Influence of diabetes mellitus on in-hospital mortality in patients with acute myocardial infarction in Japan: A report from TAMIS-II

1. Introduction 

Diabetes mellitus (DM) is an independent risk factor for coronary artery disease. In addition, DM has been regarded as an independent predictor of mortality in patients with acute myocardial infarction in the thrombolytic era [1], [2], [3], [4], [5].

The introduction of new mechanical techniques for revascularization has been shown to significantly improve the survival of patients with acute myocardial infarction (AMI) [6], [7], [8]. Although better outcome in diabetic patients is expected, there are conflicting reports from the studies addressing this issue. For example, Mathew et al. [9] demonstrated that DM was independently associated with death at 9 months in 2684 diabetics and 8798 non-diabetics undergoing percutaneous coronary intervention. Moreover, Elezi et al. [10] demonstrated that DM represents an independent risk factor for early mortality. In contrast, Fujiwara et al. [5] reported similar rates of in-hospital death in 62 diabetics and 152 non-diabetics treated with primary coronary stenting. Thus, it is still unclear whether the new techniques neutralize the excess mortality that diabetic patients present after revascularization.

The Tokai Acute Myocardial Infarction Study-II (TAMIS-II) is a multi-hospital prospective and observational study performed in the Tokai region of central Japan. All of the study subjects were adult patients who had been hospitalized for newly diagnosed AMI at any of 15 acute care hospitals between January 2001 and December 2003. Using the TAMIS-II data set, we evaluated the influence of DM on the in-hospital mortality of AMI patients.

3. Results 

We evaluated a total of 940 DM and 2284 non-DM patients. The baseline characteristics are shown in Table 1. Of 940 DM patients, 138 had insulin-requiring DM. The DM patients were the same age as the non-DM patients. The DM patients were more frequently dependent in ADLs; they had higher heart rates and higher BMI values on admission; and they had greater incidences of cardiogenic shock, Killip class≧3, and pulmonary edema. The diabetic patients had greater prevalences of hypertension, previous angina, previous heart failure, previous myocardial infarction, renal failure, and cerebrovascular disease, and had lower prevalences of COPD and peptic ulcer. There were fewer smokers among the DM patients. Also, the DM patients frequently had a reduced left ventricular function and multi-vessel coronary disease.

Table 1. Baseline characteristics and clinical features of the subjects

		DM (n=940)	%	Non-DM (n=2284)	%	p-Value
	Age (mean±S.D.)	65.70	±0.35	66.10	±0.25	NS
	Gender (female)	230	24.47	543	23.77	NS
	Independent ADL	869	92.45	2175	95.23	<0.01
	Body temperature (mean±S.D.)	36.29	±0.04	36.22	±0.02	NS
	Heart rate (beats/min, mean±S.D.)	81.73	±0.66	79.13	±0.39	<0.01
	Systolic blood pressure (mmHg, mean±S.D.)	131.72	±2.01	128.59	±0.84	NS
	Body mass index	23.92	±0.13	23.33	±0.08	<0.01
	Hypertension	461	49.04	939	41.11	<0.01
	Hypercholesterolemia	173	18.40	370	16.20	NS
	Insulin DM	138	14.68	–	–	–
	Previous angina	165	17.55	251	10.99	<0.01
	Previous heart failure	48	5.11	68	2.98	<0.01
	Previous myocardial infarction	113	12.02	206	9.02	<0.01
	Smoking	444	47.23	1200	52.54	<0.01
	Arrhythmia	48	5.11	122	5.34	NS
	Renal failure	47	5.00	46	2.01	<0.01
	Cerebrovascular disease	123	13.09	231	10.11	<0.05
	COPD	4	0.43	30	1.31	<0.05
	Aortic aneurysm	6	0.64	31	1.36	NS
	Peptic ulcer	66	7.02	230	10.07	<0.01
	Cancer	51	5.43	105	4.60	NS
	Allergy	42	4.47	121	5.30	NS
	Dementia	18	1.91	46	2.01	NS
	End-of-life stage	1	0.11	7	0.31	NS
	Shock	203	21.60	424	18.56	<0.05
	Bleeding	146	15.53	372	16.29	NS
	Killip class≧3	369	39.26	768	33.63	<0.01
	Pulmonary edema (X-ray)	272	28.94	549	24.04	<0.01
	Locations of MI (UCG)
	Antero/septal	432.00	45.96	1051.00	46.02	NS
	Lateral	69.00	7.34	170.00	7.44
	Posterior	112.00	11.91	280.00	12.26
	Inferior	354.00	37.66	835.00	36.56
	Subendocardial	7.00	0.74	19.00	0.83
	Others	23.00	2.45	65.00	2.85
	UCG-EF (%, mean±S.D.)	50.24	±0.75	52.77	±0.41	<0.01
	Number of coronary arteries narrowed >75% in AHA classification (angiographic data)
	1	415	44.15	1283	56.17	<0.01
	>1	404	42.98	718	31.44
	Left main	18	1.91	41	1.80	NS

DM, diabetes mellitus; COPD, chronic obstructive pulmonary disease; MI, myocardial infarction; ADL, activity of daily living; UCG, ultrasound-electrocardiogram; EF, ejection fraction; AHA, American Heart Association.

Table 2 shows the procedural characteristics of the subjects. The vasopressors, IABP, and mechanical ventilation were more likely to be used in the DM group, although acute PCI was less likely.

Table 2. Procecural characteristics of the subjects

		DM (n=940)	%	Non-DM (n=2284)	%	p-Value
	Transfer to ICU/CCU	771	82.02	1898	83.10	NS
	Thrombolytics	100	10.64	268	11.73	NS
	Vasopressor	344	36.60	704	30.82	<0.01
	IABP	192	20.43	360	15.76	<0.01
	Mechanical ventilation	177	18.83	245	10.73	<0.01
	PCI	740	78.72	1848	80.91	NS
	Acute PCI	655	69.68	1672	73.20	<0.05
	Stent placement	505	53.72	1268	55.52	NS

DM, diabetes mellitus; ICU/CCU, intensive care unit/coronary care unit; PCI, percutaneous coronary intervention; IABP, intra-aortic balloon pump.

Multiple regression analysis was carried out to more systematically examine the relationships between DM and in-hospital mortality while controlling for statistically significant predictors of outcome. The unadjusted and multivariable-adjusted results of in-hospital mortality are shown in Table 3. DM patients had roughly twice the in-hospital mortality rate of non-DM patients, with an unadjusted odds ratio of 1.77 (95% CI, 1.37–2.30). However, according to the multivariate analysis, DM was not identified as an independent predictor of in-hospital death, with an adjusted odds ratio of 5.73 (95% CI, 0.97–33.88).

Table 3. Comparison of in-hospital mortality between DM vs. non-DM

	Number of in-hospital deaths				Odds ratio unadjusted	95% CI	Odds ratio adjusted for age	95% CI	Odds ratio adjusted for age and other variablesa	95% CI
	DM (n=940)	%	Non-DM (n=2284)	%
	153	16.28	106	4.64	1.77	1.37–2.30	2.00	1.53–2.62	5.73	0.97–33.88

CI, confidence interval; DM, diabetes mellitus; COPD, chronic obstructive pulmonary disease; ADL, activity of daily living; EF, ejection fraction; PCI, percutaneous coronary intervention; IABP, intra-aortic balloon pump.

a Controlling for age, ADL, heart rate, body mass index, hypertension, previous angina, previous heart failure, previous myocardial infarction, smoking, renal failure, cerebrovascular disease, COPD, peptic ulcer, shock, Killip class, pulmonary edema, EF, number of coronary arteries narrowed, vasopressor, IABP, mechanical ventilation, and acute PCI.

4. Discussion 

This study examined the influence of DM on in-hospital mortality in patients with AMI undergoing PCI. Several recent reports have found that DM patients at the time of presentation with AMI have higher rates of in-hospital death than non-DM patients [1], [2], [3], [5], [11], [12] test. However, it appears that at least some of these higher in-hospital mortality rates in DM patients may be due to a higher incidence of less efficacious, though still accepted therapeutic interventions and a greater prevalence of poor clinical presentation or coronary risk profiles [5], [12], [13]. The present results are consistent with these previous studies. We also found that DM patients were more likely to suffer complications, including hypertension, previous angina, previous heart failure, previous myocardial infarction, renal failure, and cerebrovascular disease. It is well known that these disease profiles are strongly related to DM. Also, DM patients had lower levels of ADLs. Because some researchers suggested that the level of functional impairment is a reliable predictor of mortality [14], [15], the level of ADLs is a possible predictor of in-hospital mortality. In addition, DM patients showed poorer clinical conditions, such as a greater prevalence of shock or congestive heart failure on presentation and poor LV ejection fraction. The higher incidence of pump failure and decrease in left ventricular ejection fraction among diabetic patients has been reported in previous studies [9], [16], [17]. Nevertheless, a considerable increase in the clinical manifestations of heart failure occurred with a modest decrease in left ventricular ejection fractions between the groups (50% versus 52%). We may explain that the higher incidence of heart failure or cardiac shock with a relatively preserved ejection fraction is due to a preexisting diastolic dysfunction [17]. It is also possible that the difference in pump failure may be due to unsuccessful PCI or new adverse cardiac event such as restenosis or recurrent angina [5], [10], [18], although this study did not assess the rate of procedural success such as Thrombolysis in Myocardial Infarction (TIMI) flow in the culprit coronary artery or new cardiac event soon after coronary angioplasty. These would offer good explanations of our results.

Because therapeutic options could contribute to in-hospital mortality, we examined the differences in the care options between DM and non-DM patients in the present study. In our data, we detected significant differences in the use of vasopressors, IABP, mechanical ventilation, and acute PCI. The greater use of vasopressors, IABP, and mechanical ventilation in DM patients may be a consequence of poorer clinical conditions, such as cardiac shock or Killip class, among them. According to the ACC/AHA guidelines for the management of patients with myocardial infarction [19], primary PCI is required if the patient presents with cardiogenic shock. Because this clinical feature was more common in DM patients, we would not expect a lower referral rate of DM patients than non-DM patients for acute PCI. We can attribute the lower-than-expected use of acute PCI to a higher prevalence of high-risk vessel diseases for PCI, such as progressive coronary atherosclerotic change in DM patients [16], [20]. However, our explanations are limited because coronary angiographic results were not fully obtained in the study. Further research is needed to determine the related factors that account for the difference in referral for acute PCI between DM and non-DM patients.

The present study demonstrates that in-hospital mortality after AMI in patients undergoing PCI was higher among DM patients than among non-DM patients before adjustment. However, we were unable to detect differences after adjustment for other predictors of mortality. Thus, our findings are consistent with previous studies in suggesting that other baseline variables account for much of the higher in-hospital mortality in DM patients [13], [21]. There is one good explanation for the similar mortality rates between patients with DM and those without it. PCI has been shown to significantly improve the survival of patients with AMI, and this improvement has reduced the frequency of the lack of myocardial reperfusion in DM patients, who often have immediate vascular and hemodynamic complications [21].

However, the results of this study have not demonstrated that mortality rates between DM and non-DM patients are very similar, as seen in the 95% confidence interval. Additional studies are needed to determine the influence of DM on mortality.

5. Conclusions 

Using TAMIS-II data, we identified the difference in in-hospital mortality between DM and non-DM patients with AMI. Our results suggest that DM is not an independent predictor of in-hospital mortality, and that there is a need for additional studies to confirm our conclusion.