European Heart Journal (2004) 25, 663670

Clinical research

Sex, age, and clinical presentation of acute coronary syndromes

Annika Rosengrena,*, Lars Wallentinb, Anselm K Gittc, Solomon Behard, Alexander Battlere,f, David Hasdaie,f
Department of Medicine, Goteborg University, Sahlgrenska University Hospital, Ostra, SE-416 85 Goteborg, Sweden b University Hospital, Uppsala, Sweden c Herzzentrum Ludwigshafen, Department of Cardiology, Institut for Herzinfarktforschung, Ludwigshafen, Germany d Neufeld Cardiac Research Institute, Tel- Hashomer, Israel e Rabin Medical Center, Petah Tikva, Israel f Tel Aviv University, Israel
Received 28 October 2003; revised 15 February 2004; accepted 19 February 2004
a

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KEYWORDS
Myocardial infarction; Women; Sex; Age; Thrombolytic therapy; Coronary angiography

Aim To investigate sex differences in clinical presentation in younger and older patients hospitalised with a wide spectrum of acute coronary syndromes (ACS). Methods and results We analysed 10 253 patients with a discharge diagnosis of ACS in the Euro Heart Survey of patients with Acute Coronary Syndromes. There were 1010 women and 3709 men <65 years. Among patients <65 years, fewer women than men presented with ST elevation, (OR [odds ratio]: 0.62 [0.530.71]) and developed Qwave myocardial infarction (OR 0.58 [0.500.67]), whereas in patients P65 years there was no signicant sex difference. Women <65 years were more likely than men of the same age to be discharged with a diagnosis of unstable angina (OR 1.56 [1.351.79]), but there was no sex difference in older patients; the p for interaction between sex and age for both was <0.0001. Among patients who underwent coronary angiography, both younger and older women were less likely than men to have 3-vessel or main stem disease. In a logistic regression analysis stratied for age, female sex was a signicant negative determinant of presenting with ST elevation in patients <65 years (OR 0.68 [0.580.79]), whereas there was no effect of sex in patients P65 years. Conclusion In younger patients with ACS, women were less likely than men to present with ST elevation and more likely to be discharged with a diagnosis of unstable angina. In older patients there were no differences in clinical presentation. Both older and younger women had less extensive atherosclerosis. The ndings suggest a different pathophysiology of ACS in younger, but not older, women. c 2004 Published by Elsevier Ltd on behalf of The European Society of Cardiology.


Introduction

Coronary heart disease is the single most common cause of death in both women and men in large parts of the * Corresponding author. Tel.: 46-31343-4000; fax: 46-31259-254.
E-mail address: annika.rosengren@hjl.gu.se (A. Rosengren).

industrialised world, but there are several clinically important differences between men and women. Although the incidence of acute myocardial infarction (AMI) increases sharply with age, women are less prone to develop AMI than men at any given age, with a lag of approximately 910 years between the sexes.15 The difference in mortality and morbidity diminishes with

0195-668X/$ - see front matter c 2004 Published by Elsevier Ltd on behalf of The European Society of Cardiology. doi:10.1016/j.ehj.2004.02.023

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A. Rosengren et al. as a previous diagnosis by a physician. Current smoking was dened as smoking up to 1 month before admission. Chronic angina was dened as having had angina before at least 30 days before admission. Coronary angiography was done in 5437 patients. The presence of P50% stenosis in any of the three main vessels or the left coronary main stem was recorded.

age, but even between the ages of 75 and 85 years the incidence is almost twofold greater in men than in women.3 The difference in age seems to be less pronounced for non-Q-wave AMI6 and non-ST-elevation AMI,7;8 and may be still smaller for unstable angina.8;9 Women and men with acute coronary syndromes (ACS) have been found to have different clinical proles and presentation,8 with a smaller percentage of women than men presenting with ST-elevation AMI, but more presenting with unstable angina. We have previously shown, in a large population of unselected patients with ACS in Europe and the Mediterranean basin, that women have worse baseline clinical characteristics, undergo fewer revascularisation procedures, and have a higher mortality. However, after adjusting for baseline differences, sex had no impact on mortality.6 Although studies addressing differences in aspects of coronary heart disease between men and women routinely adjust for age differences, few have examined whether the effects of sex differ according to age. Because age and sex both inuence clinical presentation in ACS, it may be important to investigate age-specic sex differences. The present analysis was undertaken with the aim of investigating possible age-specic sex differences with respect to clinical presentation in a large population of patients with AMI and unstable angina.

Analysis
Patients were divided into subgroups based on sex and age <55, 5564, 6574, and P75 years. To facilitate comparisons between men and women while striving to retain sufcient statistical power in each age group, we arbitrarily selected a cutoff point of 65 years to differentiate between younger and older patients in most analyses. We analysed the ageand sex-specic clinical characteristics, reperfusion therapy (in patients with ST-elevation ACS only), and angiographic ndings.

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Statistical methods
All analyses were performed using SAS software, version 8e. All tests were two-sided and P-values below 0.05 were considered signicant. Differences in proportions were tested with MantelHaenzsel tests, with stratication into two age categories (<65 years, and P65 years). The associations between STelevation AMI, Q-wave AMI, or 3-vessel or left main disease and age as a continuous variable were tested separately for men and women with simple Pearson correlation tests. Odds ratios with 95% condence intervals for differences in proportions between women and men were calculated by logistic regression. We did not adjust for multiple statistical testing because many of the variables that were tested were intercorrelated and to do so would have increased the likelihood of type II error. However, condence intervals are presented for all main ndings. To determine whether the differences in clinical presentation between men and women at different ages, as dened by the proportion of ST-elevation ACSs, were due to differences between the sexes in baseline clinical and demographic characteristics, we adjusted for these variables by logistic regression models. Independent variables that were signicantly different between men and women in univariate analysis were entered, including age, smoking, hypertension, diabetes, prior AMI, chronic angina, and prior revascularisation. Because body mass index (BMI) was missing in 14% of the subjects, we included this variable in a second logistic analysis. A possible interaction between sex and age was tested in logistic regression with an interaction term (age sex) created with age as a continuous variable and introduced in the logistic regression model with the relevant presenting diagnosis as the dependent variable. We also included, alone or separately, interaction terms for other variables, where a possible interaction could be detected with respect to age and other clinical variables.

Methods
Euro heart survey of patients with acute coronary syndromes
The details of the Euro Heart Survey ACS have been described in detail elsewhere.10 The survey was performed in clusters composed of academic and non-academic hospitals and hospitals with and without cardiac catheterisation laboratories and cardiac surgery facilities. During the enrolment period from September 4, 2000 to May 15, 2001, 14,271 patients in 25 countries with suspected acute coronary syndrome were screened, of whom 10,484 were nally diagnosed with either AMI or unstable angina. Data on either age or sex were missing for 231 patients, leaving 10,253 who form the study population of the present analysis. For all patients, the tentative initial diagnosis made by the attending physicians was recorded based on 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, who were categorised according to the discharge diagnosis as either unstable angina, non-Q-wave AMI, or Q-wave AMI. The case report form included details of the demographic, clinical, and electrocardiographic characteristics of the patient, diagnostic and treatment modalities, in-hospital complications, and discharge status. Hyperlipidaemia was dened as a previous diagnosis by a physician, receiving lipid-lowering therapy, or either total cholesterol over 5 mmol/l or serum triglycerides over 2 mmol/l. Hypertension was dened as a previous diagnosis by a physician, receiving medication to lower blood pressure, or known blood pressure values of P140 mm Hg systolic or P90 mm Hg diastolic on two or more occasions. Diabetes was dened

Results
Coronary risk factors and prior disease
Obesity (body mass index [BMI] greater than 30 kg/m2 ) was present in 31% of women <65 years, but only in 23%

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Table 1 Baseline risk factors and prior disease by sex and age in the Euro Heart Survey of Acute Coronary Syndromes Age group Number Age, mean (SD)a Risk factors Obese (BMI > 30 kg m2 ) Diabetes mellitus Hyperlipidaemia Hypertension Current smoker Prior diseases and medication Prior MI Chronic angina Prior revascularisation Prior CVA/TIA Prior heart failure ASA prior to admission b-Blocker prior to admission Statin prior to admission Diuretic prior to admission Women <65 1010 55.3 (7.2) 31 23 53 64 35 (281) (237) (531) (645) (349) Men Odds ratio (95% CI) 3709 53.2 (7.7) 23 18 52 48 52 (768) (656) (1931) (1786) (1913) 1.53 1.43 1.02 1.90 0.50 0.73 1.39 0.75 1.24 1.29 1.09 1.11 1.00 1.80 (1.301.80) (1.211.69) (0.891.17) (1.652.20) (0.430.57) (0.620.86) (1.191.62) (0.610.91) (0.891.72) (0.971.70) (0.951.26) (0.961.29) (0.841.18) (1.432.27) 2319 75.7 (6.6) 24 30 45 70 9 30 35 12 10 17 45 34 19 29 (443) (702) (1047) (1612) (209) (702) (816) (273) (235) (398) (1045) (790) (438) (673) 3215 73.6 (6.2) 16 24 42 59 19 37 34 20 10 15 48 35 20 21 (423) (757) (1347) (1882) (622) (1188) (1088) (634) (335) (486) (1555) (1128) (653) (686) 1.71 1.41 1.14 1.62 0.41 0.74 1.06 0.54 0.97 1.16 0.88 0.96 0.91 1.51 (1.471.99) (1.251.59) (1.031.27) (1.441.81) (0.350.49) (0.660.83) (0.951.19) (0.470.63) (0.811.16) (1.011.35) (0.790.98) (0.851.07) (0.801.05) (1.331.71) Women P65 Men Odds ratio (95% CI)

21 (214) 31(311) 14 (143) 5 (49) 7 (71) 38 (380) 33 (331) 21 (211) 12 (117)

27 (1000) 24 (899) 18 (672) 4 (147) 6 (206) 36 (1318) 31 (1132) 21 (778) 7 (252)

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All gures are percentages (number), unless stated otherwise. Missing data for body mass index in 1398 subjects (327 men, 103 women below 65 years, 497 men and 471 women 65 years and older). a P < 0:0001 for women compared to men, both age groups.

of men of the same age, and in 24% and 16%, respectively, in women and men P65 years (Table 1). Diabetes and hypertension were more common in women than men, irrespective of age. Over half (52%) of the younger men were current smokers, compared to 35% among the younger women but only 19% and 9%, respectively, among the older men and women. Relatively more men than women had a prior AMI, regardless of age. However, after stratication for age there were no major differences between men and women with respect to prior heart failure, prior cerebrovascular events, or prior medication with aspirin, b-blockers, or statins.

mined electrocardiogram was slightly less common in older women than in older men, with no sex difference in the younger age group. There was a strong association between age and Qwave AMI among men (p < 0:0001), but no relation in women (p 0:67; Fig. 2). The most common discharge diagnosis among the younger women with ACS was unstable angina (47%), followed by Q-wave AMI (27%) and non-Q-wave AMI (25%). Among younger men, Q-wave AMI was the most common diagnosis (40%), followed by unstable angina (37%) and non-Q-wave AMI (23%), with highly signicant interaction effects

Clinical presentation
The highest proportion of ST-elevation ACS was found among young men <55 years (Fig. 1). With age, the proportion of ST-elevation ACS decreased in men (p < 0:0001). Among women there was a much weaker association overall between ST-elevation ACS and age (p 0:06 with age as a continuous variable). Of men <65 years, over half (51%) presented with ST elevation, compared to 39% of women of the same age, yielding an OR (odds ratio) for women compared to men of 0.62 (95% condence interval 0.53 to 0.71) (Table 2). Among men and women P65 years, 36% and 38%, respectively, presented with ST elevation (OR 0.92 [0.831.03]). There was a highly signicant interaction between age and sex (p < 0:0001). Conversely, presentation with non-ST-elevation ACS was more common in younger women than in younger men, with a much less marked sex difference among older patients. Presentation with an undeter-

60%

Men Women

40%

20%

0%
< 55 55-64 65-74 > 75

Fig. 1 Acute coronary syndrome with ST elevation by age and sex in 10,253 patients in the Euro Heart Survey of patients with Acute Coronary Syndromes. P -value for association with age in women, 0.06, and in men, <0.0001.

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Table 2 Clinical presentation by age group in women and men in the Euro Heart Survey of Acute Coronary Syndromes Age group Women <65 Men Odds ratio (95% CI) Number Initial diagnosis, % (n) ACS with ST elevation ACS, no ST elevation Undetermined Discharge diagnosis, % (n) Q-wave myocardial infarction Non-Q-wave myocardial infarction Unstable angina Any infarction Symptoms, % (n) Typical angina Atypical chest pain Heart failure Normal ECG on arrival SBP on arrival, mm Hg, mean Heart rate, beats per minute, mean Killip class I II III IV 1010 39 (393) 57 (579) 4 (38) 28 (280) 25 (251) 47 (479) 53 (531) 87 (879) 7 (69) 1 (14) 21 (209) 142 (29) 80 (18) 3709 51 (1887) 46 (1706) 3 (116) 40 (1482) 23 (866) 37 (1361) 63 (2348) 90 (3346) 4 (156) 1 (40) 17 (622) 139 (26) 78 (19) 0.62 (0.530.71) 1.58 (1.371.82) 1.21 (0.831.76) 0.58 (0.500.67) 1.09 (0.921.28) 1.56 (1.351.79) 0.64 (0.560.74) 0.73 (0.590.90) 1.67 (1.252.24) 1.29 (0.702.38) 1.30 (1.091.54) P 0:0003 P 0:002 2319 36 (846) 55 (1282) 8 (191) 28 (646) 26 (612) 46 (1061) 54 (1258) 84 (1942) 5 (116) 4 (95) 15 (350) 148 (32) 82 (21) 3215 38 (1235) 52 (1661) 10 (319) 30 (955) 26 (839) 44 (1421) 56 (1794) 85 (2726) 5 (155) 4 (119) 15 (479) 143 (29) 80 (21) 0.92 (0.831.03) 1.16 (1.041.29) 0.82 (0.680.98) 0.91 (0.811.03) 1.02 (0.901.15) 1.07 (0.961.19) 0.94 (0.841.05) 0.92 (0.801.07) 1.04 (0.811.33) 1.11 (0.841.46) 1.02 (0.871.18) P < 0:0001 P 0:001 <0.0001 <0.0001 0.02 <0.0001 0.69 <0.0001 <0.0001 Women P65 Men Odds ratio (95% CI) P for agesex interaction

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0.91 0.97 0.38 0.19 0.20 0.57

86 11 3 1

(855) (106) (25) (11)

87 (3197) 10 (367) 2 (73) 1 (37)

P 0:27a

72 (1657) 20 (449) 6 (140) 2 (49)

75 (2387) 19 (607) 4 (143) 2 (58)

P 0:009a

0.012

All gures are percentages (number). Missing data for SBP in 70 subjects, for HR in 39 subjects, and for Killip class in 92 subjects. a P-values across the whole distribution.

between age and sex for Q-wave AMI and unstable angina (p < 0:0001 for both; Table 2). The presenting symptoms did not differ much by sex when stratied for age. In the younger age group, there was no difference with respect to Killip class on arrival, whereas older women presented with a higher Killip class than men of the same age (MantelHaenzsel test across the four Killip categories: p 0:009; agesex interaction: p 0:012). Among patients <65 years with ST-elevation ACS, 65% of the men and 62% of the women received some form of reperfusion therapy. In about one third of the cases primary percutaneous coronary interventions were performed and in two thirds, brinolytic therapy was given (Table 3). In older patients, 53% of the men but only 43% of the women received reperfusion therapy (OR 0.66 [0.550.78]; agesex interaction p < 0:0001). Among patients <65 years, coronary angiography was performed in 65% of the men and 57% of the women (Table 4), with corresponding gures of 49% and 38% in men and women P65 years, respectively. Overall, more than 90% had at least one signicant stenosis. Of the

60%

Men Women

40%

20%

0%
< 55 55-64 65-74 > 75
Fig. 2 Q-wave myocardial infarction by age and sex in 10,253 patients in the Euro Heart Survey of patients with Acute Coronary Syndromes. Pvalue for association with age in women, 0.67, and in men, <0.0001.

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Table 3 Reperfusion therapy by age group in women and men with ACS with ST elevation in the Euro Heart Survey of Acute Coronary Syndromes Age group Women <65 Men Odds ratio (95% CI) Number with ST elevation 393 1887 Fibrinolytic therapy, % 40 (159) 39 (741) Primary PCI, % 21 (84) 25 (478) Any primary reperfusion therapy, % 62 (244) 65 (1223) 1.05 (0.841.31) 0.80 (0.621.04) 0.89 (0.711.11) 846 1235 28 (234) 34 (422) 15 (124) 19 (230) 43 (366) 53 (658) Women P65 Men Odds ratio (95% CI) 0.74 (0.610.89) 0.75 (0.590.95) 0.66 (0.550.78)

Table 4 Angiographic ndings by age group in women and men in the Euro Heart Survey of Acute Coronary Syndromes Age group Women <65 Men Odds ratio 95% CI) Number, total 1010 Proportion angiography, % 57 Number with angiography 572 LAD, P 50% stenosis, % 64 (368) Left circumex, P 50% stenosis, % 41 (234) Right coronary artery, P 50% stenosis, % 55 (313) Three-vessel or main stem disease,a % 27 (152) No vessel with P 50% stenosis, % 13 (72)
a

Women P65

Men Odds ratio (95% CI)

3709 65 2403 70 (1688) 52 (1249) 60 (1433) 33 (793) 5 (130)

0.71 (0.620.82) 0.76 0.64 0.82 0.74 2.52 (0.630.93) (0.530.77) (0.680.98) (0.600.90) (1.863.41)

2319 38 873 75 (657) 56 (487) 65 (567) 42 (367) 7 (64)

3215 49 1589 80 (1270) 62 (983) 68 (1082) 48 (767) 4 (61)

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0.62 (0.550.69) 0.76 0.78 0.87 0.78 1.98 (0.630.93) (0.660.92) (0.731.03) (0.660.92) (1.382.84)

All gures are percentages (number). Three-vessel or main stem disease with P 50% stenosis.

younger women, 13% had an angiogram without any stenosis P50%, compared to 5% of the younger men (OR 2.52 [1.863.41]). Among the older women and men, 7% and 4%, respectively, had an angiogram without signicant stenoses. The proportion with 3-vessel disease or left main stem disease increased with age in both men and women, but was lower in women, irrespective of age (Fig. 3). The odds ratio for women compared to men of having 3-vessel disease or left main stem disease was 0.74 (0.600.90) in patients <65 years, and 0.78

60%

Men Women

40%

20%

(0.660.92) among patients P65 years, with no signicant interaction effect. In a logistic regression analysis, female sex was a signicant negative determinant of presenting with ST elevation after adjustment for differences in age, smoking, history of hypertension, diabetes, prior AMI, prior revascularisation, and chronic angina (OR 0.83 [0.750.91]). BMI was missing in 14% of the subjects and was included in a second step, with only a marginal effect on the OR (OR 0.85 [0.770.94]). The inclusion of signicant interaction terms between age and hypertension, or age and prior revascularisation, separately or jointly, did not change the odds ratio associated with female sex. After stratication for age, there was no signicant effect of sex in the older patient group after adjustment for differences in smoking, history of hypertension, diabetes, prior AMI, prior revascularisation, and chronic angina (OR 0.92 [0.821.04]). However, among the younger patients there was still a signicantly lower likelihood in women of presenting with ST elevation after adjusting for differences in other factors (OR 0.68 [0.580.79]).This was true even if the analysis was restricted to patients discharged with a diagnosis of AMI, with an OR of 0.81 (0.660.99) among patients <65 years.

0%
< 55 55-64 65-74 > 75
Fig. 3 Three-vessel or main stem disease by age and sex in 5437 patients in the Euro Heart Survey of patients with Acute Coronary Syndromes. P-value for association with age <0.0001 for both men and women.

Discussion
In one randomised clinical trial, women were found to present with ST elevation less often than men, but more

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often with unstable angina.8 This nding may reect different pathophysiologic processes, with ST elevation being secondary to occlusive thrombus and unstable angina reecting subtotal occlusion. This study in a large, comparatively unselected, sample of patients from Europe and the Mediterranean basin expands on these prior ndings, demonstrating that this difference seems to be conned to younger patients, with a signicant interaction between age and sex.

Differences in clinical presentation

The interpretation of the available data with respect to clinical characteristics in ACS is complicated because the study populations involved have varied substantially in inclusion criteria. Some studies have included patients with a broader range of ACSs8;11 but most have investigated only AMIs.1215 Of these, some only included rst AMIs15;16 and some only included AMIs in patients below 65 years of age17;18 or only in older patients.16 Several clinical studies investigated only patients eligible for certain treatments, i.e., thrombolysis,1921 which excludes a large proportion of women because, as the present study shows, many of them are not candidates for acute reperfusion therapy. It is obvious that the selection criteria used are critical to any analysis of sex differences. The present study included patients irrespective of eligibility for any specic treatment and included patients with unstable angina who form an important subset of patients with ACS. Outcome after hospitalisation for AMI has been demonstrated to be worse in women,2224 particularly at younger ages.25 In an analysis based on the same registry as in the present study, there was no difference in inhospital mortality after adjustment for age and comorbidity.6 An interaction between age and sex has been demonstrated with respect to outcome after AMI, with younger, but not older, women having higher in-hospital mortality.25 To a great extent, however, this is explained by differences in baseline clinical characteristics.26 However, the high in-hospital mortality in younger women is counterbalanced by a higher mortality outside the hospital among men.3;16;17;26;27 This could possibly reect more ST-elevation AMI among men, with a high early mortality. Infarct size has been demonstrated to be smaller in women than in men.12;22;24;28 A systematic investigation of the consequences of including milder cases revealed that the increase in event rates and the decrease in casefatality due to the inclusion of non-fatal, probable AMIs were larger for women than for men.29 In a validation study, a diagnosis of AMI was found not to be supported in a higher proportion of women (9%) than in men (5%).13 It is probable that the pattern of more unstable angina and less ST elevation in younger patients that we observed reects the same phenomenon. The incidence and presentation of cardiovascular disease differ between men and women, possibly because of the protective effect of oestrogen. The direct actions of oestrogen on blood vessels may contribute

substantially to this cardiovascular protective effect, but a lipid-lowering effect may also be involved.30 Rupture of an atherosclerotic plaque is the most common type of plaque complication, but in some cases the thrombus appears to be superimposed on a de-endothelialised, but otherwise intact, plaque (plaque erosion). This is more often seen in younger individuals and women.31 In an autopsy study of women who had died suddenly from coronary heart disease or who had died from non-coronary causes, women >50 years were much more likely to have a ruptured plaque than were younger, premenopausal women, suggesting that oestrogen affects plaque stabilisation. Plaque erosion, which is possibly the major substrate for thrombosis in premenopausal women, may not be inhibited by oestrogen.32 It is likely that the variations in clinical presentation that we observed reect, to some extent, a different and possibly less severe disease in younger women.

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Differences in investigations and treatment

Women with AMI have been found to be less aggressively treated,20 partly because of their older age at presentation.33;34 In the present study, there was no difference in acute reperfusion therapy between younger men and women, whereas older women were less likely to be treated than men of the same age. It is not clear to what extent the high mortality in older patients is amenable to improvement, but studies suggest that older, as well as younger, patients benet from thrombolysis35 and from treatment with b-blockers and aspirin. Only half of the patients in the study underwent coronary angiography, with a smaller proportion among the women. Overall, the proportion of patients with a normal angiogram among both women and men was very low. Even among women <65 years, only 13% had no signicant stenosis. About one third of the patients with no signicant stenosis were diagnosed with AMI, regardless of age or sex. In other studies the proportion with signicant stenoses has been lower.7;8;36 This probably reects a relatively more selective strategy with respect to coronary intervention in this study population, in contrast to North American populations. An absence of signicant stenoses may be found in a proportion of patients even with documented AMI, more commonly among women.7;8 In a series of 8 women with documented AMI and normal, or not signicantly stenosed, arteries that were investigated with intravascular ultrasound, atherosclerosis was found in all infarct-related arteries.37 Vulnerable plaques may be relatively non-stenotic and such lesions may undergo outward remodelling before impinging signicantly on the vascular lumen.38

Limitations
There was no strict validation of the diagnoses of AMI or unstable angina. Even though atherosclerosis is probably the main aetiological factor for ACS, even in cases without an angiographically obvious coronary stenosis, it is

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possible that a proportion of the younger women diagnosed with ACS may have had chest pain of non-cardiac origin. Reanalysing the data only including patients with diagnosed AMI still demonstrated that younger women were at lower risk of developing ST-elevation ACS, but with a slightly less decreased odds ratio. In routine clinical practice, there is no optimal way of validating unstable angina and excluding patients with unstable angina will result in underestimation of an important subset of the ACS population, particularly women. The proportion of patients with signicant coronary artery stenoses may be different in other regions of the world, based on local practices and the thresholds for referring patients to coronary angiography. Likewise, the use of invasive strategies may be different in other regions of the world.

Conclusions
The main nding of this large survey of ACS patients from 25 countries in Europe and the Mediterranean basin was the interaction between age and sex with respect to clinical presentation, with younger women presenting with less ST elevation and more unstable angina. Among those who underwent angiography, less extensive atherosclerosis was found in women compared to men, irrespective of age. These differences suggest variations in pathophysiology, with later onset of atherosclerosis in women but different pathophysiology with respect to ACS in younger, but not in older, women. These differences may be due to the inuence of sex hormones and should be further explored in order to provide better insights into the atherosclerotic process.

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Acknowledgements
The European Heart Survey of Acute Coronary Syndromes was sponsored by Schering-Plough and Centocor. The Swedish participation was supported by the Swedish Heart and Lung Foundation.

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