either previously known or newly diagnosed diabetes was a significant independent predictor of mortality and adverse cardiovascular events at 1 year after MI.

Patients with acute MI and a history of diabetes have poorer outcomes than such patients without diabetes,^2–5,8 a finding confirmed in the present study. As in other studies, previously known diabetic patients in VALIANT were more likely to be older and female and to have more comorbid conditions than patients without diabetes. Despite having smaller MIs, as measured by creatine kinase levels, patients with diabetes also were more likely to have a greater degree of heart failure in conjunction with and in the first year after MI.

Multiple mechanisms have been implicated in the increased number of adverse outcomes in patients with diabetes. These mechanisms include an abnormal metabolic response to ischemia with inefficient energy use and accumulation of deleterious oxygen-free radicals,⁹ greater endothelial dysfunction,¹⁰ and abnormalities of thrombosis and fibrinolysis.¹¹ Patients with diabetes are known to have a greater burden of atherosclerotic disease, with more diffuse and more multivessel coronary artery disease.^5,12 The presence of a "diabetic cardiomyopathy" may lead to greater degrees of heart failure.⁸ Finally, although they derive similar therapeutic benefit, patients with diabetes have been demonstrated to be less likely to undergo thrombolysis¹³ or receive ß-blocker therapy^14,15 than were patients without diabetes, a finding seen in the present study.

In our study, the 4% of patients who received a new diagnosis of diabetes during the early phase of acute MI displayed an increased risk of death and adverse cardiovascular events. It is important to consider this hazard in light of the differences that may exist in the group of patients with newly diagnosed diabetes. Because no uniform definition was specified and no blood glucose values were available for review, new cases of diabetes were diagnosed by individual physician assessments. Given this likely heterogeneity, as well as difficulties establishing a new diagnosis of diabetes in the early post-MI setting,¹⁶ patients with newly diagnosed diabetes likely composed a spectrum of patients from those with true unrecognized diabetes to those without diabetes but with stress hyperglycemia.

Population-based studies^17–19 and recent analyses of patients who were referred for cardiac catheterization^20,21 have shown that the prevalence of previously unrecognized diabetes may range from one third to one half of the people with diabetes in the population studied and that the presence of unrecognized diabetes is associated with an increased risk of death.^19,20,22 Overall, in studies in which survivors of an acute MI have undergone oral glucose tolerance testing, fasting blood glucose testing 2 to 3 months after MI, or both, the prevalence of undiagnosed diabetes has been estimated at 4% to 6%,^16,23,24 although a recent prospective study using oral glucose testing after acute MI demonstrated a prevalence of unrecognized diabetes and impaired glucose tolerance of 31% and 35%, respectively.²⁵ It is important to note that patients with newly diagnosed diabetes have been shown to have a significantly increased risk for coronary artery disease.²¹ Additionally, vascular wall abnormalities have been demonstrated in patients before the onset of diabetes mellitus.²⁶

A significant proportion of patients with acute MI have hyperglycemia at presentation, a significant risk factor for adverse outcomes in both diabetic^27,28 and nondiabetic patients.^27,29 The mechanisms underlying the adverse association between hyperglycemia and acute MI are not fully understood, but multiple hypotheses have been proposed. Hyperglycemia may simply be a marker of stress hormones, which occur because of a catecholamine response to more extensive infarction or more severe heart failure. In our study, patients with newly diagnosed diabetes and previously known diabetes had similar heart rates and Killip classifications, suggesting that heart rate and degree of heart failure with infarction, both markers for deranged hemodynamics, may be common components between the two groups.

In addition to being a marker of stress hormone response, hyperglycemia may contribute directly to adverse outcomes. Acute hyperglycemia has been linked to impaired endothelial function,³⁰ reduced collateral coronary blood flow,³¹ and, after reperfusion therapy for acute MI, increased microvascular dysfunction.³² Acute hyperglycemia also may increase thrombus formation; blood glucose levels have been shown to independently predict platelet-dependent thrombosis.³³ Finally, hyperglycemia may itself be a marker for the degree of insulin resistance or insulin deficiency at the time of the acute MI and the subsequent associated metabolic consequences.

The present study has several limitations. As noted, blood glucose values were not available to allow a direct correlation of hyperglycemia with adverse outcomes. The lack of blood glucose levels and a uniform definition for diabetes likely led to some heterogeneity in the group with newly diagnosed diabetes. Also, individuals who were diagnosed with diabetes after randomization into the trial would not be captured in this analysis. Finally, these analyses were limited to those high-risk patients who fulfilled criteria for entry into the VALIANT trial.

	Conclusion

Top Abstract Introduction Methods Results Discussion Conclusion Disclosure References

 
As anticipated, patients with previously known diabetes had increased risks of death and major cardiovascular events at 1 year after MI. More important, the adjusted risks of death and major cardiac events associated with newly diagnosed diabetes were similar to those of patients with previously known diabetes, although the demographic characteristics and initial management of MI of patients with newly diagnosed diabetes were more similar to those of patients without diabetes.

The poorer outcomes of patients with newly diagnosed diabetes, a diagnosis likely based on the presence of hyperglycemia, support the hypothesis that metabolic abnormalities early after MI contribute to the adverse outcomes. Although it is often difficult to confirm a diagnosis of diabetes early after MI, this study underscores the importance of screening for diabetes after MI to identify a group of patients who are at high risk for adverse outcomes and deserve particular medical attention to lower their risk.

	Disclosure

Top Abstract Introduction Methods Results Discussion Conclusion Disclosure References

 
Dr Henis is a former employee of Novartis Pharmaceuticals Corporation. Drs Solomon, Rouleau, Francis, Velazquez, and Califf have served as consultants and/or received honoraria from Novartis. Dr McMurray has served as a consultant and/or received honoraria from Novartis, AstraZeneca, Bristol-Myers Squibb, and Merck. Dr Pfeffer receives honoraria/educational/research grants or serves as a consultant for AstraZeneca, Aventis, Bristol-Myers Squibb, Mitsubishi, Novartis, and Pfizer. The Brigham & Women’s Hospital has been awarded patents related to the use of inhibitors of the renin-angiotensin system in selected survivors of MI; Dr Pfeffer is among the coinventors. The licensing agreements with Abbott Laboratories and Novartis are not linked to sales.

	Acknowledgments

 
The VALIANT study was supported by Novartis Pharmaceuticals Corporation.

	References

Top Abstract Introduction Methods Results Discussion Conclusion Disclosure References

 

1. Diabetes mellitus: a major risk factor for cardiovascular disease. A joint editorial statement by the American Diabetes Association; The National Heart, Lung, and Blood Institute; The Juvenile Diabetes Foundation International; The National Institute of Diabetes and Digestive and Kidney Diseases; and The American Heart Association. Circulation. 1999; 100: 1132–1133.[Free Full Text]
   
2. Berger AK, Breall JA, Gersh BJ, et al. Effect of diabetes mellitus and insulin use on survival after acute myocardial infarction in the elderly (the Cooperative Cardiovascular Project). Am J Cardiol. 2001; 87: 272–277.[CrossRef][Medline] [Order article via Infotrieve]
   
3. Mukamal KJ, Nesto RW, Cohen MC, et al. Impact of diabetes on long-term survival after acute myocardial infarction: comparability of risk with prior myocardial infarction. Diabetes Care. 2001; 24: 1422–1427.[Abstract/Free Full Text]
   
4. Vaccarino V, Parsons L, Every NR, et al. Impact of history of diabetes mellitus on hospital mortality in men and women with first acute myocardial infarction. The National Registry of Myocardial Infarction 2 Participants. Am J Cardiol. 2000; 85: 1486–1489, A7.[CrossRef][Medline] [Order article via Infotrieve]
   
5. Mak KH, Moliterno DJ, Granger CB, et al. Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries. J Am Coll Cardiol. 1997; 30: 171–179.[Abstract]
   
6. Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003; 349: 1893–1906.[Abstract/Free Full Text]
   
7. Pfeffer MA, McMurray J, Leizorovicz A, et al. Valsartan in acute myocardial infarction trial (VALIANT): rationale and design. Am Heart J. 2000; 140: 727–750.[CrossRef][Medline] [Order article via Infotrieve]
   
8. Stone PH, Muller JE, Hartwell T, et al. The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. The MILIS Study Group. J Am Coll Cardiol. 1989; 14: 49–57.[Abstract]
   
9. Young ME, McNulty P, Taegtmeyer H. Adaptation and maladaptation of the heart in diabetes, part II: potential mechanisms. Circulation. 2002; 105: 1861–1870.[Free Full Text]
   
10. Mulvihill NT, Foley JB, Murphy RT, et al. Enhanced endothelial activation in diabetic patients with unstable angina and non-Q-wave myocardial infarction. Diabet Med. 2001; 18: 979–983.[CrossRef][Medline] [Order article via Infotrieve]
    
11. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA. 2002; 287: 2570–2581.[Abstract/Free Full Text]
    
12. Granger CB, Califf RM, Young S, et al. Outcome of patients with diabetes mellitus and acute myocardial infarction treated with thrombolytic agents. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. J Am Coll Cardiol. 1993; 21: 920–925.[Abstract]
    
13. Pfeffer MA, Moye LA, Braunwald E, et al. Selection bias in the use of thrombolytic therapy in acute myocardial infarction. The SAVE Investigators. JAMA. 1991; 266: 528–532.[Abstract]
    
14. Chen J, Marciniak TA, Radford MJ, et al. Beta-blocker therapy for secondary prevention of myocardial infarction in elderly diabetic patients: results from the National Cooperative Cardiovascular Project. J Am Coll Cardiol. 1999; 34: 1388–1394.[Abstract/Free Full Text]
    
15. Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med. 1998; 339: 489–497.[Abstract/Free Full Text]
    
16. Tenerz A, Lonnberg I, Berne C, et al. Myocardial infarction and prevalence of diabetes mellitus: Is increased casual blood glucose at admission a reliable criterion for the diagnosis of diabetes? Eur Heart J. 2001; 22: 1102–1110.[Abstract/Free Full Text]
    
17. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults: the Third National Health and Nutrition Examination Survey, 1988–1994. Diabetes Care. 1998; 21: 518–24.[Abstract]
    
18. Barzilay JI, Spiekerman CF, Kuller LH, et al. Prevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders: the Cardiovascular Health Study. Diabetes Care. 2001; 24: 1233–1239.[Abstract/Free Full Text]
    
19. Saydah SH, Loria CM, Eberhardt MS, et al. Subclinical states of glucose intolerance and risk of death in the U.S. Diabetes Care. 2001; 24: 447–453.[Abstract/Free Full Text]
    
20. Muhlestein JB, Anderson JL, Horne BD, et al. Effect of fasting glucose levels on mortality rate in patients with and without diabetes mellitus and coronary artery disease undergoing percutaneous coronary intervention. Am Heart J. 2003; 146: 351–358.[CrossRef][Medline] [Order article via Infotrieve]
    
21. Taubert G, Winkelmann BR, Schleiffer T, et al. Prevalence, predictors, and consequences of unrecognized diabetes mellitus in 3266 patients scheduled for coronary angiography. Am Heart J. 2003; 145: 285–291.[CrossRef][Medline] [Order article via Infotrieve]
    
22. Tenenbaum A, Motro M, Fisman EZ, et al. Clinical impact of borderline and undiagnosed diabetes mellitus in patients with coronary artery disease. Am J Cardiol. 2000; 86: 1363–1366, A4–A5.
    
23. Oswald GA, Corcoran S, Yudkin JS. Prevalence and risks of hyperglycaemia and undiagnosed diabetes in patients with acute myocardial infarction. Lancet. 1984; 1: 1264–1267.[CrossRef][Medline] [Order article via Infotrieve]
    
24. Madsen JK, Haunsoe S, Helquist S, et al. Prevalence of hyperglycaemia and undiagnosed diabetes mellitus in patients with acute myocardial infarction. Acta Med Scand. 1986; 220: 329–332.[Medline] [Order article via Infotrieve]
    
25. Norhammar A, Tenerz A, Nilsson G, et al. Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet. 2002; 359: 2140–2144.[CrossRef][Medline] [Order article via Infotrieve]
    
26. Henry RM, Kostense PJ, Spijkerman AM, et al. Arterial stiffness increases with deteriorating glucose tolerance status: the Hoorn Study. Circulation. 2003; 107: 2089–2095.[Abstract/Free Full Text]
    
27. Capes SE, Hunt D, Malmberg K, et al. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet. 2000; 355: 773–778.[CrossRef][Medline] [Order article via Infotrieve]
    
28. Malmberg K, Norhammar A, Wedel H, et al. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study. Circulation. 1999; 99: 2626–2632.[Abstract/Free Full Text]
    
29. Wahab NN, Cowden EA, Pearce NJ, et al. Is blood glucose an independent predictor of mortality in acute myocardial infarction in the thrombolytic era? J Am Coll Cardiol. 2002; 40: 1748–1754.[Abstract/Free Full Text]
    
30. Williams SB, Goldfine AB, Timimi FK, et al. Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation. 1998; 97: 1695–1701.[Abstract/Free Full Text]
    
31. Kersten JR, Toller WG, Tessmer JP, et al. Hyperglycemia reduces coronary collateral blood flow through a nitric oxide-mediated mechanism. Am J Physiol Heart Circ Physiol. 2001; 281: H2097–H2104.[Abstract/Free Full Text]
    
32. Iwakura K, Ito H, Ikushima M, et al. Association between hyperglycemia and the no-reflow phenomenon in patients with acute myocardial infarction. J Am Coll Cardiol. 2003; 41: 1–7.[Abstract/Free Full Text]
    
33. Shechter M, Merz CN, Paul-Labrador MJ, et al. Blood glucose and platelet-dependent thrombosis in patients with coronary artery disease. J Am Coll Cardiol. 2000; 35: 300–307.[Abstract/Free Full Text]
    

Find additional patient-related information at:

Who is at Greater Risk for Heart Problems: Newly or Previously Diagnosed Patients With Diabetes?

This article has been cited by other articles:

				R Peter, A Cox, and M Evans Management of diabetes in cardiovascular patients Heart, March 1, 2008; 94(3): 369 - 375. [Full Text] [PDF]

				P. Ferdinandy, R. Schulz, and G. F. Baxter Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning Pharmacol. Rev., December 1, 2007; 59(4): 418 - 458. [Abstract] [Full Text] [PDF]

				M. Ishihara, I. Inoue, T. Kawagoe, Y. Shimatani, S. Kurisu, T. Hata, Y. Nakama, Y. Kijima, and E. Kagawa Is admission hyperglycaemia in non-diabetic patients with acute myocardial infarction a surrogate for previously undiagnosed abnormal glucose tolerance? Eur. Heart J., October 2, 2006; 27(20): 2413 - 2419. [Abstract] [Full Text] [PDF]

				S. P. Marso, D. M. Safley, J. A. House, T. Tessendorf, K. J. Reid, and J. A. Spertus Suspected Acute Coronary Syndrome Patients With Diabetes and Normal Troponin-I Levels Are at Risk for Early and Late Death: Identification of a new high-risk acute coronary syndrome population Diabetes Care, August 1, 2006; 29(8): 1931 - 1932. [Full Text] [PDF]

				Z. T. Bloomgarden Cardiovascular Disease Diabetes Care, May 1, 2006; 29(5): 1160 - 1166. [Full Text] [PDF]

				D. S. Pinto, A. H. Skolnick, A. J. Kirtane, S. A. Murphy, H. V. Barron, R. P. Giugliano, C. P. Cannon, E. Braunwald, C. M. Gibson, and for the TIMI Study Group U-Shaped Relationship of Blood Glucose With Adverse Outcomes Among Patients With ST-Segment Elevation Myocardial Infarction J. Am. Coll. Cardiol., July 5, 2005; 46(1): 178 - 180. [Full Text] [PDF]

				Metabolic Link Between Diabetes and MI DOC News, January 1, 2005; 2(1): 22 - 22. [Full Text]

				Minerva BMJ, December 11, 2004; 329(7479): E335 - E335. [Full Text] [PDF]

				New Diabetes Linked with Poor Outcomes After MI Journal Watch (General), October 22, 2004; 2004(1022): 1 - 1. [Full Text]

				Minerva BMJ, October 2, 2004; 329(7469): 808 - 808. [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 110/12/1572    most recent 01.CIR.0000142047.28024.F2v1 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 patientINFORMation Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aguilar, D. Articles by Pfeffer, M. A. Search for Related Content PubMed PubMed Citation Articles by Aguilar, D. Articles by Pfeffer, M. A. Related Collections Type 2 diabetes Acute myocardial infarction