Abstract
Background
Coronary artery disease (CAD) is the leading cause of mortality worldwide. The present study evaluated the impact of gender in patients hospitalized with acute coronary syndromes (ACS) over a 20-year period in Qatar.
Methods
Data were collected retrospectively from the registry of the department of cardiology for all patients admitted with ACS during the study period (1991–2010) and were analyzed according to gender.
Results
Among 16,736 patients who were admitted with ACS, 14262 (85%) were men and 2474 (15%) were women. Cardiovascular risk factors were more prevalent among women in comparison to men. On admission, women presented mainly with non-ST-elevation ACS and were more likely to be undertreated with β-blockers (BB), antiplatelet agents and reperfusion therapy in comparison to men. However, from 1999 through 2010, the use of aspirin, angiotensin-converting enzyme inhibitors and BB increased from 66% to 79%, 27% to 41% and 17% to 49%, respectively in women. In the same period, relative risk reduction for mortality was 64% in women and 51% in men. Across the 20-year period, the mortality rate decreased from 27% to 7% among the Middle Eastern Arab women. Multivariate logistic regression analysis showed that female gender was independent predictor of in-hospital mortality (odd ratio 1.51, 95% CI 1.27–1.79).
Conclusions
Women presenting with ACS are high-risk population and their in-hospital mortality remains higher for all age groups in comparison to men. Although, substantial improvement in the hospital outcome has been observed, guidelines adherence and improvement in the hospital care have not yet been optimized.
Introduction
Traditional cardiovascular risk factors are overall similar for women and men across various regions of the world [1]. With advances in diagnosis and management of acute coronary syndrome (ACS), the cardiovascular mortality in men has been reduced over the past decade. However, the mortality rate among women has continued to increase every year since 1984 [2]. Previous data showed that women with ACS were less likely to undergo diagnostic and therapeutic procedures compared to men [3], [4]. Poon et al, reported an overall temporal increase in the use of invasive cardiac procedures, however, women with ACS were more likely to be treated conservatively when compared with men [5]. Underestimation of risk among women presenting with ACS by the treating physician may be an important reason. Indeed, gender-related discrepancy in treatment strategies has been observed in several trials and registries [6]–[8].
Several hypotheses have been postulated regarding the gender-related disparities for ACS treatment. These include higher prevalence of atypical presentations and vasospastic disease in women, which could make their diagnosis and subsequent management less feasible [6], [9]. Overall, women have less obstructive coronary artery disease (CAD) than men regardless of the ACS type and age [10]–[12]. Furthermore, physicians may not recommend coronary interventions in women because of the presumed increased risks when compared to men and the doubtful potential benefits if coronary obstructive lesions are not confirmed [13]–[15]. Recently, the European Society of Cardiology guidelines recommended early coronary intervention within the first 24 hrs for high-risk patients presented with non-ST-segment elevation ACS regardless of gender [16].
Generally, data from different countries have reported worse outcomes in women presenting with ACS compared to men [8], [17]–[18]. In the current study, we evaluate the impact of gender on the trends, clinical presentation, management and in-hospital mortality in a large sample of patients hospitalized with ACS across a 20-year period.
Methods
The Cardiology and Cardiovascular Surgery Database at Hamad Medical Corporation (HMC) in Qatar was used for this study. This hospital provides in-patient and out-patient tertiary care for the residents of Qatar regardless of ethnicity. More than 95% of cardiac patients in Qatar are treated at HMC which makes it an ideal center for population-based studies. A case report form with a specific registration number for each cardiac patient admitted to the cardiology department was filled by the assigned physician. Case reports were filled using standard definitions and completed before the patient’s hospital discharge. Data were collected according to predefined criteria for each variable. These records have been coded and registered electronically. Ten percent randomly selected records from the data were checked by an independent physician for its accuracy before feeding and data analysis. With the described database, all patients admitted with ACS in the 20-year period between January 1991 and end of 2010 were retrospectively reviewed. Data registered into a computer by a data entry operator were randomly cross checked by the physician at the cardiology department. Transferred patients or patients with missing data were excluded from the study. Ethical approval was obtained from the research committee at HMC before data collection and analysis. The ethics committee waived the need of informed consent for the study because of its retrospective nature and data were analyzed anonymously.
Definition
Diagnosis of different types of ACS and definitions of data variables were based on the American College of Cardiology (ACC) clinical data standards [19]. Use of adjunct therapy during hospitalization was recorded for every patient. Cardiovascular risk factors were defined previously [20]–[21]. The presence of diabetes mellitus (DM) was determined by the previous or current medical record of the patient reporting the diagnosis of DM that had been treated with oral medications or insulin. The presence of dyslipidemia was determined by the demonstration of a fasting cholesterol >5.2 mmol/L in the patient’s medical record, or any history of treatment for dyslipidemia. The presence of hypertension (HTN) was determined by documentation of HTN in the medical record or if the patient was on regular antihypertensive medications. Smoking history: patients were divided into current cigarette smokers, past smokers (defined as ≥6 months abstinence from smoking) and those who never smoked.
Statistical Analysis
Data were presented as proportions, mean ± standard deviation (SD) or median (range) as appropriate. Baseline demographics, past medical history, clinical presentation, medical therapy, cardiac procedures and clinical outcomes were compared between men and women. Data were also analyzed according to gender in different age groups (<50, 51–70 and >70 years) and across every 4-year period from (1991–1994) to (2007–2010). Statistical analyses were conducted using Student-t test and One Way ANOVA, wherever applicable, for continuous variables and Pearson chi-square (χ2) test for categorical variables. Variables influencing in-hospital mortality were also analyzed using multiple logistic regressions analysis. Adjusted Odds Ratios (OR), 95% confidence interval (CI), and p values were reported for significant predictors. All p values were the results of 2-tailed tests and values <0.05 were considered significant. Statistical Package for Social Sciences (SPSS) version 19.0 has been used for the analysis.
Results
Between 1991 to the end of 2010, a total of 16,736 patients were admitted with ACS; of them 14,262 (85%) were men and 2,474 (15%) were women. Overall, 7,200 (43%) patients presented with ST-elevation MI (STEMI), 5572 (33%) patients with Non-ST elevation MI (NSTEMI) and 3964 (24%) patients with unstable angina (UA). Over the 20-year period, there was an increase in the total number of Arab patients hospitalized with ACS regardless of gender (Figure 1A).
Figure 1. Acute coronary syndrome among Middle Eastern Arab (Men and Women): A: Trend for hospitalization. B: Trend for mortality.
Table 1 shows the clinical presentation and baseline characteristics of patients stratified by gender. Women were more likely to have HTN, DM, renal failure, dyslipidemia, prior MI and CABG. Whereas, the incidence of current smoking and prior PCI were higher in men (P = 0.001 for each). Women were more likely to present with atypical symptoms including higher frequency of dyspnea compared to men (33% vs. 19%, P = 0.001). Men had significantly higher level of mean serum triglyceride and low-density lipoprotein (P = 0.001 for each), and lower levels of high-density lipoprotein (P = 0.001) in comparison to women.
Table 1. Patients’ characteristics, co-morbidities and outcomes according to gender.
| Women | Men | P-value | |
| Number of patients | 2474 (14.8) | 14262 (85.2) | |
| Age (mean±SD) | 62±12 | 53±11 | 0.001 |
| Race | |||
| Middle-Eastern Arabs | 1892 (76.5) | 5216 (36.6) | 0.001 |
| South Asians | 321 (13) | 7164 (50.2) | |
| Others | 261 (10.5) | 1882 (13.2) | |
| Cardiovascular risk factors | |||
| Hypertension | 1684 (68.1) | 5210 (36.5) | 0.001 |
| Diabetes mellitus | 1626 (65.7) | 5333 (37.4) | 0.001 |
| Current smoker | 89 (3.6) | 5497 (38.5) | 0.001 |
| Chronic renal impairment | 164 (6.6) | 397 (2.8) | 0.001 |
| Dyslipidemia | 672 (27.2) | 2882 (20.2) | 0.001 |
| Family history of CAD | 146 (1.5) | 645 (2.0) | 0.001 |
| Prior myocardial infarction | 484 (19.6) | 2306 (16.2) | 0.001 |
| Prior coronary artery bypass grafting | 123 (5) | 570 (4) | 0.03 |
| Prior PCI | 190 (7.7) | 1546 (10.8) | 0.001 |
| Total cholesterol (mmol/L) (mean±SD) | 4.9±1.4 | 4.9±1.3 | 0.23 |
| Serum triglyceride (mmol/L) (mean±SD) | 1.8±1.14 | 1.9±1.18 | 0.001 |
| Low density lipoprotein (mmol/L) (mean±SD) | 2.6±1.04 | 2.8±1.09 | 0.001 |
| High density lipoprotein (mmol/L) (mean±SD) | 1.17±0.38 | 0.98±0.31 | 0.001 |
| Troponin T (ng/ml) | 1336 (13.7) | 7414 (23.4) | 0.001 |
| CK-MB (u/L) (mean±SD) | 75±430 | 148±623 | 0.001 |
| Atypical chest pain | 542 (5.6) | 1760 (5.6) | 1.00 |
| Ischemic chest pain | 1248 (12.8) | 4950 (15.6) | 0.001 |
| Shortness of breath | 3210 (32.9) | 6149 (19.4) | 0.001 |
| Left ventricular ejection fraction | 45.8 | 42.9 | 0.001 |
| Type of ACS | |||
| ST-elevation MI | 604 (24.4) | 6596 (46.2) | 0.001 |
| No-ST-elevation MI | 993 (40) | 4579 (32) | |
| Unstable angina | 877 (35) | 3087 (22) | |
| Stroke | 20 (0.8) | 37 (0.3) | 0.001 |
| Death | 262 (10.6) | 701(4.9) | 0.001 |
| Year of Admission | |||
| 1991–94 | 202 (8.2) | 1573 (11) | 0.001 |
| 1995–98 | 211 (8.5) | 1625 (11.4) | |
| 1999–02 | 384 (15.5) | 2028 (14.2) | |
| 2003–06 | 753 (30.4) | 3899 (27.3) | |
| 2007–10 | 924 (37.3) | 5137 (36) |
CAD: coronary artery disease, PCI: percutaneous coronary intervention, ACS: acute coronary syndrome; All values in parenthesis are percentages.
Gender and Trends of the Cardiovascular Risk Factors
Figure 2A shows an increased rate of hypertension while the rate of dyslipidemia decreased among women over the 20-year study period (p = 0.001). Also, an increasing trend in the rate of DM has been observed but was not statistically significant (p = 0.17). Among men, there was an increase in the frequency of DM and hypertension and a decrease in the rate of dyslipidemia (p = 0.001 for all) (Figure 2B).
Figure 2. Trend of cardiovascular risk factors in women (A) and men (B) across 20 years.
Age and Gender
The mean age of patients was 54±11.9 years; 41% of patients were ≤50 years old, 49% were between 51 and 70 years and 10% were above 70 years of age. Seventeen percent of women presenting with ACS were ≤50 years old, 61% were between 51–70 years and 22% were above age of 70. Eight percent of men were older than 70 years, whereas 92% were almost equally distributed in age groups ≤50 and 51–70 years.
Age, Gender and Type of ACS
Overall, more men presented with STEMI when compared to women (46% vs. 24%). In comparison to men, women were frequently presented with NSTEMI (40% vs. 32%; P = 0.001) and UA (35% vs. 22%; P = 0.001) (Table 2). The majority of women under age of 50 presented mainly with unstable angina, while the majority of women older than 70 years of age presented with STEMI. Between the age of 51 and 70, both unstable angina and NSTEMI equally dominated.
Table 2. Type of coronary syndrome and mortality in women and men at different age group.
| Variables | Overall | Age ≤50 yrs | Age 51–70 yrs | Age >70 yrs | |||||||
| Women | Men | Women | Men | P value | Women | Men | P value | Women | Men | P value | |
| N (%) | 2474(15) | 14262(85) | 410 (5.9) | 6528 (94.1) | 1510 (18.5) | 6642 (81.5) | 553 (33.7) | 1087 (66.3) | |||
| STMI | 604 (24) | 6596 (46) | 117 (28.5) | 3576 (34.8) | 0.001 | 368 (24.4) | 2729 (41.1) | 0.001 | 119 (21.5) | 288 (26.5) | 0.001 |
| NSTMI | 993 (41) | 4579 (32) | 121 (29.5) | 1747 (26.8) | 593 (39.3) | 2322 (35) | 278 (50.3) | 509 (46.8) | |||
| UA | 877 (35) | 3087 (22) | 172 (42) | 1205 (18.5) | 549 (36.4) | 1591 (24) | 156 (28.2) | 290 (26.7) | |||
| Death | 11% | 5% | 30 (7.3) | 201 (3.1) | 0.001 | 136 (9.0) | 358 (5.4) | 0.001 | 95 (17.2) | 142 (13.1) | 0.001 |
STEMI: ST-Elevation Myocardial Infarction; NSTMI: Non ST-Elevation Myocardial Infarction; UA: Unstable Angina, All values in parenthesis are percentages.
Men younger than 50 years of age presented mainly with STEMI, whereas the majority of men older than 70 years of age presented with NSTEMI. Between the age of 51 and 70, unstable angina was the predominant presentation among men admitted with ACS.
Management
Pre-admission therapy : In comparison to men, prior to the index admission, women were more likely to be on β-blockers (BB), calcium channel blockers (CCB), angiotensin-converting enzyme (ACE) inhibitors/angiotensinogen receptor blockers and antiplatelet therapy (Table 3).
On admission : Women were less likely to receive BB, antiplatelet therapies, unfractionated heparin, and thrombolytic therapy. The uses of CCB, ACE inhibitors and low molecular weight heparin were more common in women. Women were less likely to undergo coronary angiography (8% vs. 13%, P = 0.001) and PCI (5% vs. 7%, P = 0.002).
Admission medication based on patients’ age: In age group≤50 years, women were less likely to receive antiplatelet (89% vs. 93%, P = 0.001) and BB therapies (48.5% vs. 55%, P = 0.01) in comparison to men, while ACE inhibitors were more frequently prescribed to women (33.4% vs. 25.5%, P = 0.001). In age group between 51–70 years, women were less likely to receive antiplatelet agents (89% vs. 92%, p = 0.001), and BB (41.5% vs. 49%, p = 0.001). While in age group>70 years, there was no significant difference between women and men regarding admission medications except for higher percent of BB in men (P = 0.04).
At discharge : Women were less likely to be discharged on BB, and antiplatelet agents (P = 0.001). On the other hand, women were more likely to be treated with CCB (P = 0.001). There was no difference in the treatment with statin in both sexes (P = 0.90).
In-hospital management Trend: Figure 3 (A and B) demonstrates the treatment trend for men and women across the period from 1999 to 2010. Prescription of antiplatelet therapies increased from 66% to 79% in women and from 78% to 89% in men. The use of BB and ACE inhibitors increased from 17% to 49% and 27% to 41%, respectively in women and from 30% to 60% and 25 to 44%, respectively in men. However, coronary interventions were lower in women compared to men.
Table 3. Treatment according to gender.
| Women | Men | P-value | |
| Pre-admission medications | |||
| β-blockers | 454 (18.4) | 1835 (12.9) | 0.001 |
| Calcium channel blockers | 239 (9.7) | 515 (3.6) | 0.001 |
| ACE/ARB | 447 (18.1) | 1413 (9.9) | 0.001 |
| Anti-platelet agents | 1239 (50.1) | 4299 (30.1) | 0.001 |
| On Admission | |||
| β-blockers | 1006 (40.7) | 7253 (50.9) | 0.001 |
| Calcium channel blockers | 404 (16.3) | 1007 (7.1) | 0.001 |
| ACE/ARB | 840 (34) | 4326 (30.3) | 0.001 |
| Anti-platelet agents | 2264 (91.5) | 13483 (94.5) | 0.001 |
| Heparin | 723 (29) | 5687 (40) | 0.001 |
| LMW Heparin | 535 (22) | 2630 (18) | 0.001 |
| Glycoprotein blocker | 77 (3) | 668 (5) | 0.001 |
| Thrombolysis | 285 (11.5) | 4469 (31) | 0.001 |
| Coronary angiography | 192 (8) | 1837 (13) | 0.001 |
| PTCA | 130 (5) | 999 (7) | 0.002 |
| Stent | 96 (4) | 655 (5) | 0.11 |
| At Discharge | |||
| β-blockers | 577 (23.3) | 4547 (31.9) | 0.001 |
| Calcium channel blockers | 539 (21.8) | 1456 (10.2) | 0.001 |
| Diuretics | 756 (30.6) | 2232 (15.6) | 0.001 |
| ACE/ARB | 993 (40.1) | 5722 (40.1) | 0.98 |
| Anti-platelet agents | 2046 (82.7) | 13019 (91.3) | 0.001 |
| Clopidogerl | 769 (31.1) | 4981 (34.9) | 0.001 |
| Aspirin | 2007 (81.1) | 12899 (90.4) | 0.001 |
| Statin | 1284 (52) | 7381 (52) | 0.90 |
ACE/ARB: Angiotensin converting enzyme inhibitor; PTCA: Percutaneous Coronary Angioplasty; All values in parenthesis are percentages.
Figure 3. Trend of treatment in Women (A) and Men (B).
In-hospital Mortality Rate and Trend
Overall in-hospital mortality rate across the 20-year period was higher in women when compared to men (10.6% vs. 4.9%, P = 0.001). Among younger patients (<50 years), the rate of death in women was higher (7.3% vs. 3.1%, P = 0.001) and this trend for high mortality was also observed among women of age between 51–70 years (9% vs. 5.4%, p = 0.001) and above 70 years of age (17.2% vs. 13.1%, P = 0.02) in comparison to men (Figure 4).
Figure 4. Mortality rate in men and women stratified by age.
Figure 1B shows the trend of mortality in the Middle Eastern Arab women and men hospitalized with ACS. The overall in-hospital mortality rate was significantly decreased among Arab women from 27% to 6.6% between the periods (1991 to 1994) and (2007 to 2010), respectively. Relative risk reduction (RRR) in mortality between 1991–2002 and 2003–2010 was 64% and 51% in women and men, respectively. Figure 5 demonstrates the overall and trend for in-hospital mortality across 20 years in men and women.
Figure 5. Overall and trend of mortality in men and women.
Multiple logistic regression analysis
Female gender was found to be an independent predictor (OR 1.51; 95% CI 1.27–1.79, P = 0.001) for in-hospital mortality after adjusting other variables such as age, DM, hypertension, dyslipidemia, current smoking, chronic renal impairment, prior MI, type of ACS and year of admission (Table 4).
Table 4. Multivariate regression analysis for predictors of in-hospital mortality.
| Variable | Adjusted OR | 95% CI | P-value |
| Age | 1.04 | 1.03–1.05 | 0.001 |
| Female | 1.80 | 1.48–2.12 | 0.001 |
| Diabetes Mellitus | 1.60 | 1.38–1.86 | 0.001 |
| Hypertension | 0.91 | 0.78–1.07 | 0.25 |
| Dyslipidemia | 0.66 | 0.55–0.80 | 0.001 |
| Chronic renal impairment | 2.40 | 0.78–3.23 | 0.001 |
| Current smoking | 0.75 | 0.62–0.90 | 0.002 |
| Prior myocardial infarction | 1.61 | 1.35–1.91 | 0.001 |
| Diagnosis | |||
| Unstable angina | 1 | – | – |
| Non-ST-elevation MI | 19.38 | 13.2–28.5 | 0.001 |
| ST-elevation MI | 6.53 | 4.44–9.60 | 0.001 |
| Year of Admission | |||
| 1991–94 | 1 | – | – |
| 1995–98 | 1.17 | 0.91–1.50 | 0.23 |
| 1999–02 | 1.64 | 1.29–2.09 | 0.001 |
| 2003–06 | 0.90 | 0.70–1.14 | 0.37 |
| 2007–10 | 0.72 | 0.56–0.93 | 0.01 |
Adjusted OR: Adjusted Odd Ratio; 95% CI: 95% Confidence Interval.
Discussion
The present study reports a large data of patients hospitalized with ACS over 20 years in Qatar. According to 2010 census, Qatar has a population of about 1.7 million with female to male ratio of 1∶3. Our study demonstrates important differences between women and men presenting with ACS. There are several key findings in this study. First, female gender was independent predictor of in-hospital mortality in patients presenting with ACS. The current analysis shows that women had higher mortality rates compared to men in all age groups. However, data from US National Registry of Myocardial Infarction-2 found an increased mortality risk for young women compared with young men, with no mortality difference in the older population [22].
Second, gender differences exist in many aspects of ACS; including presentation, diagnosis, treatment and outcomes. Third, over the study period there was a substantial increase in the number of patients admitted with ACS regardless of gender. Furthermore, the rate of ACS admissions from (1991–1994) to (2007–2010) increased four times among Arab women patients and seven times among South Asian patients. Fourth, although women were less likely to be prescribed evidence based medications, there were upward trends in the use of aspirin, BB, ACE inhibitors across the study period regardless of gender. The period between 1999 through 2010 showed improvement in the utilization of evidence-based therapies in our institution, although the use of early invasive therapy remained low. Fifth, the current study reports a significant reduction of the in-hospital mortality rate among ACS women and men, and this improvement in outcome most likely attributes to the increased use of evidence-based therapies. Similarly, Lundblad et al [23] analyzed MI patients in Northern Sweden across a 20-year period (1985–2004) and reported a mortality reduction of 69% and 45% in men and women, respectively. This improvement in outcome was relatively better for women between 1991 and 2010 in our study. Sixth, the present report demonstrates differential trends in the cardiovascular risk factors across 20 years in men and women. Generally, women were more likely older and had greater cardiovascular risk factors compared to men. The mean age of patients in the current registry is comparable to the CREATE registry from India and almost a decade younger than those reported from developed countries [24]–[28].
The diagnosis of ACS in women is more challenging especially when it is based on history alone [29]–[31]. Women are more likely to present with atypical symptoms including higher frequency of dyspnea when compared to men; a factor that increases the likelihood of misdiagnosis among women. These atypical presentations could be attributed to difference in anatomy and pathophysiology of CAD in women compared to men which needs high index of suspicion for the prompt diagnosis of ACS in women [28].
Serum troponin is the biochemical marker of choice for evaluating the acute risk of patients with ACS without persistent ST elevation and to guide further management [32]. In our study, the prevalence of positive troponin T and mean CK-MB level were significantly lower in women compared to men. Complete plaque rupture is the frequent pathology in ACS men that leads to more severe stimulus for repetitive thrombus embolization with consecutive troponin release [33]. On the other hand, plaque erosion is more common in women. According to the Universal Classification of MI, spontaneous MI (MI type 1) that occurs due to atherosclerotic plaque rupture, ulceration, fissuring, erosion, or dissection were found particularly in women without angiographic evidence of severe CAD [34].
Moreover, along with previous registries, our findings show that females with ACS without ST elevation MI are more likely to have higher Killip class than their male counterparts [5]. In terms of ACS types, the present study demonstrates that the proportion of women with STEMI is significantly lower than that of men, whereas the proportion of women with unstable angina and NSTEMI is significantly greater when compared to men. However, the influence of age at the time of presentation should be taken into consideration i.e., women younger than 50 years of age are more likely to have unstable angina whereas; women older than 70 years of age are mainly presented with STEMI. This finding could be related to the pathophysiology of the vulnerable plaques (i.e., erosion vs. rupture) in each gender among young versus older age. Also, discrepancy between both sexes in the ACS may attribute to the differences in thrombotic and fibrinolytic activity, variability in the extent and severity of coronary lesions and presence of collateral blood flow [35]–[39].
Despite the fact that women with ACS represent higher risk group compared to men, they are undertreated with evidence-based therapies. Previous studies showed that both acute and discharge therapies according to guidelines were applied less frequently to women who were treated mainly with conservative management [3], [6], [7], [40]–[43]. Further, a sort of unexplained “treatment paradox” has been observed in the current study. The rate of BB and ACE inhibitors use at admission (41% and 91.5%, respectively) declined at discharge (23% and 83%, respectively) among women. To a less extent a similar trend has also been observed among men. Therefore, the impact of this treatment paradox needs further evaluation.
In our study, women presented with AMI are not only having a downward trend in the use of fibrinolytic therapy but also have declined interventional management. This low rate of cardiac catheterization and PCI in women is consistent with several reports from different ethnicities [3], [7], [37], [43]. The rate of diagnostic angiography and angioplasty was greater in men (p = 0.001), whereas the rate of stent insertion was comparable in both sexes (P = 0.90) in the present study. However, the overall rate of invasive procedures was very low which is consistent with previous reports from our region [44].
Several investigators reported controversial findings for the hospital outcome in women with unstable ACS after invasive reperfusion therapy [45]–[48]. According to ACC/AHA guidelines in 2007, women with higher risk of unstable ACS appeared to benefit from early intervention. Whereas, no direct benefit from invasive strategy for low risk features (i.e., without elevated markers or ST depression) was reported [30]–[31]. A recent study advocates an early invasive strategy in women on the same principles as in men [16].
Under treatment of women presenting with ACS is likely multifactorial [33]. This could be in part explained by the delay in symptom recognition and initial assessment, lack of participation in clinical trials and fear of complications.
In summary, the present analysis is the first report from a small developing country in the Middle East that describes the epidemiology and trends of ACS over a 20- year period. Our study confirms that women presenting with ACS are characterized with worse clinical profiles, undertreatment and higher mortality rate regardless of age in comparison to men. The novel finding in the current study is the significant improvement in the mortality among females despite the substantial increase in the number of females admitted with ACS over the last 2 decades. It is useful to highlight the different pathophysiology of ACS in females based on their age. Further, the study addresses the relationship of adherence to the use of evidence based therapy and the improvement of outcome in women presenting with ACS.
Limitation of the Study
Our study is constrained by the limitations inherent to its observational design. Inaccuracies in the diagnosis and coding of ACS in routine data are well recognized, so we have to rely on the accuracy of such data. Temporal changes in referral and coding practices, diagnostic accuracy, and awareness of ACS as a diagnostic entity may have influenced our findings. Presence of missing data or measurement errors and possible confounding by variables not controlled for also adds to our limitations. Furthermore, our study did not address the angiographic data and long-term outcomes. There have been some changes in treatment options since the data were recorded. The broader applicability of our findings to other countries or regions is questionable. A recent report from Qatar showed that the unique social, cultural, religious, environmental, and economic factors are influencing the healthy lifestyle of the Qatari women [49].
Conclusions
Gender discrepancy exists in many aspects of ACS patients and the mortality rate was higher in women of all age groups, which may be due to underestimation of patient risk. However, a significant improvement in the outcome of ACS patients, particularly women has been observed over the study period. Greater awareness of the treatment risk paradox may help to eliminate the gender gap between current guidelines and management practices and may potentially help to improve short-term outcome. Although, substantial improvement in the hospital outcome has been noticed, guidelines adherence and improvement in the hospital care have not been optimized yet.
Acknowledgments
We thank all the cardiology staff at HMC for their efforts to collect and enter the CCU data.
This study was presented in part at the American College of Cardiology (ACC.13) 62nd Annual Scientific Session, March 9–11, 2013, in San Francisco, CA,USA
Funding Statement
No current external funding sources for this study.
References
- 1. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, et al. (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364: 937–952. [DOI] [PubMed] [Google Scholar]
- 2.American Heart Association. Heart Disease and Stroke Statistics– 2004 Update. Dallas, TX: American Heart Association, 2003.
- 3. Ayanian JZ, Epstein AM (1991) Differences in the use of procedures between women and men hospitalized for coronary heart disease. N Engl J Med 325: 221–225. [DOI] [PubMed] [Google Scholar]
- 4. Healy B (1991) The Yentl syndrome. N Engl J Med 325: 274–276. [DOI] [PubMed] [Google Scholar]
- 5. Poon S, Goodman SG, Yan RT, Bugiardini R, Bierman AS, et al. (2012) Bridging the gender gap: Insights from a contemporary analysis of sex-related differences in the treatment and outcomes of patients with acute coronary syndromes. Am Heart J 163: 66–73. [DOI] [PubMed] [Google Scholar]
- 6. Blomkalns AL, Chen AY, Hochman JS, Peterson ED, Trynosky K, et al. (2005) Investigators. Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative. J Am Coll Cardiol 45: 832–837. [DOI] [PubMed] [Google Scholar]
- 7. Radovanovic D, Erne P, Urban P, Bertel O, Rickli H, et al. (2007) Gender differences in management and outcomes in patients with acute coronary syndromes: results on 20,290 patients from the AMIS Plus Registry. Heart 93: 1369–1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Jneid H, Fonarow GC, Cannon CP, Hernandez AF, Palacios IF, et al. (2008) Sex differences in medical care and early death after acute myocardial infarction. Circulation 118: 2803–2810. [DOI] [PubMed] [Google Scholar]
- 9. Anderson RD, Pepine CJ (2007) Gender differences in the treatment for acute myocardial infarction: bias or biology? Circulation 115: 823–826. [DOI] [PubMed] [Google Scholar]
- 10. Heer T, Schiele R, Schneider S, Gitt AK, Wienbergen H, et al. (2002) Gender differences in acute myocardial infarction in the era of reperfusion (the MITRA registry). Am J Cardiol 89: 511–517. [DOI] [PubMed] [Google Scholar]
- 11. Berger JS, Elliott L, Gallup D, Roe M, Granger CB, et al. (2009) Sex differences in mortality following acute coronary syndromes. JAMA 302: 874–882. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Rosengren A, Wallentin L, K Gitt A, Behar S, Battler A, et al. (2004) Sex, age, and clinical presentation of acute coronary syndromes. Eur Heart J 25: 663–670. [DOI] [PubMed] [Google Scholar]
- 13. Xhyheri B, Bugiardini R (2010) Diagnosis and treatment of heart disease: are women different from men? Prog Cardiovasc Dis 53: 227–236. [DOI] [PubMed] [Google Scholar]
- 14. Shaw LJ, Bugiardini R, Bairey Merz N (2009) Women and ischemic heart disease: evolving knowledge. J Am Coll Cardiol 54: 1561–1575. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Bugiardini R, Bairey Merz N (2005) Angina with “normal” coronary arteries: a changing philosophy. JAMA 293: 477–484. [DOI] [PubMed] [Google Scholar]
- 16. Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, et al. (2011) ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 32(23): 2999–3054. [DOI] [PubMed] [Google Scholar]
- 17. Novack V, Cutlip DE, Jotkowitz A, Lieberman N, Porath A (2008) Reduction in sex-based mortality difference with implementation of new cardiology guidelines. Am J Med 121: 597–603. [DOI] [PubMed] [Google Scholar]
- 18. Setoguchi S, Solomon DH, Levin R, Winkelmayer WC (2008) Gender differences in the management and prognosis of myocardial infarction among patients’ ≥65 years of age. AmJ Cardiol 101: 1531–1536. [DOI] [PubMed] [Google Scholar]
- 19. Cannon CP, Battler A, Brindis RG, Cox JL, Ellis SG, et al. (2001) American College of Cardiology key data elements and definitions for measuring the clinical management and outcomes of patients with acute coronary syndromes. A report of the American College of Cardiology Task Force on Clinical Data Standards (Acute Coronary Syndromes Writing Committee) J Am Coll Cardiol 38(7): 2114–2130. [DOI] [PubMed] [Google Scholar]
- 20. Al Suwaidi J, Al-Qahtani A, Asaad N, Al-Mulla AW, Singh R, et al. (2012) Comparison of women versus men hospitalized with heart failure; (From a 20-years registry in a Middle-Eastern country 1991–2010). Am J Cardiol 109(3): 395–400. [DOI] [PubMed] [Google Scholar]
- 21. Al Suwaidi J, Asaad N, Al-Qahtani A, Al-Mulla AW, Singh R, et al. (2012) Prevalence and outcome of Middle-eastern Arab and South Asian patients hospitalized with heart failure: insight froma 20-year registry in a Middle-Eastern country (1991–2010). Acute Card Care 14(2): 81–89. [DOI] [PubMed] [Google Scholar]
- 22. Vaccarino V, Parsons L, Every NR, Barron HV, Krumholz HM (1999) Sex-based differences in early mortality after myocardial infarction: National Registry of Myocardial Infarction 2 Participants. N Engl J Med 341: 217–225. [DOI] [PubMed] [Google Scholar]
- 23. Lundblad D, Holmgren L, Jansson JH, Näslund U, Eliasson M (2008) Gender differences in trends of acute myocardial infarction events: the Northern Sweden MONICA study 1985–2004. BMC Cardiovasc Disord Jul 25 8: 17 doi: 10.1186/1471-2261-8-17 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Xavier D, Pais P, Devereaux PJ, Xie C, Prabhakaran D, et al. (2008) CREATE registry investigators.Treatment and outcomes of acute coronary syndromes in India (CREATE): a prospective analysis of registry data. Lancet 371: 1435–1442. [DOI] [PubMed] [Google Scholar]
- 25. Hasdai D, Behar S, Wallentin L, Danchin N, Gitt AK, et al. (2002) A prospective survey of the characteristics, treatments and outcomes of patients with acute Coronary syndromes in Europe and the Mediterranean basin; the Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS). Eur. Heart J 23: 1190–1201. [DOI] [PubMed] [Google Scholar]
- 26. Mandelzweig L, Battler A, Boyko V, Bueno H, Danchin N, et al. (2006) The second Euro Heart Survey on acute coronary syndromes (EHS-ACS-II): Characteristics, treatment, and outcome of patients with ACS in Europe and the Mediterranean basin in 2004. Eur. Heart J 27: 2285–2293. [DOI] [PubMed] [Google Scholar]
- 27. Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, et al. (2003) Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med 163: 2345–2353. [DOI] [PubMed] [Google Scholar]
- 28. Hochman JS, Tamis JE, Thompson TD, Weaver WD, White HD, et al. (1999) Sex, clinical presentation, and outcome in patients with acute coronary syndromes. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes IIb Investigators. N Engl J Med 341: 226–232. [DOI] [PubMed] [Google Scholar]
- 29. El-Menyar A, Zubaid M, Sulaiman K, AlMahmeed W, Singh R, et al. (2011) Gulf Registry of Acute Coronary Events (Gulf RACE) Investigators. Atypical presentation of acute coronary syndrome: a significant independent predictor of in-hospital mortality. J Cardiol 57(2): 165–171. [DOI] [PubMed] [Google Scholar]
- 30. El-Menyar A, Zubaid M, Rashed W, Almahmeed W, Al-Lawati J, et al. (2009) Comparison of men and women with acute coronary syndrome in six Middle Eastern countries. Am J Cardiol 104(8): 1018–1022. [DOI] [PubMed] [Google Scholar]
- 31. El-Menyar AA, Al Suwaidi J (2009) Impact of gender in patients with acute coronary syndrome. Expert Rev Cardiovasc Ther 7(4): 411–421. [DOI] [PubMed] [Google Scholar]
- 32. Elsaesser A, Hamm CW (2004) Acute coronary syndrome: the risk of being female. Circulation 109: 565–575. [DOI] [PubMed] [Google Scholar]
- 33. Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R (2013) Update on acute coronary syndromes: the pathologists' view. Eur Heart J 34(10): 719–728. [DOI] [PubMed] [Google Scholar]
- 34. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, et al. (2012) Third universal definition of myocardial infarction. J Am Coll Cardiol 60(16): 1581–1598. [DOI] [PubMed] [Google Scholar]
- 35. Conlan MG, Folsom AR, Finch A, Davis CE, Sorlie P, et al. (1993) Associations of factor VIII and von Willebrand factor with age, race, sex, and risk factors for atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study. Thromb Haemost 70: 380–385. [PubMed] [Google Scholar]
- 36. Stegnar M, Pentek M (1993) Fibrinolytic response to venous occlusion in healthy subjects: relationship to age, gender, body weight, blood lipids and insulin. Thromb Res 69: 81–92. [DOI] [PubMed] [Google Scholar]
- 37. Cucuianu M, Lanczek M, Roman S (1993) Plasminogen activator inhibitor (PAI) in obese men and obese women. Rom J Intern Med 31: 183–192. [PubMed] [Google Scholar]
- 38. Hochman JS, McCabe CH, Stone PH, Becker RC, Cannon CP, et al. (1997) Outcome and profile of women and men presenting with acute coronary syndromes: a report from TIMI IIIB. J Am Coll Cardiol 30: 141–148. [DOI] [PubMed] [Google Scholar]
- 39. Krumholz HM, Douglas PS, Lauer MS, Pasternak RC (1992) Selection of patients for coronary angiography and coronary revascularization early after myocardial infarction: is there evidence for a gender bias? Ann Intern Med 116: 785–790. [DOI] [PubMed] [Google Scholar]
- 40. Daly C, Clemens F, Lopez Sendon JL, Tavazzi L, Boersma E, et al. (2006) Gender differences in the management and clinical outcome of stable angina. Circulation113: 490–498. [DOI] [PubMed] [Google Scholar]
- 41. Anand SS, Xie CC, Mehta S, Franzosi MG, Joyner C, et al. (2005) Differences in the management and prognosis of women and men who suffer from acute coronary syndromes. J Am Coll Cardiol 46: 1845–1851. [DOI] [PubMed] [Google Scholar]
- 42. Chandra NC, Ziegelstein RC, Rogers WJ, Tiefenbrunn AJ, Gore JM, et al. (1998) Observations of the treatment of women in the United States with myocardial infarction: a report from the National Registry of Myocardial Infarction-I. Arch Intern Med 158: 981–988. [DOI] [PubMed] [Google Scholar]
- 43. Rathore S, Rhys J, Buchalter MB, Gerning NO, Groves PH, et al. (2006) Impact of age on the outcomes of women following percutaneous coronary intervention in the baremetal stent era. J Interv Cardiol 19: 245–249. [DOI] [PubMed] [Google Scholar]
- 44. Panduranga P, Sulaiman K, Al-Zakwani I, Zubaid M, Rashed W, et al. (2010) Utilization and determinants of in-hospital cardiac catheterization in patients with acute coronary syndrome from the Middle East. Angiology 61(8): 744–750. [DOI] [PubMed] [Google Scholar]
- 45. Long-term low-molecular-weight heparin in unstable coronary-artery disease (1999) FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease investigators. Lancet 354: 701–707. [PubMed] [Google Scholar]
- 46. Fox KA, Poole-Wilson PA, Henderson RA, Clayton TC, Chamberlain DA, et al. (2002) Interventional versus conservative treatment for patients with unstable angina or non-ST elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina. Lancet 360: 743–751. [DOI] [PubMed] [Google Scholar]
- 47. Cannon CP, Weintraub WS, Demopoulos LA, Vicari R, Frey MJ, et al. (2001) Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med 344: 1879–1887. [DOI] [PubMed] [Google Scholar]
- 48. Rathore SS, Chen J, Wang Y, Radford MJ, Vaccarino V, et al. (2001) Sex differences in cardiac catheterization: the role of physician gender. JAMA 286: 2849–2856. [DOI] [PubMed] [Google Scholar]
- 49. Donnelly TT, Al Suwaidi J, Al Enazi NR, Idris Z, Albulushi AM, et al. (2012) Qatari women living with cardiovascular diseases-challenges and opportunities to engage in healthy lifestyles. Health Care Women Int 33 1114–1134. [DOI] [PubMed] [Google Scholar]