Reibido 04-ABRIL-18 – ACEPTADO despues de revisión el 17-MAYO-2018.
There are no conflicts of interest to disclose.
Introduction: Despite advances in the treatment of infarction, the prognosis remains related to classic factors such as age, heart failure, ventricular function and sex. Previous studies showed higher mortality in women, attributed to differences in age, comorbidities and access to therapies. Objective: To compare clinical characteristics and hospital prognosis according to gender in patients with acute myocardial infarction with ST elevation (STEMI). Material and methods: A prospective, observational, multicenter study in the Argentine Republic carried out in 247 centers (all provinces and the city of Buenos Aires) including a total of 1759 pts, with a diagnosis of STEMI of up to 36 hours of evolution, performed from March to December 2015. Of these, 394 (22.39%) were women. Results: The median age of the women was higher (66 vs 59.7 years, p <0.001). The prevalence of coronary risk factors was different; less smoking was observed (25% vs 46.7%, p <0.001), more diabetes (29.8 v 24.9%, p=0.018), and HTN (70.7% vs 55.7%, p <0.001). Women had less coronary heart disease (10.1% vs 14.5%, p=0.016) and previous PTCA (7.5% vs 10.6%, p=0.04). The pain-admission time was greater in women (150 vs 120 min, p=0.03). The reperfusion rate was similar with a slight tendency to lower use of fibrinolytics. Hospital mortality was higher in women (11.2% vs 8.1%, p=0.04), with a similar rate of re-infarction (2 vs 1.6%, p = 0.35), post-infarction angina (3 vs 2.3%, p=0.43) and cardiogenic shock (23.7 vs 21%, p=0.26), HF (14.2 vs 11.4, p=0.07). However, in the multiple logistic regression model, gender was not an independent predictor of higher mortality. Associated variables were age (HR=1.087, 95% CI 1.037-1.139, p=0.006), blood pressure at admission (HR = 0.98, CI 95% 0.966-0.999, p=0.043) and the presence of heart failure (HR = 9.280, CI 95% 2.441-35.281, p=0.004). Conclusions: Women admitted for STEMI have a different risk profile than men, receive fewer therapies recommended by the guidelines, but with similar use of invasive strategy. Although hospital mortality was higher, sex was not an independent predictor of risk.
Infarction. Women. Prognosis.
In spite of the advancements in the treatment of infarction, the prognosis of survivors from the acute phase depends on factors as age, heart failure, ventricular function and gender, among others . Previous studies showed a greater mortality in women, attributed to age differences, co-morbidities and access to therapies .
Coronary artery disease (CAD) was traditionally considered a male disease; however, in recent times, there were reductions in cardiovascular mortality in women, partly as a result of awareness, greater focus on them, their risk and application of treatments based on evidence [2-4].
In spite of the load risk factors being greater, presenting more angina and morbi-mortality, paradoxically women present less severe obstructive disease in their epicardial arteries in angiography compared to men [4-6].
Multiple studies have shown that women with acute coronary syndromes have less chances to be treated with the main medical therapies , of undergoing an invasive strategy and less chances of receiving timely reperfusion [8-10].
Data about infarction evolution in women in Argentina are scarce . Recently, the Argentine registry of ST-elevation myocardial infarction (STEMI), included centers distributed in all Argentine provinces, through the joint effort of the Federación Argentina de Cardiología (FAC) and the Sociedad Argentina de Cardiología (SAC).
The hypothesis of this subanalysis was that in our country, women admitted with STEMI present clinical and therapeutic differences with men, which could have implications on the prognosis. For this reason, the aims of this report were to compare the risk profile, hospital management and evolution of women in comparison to males, with STEMI.
MATERIAL AND METHODS
The ARGEN-IAM-ST Registry was a prospective, observational, multicenter study conducted jointly by the Federación Argentina de Cardiología (FAC) and the Sociedad Argentina de Cardiología (SAC) in 247 centers of the Argentine Republic, including all the provinces and the city of Buenos Aires, where 1759 patients were included with diagnosis of STEMI of up to 36 h of evolution, recruited in the term March to December, 2015 .
The inclusion criteria for the registry were suspicion of acute myocardial infarction (AMI) and some of the following: 1. ST-segment elevation ≥1 mV in at least two limb leads or ≥2 mV in at least two contiguous precordial leads; 2. AMI evolving with new Q waves of less than 36 h evolution; 3. Suspicion of inferoposterior infarction (horizontal ST depression from V1 through V3 suggesting acute occlusion of circumflex coronary artery); or 4. New or supposedly new complete left bundle branch block.
The exclusion criteria were diagnosis of non-ST elevation ACS and infarctions with more than 36 h of evolution.
The period of inclusion was for at least 3 consecutive months in every center. A pilot stage was conducted since November 2014 to March 2015 in selected centers, and later extended to the whole country until December 31 2015. The general characteristics of the population were analyzed according to gender, the indicated treatment, evolution, incidence of complications and in-hospital mortality.
Data collection was done through the Web, in an electronic file especially designed by the Medical Center of Telecomputing (CETIFAC), which enabled online monitoring of the uploaded variables. The privacy of patients in the registry was guaranteed as the names or initials of the patients were not stored in the database, and were identified by a correlative number by center.
The qualitative variables are presented as frequencies and percentages, and the quantitative ones as mean±standard deviation (SD) or median and interquartile range 25-75% (IQR) according to distribution. The analysis of discrete variables was made through the chi-squared test, and of continuous variables by the t or Kruskall Wallis test for unpaired data or analysis of variance (ANOVA) as it corresponded. With variables associated in a significant manner with mortality in univariate analysis, a multiple logistic regression model was built to identify independent predictors of mortality. A value of p<0.05 was considered significant. The analysis was made with the IBM SPSS 24 software.
RESULTS Baseline characteristics
In this analysis, 1759 patients were included, of whom 22.4% corresponded to the female gender. In Table 1, the general characteristics of the population are shown. Women presented more diabetes, hypertension, smoked less and had a pain-to-consultation time significantly greater than men.
Table 1. Demographic characteristics of the population
In admission, a greater prevalence of signs of heart failure was observed (Killip and Kimball class ≥II 28.1% vs 22.1%) (p=0.014). The reported ejection fraction by echocardiography was similar in both groups (Table 2).
Table 2. Hemodynamic state in admission
HR in admission (bpm) Systolic BP in admission (mmHg) EF (%) KK I KK II KK III KK IV
Reperfusion strategies and treatment
The indication of reperfusion was significantly lower in women (79.7% vs 84.6%; p=0.02) with less use of fibrinolytic agents (15.2% vs 19%; p=0.05), a mild tendency to a lower indication of angioplasty in spite of a similar indication of angiography within the first 24 h (Table 3).
Table 3. Use of angiography and reperfusion strategies
Coronary angiography first 24 h
Culprit coronary artery
- Anterior descending
- Right coronary
- First diagonal
- Left main
- Normal arteries
The treatment with drugs with proven evidence was less, both in admission and in discharge in women in regard to men. Thus, women received less ticagrelor in admission, less beta blockers and conversion enzyme inhibitors in admission and discharge, received more insulin and diuretics in admission (Table 4).
Table 4. Medication in admission and discharge
Ticagrelor load in admission
Aspirin in admission
B blockers in admission
ACEI in admission
Diuretics in admission
Clopidogrel in admission
Ticagrelor in admission
Prasugrel in admission
Aspirin at discharge
B blockers at discharge
ACEI at discharge
Statins at discharge
Insulin at discharge
In-hospital evolution and prognosis
Women presented greater in-hospital mortality (11.2% vs 8.1%; p=0.04), no differences in the rest of complications recorded, as well as in the indication of invasive procedures as temporary pacemaker, Swan Ganz catheter and mechanical ventilation (Table 5).
Table 5. In-hospital mortality, complications and invasive procedures
In multivariate analysis, the gender was not an independent predictor of in-hospital mortality, after adjustment by other variables like age, presence of heart failure, blood pressure, diabetes, Killip. The independent predictors were: age (OR=1.087 CI 95% 1.037-1.139; p=0.006), blood pressure in admission (OR=0.98 CI 95% 0.966-0.999; p=0.043) and the presence of heart failure (OR=9.280 CI 95% 2.441-35.281; p=0.004).
The women admitted by myocardial infarction have risk profiles different from men, receive less therapies recommended by guidelines, similar invasive strategies, and more in-hospital mortality. However, gender was not an independent predictor of risk after adjusting by other variables.
The pathophysiology of acute coronary syndrome, including the characteristics of the plaque, is different in women in regard to men. Recent data suggest a greater role of microvascular disease in the female gender . Plaque rupture is responsible for 76% of deaths by fatal infarction in men; instead, it was just 55% in women , while autopsy studies have shown a greater prevalence of plaque erosion in them, especially in younger women [4,14]. With the advent of optical coherence tomography, it has become evident that plaque erosion [13-15] presented in 27% of patients with ST-segment elevation myocardial infarction and 31% of non-ST segment elevation acute coronary syndromes in these studies [4,14,16]. Female gender and pre-menopausal state are the only risk factors predicting thrombosis [17,18].
Women are also more prone to presenting unusual pathophysiological mechanisms of nonobstructive CAD as spontaneous dissection or coronary artery spasm [4,19]. In this study there were no differences as to the location in the artery culprit of MI between both genders.
Currently, smoking has an effect of similar risk in men and women; former smokers present more risk in male ones. Hypertension, diabetes, psychosocial factors, lack of physical activity, are more powerful risk factors for the development of infarction in women more than in men. The researchers of the INTERHEART study suggested that this was due to women with infarction being in general, 10 years older in regard to men .
Several studies reported a greater prevalence of diabetes mellitus, heart failure, hypertension, depression and renal dysfunction in women in comparison to men. Besides, they more commonly present with NSTEMI [18-20] and nonobstructive CAD .
In this study, women presented the following more frequently: diabetes, hypertension, less smoking, and consulted later than men. Diabetes was still a significant disease in the generation of atherosclerosis and infarction, so its identification and early treatment are extremely relevant [4,22]. There was an incentive in the fact that in spite of the increase in smoking in women, they do smoke less than men. In this study, it was observed that women increased smoking in comparison to other registries; however, they smoked less than men.
The delay of patients is still significant, and is more problematic in the elderly, diabetic patients, women and when symptoms arise during the night [21,22]. Currently, several quality programs work with the delay variable; in spite of the time until the consultation having reduced in the last 10 years, it is still a challenge for the female gender, as shown in this study. Hypertension is a significant risk factor of myocardial infarction in women, with a 36% risk attributable to the population.
We should highlight that women were more tachycardic in admission, with worse Killip Kimball class and this difference between both genders was significant .
The goals of pharmacotherapy are reducing morbidity and mortality, preventing complications and improving quality of life. The foundations of the pharmacological treatment after myocardial infarction are antiplatelet agents, β-blockers, ACEIs, ARBs and statins [4,23]. The efficacy and safety of these drugs has been established through clinical trials that included both genders with similar benefits [23-25]. However, the female group has been underrepresented in several of them [23-25].
Women received less ticagrelor in admission, less beta blockers and ACEIs in admission and discharge, and received insulin and diuretics more frequently in admission.
In women, the complications of thrombolytic therapy and their noneligibility have limited their use in most developed countries. An analysis of 22 trials  that randomized 6763 patients with STEMI to primary angioplasty vs thrombolytic agents, found that women had less mortality in 30 days with primary angioplasty, regardless of whether they consulted within the first 2 hours from the onset of symptoms (7.7% vs 9.6%) or later (8.5% vs 14.4%). It was observed that mortality was extremely high in women, with delay in presentation, treated with thrombolytic therapy; so the steps to be followed would be those to reduce the time to consultation [26,27].
In this registry women had more in-hospital mortality with a similar rate of ischemic events and requirement of invasive procedures. Regardless of age, women will die more than men within a year of a first infarction (26% vs 19%) and within 5 years (47% vs 36%), with more incidence of heart failure and stroke [4,28]. Nonadjusted mortality excess in women in 5 to 10 years post-infarction could be partly explained by the differences in age, risk factors, clinical presentation and management .
In this study, gender was not an independent predictor of mortality, but the following were: age, blood pressure in admission, and heart failure.
It is known that women experimented their first infarction in average 9 years after men, and the difference in age was similar in all regions . This could put them in a higher risk of mortality both in the short and long term [31,32]. Studies that examined stratified analyses by age tend to display more mortality between younger women, although it is lower for women in comparison to men in the same age [29,31]. These findings are consistent with previous reports on differences in mortality in the short term, according to gender, after an infarction [31,33].
This study shows the results of the analysis of a subset of patients, in a prospective cohort, with a design that was not addressed to evaluate the impact of gender. However, the wide coverage of patients’ enrollment in the whole country reinforces the fact of having national representation.
First, we should warn that in spite of a difference existing in the delay from the onset of symptoms to the consultation, this has been reduced, though it is still a significant factor to consider as time is short, and could justify in this study the mortality excess in women [3,4].
In spite of the theoretical pathophysiological differences and clinical presentation of STEMI between genders [4,24], interventionist treatment and pharmacological reperfusion was similar in both groups, even considering that the risks of bleeding and other complications are still higher in women [26,33].
The limitations observed in clinical trials as to the inclusion of women is reflected in an underutilization of the proper treatment advised by guidelines, and this could be translated into worse results after the index event [4,34,35]. Clinical trials always included more men, but new approaches to increase the participation of women are promising. There is a need for intense and continuous public health campaigns, as well as from scientific societies addressed to women, including racial and ethnical minorities, given the load of risk factors and the ongoing disparity of results [4,36-38]. For this reason, it is considered relevant to encourage multidisciplinary investigation teams to examine innovative models of secondary prevention with proper care, that are culturally sensitive and customized for women, with particular psychosocial and physiological characteristics [1,14,18].
Women admitted by STEMI have a risk profile different from men, receive less therapies recommended by guidelines, but with a similar use of invasive strategies. Although in-hospital mortality was greater, gender was not an independent risk predictor.
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