Sie sind auf Seite 1von 7

European Heart Journal (2006) 27, 789795 doi:10.

1093/eurheartj/ehi774

Clinical research
Coronary heart disease

Age, clinical presentation, and outcome of acute coronary syndromes in the Euroheart acute coronary syndrome survey
Annika Rosengren1*, Lars Wallentin2, Maarten Simoons3, Anselm K Gitt4, Solomon Behar5, Alexander Battler6, and David Hasdai6
1 teborg, Sweden; 2 University Hospital, Department of Medicine, Sahlgrenska University Hospital/Ostra, SE-416 85 Go Uppsala, Sweden; 3 Thoraxcenter, Rotterdam, The Netherlands; 4 Klinikum der Stadt Ludwigshafen, Germany; 5 Neufeld Cardiac Research Institute, Tel-Hashomer, Israel; and 6 Rabin Medical Center, Petah Tikva, Israel

Received 31 August 2005; revised 9 January 2005; accepted 19 January 2006; online publish-ahead-of-print 7 February 2006

Downloaded from http://eurheartj.oxfordjournals.org/ by guest on May 11, 2013

KEYWORDS
Acute myocardial infarction; Unstable angina; Coronary disease; Aging

Aims Age is one of the most powerful determinants of prognosis in myocardial infarction, but there is comparatively little recent data across the whole spectrum of acute coronary syndromes (ACS). We examined the impact of increasing age on clinical presentation and hospital outcome in a large sample of patients with ACS. Methods and results Patients (n 10 253) from the Euroheart ACS survey in 103 hospitals in 25 countries were investigated. There was a signicant inverse association between the age and the likelihood of presenting with ST-elevation. For each decade of life, the odds of presenting with ST-elevation decreased by 0.82 [95% condence interval (CI) 0.790.84]; P , 0.0001. Elderly patients were considerably less often treated by cardiologists, less extensively investigated, and, when presenting with ST-elevation ACS, less likely to be treated with reperfusion. Compared with patients , 55 years, the odds ratios of hospital mortality were 1.87 (1.212.88) at age 5564, 3.70 (2.515.44) at age 6574, 6.23 (4.259.14) at age 7584, and 14.5 (9.4722.1) among patients  85 years, with no major differences across different types of admission or discharge diagnoses. Conclusion Elderly ACS patients were less likely to present with ST-elevation but had substantial in-hospital mortality, yet they were markedly less intensively treated and investigated.

Introduction
In recent years, there has been a shift in the clinical presentation of acute coronary syndromes (ACS) to milder forms, with evidence to suggest that case severity in acute myocardial infarction (AMI) may be decreasing13 and that hospitalized patients with AMI have smaller infarcts4 with lower case fatality.5 Concomitantly, there is an increase in the rates of unstable angina,6 which is a milder form of the ACS. Old age is a powerful predictor of mortality of patients with AMI.715 Even though the impact of age on clinical presentation and outcome in AMI is well characterized, the effects of age with these emerging characteristics of ACS have not been well studied. With increasing life expectancy, the mean age of ACS patients is growing steadily, emphasizing the need to dene the impact of age across the whole spectrum of ACS. Toward this end, we investigated the impact of increasing age on clinical presentation and hospital outcome in a large population of patients with different manifestations of ACS.

Methods
The details of the Euroheart ACS survey have been previously described in detail.16 The survey was performed in clusters composed of academic and non-academic hospitals and hospitals with and without cardiac catheterization laboratories, and cardiac surgery facilities. During the enrolment period lasting from 4 September 2000 to 15 May 2001, 14 271 patients in 25 countries admitted with suspected ACS were registered, of whom 10 484 were nally diagnosed with either AMI or unstable angina. In 231 patients, there were missing data on either age or sex, leaving 10 253 who form the study population for the present analysis. For all patients, the tentative initial diagnosis made by the attending physicians was recorded on the basis of the initial electrocardiographic pattern: ACS with ST-elevation, ACS without ST-elevation, and ACS with an undetermined electrocardiographic pattern. The full case report form was lled out for patients with a conrmed diagnosis of unstable angina or AMI and categorized according to the discharge diagnosis as either unstable angina, non-Q-wave AMI, or Q-wave AMI. The case report form included details regarding the demographic, clinical, and electrocardiographic characteristics of the patient, the diagnostic and treatment modalities, the in-hospital complications, and the discharge status. Body mass index was calculated as weight in kilograms divided by height in meters squared. Hypertension was dened as previously diagnosed by a physician, receiving medication to lower blood

*Corresponding author. Tel: 46 31 3434000; fax: 46 31 259254.


E-mail address: annika.rosengren@hjl.gu.se

& The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

790 pressure, or known blood pressure values of  140 mmHg systolic or  90 mm diastolic on two or more occasions. Diabetes was dened as previously diagnosed by a physician. Current smoking was dened as smoking cigarettes up to 1 month before admission. Angina pectoris of recent or prior onset was recorded and dened as chronic if present at least 30 days before admission, or of unknown duration. Hospital mortality was dened as any death occurring before discharge from any cause. Coronary angiography was done in 5437 patients (53%). Among patients  85 years, only 63 patients (13%) underwent coronary angiography, and because they were so few and, in all probability, heavily selected, we excluded them from the analyses pertaining to angiographic ndings. The presence of  50% stenosis in any of the three main vessels or left coronary main stem was recorded.

A. Rosengren et al. presentation or outcome were due to differences in baseline clinical and demographic characteristics, multiple logistic regression models were tted with hospital mortality as the dependent variables while controlling for potentially confounding factors. Of the factors present on admission, we considered gender, prior AMI, hypertension, diabetes, chronic angina, prior revascularization, and known prior heart failure. A similar analysis was conducted with ST-elevation ACS as the dependent variable, which also included an interaction term for sex and age. The clustering of observations within countries was taken into account by using multilevel techniques (university/non-university hospital and country). This method adjusts the estimation of model coefcients for the correlation among the observations, which is due to clustering within countries. Because of the large number of statistical comparisons in this report, P , 0.01 was considered to provide borderline evidence for an association and P , 0.001 was considered signicant.

Statistical methods
All analyses were performed using the SAS software version 8e. Baseline characteristics of the patients in the study were summarized in terms of frequencies and percentages. Correlations were tested by linear regression, with age as a continuous variable. With respect to angiographic ndings, a summary score was created for the number of vessels with signicant (. 50%) stenosis, ranging from 0 to 3 and tested against age as a continuous variable. To determine whether the age differences in clinical

Results
Of the 10 253 patients enrolled in the Euroheart ACS survey, 2321 (23%) were , 55 years and 2544 (25%) were  75 years. The proportion of women increased from 17% among patients aged , 55 to 56% among patients aged  85 (Table 1).
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on May 11, 2013

Table 1 Baseline risk factors and prior disease by age in the Euroheart ACS Age group Men Women % Women Obese (. 30 kg m22)a Diabetes mellitus Hypertension Hyperlipidaemia Family history of CAD Ever smoker Current smoker Prior AMI Chronic angina Prior revascularization Prior CVL/TIA Prior heart failure ASA prior to admission Beta-blocker prior to admission Statin prior to admission Diuretic prior to admission , 55 1915 406 17.5 23.4 27.1 13.5 20.4 41.0 54.2 53.2 48.5 33.0 38.1 83.8 63.3 62.1 47.0 22.6 19.2 20.5 28.1 15.1 14.5 1.9 2.2 3.8 5.2 30.4 35.0 26.4 29.8 18.2 21.2 4.8 10.8 (406) (410) (100) (259) (83) (786) (220) (1018) (197) (631) (155) (1605) (257) (1189) (191) (433) (78) (392) (114) (289) (59) (36) (9) (73) (21) (583) (142) (506) (121) (348) (86) (91) (44) 5564 1794 604 25.2 21.9 33.6 23.9 27.3 55.7 70.4 50.9 55.3 25.4 27.8 73.3 45.4 40.4 26.2 31.6 22.5 28.3 32.6 21.4 13.9 6.2 6.6 7.4 8.3 41.0 39.4 34.9 34.8 24.0 20.7 9.0 12.1 (604) (358) (181) (429) (165) (1000) (425) (913) (334) (456) (168) (1315) (274) (724) (158) (567) (136) (507) (197) (383) (84) (111) (40) (133) (50) (735) (238) (626) (210) (430) (125) (161) (73) 6574 1946 1046 35.0 17.7 28.1 25.2 30.5 59.2 71.0 48.3 52.7 18.4 21.5 69.2 32.6 23.7 13.2 34.8 29.1 32.5 36.6 21.3 15.4 9.3 7.7 11.7 12.3 45.9 42.0 34.3 35.0 23.2 23.1 16.8 22.1 (1046) (303) (251) (491) (319) (1151) (743) (940) (551) (357) (225) (1347) (341) (461) (138) (678) (304) (632) (383) (415) (161) (181) (81) (228) (129) (894) (439) (668) (366) (451) (242) (326) (231) 7584 1058 1002 48.6 (1002) 12.8 (111) 21.8 (171) 22.9 (242) 32.6 (327) 58.1 (615) 69.0 (691) 34.2 (362) 43.1 (432) 12.4 (131) 13.6 (136) 68.0 (719) 28.2 (283) 13.9 (147) 6.2 (62) 40.2 (425) 30.9 (310) 36.5 (386) 33.9 (340) 19.8 (209) 10.1 (101) 12.0 (127) 12.5 (125) 18.5 (196) 19.8 (198) 52.2 (552) 47.5 (476) 37.7 (399) 33.8 (339) 17.7 (187) 17.8 (178) 26.8 (284) 31.0 (311) 85 211 271 56.2 (271) 6.4 (9) 12.2 (21) 24.2 (51) 26.9 (73) 55.0 (116) 65.7 (178) 21.3 (45) 23.6 (64) 5.2 (11) 8.5 (23) 57.8 (122) 24.4 (66) 6.6 (14) 3.3 (9) 40.3 (85) 32.5 (88) 33.2 (70) 34.3 (93) 4.7 (10) 4.1 (11) 12.8 (27) 10.7 (29) 29.4 (62) 26.2 (71) 51.7 (109) 48.0 (130) 28.9 (61) 31.4 (85) 7.1 (15) 6.6 (18) 36.0 (76) 48.3 (131) P for trend

Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women

, 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 0.018 0.01 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 0.63 0.35 , 0.0001 , 0.0001 , 0.0001

CAD, coronary artery disease; CVL, cerebrovascular lesion; TIA, transient ischaemic attack. a Missing in 1398 subjects.

Age and acute coronary syndrome

791

The distribution of coronary risk factors varied strongly with age, with few exceptions. Younger patients were more often obese and smokers, and they had a higher prevalence of a positive family history, whereas older patients had more hypertension and diabetes. Prior angina, prior AMI, cerebrovascular events, and heart failure prior to admission were more prevalent with increasing age, as were use of aspirin, beta-blockers, and diuretics. In the youngest age group, , 55 years, 56% of men and 44% of women presented with ST-elevation ACS (Table 2). This proportion decreased with age for the men, whereas there was no signicant decrease with age among women. The proportion of ACS with undetermined ECG pattern increased with age. With respect to diagnosis at discharge, the proportion of ACS patients , 55 years with Q-wave MI was 44% for men and 29% for women, decreasing to 33% for men 85 years and older, whereas there was no decrease with age in women. The majority of patients in all age groups presented with typical anginal pain, but less frequently so with increasing age. Conversely, the proportion presenting with heart failure (Killip class 34) increased markedly with age. The proportion of patients undergoing a coronary angiogram decreased with age (Table 3). The proportion with a normal coronary angiogram was low overall and became less common with age. Almost one in ve had a left main stenosis among patients aged 7584, and approximately half had either left main stenosis  50% or three-vessel disease. Complications such as heart failure or pulmonary oedema or shock were increasingly more common with age, particularly pulmonary oedema, which occurred in 18% of men and 16% of women 85 years or older (Table 4). Overall, over 40% of ACS patients  85 years displayed some form of heart failure, including shock, during their hospital stay. Atrial

brillation occurred in few of the youngest patients, but in 16% of men and 9% of women  85 years. Recurrent ischaemia and re-infarction increased only very slightly with age in men and not at all in women. Of patients who were , 55 years, 91% of men and 85% of women were treated in a coronary care unit or cardiology ward from the start (Table 5). One in ve of patients aged 7584, and one in four among those aged  85, were initially treated in non-cardiology units. Among patients presenting with ST-elevation and presenting within 12 h, only 31 and 21% among men and women, respectively,  85 years were treated with primary reperfusion, compared with 70% of men and 76% of women , 55 years. Use of angiography and evaluation of left ventricular function decreased markedly with age. Angiotensin converting enzyme inhibitors prescribed on discharge were slightly higher in the higher age groups, whereas prescription of beta-blockers and statins were lower. The proportion of ST-elevation ACS decreased with age, also after considering potential confounders (Table 6). For each decade of life, the odds of presenting with ST-elevation decreased by 0.82 (95% CI 0.790.84); P , 0.0001 (data not shown). Overall, in-hospital death increased from 1% among patients , 55 years to 17% in patients  85 years. There were no signicant interactions between age and type of ACS, or type of AMI, and hospital mortality (all P . 0.2). The overall worst prognosis was found among patients with an undetermined electrocardiogram at admission, but this was largely due to the high average age in this category. Introducing potential confounders into the models including random effects in a multilevel analysis (university/non-university hospital and country) did not inuence the odds ratios associated with age to any great extent. Slightly more than half of the patients were  65 years, but 81% of the deaths occurred in this group.

Downloaded from http://eurheartj.oxfordjournals.org/ by guest on May 11, 2013

Table 2 Clinical presentation and initial and discharge diagnoses by age in the Euroheart ACS survey Age group Men Women Symptoms Typical angina Atypical chest pain Killip class 34 on arrival Initial diagnosis, % (n) ACS with ST-elevation ACS, no ST-elevation Undetermined Discharge diagnosis, % (n) Q-wave MI Non-Q-wave MI Unstable angina , 55 1915 406 5564 1794 604 6574 1946 1046 7584 1058 1002  85 211 271 P for trend

Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women

90.9 88.2 4.9 5.4 2.6 2.3 55.6 43.8 45.7 53.9 1.7 2.2 44.0 28.8 23.0 26.1 33.0 45.1

(1740) (358) (93) (22) (50) (9) (1064) (178) (818) (219) (33) (9) (843) (117) (441) (106) (631) (183)

89.5 (1606) 86.3 (521) 3.5 (63) 7.8 (47) 3.4 (60) 4.5 (27) 45.9 (823) 35.6 (215) 49.5 (888) 59.6 (360) 4.6 (83) 4.8 (29) 35.6 (639) 27.0 (163) 23.7 (425) 24.0 (145) 40.7 (730) 49.0 (296)

85.9 (1672) 86.3 (903) 5.3 (104) 4.7 (49) 4.8 (93) 5.4 (56) 39.6 (771) 36.7 (384) 52.5 (1022) 56.8 (594) 7.9 (153) 6.5 (68) 30.8 (600) 27.3 (285) 23.2 (452) 22.8 (238) 45.9 (894) 50.0 (523)

83.7 (886) 83.4 (836) 4.3 (45) 4.9 (49) 7.5 (79) 8.7 (87) 36.3 (384) 35.6 (357) 51.2 (542) 55.3 (554) 12.5 (132) 9.1 (91) 27.0 (286) 27.4 (274) 30.1 (318) 27.2 (272) 42.9 (454) 45.5 (456)

79.6 (168) 74.9 (203) 2.8 (6) 6.6 (18) 13.7 (29) 17.0 (46) 37.9 (80) 38.8 (105) 46.0 (97) 49.5 (134) 16.1 (34) 11.8 (32) 32.7 (69) 32.1 (87) 32.7 (69) 37.6 (102) 34.6 (73) 30.3 (82)

, 0.0001 , 0.0001 0.52 0.61 , 0.0001 , 0.0001 , 0.0001 0.06 , 0.0001 0.19 , 0.0001 , 0.0001 , 0.0001 0.66 0.0002 0.004 , 0.0001 0.003

792

A. Rosengren et al.

Table 3 Angiographic ndings by age in the Euroheart ACS survey among 5374 patients , 85 years Age group Men with angiography (% with angiography) Women with angiography (% with angiography) Normal angiogram (%) Number of diseased vessels ( 50% stenosis) (%) 0 1 2 3 Left main stem  50% stenosis (%) Three-vessel disease or main stem (%) PCI or CABG while in hospital Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women , 55 1272 (66) 240 (59) 5.6 (71) 13.3 (32) 6.5 15.0 40.3 43.3 29.1 25.0 24.1 16.7 6.1 5.0 27.1 18.3 71.6 62.5 (83) (36) (513) (104) (370) (60) (306) (40) (78) (12) (345) (44) (911) (150) 5564 1131 (63) 332 (55) 3.8 (43) 10.8 (36) 4.9 (55) 12.1 (40) 31.0 (351) 33.7 (112) 28.9 (327) 24.4 (81) 35.2 (398) 29.8 (99) 10.6 (120) 6.9 (23) 39.6 (448) 32.5 (108) 70.0 (792) 62.1 (206) 6574 1107 (57) 499 (48) 2.7 (30) 7.2 (36) 4.4 (49) 8.2 (41) 24.2 (268) 27.9 (139) 32.5 (360) 29.9 (149) 38.8 (430) 34.1 (170) 17.3 (192) 10.6 (53) 46.0 (509) 37.9 (189) 63.7 (705) 59.9 (299) 7584 444 (42) 349 (35) 2.3 (10) 5.7 (20) 3.8 6.9 19.6 23.2 30.0 29.8 46.6 40.1 18.2 17.2 54.1 47.6 61.0 63.3 (17) (24) (87) (81) (133) (104) (207) (140) (81) (60) (240) (166) (271) (221) P for trend

, 0.0001 , 0.0001

, 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001

Downloaded from http://eurheartj.oxfordjournals.org/ by guest on May 11, 2013

Table 4 Hospital complications by age in the Euroheart ACS survey Age group Men Women Mild to moderate heart failure (%) Pulmonary oedema (%) Shock (%) Any heart failure, including shock (%) Asystole (%) Atrial brillation (%) Recurrent ischaemia (%) Re-infarction (%) Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women , 55 1915 406 10.2 (196) 11.3 (46) 2.3 (44) 4.2 (17) 3.0 (57) 4.7 (19) 12.8 (245) 14.5 (59) 1.3 (25) 1.7 (7) 2.7 (51) 2.7 (11) 10.6 (202) 13.6 (55) 1.3 (24) 2.5 (10) 5564 1794 604 14.6 14.9 3.8 5.1 3.3 5.3 17.6 20.2 1.5 2.7 5.4 4.3 10.6 13.1 1.6 2.0 (261) (90) (68) (31) (59) (32) (316) (122) (27) (16) (97) (26) (190) (79) (29) (12) 6574 1946 1046 18.1 17.4 5.6 7.0 4.9 5.0 22.2 22.8 3.6 3.8 8.4 7.0 12.4 11.9 2.4 1.9 (352) (182) (109) (73) (95) (52) (431) (238) (69) (40) (163) (73) (242) (124) (47) (20) 7584 1058 1002 21.0 (222) 23.5 (235) 10.2 (108) 12.0 (120) 5.8 (61) 6.4 (64) 28.1 (297) 30.6 (307) 4.5 (48) 5.5 (55) 11.6 (123) 11.6 (116) 12.6 (133) 14.7 (147) 2.6 (27) 2.4 (24)  85 211 271 31.8 (67) 29.5 (80) 17.5 (37) 15.5 (42) 8.5 (18) 6.6 (18) 43.1 (91) 40.6 (110) 9.0 (19) 10.0 (27) 15.6 (33) 9.2 (25) 13.3 (28) 11.4 (31) 2.4 (5) 0.7 (2) P for trend

, 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 0.11 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 0.01 0.75 0.006 0.46

Discussion
Major ndings
Despite improvement in treatment in ACS, the short-term outcome in elderly patients is still very poor. In this international cohort of comparatively unselected ACS patients, we found that overall in-hospital mortality was , 5%, but this varied widely across the different ACS and across age groups. For example, in-hospital mortality was , 1% in patients aged , 55 without ST-elevation, whereas almost one in four of patients  85 years with ST-elevation ACS died. Older patients had less ST-elevation ACS and Q-wave AMI but had more ACS with undetermined ECG pattern, which, in turn, had a poor prognosis, as described in a prior publication.17 The risk factor pattern also varied with

age, in that younger patients more often had a positive family history, were smokers, or obese, whereas older patients more often had a history of diabetes, hypertension or prior cardiovascular disease, and more medical treatment. Heart failure and atrial brillation were common complications during the hospital stay and were signicantly more common with higher age, whereas recurrent ischaemia and re-infarction displayed only weak or non-existent associations with age.

Risk factors and treatments


Manifestations of coronary disease in populations undergo rapid changes over time. In many European countries, as well as in the USA, there have been decreases in the

Age and acute coronary syndrome

793

Table 5 Selected treatments and investigations by age in the Euroheart ACS survey Age group Men Women First ward coronary care unit (%) First ward any cardiology unit (%) ASA or any other anti-trombotic treatment on discharge, % (n) ACE inhibitors on discharge (%) Beta-blockers on discharge (%) Statins on discharge (%) Angiography while in hospital (%) Evaluation of left ventricular function in hospital (%) PCI while in hospital, % (n) In patients with ACS with ST-elevation (n) and presenting within 12 h Thrombolytic therapy, % (n) Primary PCI, % (n) Thrombolytic or primary PCI, % (n) Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women Men Women , 55 1915 406 72.8 (1394) 62.1 (252) 90.8 (1738) 84.7 (344) 94.1 (1802) 94.3 (383) 50.4 (966) 46.3 (188) 81.6 (1562) 76.1 (309) 61.5 (1177) 57.1 (232) 66.4 (1272) 59.1 (240) 81.9 (1569) 81.8 (332) 44.5 (852) 35.2 (143) 769 123 5564 1794 604 64.2 (1151) 60.8 (367) 86.4 (1550) 86.6 (523) 92.9 (1667) 90.6 (547) 55.4 (994) 58.1 (351) 77.8 (1395) 76.0 (459) 59.9 (1075) 56.3 (340) 63.0 (1131) 55.0 (332) 80.9 (1452) 79.8 (482) 39.7 (712) 30.8 (186) 586 158 6574 1946 1046 61.9 (1205) 58.3 (610) 83.5 (1625) 82.5 (863) 89.7 (1746) 88.4 (925) 59.3 (1153) 58.9 (616) 68.6 (1334) 70.9 (742) 52.8 (1028) 53.4 (558) 56.9 (1107) 47.7 (499) 75.4 (1467) 76.2 (797) 30.5 (593) 24.7 (258) 524 263 7584 1058 1002 58.1 (615) 56.1 (562) 82.3 (871) 77.6 (778) 87.2 (922) 87.4 (876) 55.9 (591) 56.7 (568) 65.2 (690) 62.7 (628) 38.2 (404) 42.3 (424) 42.0 (444) 34.8 (349) 70.4 (745) 68.7 (688) 22.5 (238) 19.7 (197) 263 235  85 211 271 49.8 (105) 47.2 (128) 74.4 (157) 72.0 (195) 82.5 (174) 80.8 (219) 46.5 (98) 52.8 (143) 48.8 (103) 53.5 (145) 15.6 (33) 17.7 (48) 18.0 (38) 9.2 (25) 55.9 (118) 52.0 (141) 10.9 (23) 7.0 (19) 64 58 P for trend

, 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 0.002 0.06 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001 , 0.0001

Downloaded from http://eurheartj.oxfordjournals.org/ by guest on May 11, 2013

Men Women Men Women Men Women

43.2 (332) 47.2 (58) 26.5 (204) 29.3 (36) 69.7 (536) 76.4 (94)

44.2 (259) 44.9 (71) 27.1 (159) 21.5 (34) 71.3 (418) 66.5 (105)

44.9 (235) 43.4 (114) 21.0 (110) 17.9 (47) 65.8 (345) 61.2 (161)

35.0 (92) 31.1 (73) 20.9 (55) 16.6 (39) 55.6 (147) 47.7 (112)

17.2 (11) 13.8 (8) 14.1 (9) 6.9 (4) 31.3 (20) 20.7 (12)

0.02 , 0.0001 0.002 , 0.0001 , 0.0001 , 0.0001

incidence of AMIs18,19 and in mortality from coronary disease.20 Although these changes have not been universal, most of the participating centres in the Euroheart ACS survey represent countries with these characteristics. Another feature of recent developments is that the severity of ACS seems to be decreasing,13 with better prognosis.4,5 To a large extent, this will be due to better treatment.19 Out-of-hospital mortality, however, has also decreased,21 indicating that other factors, such as changes in risk factor pattern may play a role.22 One recent study found that modest reductions in major risk factors led to gains in lifeyears four times higher than did the various treatments.23 The different risk factor patterns in younger and older patients might reect variations related to aging and differences between birth cohorts. To what extent elderly patients would benet from better implementation of proven therapies or improvement of risk factors remains undetermined.

Prior studies
Relative odds of 1.44 and 1.82 for hospital mortality for a 10 year increment in age in women and men, respectively, have been found in AMI patients.24 Other studies, however, in non-ST-elevation ACS have found higher increments in shortterm mortality with age.25 Among Spanish patients with AMI, and investigated from 1995 to 2001, hospital mortality almost doubled from each age group from 2.6% in patients

, 55 years to 25.8% in the . 84 years group, gures similar to that of the present study,26 even though, unlike the Euroheart survey, only patients treated in coronary care units or intensive care were included. Improvement in hospital outcome seems to have been greater in younger age groups. In the Worcester study, improvement in outcome over two decades was demonstrated to be less in older patients.8 Some of the improvement in younger patients could be due to the fact that proven therapies are better implemented among the younger patients. A substantial proportion of patients who are eligible for reperfusion therapy still do not receive this treatment, particularly among the elderly27,28 although a benet has been demonstrated also in the elderly,29 and other proven therapies are also underused,13 even in the absence of contraindications.30 Despite having more severe and extensive coronary disease, elderly patients have been shown to receive less aggressive anti-ischaemic therapy and to be less likely to undergo coronary angiography, with fewer revascularization procedures than their younger counterparts.31 Consistent with previous studies,32 older patients had less typical symptoms which partly might explain their different treatment. However, although older patients have an increased risk for major bleeding, a routine early invasive strategy has been shown to signicantly improve ischaemic outcomes in elderly patients with non-ST-segment elevation ACS.33 This study supports the notion that older patients may not be

794

A. Rosengren et al.

Table 6 Impact of age on risk of ST-elevation ACS and on-hospital mortality by diagnosis n ST elevation ACS , 55 5564 6574 7584  85 Total Hospital mortality ACS with ST elevation , 55 5564 6574 7584  85 Total ACS without ST elevation , 55 5564 6574 7584  85 Total ACS with undetermined ECG , 55 5564 6574 7584  85 Total All , 55 5564 6574 7584  85 Total
a

Odds ratio (95% CI)

Odds ratioa (95% CI)

2321 2398 2992 2060 482 10 253

53.5 43.3 38.6 36.0 38.4

(1242) (1038) (1155) (741) (185)

1.00 0.66 0.55 0.49 0.54

(0.590.74) (0.490.61) (0.430.55) (0.440.66)

1.00 0.67 (0.610.75) 0.55 (0.490.63) 0.50 (0.420.61) 0.57 (0.440.74)

42.5 (486)

1242 1038 1155 741 185 4361 1037 1248 1616 1096 231 5228 42 112 221 223 66 664 2321 2398 2992 2060 482 10 253

1.8 4.0 8.4 12.2 23.2

(22) (41) (97) (90) (43)

1.00 2.28 5.08 7.67 16.79

(1.353.85) (3.188.14) (4.7612.34) (9.7628.88)

1.00 2.29 (1.373.82) 5.07 (2.888.92) 7.78 (4.6512.99) 16.91 (9.2830.79)

6.7 (293)

Downloaded from http://eurheartj.oxfordjournals.org/ by guest on May 11, 2013

0.9 1.0 2.0 4.1 8.7

(9) (13) (32) (45) (20)

1.00 1.20 2.31 4.89 10.83

(0.512.82) (1.104.85) (2.3810.06) (4.8624.11)

1.00 1.21 (0.612.38) 2.20 (1.084.47) 4.50 (2.348.65) 9.74 (4.5121.06)

2.3 (119) 2.4 6.3 8.1 13.5 27.3 (1) (7) (18) (30) (18) 1.00 2.73 3.64 6.37 15.37 1.00 2.82 (0.4916.35) 3.82 (0.6024.44) 6.71 (1.0144.40) 15.68 (2.25109.42)

(0.3322.91) (0.4727.99) (0.8548.06) (1.97120.15)

11.1 (74) 1.4 2.5 4.9 8.0 16.8 (32) (61) (147) (165) (81) 1.00 1.87 3.70 6.23 14.45 1.00 1.83 (1.252.67) 3.54 (2.365.30) 5.97 (4.138.63) 13.47 (8.6321.03)

(1.212.88) (2.515.44) (4.259.14) (9.4722.1)

4.7 (486)

Adjusted for sex, prior MI, hypertension, diabetes, chronic angina, prior revascularization, and known prior heart failure.

as well treated as they should be, and consequently, there may be considerable scope for improvement with respect to hospital outcome in elderly patients.

different diagnoses were considerable. The age gradient with respect to mortality, however, was similar across all ACS diagnoses.

Limitations
In the Euroheart ACS survey, there was no strict validation of the AMI or unstable angina diagnoses. The discharge diagnosis of the attending physician was accepted. About a quarter of patients diagnosed with AMI had normal creatine kinase status, indicating either that the test was not done within the optimal time frame or that the traditional denition was used, with symptoms and electrocardiographic changes sufcient to diagnose infarction.34 Likewise, 23% of patients diagnosed with unstable angina had elevated creatine kinase, although for the most part only moderately so. The new denition of AMI was published on the same day as this survey started,34 and these inconsistencies reect clinical practice during this transitional period. Even so, the differences in mortality between

Conclusions
In this large survey of ACS patients from 25 countries in Europe and the Mediterranean basin, we found that old age remains a strong predictor of increased hospital mortality across all types of ACS. Old patients with ACS have their hospital course frequently complicated, in particular, with heart failure. Young patients had comparatively low mortality, four out of ve deaths were in patients  65years, indicating that improvement in hospital care for older patients may potentially save a substantial number of lives. However, more detailed data with respect to comorbid conditions and contraindications are needed to estimate the size of this potential benet.

Age and acute coronary syndrome

795
Europe and the Mediterranean basin; the Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS). Eur Heart J 2002; 23:11901201. Lev EI, Battler A, Behar S, Porter A, Haim M, Boyko V, Hasdai D. Frequency, characteristics, and outcome of patients hospitalized with acute coronary syndromes with undetermined electrocardiographic patterns. Am J Cardiol 2003;91:224227. Kuulasmaa K, Tunstall-Pedoe H, Dobson A, Fortmann S, Sans S, Tolonen H, Evans A, Ferrario M, Tuomilehto J. Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations. Lancet 2000;355:675687. Tunstall-Pedoe H, Vanuzzo D, Hobbs M, Mahonen M, Cepaitis Z, Kuulasmaa K, Keil U. Estimation of contribution of changes in coronary care to improving survival, event rates, and coronary heart disease mortality across the WHO MONICA Project populations. Lancet 2000;355:688700. Sans S, Kesteloot H, Kromhout D. The burden of cardiovascular diseases mortality in Europe. Task Force of the European Society of Cardiology on Cardiovascular Mortality and Morbidity Statistics in Europe. Eur Heart J 1997;18:12311248. Capewell S, MacIntyre K, Stewart S, Chalmers JW, Boyd J, Finlayson A, Redpath A, Pell JP, McMurray JJ. Age, sex, and social trends in out-of-hospital cardiac deaths in Scotland 1986-95: a retrospective cohort study. Lancet 2001;358:12131217. Unal B, Critchley JA, Capewell S. Explaining the decline in coronary heart disease mortality in England and Wales between 1981 and 2000. Circulation 2004;109:11011107. Unal B, Critchley JA, Fidan D, Capewell S. Life-years gained from modern cardiological treatments and population risk factor changes in England and Wales, 19812000. Am J Public Health 2005;95:103108. Greenland P, Reicher-Reiss H, Goldbourt U, Behar S. In-hospital and 1-year mortality in 1,524 women after myocardial infarction. Comparison with 4,315 men. Circulation 1991;83:484491. Hasdai D, Holmes DR Jr, Criger DA, Topol EJ, Califf RM, Harrington RA. Age and outcome after acute coronary syndromes without persistent ST-segment elevation. Am Heart J 2000;139:858866. Ruiz-Bailen M, Aguayo de Hoyos E, Ramos-Cuadra JA, Diaz-Castellanos MA, Issa-Khozouz Z, Reina-Toral A, Lopez-Martinez A, Calatrava-Lopez J, Laynez-Bretones F, Castillo-Parra JC, De La TorrePrados MV. Inuence of age on clinical course, management and mortality of acute myocardial infarction in the Spanish population. Int J Cardiol 2002;85:285296. Eagle KA, Goodman SG, Avezum A, Budaj A, Sullivan CM, Lopez-Sendon J. Practice variation and missed opportunities for reperfusion in ST-segment-elevation myocardial infarction: ndings from the Global Registry of Acute Coronary Events (GRACE). Lancet 2002;359:373377. Chandra H, Yarzebski J, Goldberg RJ, Savageau J, Singleton C, Gurwitz JH, Gore JM. Age-related trends (19861993) in the use of thrombolytic agents in patients with acute myocardial infarction. The Worcester Heart Attack Study. Arch Intern Med 1997;157:741746. Stenestrand U, Wallentin L. Fibrinolytic therapy in patients 75 years and older with ST-segment-elevation myocardial infarction: one-year follow-up of a large prospective cohort. Arch Intern Med 2003;163: 965971. Tran CT, Laupacis A, Mamdani MM, Tu JV. Effect of age on the use of evidence-based therapies for acute myocardial infarction. Am Heart J 2004;148:834841. Stone PH, Thompson B, Anderson HV, Kronenberg MW, Gibson RS, Rogers WJ, Diver DJ, Theroux P, Warnica JW, Nasmith JB, Kells C, Kleiman N, McCabe CH, Schactman M, Knatterud GL, Braunwald E. Inuence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: The TIMI III registry. JAMA 1996;275:11041112. Canto JG, Shlipak MG, Rogers WJ, Malmgren JA, Frederick PD, Lambrew CT, Ornato JP, Barron HV, Kiefe CI. Prevalence, clinical characteristics, and mortality among patients with myocardial infarction presenting without chest pain. JAMA 2000;283:32233229. Bach RG, Cannon CP, Weintraub WS, DiBattiste PM, Demopoulos LA, Anderson HV, DeLucca PT, Mahoney EM, Murphy SA, Braunwald E. The effect of routine, early invasive management on outcome for elderly patients with non-ST-segment elevation acute coronary syndromes. Ann Intern Med 2004;141:186195. Hasdai D, Behar S, Boyko V, Danchin N, Bassand JP, Battler A. Cardiac biomarkers and acute coronary syndromesthe Euro Heart Survey of Acute Coronary Syndromes Experience. Eur Heart J 2003;24:11891194.

Acknowledgement
The Euroheart ACS survey was sponsored by Schering-Plough and Centocor. The Swedish participation was supported by the Swedish Heart and Lung Foundation. We thank Georg Lappas for help with the statistical analyses. Conict of interest: none declared.
17.

18.

References
1. Dauerman HL, Lessard D, Yarzebski J, Furman MI, Gore JM, Goldberg RJ. Ten-year trends in the incidence, treatment, and outcome of Q-wave myocardial infarction. Am J Cardiol 2000;86:730735. 2. Goff DC Jr, Howard G, Wang CH, Folsom AR, Rosamond WD, Cooper LS, Chambless LE. Trends in severity of hospitalized myocardial infarction: the atherosclerosis risk in communities (ARIC) study, 19871994. Am Heart J 2000;139:874880. 3. Hellermann JP, Reeder GS, Jacobsen SJ, Weston SA, Killian JM, Roger VL. Longitudinal trends in the severity of acute myocardial infarction: a population study in Olmsted County, Minnesota. Am J Epidemiol 2002;156:246253. 4. Salomaa V, Miettinen H, Palomaki P, Arstila M, Mustaniemi H, Kuulasmaa K, Tuomilehto J. Diagnostic features of acute myocardial infarction changes over time from 1983 to 1990: results from the FINMONICA AMI Register Study. J Intern Med 1995;237:151159. 5. Abildstrom SZ, Rasmussen S, Rosen M, Madsen M. Trends in incidence and case fatality rates of acute myocardial infarction in Denmark and Sweden. Heart 2003;89:507511. 6. McGovern PG, Jacobs DR Jr, Shahar E, Arnett DK, Folsom AR, Blackburn H, Luepker RV. Trends in acute coronary heart disease mortality, morbidity, and medical care from 1985 through 1997: the Minnesota heart survey. Circulation 2001;104:1924. 7. Goldberg RJ, Gore JM, Gurwitz JH, Alpert JS, Brady P, Strohsnitter W, Chen ZY, Dalen JE. The impact of age on the incidence and prognosis of initial acute myocardial infarction: the Worcester Heart Attack Study. Am Heart J 1989;117:543549. 8. Goldberg RJ, McCormick D, Gurwitz JH, Yarzebski J, Lessard D, Gore JM. Age-related trends in short- and long-term survival after acute myocardial infarction: a 20-year population-based perspective (19751995). Am J Cardiol 1998;82:13111317. 9. Lee KL, Woodlief LH, Topol EJ, Weaver WD, Betriu A, Col J, Simoons M, Aylward P, Van de Werf F, Califf RM. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Results from an international trial of 41,021 patients. GUSTO-I Investigators. Circulation 1995;91:16591668. 10. Newby LK, Bhapkar MV, White HD, Topol EJ, Dougherty FC, Harrington RA, Smith MC, Asarch LF, Califf RM. Predictors of 90-day outcome in patients stabilized after acute coronary syndromes. Eur Heart J 2003;24:172181. 11. Rosengren A, Spetz CL, Koster M, Hammar N, Alfredsson L, Rosen M. Sex differences in survival after myocardial infarction in Sweden; data from the Swedish National Acute Myocardial Infarction Register. Eur Heart J 2001;22:314322. 12. Vaccarino V, Parsons L, Every NR, Barron HV, Krumholz HM. Sex-based differences in early mortality after myocardial infarction. National Registry of Myocardial Infarction 2 Participants. N Engl J Med 1999; 341:217225. 13. Avezum A, Makdisse M, Spencer F, Gore JM, Fox KA, Montalescot G, Eagle KA, White K, Mehta RH, Knobel E, Collet JP. Impact of age on management and outcome of acute coronary syndrome: observations from the Global Registry of Acute Coronary Events (GRACE). Am Heart J 2005;149:6773. 14. Halon DA, Adawi S, Dobrecky-Mery I, Lewis BS. Importance of increasing age on the presentation and outcome of acute coronary syndromes in elderly patients. J Am Coll Cardiol 2004;43:346352. 15. Stern S, Behar S, Leor J, Harpaz D, Boyko V, Gottlieb S. Presenting symptoms, admission electrocardiogram, management, and prognosis in acute coronary syndromes: differences by age. Am J Geriatr Cardiol 2004;13:188196. 16. Hasdai D, Behar S, Wallentin L, Danchin N, Gitt AK, Boersma E, Fioretti PM, Simoons ML, Battler A. A prospective survey of the characteristics, treatments and outcomes of patients with acute coronary syndromes in

19.

20.

21.

22.

Downloaded from http://eurheartj.oxfordjournals.org/ by guest on May 11, 2013

23.

24.

25.

26.

27.

28.

29.

30.

31.

32.

33.

34.