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European Journal of Heart Failure 2005 7(5):834-839; doi:10.1016/j.ejheart.2004.09.007
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© 2004 European Society of Cardiology

Diabetes mellitus and cardiogenic shock in acute myocardial infarction

M.G. Lindholm*, S. Boesgaard, C. Torp-Pedersen, L. Køber and on behalf of the TRACE registry study group

Medical Department B, Division of Cardiology, Rigshospitalet University Hospital of Copenhagen, Denmark Department of Cardiology, Bispebjerg Hospital Copenhagen, Denmark

* Corresponding author. Medical Department B 2141, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Tel.: +45 25 38 36 01; fax: +45 35 45 25 13. E-mail address: Matiasgl{at}dadlnet.dk


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 Acknowledgments
 References
 
Aims: Cardiogenic shock is the leading cause of in-hospital mortality after acute myocardial infarction (MI). This study investigates the importance of age and preexisting diabetes mellitus on the incidence and prognosis of cardiogenic shock in a large group of consecutive patients with MI.

Methods and results: Baseline characteristics and in-hospital complications to the infarction were prospectively recorded in 6676 patients with MI. Ten-year mortality was collected. Diabetes was present in 10.8% of the total population. A total of 443 developed cardiogenic shock with an incidence of 6.2% among nondiabetics and 10.6% among diabetics. Age, wall motion index, reinfarction, and the absence of thrombolytic treatment were significant independent predictors of mortality in patients with cardiogenic shock. Intriguingly, diabetes was not a significant predictor for short- and long-term mortality in this population. The 30-day and 5-year mortality rate was equally poor in both diabetic and nondiabetic patients with cardiogenic shock (diabetics: 30-day 63%, 5-year 91%; nondiabetics: 30-day 62%, 5-year 86%; p>0.05).

Conclusions: Cardiogenic shock develops approximately twice as often among diabetics as among nondiabetic patients with acute MI. The prognosis of diabetics with cardiogenic shock is similar to the prognosis of nondiabetic patients with cardiogenic shock.

Key Words: MI • Cardiogenic shock • Heart failure • Diabetes

Received June 7, 2004; Revised August 7, 2004; Accepted September 20, 2004


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 Acknowledgments
 References
 
Cardiogenic shock remains the leading cause of in-hospital mortality after acute myocardial infarction (MI) [1–3]. Although recent data suggest that the mortality of cardiogenic shock is declining after introduction of primary percutaneous interventions [4–7], prevention of shock development in MI patients is of major importance. The incidence of cardiogenic shock among MI patients is approximately 7%, and in the total infarct population, several important risk factors such as previous MI, infarct size, and location have been identified as predictors of cardiogenic shock [3,8]. Thus, recognition of critical MI characteristics may help to identify patients with increased risk of an adverse outcome.

Recent studies suggest that patients with diabetes mellitus are at increased risk of death after MI [9–12], but the presence of diabetes among patients with cardiogenic shock, the influence of diabetes on the risk of shock development in acute MI and the survival rate of diabetic patients with cardiogenic shock is less clear. Limited data from the SHOCK trial registry show that in-hospital mortality may be slightly increased in diabetic patients with cardiogenic shock when compared to corresponding nondiabetic patients [13].

Focusing on this high-risk subpopulation of MI patients, the present study investigates the importance of preexisting diabetes mellitus as a predictor of cardiogenic shock development and the impact of diabetes on the short- and long-term prognosis of cardiogenic shock in a large group of consecutive patients with MI.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 Acknowledgments
 References
 
2.1. Study population and design
The Trandolapril Cardiac Evaluation (TRACE) Register recorded data on consecutive patients above 18 years of age admitted with an MI in 27 coronary care units between May 1990 and July 1992. The register was compiled while screening patients for the TRACE trial, a randomised study of trandolapril in patients with left ventricular dysfunction after a myocardial infarction. All in all, 7001 consecutive cases of MI were recorded in the TRACE registry, representing 6676 patients. For the purpose of the present study, each patient was only included once using the first MI of the study period. In the registry demographic data, medical history and in-hospital complications to the infarction were recorded. The investigation conforms with the principles outlined in the Declaration of Helsinki and was carried out in accordance with the local ethics department.

The rationale, design, and baseline characteristics have been previously published [14].

2.2. Definitions
Acute MI was defined as typical chest pain and/or specific electrographic changes accompanied by elevation of cardiac enzymes to at least twice the upper normal value. Cardiogenic shock was defined as the presence or development of Killip class IV heart failure during the in-hospital period. The diagnosis of diabetes mellitus was based on the patient's history on admission and was classified as insulin-treated, treated with oral hypoglycaemic agents, or treated with diet alone. Thus, patients diagnosed with diabetes during hospitalisation are not included. Heart failure without cardiogenic shock was based on a history of heart failure requiring diuretic treatment or development of Killip class II–III during the in-hospital period.

2.3. Follow-up
Follow-up was carried out via the Danish Central Person Register. Eight patients were lost to follow-up (emigration), and their survival data were censored at the time they were last known to be alive. Additional 31 patients (non-Danish patients) with missing data were censored at time of discharge from the hospital. Patients were followed for up to 10 years.

2.4. Statistics
Characteristics of the study population were analysed using the chi-square test for discrete variables and the rank sum test for continuous variables. Discrete variables are presented as percentages, and continuous variables as presented as mean values with 5th to 95th percentiles. Mortality curves were generated by means of Kaplan–Meier estimates and were compared by log-rank test. Relative risk (RR) of all cause mortality was estimated by a Cox proportional hazards regression model, including variables with prognostic importance in univariate analyses. Interaction analysis was conducted by means of a likelihood ratio test. The proportional hazard assumption and linearity of continuous variables were checked and found valid. A logistic regression model was used for identifying independent predictors of development of cardiogenic shock. Only variables present prior to development of shock were included in the model.

Calculations were made with the Statistical Analysis System software version 8.2 (SAS Institute, Cary, NC). For all analyses, a p-value <0.05 was considered significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 Acknowledgments
 References
 
Among the 6676 patients, cardiogenic shock could not be evaluated in six patients, and diabetes could not be evaluated in eight patients, thus baseline characteristics in relation to cardiogenic shock and diabetes from 6662 patients are shown in Table 1. Diabetes was present in 10.8% of the total population. A total of 443 patients (6.6%) developed cardiogenic shock with an incidence of 6.2% among nondiabetics and 10.6% among diabetics. Among patients with cardiogenic shock, 17.2% had diabetes at admission compared to 10.3% of patients without cardiogenic shock. Fig. 1 shows the incidence of cardiogenic shock in diabetics and nondiabetics stratified by three age subgroups: <65 years, 65–75 years, and >75 years. Of the 105 shock patients below 65 years, 18 (7.8%) had diabetes and 87 (3.4%) were nondiabetics. Thirty-two patients (12.0%) were diabetics and 127 (6.5%) were nondiabetics in the middle age group (p<0.05). A similar difference was, however, not observed in patients >75 years. In the three age groups, <65, 65–75, and >75, a total of 8.3%, 12.0%, and 13.3% had diabetes on admission, and 3.8%, 7.1%, and 10.8% developed cardiogenic shock, respectively.


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  		Table 1 Baseline demographics of diabetic and nondiabetic patients with myocardial infarction

 


Figure 1
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  		Fig. 1 The incidence of cardiogenic shock in patients with and without diabetes, subdivided according to age.

 
Among patients whose MI was not complicated by cardiogenic shock, the diabetic subgroup were more likely than the nondiabetics to have a known history of hypertension, angina pectoris, congestive heart failure, and a prior MI (Table 1). In addition, patients with diabetes were older, more likely to be female, had a higher body mass index, a lower wall motion index, and a significantly lower creatinine clearance. Thrombolytics were used in 28% of the diabetics without cardiogenic shock and 44% of the nondiabetics without shock (p<0.05; Table 1). Patients with cardiogenic shock and diabetes were more likely to have a history of hypertension (36%) and heart failure (47%) compared to nondiabetic patients with cardiogenic shock (24% and 29%, respectively). The use of thrombolytics was low in cardiogenic shock patients (25%), but no difference was observed when subdividing according to the presence of diabetes (27% in nondiabetics and 20% in diabetics). With regard to other available baseline characteristics, no differences were observed (Table 1).

Predictors of development of cardiogenic shock in patients with and without diabetes are shown in Table 2. Data were derived from multivariable models, including information present at time of hospitalisation. In the nondiabetic group, a history of heart failure, anterior MI, ST-segment depression, bundle branch block, lack of thrombolytic treatment, in-hospital reinfarction, and reduced kidney function as estimated by creatinine clearance were independent predictors of development of cardiogenic shock. Only renal function and in-hospital reinfarction significantly predicted the development of cardiogenic shock in the diabetic group. However, in a model including all patients, predictors of cardiogenic shock in diabetics were renal function, age, history of heart failure, ST-elevation infarction, in-hospital reinfarction, and lack of thrombolysis. Among patients with cardiogenic shock and diabetes, age, WMI, lack of thrombolytic treatment, and reinfarction were significant independent predictors of mortality (Table 3).


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  		Table 2 Predictors of cardiogenic shock in patients with and without diabetes

 


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  		Table 3 Predictors of mortality in patients with and without cardiogenic shock

 
Short- and long-term mortality of diabetic and nondiabetic patients with MI is shown in Fig. 2. Unadjusted 30-day mortality in the diabetic and nondiabetic patients without cardiogenic shock was 12% and 9%, respectively. In a logistic regression model that adjusted for the significant baseline and treatment differences, diabetes remained an independent risk factor for 30-day mortality in noncardiogenic shock patients with an odds ratio of 1:4. In this nonshock subgroup, 5-year mortality rate was also markedly increased in post-MI diabetics compared with nondiabetics (62% vs. 39%; p<0.05). Intriguingly, diabetes was not a significant predictor for short- and long-term mortality in patients with cardiogenic shock (Table 3; Fig. 2). The 30-day and 5-year mortality rate was equally poor in both diabetic and nondiabetic patients with cardiogenic shock (diabetics: 30-day 63%, 5-year 91%; nondiabetics: 30-day 62%, 5-year 86%; p>0.05). The difference in odds ratio 1.11 vs. 1.89 was significantly different (p for interaction 0.001) in univariate analyses, but in a multivariate analysis including all patients, this interaction was no longer significant. This is partly explained by diabetic patients being older.


Figure 2
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  		Fig. 2 Kaplan–Meier survival curves for consecutive patients with acute myocardial infarction with and without diabetes.

 
Late shock development was associated with a markedly increased risk of death. In the diabetic group, the risk of death was increased by a factor 15 when cardiogenic shock developed later than 4 days after index MI.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
Acknowledgments
 References
 
The main findings in the present study are (1) that cardiogenic shock develops approximately twice as often among diabetics as among nondiabetics patients with acute MI and (2) that the prognosis of diabetics with cardiogenic shock is similar to the prognosis of nondiabetic patients with cardiogenic shock.

The nationwide TRACE registry includes data from 6676 patients consecutively admitted to 27 Danish hospitals during the period 1990–1992. In this study, 10.3% of the MI patients without cardiogenic shock had diabetes. Patients with diabetes had a higher risk profile than nondiabetics. However, even after correction for variables associated with an increased risk profile, including age, hypertension, heart failure, and less use of thrombolytics, the nonshock diabetics had a significantly increased mortality risk (unadjusted RR=1.9, adjusted RR=1.4) when compared to nondiabetic patients. This is in line with previous reports [9,10,12,15] and confirms that diabetics with MI should be considered a high-risk MI population.

Death from cardiogenic shock complicating MI is a main contributor to the in-hospital mortality of MI [1–3]. In diabetics, the incidence of cardiogenic shock was significantly increased from 6.2% in nondiabetics to 10.8% in the diabetic subgroup. In fact, the incidence of cardiogenic shock was approximately twofold-increased in diabetics aged below 75 years as compared to nondiabetic patients. Thus, MI patients with diabetes have an increased risk of cardiogenic shock development compared to nondiabetic MI patients. The use of thrombolytics protected significantly against shock, and renal function and in-hospital reinfarction significantly predicted development of cardiogenic shock in the diabetic subgroup. Diabetic patients with cardiogenic shock more often had a history of hypertension and heart failure as compared to nondiabetic shock patients, whereas other important baseline demographics were similar. This is in contrast to the finding in the SHOCK trial registry where diabetics had a significantly higher risk profile than nondiabetics [13]. The reason for this difference is not clear but may be related to the consecutive patient enrolment with less selection bias and/or more standardised treatment strategies in the present study.

Data on the prognostic implications of diabetes in the setting of cardiogenic shock after MI are very limited, and this study is the first to systematically address this issue in an unselected population of MI patients. Intriguingly, the 30-day mortality rate of 63% in the diabetic group of patients with cardiogenic shock was similar to the 62% among nondiabetics with cardiogenic shock. In a smaller study from the Mayo Clinic, diabetics with cardiogenic shock (n=16) had a twofold increased risk of short- and long-term mortality when compared with nondiabetic shock patients (n=57) [16]. In the SHOCK trial registry (n=1163), diabetics with cardiogenic shock also had a worse in-hospital prognosis than the nondiabetic shock patients. However, depending on the adjustments for baseline/treatment differences, their in-hospital survival was either only marginally lower or similar to that of nondiabetics [13]. Our short- and long-term survival data (10 years) suggest that once diabetic MI patients have developed cardiogenic shock, their survival rates are low but similar to nondiabetic patients with cardiogenic shock. However, we cannot exclude that diabetes has a small prognostic importance in patients with cardiogenic shock, as the difference in odds ratio for diabetes in patients with and without cardiogenic shock is not significantly different in multivariate analysis (odds ratio 1.40 vs. 1.16; p-value of interaction NS).

All patients in the TRACE registry received contemporary community-based noninvasive treatment. The results indicate that this approach is associated with a poor short- and long-term outcome in both nondiabetic and diabetic patients with cardiogenic shock after MI. The consequences of modern invasive revascularisation and heart failure therapy in this diabetic and nondiabetic cardiogenic shock population are unknown, but recent data suggest that both patient subgroups may derive a survival benefit from such measures [13,17,18].

In conclusion, the present results suggest that the risk of cardiogenic shock I s increased approximately twofold in diabetic MI patients when compared to nondiabetic patients. However, once shock has developed, short- and long-term survival is similar to survival in nondiabetic patients.


   Acknowledgments
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 Acknowledgments
References
 
This study was supported by Jørgen Møller Foundation, Alice and Jørgen Rasmussens Foundation, Carl and Katy Kajsings Foundation, Eva and Robert Voss Hansens Foundation, and Lauritz Peter Christensen and Kirsten Sigrid Christensens Foundation.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 Acknowledgments
 References
 

  1. Holmes D.R.J., Bates E.R., Kleiman N.S., Sadowski Z., Horgan J.H., Morris D.C., et al. Contemporary reperfusion therapy for cardiogenic shock: the GUSTO-I trial experience. The GUSTO-I investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries. J. Am. Coll. Cardiol. (1995) 26(3):668–674.[Abstract]
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