Hospital and 1-year outcome after acute myocardial infarction in patients with diabetes mellitus and hypertension

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1 (2003) 17, & 2003 Nature Publishing Group All rights reserved /03 $ ORIGINAL ARTICLE Hospital and 1-year outcome after acute myocardial infarction in patients with diabetes mellitus and hypertension M Jonas 1, H Reicher-Reiss 1, V Boyko 1, S Behar 1 and E Grossman 2 1 Neufeld Cardiac Research Institute; 2 Department of Internal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel Hypertension () and diabetes mellitus () lead to structural and functional cardiac impairment and worsen the prognosis after myocardial infarction (MI). However, the prognosis of male or female patients with the coexistence of and after MI has not been clearly demonstrated. The study sample comprised 4317 consecutive patients with an acute MI from a prospective nationwide survey conducted in 1992, 1994 and 1996 in all 25 coronary care units operating in Israel. The in-hospital, 30-day and 1-year outcome of diabetic hypertensive patients (n ¼ 546) was compared with that of diabetic normotensive patients (n ¼ 547) and with that of nondiabetic hypertensive patients (n ¼ 1192) and nondiabetic normotensive subjects (n ¼ 2032). The crude in-hospital, 30-day and 1-year mortality rates of diabetic hypertensive patients (11.7, 16.5 and 27.6%, respectively) were significantly higher than those of the diabetic normotensive patients (9.5, 15.4 and 22.9%, respectively) and nondiabetic hypertensive patients (7.1, 11.6 and 17.6%, respectively). Kaplan Meier survival curves showed increased mortality rates during the 1- year follow-up in diabetic hypertensive patients. Adjusted risk for 1-year mortality was increased in diabetic patients. However, the risk was similar in diabetic hypertensive and normotensive patients (hazard ratio (HR) 1.55, 95% confidence interval (CI) , and 1.62, 95% CI , respectively). Adjusted Kaplan Meier survival curves of diabetic hypertensive patients converged with those of the diabetic normotensives. The existence of increases the 1-year mortality after MI by about 60%. However, controlled hypertension did not worsen the outcome of diabetic male or female patients after MI. (2003) 17, doi: /sj.jhh Keywords: diabetes mellitus; myocardial infarction; outcome Introduction Diabetes mellitus () and hypertension () are among the most common diseases in the modern world. 1,2 The prevalence of is approximately twice as high in diabetic patients as in the nondiabetic population 3 5 and the frequency of both disorders increases with age. 1,2,6 These two disorders lead to structural and functional cardiac impairment and finally contribute to cardiovascular illness and mortality. 7,8 Previous studies in the prethrombolytic and thrombolytic eras concur that diabetes is an independent risk for mortality postmyocardial-infarction (MI) The worse post-mi outcome of diabetic patients was more pronounced in women Several studies have shown that is also associated with a worse prognosis post- Correspondence: Dr E Grossman, Internal Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel. gross-e@zahav.net.il Received 20 January 2003; revised 20 May 2003; accepted 29 May 2003 MI However, the effect of the coexistence of and on the prognosis post-mi has not been clearly demonstrated. The aim of this study was to assess, in a large group of diabetic men and women, the effect of a history of on the prognosis after MI. Methods Nationwide surveys, including all patients admitted with acute MI, were conducted during a 2-month period in 1992 and 1994 (January and February) in all 25 coronary care units operating in Israel. During 1996, the survey was extended to 5 months (January, February, May, June and July). Demographic, clinical data and medical history were collected on special forms for 4317 consecutive patients with acute MI. The studied population included immigrants coming to Israel from various countries. Inhospital course, 30-day and 1-year mortality was assessed from the medical charts and by matching the identification number of patients with the Israeli

2 666 National Population Registry. Only patients who survived the onset of MI and reached the ICCU where included in the surveys. The 30-day mortality data were missing for nine patients (0.2%), and 1- year mortality data were missing for 161 patients (3.7%). Definitions The diagnosis of acute MI was based on the presence of two of the following criteria: pain suggestive of MI lasting for at least 30 min; unequivocal new electrocardiographic alterations; or increase of creatinine kinase (CK) and MB isoenzyme to more than 1.5 the upper limit. We included in the study patients with ST elevation or non-st elevation MI. Stroke was defined as a new irreversible neurological event. Hyperlipidaemia was defined when the patient was treated for hyperlipidaemia or when previously diagnosed as having hyperlipidaemia by the primary physician. The diagnosis of and was made on the basis of the reported history and medical records. was defined by chronic use of antihyperglycaemic drugs or previous documentation of fasting glucose levels 4140 mg/dl (7.77 mmol/l). was defined by chronic use of antihypertensive drugs or a previously documented blood pressure X160/95 mmhg. Statistical analysis Outcome after myocardial infarction in diabetic hypertensive patients Data are presented as mean 7 SD. SAS statistical software was used for analysis. 17 Comparisons between groups were made using w 2 tests for discrete variables and one-way ANOVA for continuous variables. To estimate 7- and 30-day mortality in terms of odds ratio (OR) with 95% confidence interval (CI), a stepwise logistic regression analysis (SAS Logistic Procedure) was performed, adjusting for age, sex, past MI, history of angina, Killip class, anterior location of MI, thrombolytic therapy and angioplasty or bypass surgery during hospitalization. As a reference we used the group of nondiabetic normotensive patients. A stepwise Cox proportional hazards regression model (SAS PHREG Procedure) adjusting for the same variables was used to compare cumulative 1-year mortality in terms of hazard ratio (HR) and 95% CI. As a reference we used the group of nondiabetic normotensive patients. A variable was allowed to enter into the model if it made a significant contribution at the 0.15 level of significance and was removed if after subsequent addition of other variables to the model, it no longer made a contribution at the 0.10 level of significance. Kaplan Meier survival curves were produced using the SAS Lifetest Procedure. Adjusted survival curves were computed using variables entered into the best-selected Cox model (SAS PHREG Procedure). Results Patient characteristics and admission parameters A total of 4317 MI patients were included in the study. A total of 1093 patients had of whom 11.4% were treated with insulin. Of these, 546 patients also had a history of and 547 were normotensive. In all, 3224 patients were nondiabetic, among whom 1192 patients were hypertensive and 2032 patients were normotensive. Patient characteristics and parameters on admission to the coronary care units are given in Table 1. Patients having and were older, more frequently women and more likely to have a previous history of MI, angina and stroke. Risk factors such as smoking and family history were relatively less frequent in those with coexistence of and. On admission to the coronary care unit, patients with the coexistence of and had a higher heart rate and Killip grade than the other groups (Table 1). In-hospital complications and management Congestive heart failure and shock were significantly more frequent in those with and (Table 2). Hypertensive patients with and without received less thrombolytic therapy and were less likely to undergo coronary catheterization during hospitalization (Table 3). Diabetic patients with had relatively more revascularization by bypass surgery than with angioplasty. They were also treated more frequently with angiotensin converting enzyme (ACE) inhibitors, nitrates and calcium channel blockers and less frequently with beta-blockers (Table 3). Mortality The crude in-hospital, 30-day, 1-year and 30-day to 1-year mortality rates of the diabetic hypertensive patients were significantly higher in comparison with the other groups (Table 4). After adjustments were made for age, sex, past MI, history of angina, Killip class, anterior location of MI, thrombolytic therapy and angioplasty or bypass surgery, the risk of death in diabetic patients remained significantly higher (Table 5). However, the risk was similar in those with or without a history of (Table 5). Interactions of and were nonsignificant (P ¼ 0.74, 0.23, 0.28 and 0.92 for in-hospital, 30- day, 1-year and 30-day to 1-year mortality, respectively). Kaplan Meier survival curves (Figure 1a) show increased mortality rates during the 1-year follow-up in diabetic hypertensive patients. However, after adjustment for the above variables, the curves of diabetic patients with and those without a history of converged (Figure 1b).

3 Outcome after myocardial infarction in diabetic hypertensive patients Table 1 Baseline characteristics of MI patients with or without and/or 667 Characteristics and n=546 n=547 n=1192 n=2032 P-value Age (years) o0.001 Female (%) 233 (42.7) 148 (27.1) 396 (33.2) 340 (16.7) o0.001 Risk factors Current smoker (%) 97 (17.8) 166 (30.3) 327 (27.4) 952 (46.9) o0.001 Hyperlipidaemia (%) 177 (32.4) 161 (29.4) 344 (28.9) 442 (21.8) o0.001 Family history (%) 60 (11.0) 61 (11.2) 158 (13.3) 294 (14.5) 0.67 History Previous MI (%) 180 (33.1) 147 (27.0) 324 (27.2) 442 (21.9) o0.001 Previous angina (%) 230 (42.1) 195 (35.6) 458 (38.4) 586 (28.8) o0.001 Stroke (%) 54 (9.9) 27 (4.9) 83 (7.0) 42 (2.1) o0.001 Previous bypass surgery (%) 19 (3.5) 14 (2.6) 44 (3.7) 59 (2.9) 0.50 Previous angioplasty (%) 21 (3.8/0) 23 (4.2) 53 (4.4) 79 (3.9) 0.87 Presenting characteristics Systolic BP (mmhg) o0.001 Diastolic BP (mmhg) o0.001 Heart rate (beats/min) o0.001 Killip class XII (%) 220 (41.3) 166 (31.3) 316 (27.1) 397 (20.3) o0.001 Anterior MI (%) 254 (46.5) 250 (45.7) 546 (45.8) 899 (44.2) 0.71 Q wave MI (%) 373 (72.9) 394 (75.6) 795 (70.4) 1446 (74.6) 0.04 Peak CK (IU/l) o0.001 CK=creatine kinase. Values are n (%) or mean 7 s.d. Table 2 Complications during hospital course of patients with an acute MI, with or without and/or and n=546 n=547 n=1192 n=2032 P-value Atrial fibrillation (%) 58 (10.6) 59 (10.8) 114 (9.6) 131 (6.4) Ventricular tachycardia/fibrillation (%) 66 (12.1) 62 (11.3) 148 (12.4) 267 (13.1) 0.7 Advanced AV block (%) 42 (7.7) 52 (9.5) 84 (7.0) 113 (5.6) Cardiogenic shock (%) 58 (10.6) 37 (6.8) 57 (4.8) 83 (4.1) o0.001 Congestive heart failure (%) 190 (34.8) 145 (26.5) 262 (22.0) 309 (15.2) o0.001 Tamopnade (%) 2 (0.4) 2 (0.4) 10 (0.8) 10 (0.5) 0.46 Stroke (%) 10 (1.8) 7 (1.3) 17 (1.4) 12 (0.6) 0.3 AV=atrioventricular. Table 3 In-hospital management of patients with an acute MI, with or without and/or and n=546 n=547 n=1192 n=2032 P-value Thrombolysis (%) 225 (41.2) 258 (47.2) 489 (41.1) 1037 (51.2) o0.001 Primary PTCA (%) 11 (2.0) 19 (3.5) 33 (2.8) 60 (3.0) 0.52 Coronary angiography (%) 151 (27.7) 149 (27.2) 383 (32.1) 706 (34.7) o0.001 Angioplasty (%) 63 (11.5) 83 (15.2) 191 (16.0) 387 (19.0) o0.001 Bypass surgery (%) 32 (5.9) 14 (2.6) 70 (5.9) 87 (4.3) Nitrates (%) 428 (78.4) 417 (76.2) 945 (79.3) 1427 (70.2) o0.001 Beta-blockers (%) 226 (41.4) 234 (42.8) 602 (50.5) 970 (47.7) o0.001 Heparin (%) 429 (78.6) 436 (79.7) 957 (80.3) 1629 (80.2) 0.84 Aspirin (%) 457 (83.7) 468 (85.6) 1000 (83.9) 1738 (85.5) 0.50 ACE inhibitors (%) 290 (53.1) 231 (42.2) 545 (45.7) 672 (33.1) o0.001 Calcium channel blockers (%) 115 (21.1) 96 (17.6) 265 (22.2) 324 (15.9) o0.001 Digoxin (%) 63 (11.5) 78 (14.3) 103 (8.6) 115 (5.7) o0.001 ACE=angiotensin converting enzyme. Influence of and by gender Of the 4317 MI patients, 1117 (25.9%) were females. Female patients were older than males (mean vs years) and were more likely to be hypertensive (56.3 vs 34.6%) and diabetic (34.1 vs 22.3%). The coexistence of and was present in 233 (20.9%) female and 313 (9.8%) male patients. The crude in-hospital, 30-day, 1-year and 30-day to 1-year mortality rates of diabetic hypertensives were significantly higher in both male and female patients. After adjustments were made for

4 Outcome after myocardial infarction in diabetic hypertensive patients 668 Table 4 In-hospital and follow-up crude mortality rates of patients with an acute MI, with or without and/or Mortality and n=546 No. (%) n=547 No. (%) n=1192 No. (%) n=2032 No. (%) 7-Day 64/546 (11.7) 52/547 (9.5) 85/1192 (7.1) 108/2032 (5.3) 30-Day 90/546 (16.5) 84/547 (15.4) 138/1189 (11.6) 162/2026 (8.0) 1-Year P 147/532 (27.6) 120/525 (22.9) 200/1135 (17.6) 232/1955 (11.9) 30-Day to 1-year 57/442 (12.9) 36/441 (8.2) 62/997 (6.2) 70/1793 (3.9) Table 5 Multivariate analysis of mortality rates of MI patients with or without and/or Mortality and n=546 Ratio (95% CI) n=547 Ratio (95% CI) n=1192 Ratio (95% CI) 7-Day# 1.40 ( ) 1.35 ( ) 0.95 ( ) 30-Day# 1.36 ( ) 1.61 ( ) 1.11 ( ) 1-Year P 1.55 ( ) 1.62 ( ) 1.14 ( ) 30-Day to 1-year P 2.24 ( ) 1.85 ( ) 1.18 ( ) # Odds ratio and P hazard ratio by multivariate analysis compared to the risk of dying of patients without nor after adjusting for age and other variables (see text). CI=confidence interval. for both male and female patients. Nondiabetic, male or female patients, both with or without a history of, had a similar prognosis. Figure 1 (a) Kaplan Meier survival curve after acute MI of diabetic patients with (DIABETES and HBP), diabetic normotensive patients (DIABETES), nondiabetic hypertensive patients (HBP) and nondiabetic normotensive patients. (b) Adjusted Kaplan Meier survival curve after acute MI of diabetic patients with hypertension (DIABETES and HBP), diabetic normotensive patients (DIABETES), nondiabetic hypertensive patients (HBP) and nondiabetic normotensive patients (see text). age, past MI, history of angina, Killip class, anterior location of MI, thrombolytic therapy and angioplasty or bypass surgery, the risk of death in diabetic patients with or without a history of was similar Discussion In the present nationwide survey we failed to observe, in diabetic patients, an added risk of a history of on short and 1-year mortality of patients with acute MI. Although mortality rates were significantly higher in diabetic patients suffering from, adjustment for baseline characteristics, in male or female patients, did not show any interaction between and. As in previous studies, 3 5 we found that the coexistence of and was common (12.6%) among patients with MI. History of was recorded in 37% of the nondiabetic patients and its prevalence increased in diabetics to 44% in male and 61% in female patients. Since the definition of in diabetic patients has been changed, 18 the number of diabetic patients with would increase considerably. Thus, the 12.6% prevalence of coexisting and in the present survey is an underestimation of the association between and among patients with acute MI. Considerable experimental and clinical evidence indicates that elevated blood pressure is critically important in the pathogenesis of diabetic heart disease. 2,7 Coronary artery disease is much more common in patients with both and than in patients with or alone, and the development of atherosclerosis was found to be accelerated, with more plaque fissuring and a lower coronary perfusion reserve index, when and coexist. 2,7,19,20 Patients with combined and also tend to

5 have impaired systolic and diastolic ventricular function with more left ventricular hypertrophy and congestive heart failure than counterparts with or alone. 7,21,22 As expected, we found that in diabetic hypertensive patients the in-hospital and 1- year outcome was significantly worse compared to patients with or alone. However, after adjustments were made for different clinical variables, the risk of diabetic patients with or without a history of was similar. Elevated blood pressure accelerates diabetic heart disease. It is possible that 1-year of follow-up is not enough to see the effect of a history of on mortality post-mi. Alternatively, a history of may not increase mortality if blood pressure is well controlled. In the present study, the hypertensive patients received more treatment than the normotensive patients and their blood pressure was well controlled. Patients with coexisting and were more likely to be treated with ACE inhibitors, nitrates and calcium antagonists than those with alone. The average blood pressure on admission was 142.1/83.7 mmhg in the diabetic hypertensive patients and 139.7/82.2 mmhg in the nondiabetic hypertensive patients suggesting a good control of blood pressure. It is also possible that in some hypertensive patients blood pressure dropped after MI and therefore hypertension was even better controlled. If this is the case, strict blood pressure control can eliminate the added risk of to and thereby improve prognosis of diabetic patients with ischaemic heart disease. 23,24 Tenenbaum et al 25 recently showed that is an independent predictor of increased mortality in diet-treated but not in pharmacologically treated diabetic patients with chronic ischaemic heart disease, suggesting the possible benefit of early blood pressure control in this population. The protection conferred on the diabetic patients treated intensively for was also evident in the Hypertension Optimal Treatment (HOT) study. 26 In this study, diabetic hypertensive patients benefited the most from intensive blood pressure lowering, with a 51% reduction in major cardiovascular events in the target group of diastolic blood pressure p80 mmhg compared with the p90 mmhg group. 26 Different studies noted a gender difference in the impact of diabetes on the outcome post-mi, with females having a worse prognosis In the present analysis of patients with MI, the combination of and was more common in females, but after multiple adjustments the risk of death was similar among male and female patients with combined and. Limitations Outcome after myocardial infarction in diabetic hypertensive patients Information on blood pressure and diabetes control over the follow-up period is lacking and therefore we cannot assess directly its impact on prognosis. The present study includes data on in-hospital complications and 1-year mortality but no information on nonfatal cardiovascular events is available. We cannot exclude an independent significant morbidity effect of combined diabetes and after MI. Conclusions The prevalence of coexisting and was high in unselected, consecutive patients with an acute MI. Diabetic patients exhibit a remarkable higher 1-year mortality post-mi than nondiabetic patients. We did not find the expected independent added risk of a history of in diabetic male or female patients. References 1 Reaven GM, Hoffman BB (eds). Symposium on diabetes and hypertension. Am J Med 1989; 87(Suppl 6A): 1S 42S. 2 Epstein M, Sowers JR. Diabetes mellitus and hypertension. Hypertension 1992; 19: Fuller JH. Epidemiology of hypertension associated with diabetes mellitus. Hypertension 1985; 2: Teuscher A, Egger M, Herman JB. Diabetes and hypertension: blood pressure in clinical diabetic patients and a control population. Arch Int Med 1989; 149: Klein BEK, Klein R, Moss SE. Blood pressure in a population of diabetic persons diagnosed after 30 years of age. Am J Public Health 1984; 74: Sowers JR. Hypertension in the elderly. Am J Med 1987; 82(Suppl 1B): Grossman E, Messereli FH. Diabetic and hypertensive heart disease. Ann Intern Med 1996; 125: Malmberg K, Ryden L. Myocardial infarction in patients with diabetes mellitus. Eur Heart J 1988; 9: Behar S et al. Ten-year survival after acute myocardial infarction: comparison of patients with and without diabetes. Am Heart J 1997; 133: Mak KH et al for the GUSTO-I investigators. Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. JAm Coll Cardiol 1997; 30: Abbot RD et al. The impact of diabetes on survival following myocardial infarction in men vs women: the Framingham Study. JAMA 1988; 260: Donahue RP et al. The influence of sex and diabetes on survival following acute myocardial infarction: a community-wide perspective. J Clin Epidemiol 1993; 46: Behar S et al for the SPRINT study group. Ten-year survival after myocardial infarction: comparison of patients with and without diabetes. Am Heart J 1997; 133: Fresco C et al. Prognostic value of a history of hypertension in 11,483 patients with acute myocardial infarction treated with thrombolysis. J Hypertens 1996; 14: Lee KL et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Results 669

6 670 Outcome after myocardial infarction in diabetic hypertensive patients from an international trial of 41,021 patients. GUSTO-I investigators. Circulation 1995; 91: Herlitz J, Bang A, Karlson BW. Five year prognosis after acute myocardial infarction in relation to a history of hypertension. J Hypertens 1996; 9: SAS Technical Report P-229, SAS/STAT software: changes and enhancement, release Cary, NC: SAS Institute Inc., Joint National Committee. The sixth report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure (JNC-VI). Arch Intern Med 1997; 157: Fernandez-Britto JE et al. Atherosclerosis in diabetes and hypertension. A comparative morphometric study of their progression using an atherometric system. Zentralbl Pathol 1991; 137: Arora GD, Reeves WC, Movahed A. Alteration of coronary perfusion reserve in hypertensive patients with diabetes. J Hum Hypertens 1994; 8: Grossman E et al. Left ventricular mass in diabetes hypertension. Arch Intern Med 1992; 152: Nagano N et al. Role of glucose intolerance in cardiac diastolic function in essential hypertension. Hypertension 1994; 23: American Diabetes Association. Clinical practice recommendations 1996: treatment of hypertension in diabetes. Diabetes Care 1996; 19(Suppl 1): S107 S Grossman E, Messerli FH, Goldbourt U. High blood pressure and diabetes mellitus: are all antihypertensive drugs created equal? Arch Intern Med 2000; 160: Tenenbaum A et al. Hypertension in diet versus pharmacologically treated diabetes. Mortality over a 5-year follow-up. Hypertension 1999; 33: Hansson L et al. Effect of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principle results of the Hypertension Optimal Treatment (HOT) randomized trial. Lancet 1998; 351: