Symptoms in acute coronary syndromes: does sex make a difference?

Background

Coronary heart disease is a major problem in both men and women, but several studies have shown sex differences in symptoms of acute coronary syndromes (ACS). Some findings, however, have been disparate and inadequate, and thus a comprehensive overview of this literature would be of value.

Method

Fifteen studies that identified symptoms of ACS for both women and men were examined through a review of the literature from 1989 to 2002. Terms used for the search included “myocardial infarction,” “symptoms,” “gender differences,” and “acute coronary syndromes.”

Results

Although chest pain was the most common symptom in both men and women, several differences were also noted. In all types of ACS, women had significantly more back and jaw pain, nausea and/or vomiting, dyspnea, indigestion, and palpitations. In a number of studies, which solely sampled patients with acute myocardial infarction, women demonstrated more back, jaw, and neck pain and nausea and/or vomiting, dyspnea, palpitations, indigestion, dizziness, fatigue, loss of appetite, and syncope. Men reported more chest pain and diaphoresis in the myocardial infarction sample. The designs and methodologies of the studies varied considerably.

Conclusion

In addition to the typical symptom of chest pain in ACS, women experience other atypical symptoms more frequently than men. Thus, there may be sex differences in the symptoms of ACS, differences that have a bearing not only on clinical practice, but also on the interpretation of available clinical studies and the design of future investigations.     

Symptom presentation of women with acute coronary syndromes: myth vs reality

BACKGROUND: Optimal diagnosis and timely treatment of patients with an acute coronary syndrome (ACS) depends on distinguishing differences between popular "myths" about ischemic symptoms in women and men. Chest pain or discomfort is regarded as the hallmark symptom of ACS, and its absence is regarded as "atypical" presentation. This review describes the presenting symptoms of ACS in women compared with men and ascertains whether women should have a symptom message that is separate or different from that for men. METHODS: MEDLINE (1970-2005), bibliographies of articles, and pertinent abstracts were reviewed, focusing on studies of ACS presentation, especially those reporting differences in symptoms by sex. This analysis included 69 of 361 possible studies. Data regarding symptom presentation were recorded. RESULTS: The published literature lacks standardization in characterizing ACS presentation, data collection, and reporting of symptoms. Approximately one-third of patients in the large cohort studies and one-quarter of patients in the smaller reports and direct patient interviews presented without chest pain or discomfort. The absence of chest pain or discomfort with ACS was noted more commonly in women than in men in both the cumulative summary from large cohort studies (37% vs 27%) and the single-center and small reports or interviews (30% vs 17%). CONCLUSIONS: Women are significantly less likely to report chest pain or discomfort compared with men. These differences, however, are not likely large enough to warrant sex-specific public health messages regarding the symptoms of ACS at the present time. Further research must systematically investigate sex differences in the clinical presentation of ACS symptoms and must include standardized data collection efforts.     

Typical symptoms are predictive of acute coronary syndromes in women

Background Previous research suggests that the presentation of acute coronary syndromes (ACS) may differ in women and men. No study has prospectively evaluated the role of a comprehensive set of typical and atypical symptoms and whether different symptoms on presentation predict ACS diagnosis in women and men. Methods and Results We directly observed 246 women and 276 men seen in the emergency department with symptoms suggestive of ACS and documented their symptoms verbatim. ACS was eventually diagnosed in 89 (36%) women and 124 (45%) men on the basis of standard electrocardiogram and cardiac enzyme criteria. Presence of typical symptoms (chest pain or discomfort, dyspnea, diaphoresis, and arm or shoulder pain) was significantly associated with a diagnosis of ACS in women but not in men. On the other hand, atypical symptoms were not related to ACS diagnosis in women, whereas in men some atypical symptoms (dizziness or faintness) were inversely associated with ACS (P = .007). In multivariate analysis, the only symptoms that showed significant or borderline associations with ACS in women were diaphoresis (P = .019) and chest pain or discomfort (P = .069). Chest pain or discomfort and other typical symptoms were not significantly associated with ACS in men. Adjusted relative risks for ACS associated with the presence of typical symptoms in women compared with men were close to 1.0, indicating no sex differences. Conclusions Typical symptoms are the strongest symptom predictors of ACS in women, and they are as important in women as in men. Clinicians need to take very seriously any woman who has typical symptoms and pursue a full cardiac work-up. (Am Heart J 2002;143:283-8.)     

症状对不同性别急性冠状动脉综合征的预测价值

目的 :前瞻性研究症状对不同性别急性冠状动脉综合征 (ACS)的诊断是否有预测价值。方法 :2 0 0 0年 1月 1日～ 2 0 0 3年 3月 31日 ,我们对连续拟诊ACS行急诊冠状动脉介入的 74 0例患者进行了观察 ,男 5 2 8例 ,女 2 12例 ,对比分析男女患者的预测症状。结果 :根据心电图、心脏标志物和冠状动脉造影 ,最后诊断为ACS女性 184例 ( 86 .8% ) ,男性 4 80例 ( 90 .9% )。女性有典型症状 (胸痛或不适、呼吸困难、出汗、臂或肩痛 )者诊断为ACS明显多 ,男性则不 ;相反 ,女性有不典型症状者诊断ACS不多 ,而在男性 ,一些不典型症状 (头晕或头昏 )与ACS的诊断呈反相关系 (P <0 .0 5 )。多因素分析表明 ,出汗 (P <0 .0 5 )和胸痛 (P >0 .0 5 )与女性ACS的诊断呈显著或边缘相关 ;而胸痛等典型症状与男性ACS无明显相关 ( P >0 .0 5 )。与男性相比 ,有典型症状的女性诊断ACS的调整相对危险性接近 1.0 ,提示无性别差异。结论 :典型症状是诊断女性ACS的最强症状预测因素 ,与男性一样重要     

Sex differences in prodromal symptoms of patients with acute coronary syndrome: a pilot study

Increasing evidence suggests that there are sex/gender differences in the presentation and prodromal symptoms of acute coronary syndrome (ACS). The purpose of this pilot study was to identify sex differences in the prodromal symptoms of ACS using the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey (MAPMISS). Telephone surveys using the MAPMISS were conducted between 4 and 6 months after the ACS event. Seventy-six patients (24 women) participated in the study. The women generally reported higher prodromal scores. Moreover, scores demonstrated differences in prodromal symptoms based on menopausal status. The premenopausal and perimenopausal women reported a greater number and higher frequency of symptoms compared with the men and menopausal women. The results of this study suggest that both men and women report nontraditional prodromal symptoms of ACS. In addition, there appears to be a difference in the frequency and number of symptoms reported based on menopausal status.     

Symptoms of men and women presenting with acute coronary syndromes

This study evaluated symptom similarities and differences between men and women presenting with acute coronary syndromes (ACSs) and determined whether differences in presentation are intrinsic to patient gender or to other factors. This study was a subgroup analysis of patients from an ACS registry. We compared differences in symptom presentation between men and women and analyzed them using binary logistic regression with all variables and 2 x 2 interactions. Patient gender was forced to remain in the models. Women comprised 35% of the 1,941 patients admitted with confirmed ACS. Men were more likely to present with chest pain, left arm pain, or diaphoresis. Nausea was more common in women. Dyspnea did not differ between groups. After binary logistic regression, gender remained a statistically significant predictor of diaphoresis and nausea, but not of chest or left arm pain. We found that differences in occurrence of chest pain and left arm pain between men and women are explainable by differences in co-morbidities and history; the higher occurrence of diaphoresis in men and of nausea in women is partly related to maleness or femaleness. In conclusion, gender should be considered when evaluating patients with symptoms of ACS.     

Sex, age, and clinical presentation of acute coronary syndromes.

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 10253 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 [0.53-0.71]) and developed Q-wave myocardial infarction (OR 0.58 [0.50-0.67]), whereas in patients > or =65 years there was no significant 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 [1.35-1.79]), 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 stratified for age, female sex was a significant negative determinant of presenting with ST elevation in patients <65 years (OR 0.68 [0.58-0.79]), whereas there was no effect of sex in patients > or =65 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 findings suggest a different pathophysiology of ACS in younger, but not older, women.     

Spectrum of acute coronary syndromes: history and clinical presentation in relation to sex and age

OBJECTIVES: To study sex-based differences in the clinical presentation in relation to age and type of acute coronary syndrome (ACS) in patients under 80 years of age. METHODS: The study includes 1,744 consecutive patients with the full spectrum of ACS (ST elevation myocardial infarction (MI), non-ST elevation MI, and unstable angina of high- and low-risk types) admitted to the coronary care unit in a university hospital. RESULTS: The women were older than the men and were as likely to present with ST elevation MI. They had lower rates of prior MI and prior coronary artery bypass surgery than men but similar rates of percutaneous coronary interventions. Further, women were less likely to have a short delay before admission to hospital and they were attended to less rapidly in the emergency department. The prevalence of risk factors, prior cardiovascular disease and ongoing treatment with cardiovascular drugs were strongly associated with less severe type of ACS with no significant sex interaction. Presentation with non-ST elevation MI was significantly associated with older age while the opposite was true for unstable low-risk angina. ECG signs of acute ischemia were not associated with age. Significant interactions between age and sex were observed for the prevalence of treatment with diuretics as well as hypotension at presentation, both more prevalent among women than men below 65 years of age. CONCLUSIONS: Women are struck by ACS at a higher age than men, are less likely to present early for hospital care, and at younger age women are more likely to present with hypotension. There is a striking difference in risk factors and previous history depending on type of ACS in both sexes.     

Sex Differences in the Clinical Presentation of Acute Coronary Syndromes

The clinical presentation of acute coronary syndromes (ACS) as ST-elevation ACS (STEACS) or non-ST-elevation ACS (NSTEACS) differs between women and men. The aim of this study was to describe the difference in the clinical presentation of ACS between sexes. A total of 10,019 patients included in the Epi-Cardio Registry were analyzed. A higher proportion of women than men presented with NSTEACS (60.3% vs 46.7%; P <0.001). The difference between sexes was driven by a higher prevalence of ACS with non-obstructive coronary arteries (20.9% vs 6.6%) mainly in young women, since ACS without coronary lesions were mostly NSTEACS (77.7% vs 22.3%). In patients with obstructive coronary heart disease, there were no differences in the clinical presentation between sexes. In conclusion, younger women are more likely than men to present ACS with non-obstructive coronary arteries, whereas no significant difference exists between sexes regarding the prevalence of ACS with obstructive coronary artery disease.     

Female sex as a biological variable: A review on younger patients with acute coronary syndrome

Although acute coronary syndrome (ACS) mainly occurs in individuals >60 years, younger adults can be affected as well. Women continue to be at higher risk of 30-day mortality after ST-segment elevation myocardial infarction (STEMI) even in the current era of percutaneous coronary intervention (PCI). Importantly, the excess mortality among women is only significant at younger ages. Previous work has suggested that the reason for the differences in outcome is likely multifactorial and may partially be explained by some of the following factors: atypical presentation, delayed presentation, under-recognition of STEMI at initial medical contact, and underuse of medications because of concern regarding increased risk of bleeding. While these hypotheses may be true in some occasions, recent studies pointed out that the proportion of women presenting within 2 h after symptom onset was greater in the younger than in older cohorts. In addition, sex differences in administration of adjunctive medical therapies were greater in the older than in the younger cohort. Thus, there is not any one of the abovementioned factors able to explain the increase in mortality in the young women. Disparities alone could not account for the gap in mortality across sexes. Unless the effects of sex are studied, we will continue to have gaps in the knowledge of potential different mechanisms leading young women and men to die after ACS, which may result in missed opportunities for implementing a better health in our community. Randomizing or balancing the sexes as well as powering studies to detect sex differences is warranted in future research.     

Sex Differences in Acute Coronary Syndrome in a Multiethnic Asian Population: Results of the Malaysian National Cardiovascular Disease Database—Acute Coronary Syndrome (NCVD-ACS) Registry

BackgroundSex differences in acute coronary syndrome (ACS) have been well studied in major registries and clinical trials in Western populations. Limited studies have examined the sex differences in ACS using a large number of Asian women as the subjects.ObjectivesThe aim was to study the sex differences in ACS using the NCVD-ACS (National Cardiovascular Disease Database—Acute Coronary Syndrome) registry.MethodsWe analyzed 13,591 ACS patients, of which 75.8% were men and 24.2% were women, from March 2006 to February 2010. Data were collected on demographic characteristics, risk factors, anthropometrics, treatments, procedures, mortalities, and complications. The results were compared among 3 cohorts of ACS (ST-segment elevation myocardial infarction [STEMI], non–STEMI, and unstable angina).ResultsWomen were older and more likely to have diabetes, hypertension, previous heart failure, and cerebral vascular accidents than men were. Women were less likely to receive in-hospital administration of aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers, and they were less likely to undergo angiography and percutaneous coronary intervention. In STEMI, a significantly lower proportion of women than men received primary percutaneous coronary intervention (6.2% vs. 6.7%, respectively, p = 0.000) and fibrinolysis (64.4% vs. 74.6%, respectively, p = 0.000). In addition, with regard to STEMI, women had a significantly higher unadjusted in-hospital mortality rate than men did (15.0% vs. 8.1%, respectively, p < 0.000). There was no statistically significant in-hospital mortality difference between sexes for non-STEMI and unstable angina. After adjustment for age and other covariates, a multivariate analysis showed no sex differences in the in-hospital mortality in all spectrums of ACS.ConclusionsOur study showed significant sex differences in the demographic characteristics, risk factors, treatments, and outcomes of ACS. More importantly, in ACS patients, we found evidence of suboptimal treatments and interventions in women versus men. Our findings provide an opportunity to narrow the sex gap in the care of women with ACS in Malaysia.     

Basis for Sex-Dependent Outcomes in Acute Coronary Syndrome

This review aims to provide new insights into the basis for sex differences in acute coronary syndrome (ACS). Sex differences in mortality after ACS depend on age and the type of ACS, with the greatest gap being observed among younger adults and patients with ST-segment elevation myocardial infarction (STEMI). The sex gap diminishes with increasing age and does not appear to exist to the same extent among patients with non–STEMI or unstable angina. Although it is clear that younger women with acute myocardial infarction have higher mortality than do men in the short term; whether this difference is present in the long term remains unclear. Furthermore, women with ACS face delays in diagnosis and treatment, undergo less invasive management, have more bleeding complications, and receive less evidence-based medical therapy than do their male counterparts. Finally, women with ACS consistently report lower health-related quality of life than do men. To date, our understanding of the sex differences in ACS remains limited. The impact of biological factors and nonbiological factors (especially gender roles) need to be explored to elucidate the disparities in health outcomes between men and women.     

Differences in the management and prognosis of women and men who suffer from acute coronary syndromes.

OBJECTIVES: The purpose of this research was to determine if sex and gender differences in the management of acute coronary syndromes (ACS) are associated with differences in prognosis after ACS. BACKGROUND: Previous investigators have reported sex/gender differences in the management of patients with ACS, but the impact of these differences on prognosis is unclear. METHODS: We analyzed data from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, which enrolled 4,836 women and 7,726 men with ACS. Patients were classified into risk strata using the Thrombolysis In Myocardial Infarction (TIMI) score. RESULTS: Women underwent fewer invasive procedures including angiography, angioplasty, and coronary artery bypass graft (CABG) surgery (47.6% vs. 60.5%; p = 0.0001) compared to men. No significant differences in cardiovascular death, myocardial infarction (MI), or stroke were observed (9.8% vs. 10.9%; p = 0.04), although women were more likely than men to develop refractory ischemia and to be rehospitalized for chest pain during follow-up (16.6% vs. 13.9%; p = 0.0001). These differences were particularly evident among TIMI high-risk women. A significant interaction between TIMI risk and gender for the outcome of refractory angina and rehospitalization for angina was present. CONCLUSIONS: Compared to men, high-risk women with ACS undergo less coronary angiography, angioplasty, and CABG surgery, and while they do not have higher incidence cardiovascular death, recurrent MI, or stroke, they suffer an increased rate of refractory ischemia and rehospitalization. All high-risk women and men with ACS should receive optimal medical management, and be considered for coronary angiography with possible revascularization if their coronary anatomy warrants it.     

In-vivo comparison of coronary plaque characteristics using optical coherence tomography in women vs. men with acute coronary syndrome

OBJECTIVE: Women with acute coronary syndromes (ACS) have worse outcomes than men. Data on sex differences of culprit plaque characteristics are lacking. Intravascular optical coherence tomography (OCT) is a high-resolution imaging technique capable of in-vivo plaque characterization. The aim of this study was to compare culprit plaque characteristics in women and men presenting with ACS. METHODS: Patients undergoing coronary angiography after ACS were enrolled. We performed OCT imaging on the culprit lesions. Previously validated criteria for OCT plaque characterization were used: lipid was quantified on cross-sectional image and lipid-rich plaque was defined as > or = 2 involved quadrants; fibrous cap thickness was measured at the thinnest point and thin-cap fibroatheroma was defined as lipid-rich plaque with fibrous cap thickness less than 65 microm. RESULTS: Forty-two patients (33 men and nine women) were included. No significant sex differences were found in baseline characteristics. Lipid-rich plaques were identified in majority of patients. No significant difference, however, was seen in the frequency of lipid-rich plaques, thin-cap fibroatheroma or minimum fibrous cap thickness (79 vs. 89%; 45 vs. 67%; 53.8 vs. 45.4 microm, respectively; P=NS) between men and women. Incidence of calcification, thrombus and plaque disruption were also similar. CONCLUSIONS: No significant sex difference was seen in culprit plaque characteristics determined by OCT imaging in patients who presented with ACS.     

Sex differences in nonobstructive coronary artery disease: Recent insights and substantial knowledge gaps

The existence of sex differences in the epidemiology, presentation, diagnosis, and management of coronary artery disease (CAD) has been a subject of growing inquiry for the past several decades. The prevailing paradigm is that the prevalence of anatomically obstructive disease of the epicardial coronary arteries is less common in women than similarly aged men, while nonobstructive and microvascular ischemic disease is more prevalent in women. Although both “patterns” of coronary atherosclerosis are associated with angina and cardiovascular events, the dominant diagnostic and therapeutic tools used in cardiology have focused on the male-predominant pattern of anatomically obstructive epicardial CAD. This has raised justified concerns about the under-diagnosis and under-treatment of symptomatic women with nonobstructive CAD. However, as recent research has begun to highlight the importance of nonobstructive CAD and coronary physiology in men as well as women, adjustments to this paradigm and greater attention to nonobstructive CAD are necessary. The present article seeks to review key insights as well as substantial knowledge gaps regarding sex differences and nonobstructive CAD.     

Age and sex differences in presentation of symptoms among patients with acute coronary disease: the REACT Trial. Rapid Early Action for Coronary Treatment

BACKGROUND: There are few data on possible age and sex differences in presentation of symptoms for patients with acute coronary disease. OBJECTIVE: To investigate demographic differences in presentation of symptoms at the time of hospital presentation for acute myocardial infarction (AMI) and unstable angina. METHODS: The medical records of patients who presented with chest pain and who also had diagnoses of AMI (n = 889) or unstable angina (n = 893) on discharge from 43 hospitals were reviewed as part of data collection activities of the Rapid Early Action for Coronary Treatment trial based in 10 pair-matched communities throughout the USA. RESULTS: Dyspnea (49%), arm pain (46%), sweating (35%), and nausea (33%) were commonly reported by men and women of all ages in addition to the presenting complaint of chest pain. After we had controlled for various characteristics through regression modeling, older persons with AMI were significantly less likely than were younger persons to complain of arm pain and sweating, and men were significantly less likely to report vomiting than were women. Among persons with unstable angina, arm pain and sweating were reported significantly less often by elderly patients. Nausea and back, neck, and jaw pain were more common complaints of women. CONCLUSIONS: Results of this study suggest that there are differences between symptoms at presentation of men and women, and those in various age groups, hospitalized with acute coronary disease. Clinicians should be aware of these differences when diagnosing and managing patients suspected to have coronary heart disease.     

Acute Coronary Syndromes: Differences in Men and Women

Purpose of Review

Increased awareness of cardiovascular disease in women has prompted studies to investigate gender-related disparities in acute coronary syndromes (ACSs). In this review, we discuss findings from current literature on the clinical presentation, pathophysiology, diagnosis, and management of ACS in women as compared to men.

Recent Findings

Emerging data show that cardiovascular disease (CVD) continues to be the leading cause of death in women and the annual mortality rate from CVD remains higher in women compared to men. Recent studies demonstrate sex-specific differences in patients presenting with ACS. Comorbidities, especially diabetes, are more common in young women compared with age-matched men who develop acute myocardial infarction (AMI). Women are more likely to have atypical symptoms and nonobstructive coronary disease on angiography. Women are less likely to receive guideline-based therapies. They have higher rates of peri-procedural complications with PCI and are less likely to be referred to cardiac rehabilitation.

Summary

Awareness of differences in the underlying pathophysiology of coronary disease in women compared to men may lead to improved gender-based diagnostic and treatment modalities. However, until more studies are performed, efforts should be directed toward improving delivery of current, gender-neutral guidelines in women just as in men.

     

女性急性冠状动脉综合征患者危险因素及住院期间不良事件的分析

目的:探讨女性急性冠状动脉综合征(ACS)患者的危险因素及住院期间不良事件的分析。方法:分析急性冠状动脉事件全球注册(GRACE)研究中登记的明确诊断为ACS的住院313例女性患者的病例资料,与857例男性患者的危险因素及预后进行比较。结果:1.女性ACS患者合并糖尿病、高血压的比例大,2组比较差异有统计学意义(P<0.05)。2.女性患者并发症多,预后较男性差,2组比较差异有统计学意义(P<0.05)。3.应用Logistic回归分析影响女性ACS患者住院期间不良预后的危险因素为发病年龄、糖尿病及高血压,而男性住院期间不良预后的危险因素为发病年龄及体质量指数。结论:女性ACS患者较男性ACS患者危险因素多,预后差。     

Diabetes mellitus: clinical presentation and outcome in men and women with acute coronary syndromes. Data from the Euro Heart Survey ACS.

AIMS: To study clinical presentation, in-hospital course and short-term prognosis in men and women with diabetes mellitus and acute coronary syndromes (ACS). METHODS: Men (n = 6488, 21.2% with diabetes) and 2809 women (28.7% with diabetes) < or = 80 years old, with a discharge diagnosis of ACS were prospectively enrolled in the Euro Heart Survey of ACS. RESULTS: Women with diabetes were more likely to present with ST elevation than non-diabetic women, a difference that became more marked after adjustment for differences in smoking, hypertension, obesity, medication and prior disease [adjusted odds ratio (OR) 1.46 (1.20, 1.78)], whereas there was little difference between diabetic and non-diabetic men [adjusted OR 0.99 (0.86, 1.14)]. In addition, women with diabetes were more likely to develop Q-wave myocardial infarction (MI) than non-diabetic women [adjusted OR 1.61 (1.30, 1.99)], while there was no difference between men with and without diabetes [adjusted OR 0.99 (0.85, 1.15)]. There were significant interactions between sex, diabetes and presenting with ST-elevation ACS (P < 0.001), and Q-wave MI (P < 0.001), respectively. Of the women with diabetes, 7.4% died in hospital, compared with 3.6% of non-diabetic women [adjusted OR 2.13 (1.39, 3.26)], whereas corresponding mortality rates in men with and without diabetes were 4.1% and 3.3%, respectively [OR 1.13 (0.76, 1.67)] (P for diabetes-sex interaction 0.021). CONCLUSION: In women with ACS, diabetes is associated with higher risk of presenting with ST-elevation ACS, developing Q-wave MI, and of in-hospital mortality, whereas in men with ACS diabetes is not significantly associated with increased risk of either. These findings suggest a differential effect of diabetes on the pathophysiology of ACS based on the patient's sex.