Although coronary heart disease (CHD) mortality has markedly fallen in Europe in the last 20 years, it is still the leading cause of death in most countries.1 Despite an increase in the number of incident ST-segment elevation myocardial infarction (STEMI) cases as the population ages, the number of STEMI patients in Europe has declined and stabilized.2,3

Data from the latest European registries show that men are at higher risk of incident STEMI at any age vs women but that STEMI incidence with age increases linearly in men but exponentially in women.4 Recent studies have shown that improvements in STEMI prognosis are due to both the implementation of a standard of care for reperfusion programs and the universalization of evidence-based medical treatments.5 STEMI networks increase reperfusion rates, reduce mortality, improve survival, and decrease the risk of recurrent ischemic events. Nationwide registries are essential to monitor STEMI treatments and outcomes, to evaluate the true effectiveness of treatments, and to account for changes in outcomes.3 Besides the exponential increase in STEMI in women, various studies have shown that women's prognosis after STEMI is worse than men's, not only because the condition affects women at older ages6 and those with clustering of risk factors,7 but also due to longer delays before medical help is sought,8,9 lower use of evidence-based treatments, and higher rates of kidney disease and bleeding.10

The aim of this study was to investigate the effect of sex on 30-day mortality and complications and on 1-year mortality in first STEMI patients during the first 7 years of implementation of the Codi IAM Emergency STEMI Care network (2010-2016) in Catalonia, Spain.

The Codi IAM Catalan Emergency STEMI Care network was launched in 2010 in a region with 7.6 million inhabitants. The 3 main objectives of the network are to increase the rate of reperfusion therapy among STEMI patients, to achieve primary percutaneous coronary intervention (pPCI) in less than 120minutes from first contact with the health system,5 and to monitor the results of the program through a registry. The network was initially integrated into 5 hospitals with a 24-hour a day, 7-day a week pPCI facility and 5 daytime pPCI facilities. From 2015, the network spread across Catalonia, with 9 pPCI hospitals open 24hours a day, 7 days a week and 2 hospitals with daytime pPCI. The operational details of the Codi IAM have been published elsewhere.11 Briefly, the Emergency Medical Service organization coordinates the link between patients, ambulance transfers, and pPCI facilities according to the delay until treatment. Fibrinolysis is only considered if the pPCI transfer delay is unacceptable and there are no prior contraindications. Postfibrinolysis PCI (rescue PCI) is urgently performed in patients with no evidence of effective reperfusion. In those with effective fibrinolysis, PCI is performed after between 3 and 24hours, in line with ESC guidelines.5 STEMI was defined according to guidelines as acute myocardial infarction with ST-segment elevation ≥ 1mm in at least 2 contiguous leads (2mm in precordial leads) in the qualifying electrocardiogram (ECG).5

The Codi IAM registry was started in 2010 and includes demographic, clinical, care, therapeutic, and discharge data on patients with a STEMI onset ≤ 12hours. The Principal Investigator of the Codi IAM team of each participating hospital entered the data into an electronic case report form. Epicardial coronary flow in the STEMI culprit artery was graded according to the Thrombolysis in Myocardial Infarction (TIMI) flow grade,12 and reperfusion was considered optimal when TIMI 3 flow was obtained at the culprit lesion in less than 120minutes from first medical contact. Data collection was extended to new variables in 2012 (acute pulmonary edema, number of diseased vessels, and TIMI flow) and in 2015 (hypertension, dyslipidemia, smoking status, previous stroke, previous treatment, and type and number of stents). Bleeding was only included in the registry when the patient required transfusion.

The study included patients from the Codi IAM Registry who had been diagnosed with a STEMI from 2010 to 2016. Patients with cardiac arrest or death during first medical contact were also included if ST-segment elevation or a new left bundle branch block was diagnosed in any ECG during the initial care. All patients with known previous CHD (previous myocardial infarction or any revascularization) were excluded.

Patients’ mortality data were obtained from the Spanish mortality registry. The quality of the data included in the registry is periodically verified by external audits.

This project was approved by the ethics committee of Hospital del Mar (2020/9134) and all data are anonymous. Procedures and data collection were performed in accordance with the Declaration of Helsinki and Spanish Data Protection Laws.

From January 2010 to December 2016, 23 507 STEMI patients were included in the Codi IAM registry. The selection flowchart for the present study is shown in figure 1. The final cohort consisted of 14 690 patients (24% women) without previous CHD and with a discharge diagnosis of myocardial infarction and 1-year follow-up data.

Figure 1.

Flowchart of the inclusion of Codi IAM STEMI. pPCI, primary percutaneous intervention; STEMI, ST-segment elevation myocardial infarction.

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The proportion of women was similar over the 7-year study period (P=.12).

The baseline and complication characteristics of the cohort are shown in table 1. Women were older and had higher prevalence of diabetes mellitus, hypertension, and dyslipidemia and higher rates of heart failure. Women tended to be more frequently first attended in non-pPCI centers and less often cared for by the emergency ambulance system (P=.01). Women more frequently had left bundle branch block and had higher rates of heart failure and atrioventricular blockade (P <.01). Men had higher rates of ventricular fibrillation and need for mechanical ventilation.

Crude 30-day mortality, 30-day composite end point, and 1-year mortality rates were significantly lower in men than in women. Univariate analysis of factors associated with 30-day complications and 1-year mortality are shown in table 1 of the supplementary data.

First medical contact and angiography and pPCI characteristics according to sex are shown in table 2. Time delays in STEMI care were longer in women than in men. Compared with men, women undergoing pPCI had significantly less initial TIMI 0 at the initial coronary angiography and less TIMI 3 at the final coronary angiography. Significant coronary disease (< 70% stenosis in epicardial vessels) was significantly less frequent in women; however, the coronary disease extension and severity (3-vessel disease or left main involvement) did not differ according to sex. Women waited a significant median of 22minutes longer for the first ECG than men and the time from ECG to reperfusion or to hospitalization was longer in women than in men.

The trends in treatment delays, mortality, and the composite end point at 30 days are shown in table 3. Times from ECG to artery opening decreased during the study period for both sexes but the total ischemic time decreased only in men. At the end of the study period, a significantly lower proportion of women were reperfused in less than 120minutes than men (table 3). Survival curves at 30 days and 1 year are shown in figure 2: no significant differences were observed in these crude mortality curves between men and women.

Figure 2.

Survival curves for 30-day mortality in women and men with STEMI (A) and 1-year mortality in 30-day STEMI survivors (B) in the Codi IAM network from 2010 to 2016. STEMI, ST-segment elevation myocardial infarction.

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The effects of female sex on 30-day mortality and complications and 1-year mortality were tested with multivariate analyses with progressive adjustment for potential confounders: for the whole cohort in table 4A and for the male-female 2:1 age-matched subcohort in table 4B. Female STEMI patients had no increased risk of 30-day mortality or complications but had a significantly lower risk of 1-year mortality after adjustment for diabetes mellitus, year and center of recruitment, time from symptom onset to culprit coronary artery opening, age, and Killip class. Interestingly, the model not adjusted for age and Killip class showed an increased risk of 1-year mortality in women, indicating that age and STEMI severity are determinants of mortality in 30-day STEMI survivors (table 4A). The models fit to the age-matched cohort showed results of a similar magnitude and consistency to the findings for the full cohort but did not reach statistical significance due to lower statistical power.

Our results show that women with a first STEMI are older, have more cardiovascular risk factors, and have longer delays vs men. In addition, although mortality and a composite of mortality and other complications (ventricular fibrillation, acute pulmonary edema, or cardiogenic shock) at 30 days are similar in men and women with a first STEMI, women have significantly lower mortality within 1 year.

Previous studies have evaluated the influence of female sex on STEMI prognosis. Female sex is generally considered to be a prognostic confounder due to its multiple divergent interactions with age and the related clinical profile and due to sex-related increases in treatment delays.8,9 However, the relationship between sex and outcomes after STEMI may also be due to global undercare or sex-based treatments: increased treatment delays and ischemic times,13 lower reperfusion rates, and underuse of evidence-based treatments during all STEMI phases.6 Optimal care is therefore a cornerstone of a favorable STEMI prognosis and of the utmost importance in female patients. In our cohort, women had longer treatment times than men. Delayed diagnoses are driven by sex-related pathophysiological differences such as an absence of typical male-related symptoms (chest pain) and less frequent ST-elevation on first ECG.14 In our cohort, female patients waited longer to ask for help (mean, 22minutes) and the ECG was performed with a longer delay than in men. The time between symptom onset and first medical contact accounted for 38% of the total ischemic time in women and for 34% of that in men. “Patient-related” delays are consistent across time periods and throughout literature and are challenging to reduce.15 Decreases in prehospital delays might have tremendous benefits on STEMI morbidity and mortality prognoses because many deaths occur in the very early phase from malignant arrhythmias16 and other acute-phase complications, which are known to be sex-specific, such as heart failure. Despite a general tendency for a decrease in pretreatment delays during the study period, women had a longer pretreatment delay than men. This may be partially because, compared with men, women more frequently first attended a non-pPCI center17 and also less frequently called emergency medical services, resulting in longer delays to STEMI revascularization treatment.18 Recent data from European registries showed that a decrease in delays could be influenced by media campaigns tailored not only to help women to identify the symptoms of CHD and thus rapidly access the health care system,19 but also to alert all health care providers participating in STEMI emergency care networks of the need to prevent possible gender gaps. In previous work, patients with prior myocardial infarction or prior revascularization had a shorter treatment delay, underlining the importance of knowledge or understanding of CHD pathophysiology to promote STEMI treatment.20

There is strong evidence that health care system delays are associated with mortality and heart failure-related readmission.21 However, despite the decrease in the ECG to artery opening time and the increase in the rate of pPCI in less than 120minutes during the study period, we observed no significant reduction in mortality in either sex in our cohort. The absence of a mortality decrease from 2010 to 2016 may be explained by the short study period and a slight increase in the mean age but warrants further and longer studies. Previous work from the same decade showed no further reduction in mortality, reinforcing the idea of a plateau in mortality after STEMI.3

In our cohort, sex did not have a significant effect on 30-day mortality or complications. Similar results were obtained in a subanalysis of age-matched male and female patients. The absence of a significant association remained after adjustment for time to treatment and year and hospital of treatment.

Women were about 9 years older than men in the STEMI cohort. The lack of an association of female sex with 30-day complications after age-matching of men and women is in contrast to some studies2,22 but in accordance with others.23–27 Several factors may explain this inconsistency. The first is that the vast majority of patients underwent coronary angiography catheterization during the acute phase (97.4% of women and 96.4% of men), reflecting the extensive implementation of systematic reperfusion, which reduced the “gender gap” observed several decades ago.26,28 It may also reflect the distinct nature of the underlying CHD affecting women: less angiographical evidence of significant epicardial disease than in men,29 with more plaque disruption or coronary dissection30 and CHD that affects smaller vessels with less ischemic burden.31 It may also reflect the incorporation of evidence-based therapies for both sexes in terms of primary prevention, baseline risk factors, and cardiovascular treatments after the first ischemic event.3,32 In our study, the 1-year crude mortality rate was higher in women than in men. This association was mostly accounted for by women's higher age and more comorbidities, as reflected by the regression analysis, which showed that women actually have better prognosis after 1 year than men after a first STEMI. The worse prognosis of men after STEMI has previously been reported and may reflect the higher cardiovascular risk burden and the higher risk of reinfarction25,33 at 1 year.

In the Codi IAM emergency STEMI transportation network, women underwent PCI with a greater delay than their male counterparts but showed similar 30-day mortality and complication rates and lower mortality 1 year after STEMI.

We thank Carme Carrel for data preparation and statistical management.

This project received a research grant from Departament de Salut, Generalitat de Catalunya, in 2016.

None declared.