Introduction

Ischemic heart disease represents the primary cause of death in Mexico¹-⁵, mostly attributed to acute myocardial infarction. Women have been underrepresented in most trials regarding ischemic heart disease and it is well known that women have risk factors of their own, which makes it questionable to say that treatment tested is as effective in this group, because differences in survival and mortality have been significantly different through the years. Globally, coronary artery disease has been more prevalent in women than in men. Around the world, the mean age of presentation of myocardial infarction in women is 64.5 years of age, and it carries a worst prognosis. Those who have a first event before the age of 50 double the risk of mortality compared to men¹-³,⁶-¹⁰. Bowles et al. acknowledged that women in his study did not attribute cardiovascular symptoms to ST-segment elevation myocardial infarction (STEMI), but to extracardiac causes¹⁰. As we know, timely reperfusion for STEMI carries better outcomes. Pharmacoinvasive strategy (PS) has proven in several clinical trials to be as effective as primary percutaneous coronary intervention (PPCI) especially when is implemented in places were demographic and socioeconomics represent an issue when it comes to perform PPCI. Even though PS is equally effective than PPCI, women keep having higher mortality rates. The national program for the reduction of mortality in STEMI carried out by health department and by the National Heart Institute in Mexico, revealed that 8 out of every 19 patients did not have information regarding STEMI, and only one-third of females had a correct identification of symptoms. Interviewed women had less knowledge or wrong concept of STEMI. Most women did acknowledge that they would search for medical attention if having an event, but this does not correlate to the real world because the first medical contact for women tends to be higher than men¹¹. There is a high percentage of death in women than in men, being consistently higher in every age group, even when the cases are more frequent in men¹¹. For this reason, the aim of this study was to determine the differences in gender and outcomes in patients with STEMI in the Mexican population who were taken either to PS or PPCI within the PHASE-MX registry¹².

Methods

A cohort from the PHASE-MX trial was taken, which included patients with both genders, between 18 and 80 years of age, with a diagnosis of STEMI, that were admitted in the Emergency Department and Coronary Care Unit of the National Heart Institute Ignacio Chavez from April 1 of 2018 to March 31 of 2019. The area of care and reference of the Mexico City metropolitan area comprise a calculated area of 7954 km², with a population of 20.4 million inhabitants. Patients from 60 hospitals from the metropolitan area were received. At admission, the following data were collected: age, gender, date of admission, the presence of diabetes mellitus, systemic arterial hypertension, smoking, chronic kidney disease, obesity, previous history of myocardial infarction, previous revascularization, vital signs, TIMI, GRACE and CRUSADE scores, blood biometrics, blood glucose, troponin, NT proBNP, total ischemic time, first medical contact time, door-to-needle time, door-to-wire crossing or device time, medical treatment before reperfusion, time to PS, and treatment success. In-hospital follow and date of home discharge were registered.

Results

A total of 340 patients were analyzed, 296 males and 44 females (Table 1). Mean age of the female group was 64.3 ± 12.3 years. Among the female group, 56.8% had diabetes mellitus, 50.1% had systemic arterial hypertension, 5.9% had dyslipidemia, 18.2% actively smoking, 2.3% had chronic kidney disease, 15.9% had obesity, 11.4% had previous myocardial infarction, 9.7% had previous percutaneous coronary intervention, 2.3% had previous coronary artery bypass graft, 2.3% had some sort of valvular heart disease, and 2.3% had heart failure. There were no cases with atrial fibrillation (Table 2).

At arrival, 98% of females were among Killip-Kimball Class I-II. The mean heart rate was 77 bpm, mean respiratory rate was 18 bpm, mean systolic arterial pressure was 116 mmHg, mean diastolic arterial pressure was 71.5 mmHg, and mean pulse oximetry was 92%. As far as clinical risk scores, mean TIMI score was 5 points, mean GRACE score was 146.5 points, and mean CRUSADE score was 39.5 points with statistically significant difference compared to men (Table 3).

Within the laboratory evaluation at arrival in the women's group, the mean hemoglobin was 14.2 g/dl, mean creatinine was 0.84 g/dl, mean urea nitrogen was 19.2 mg/dl, mean leukocytes was 10.7 × 10*³ μL, and NT proBNP value was significantly higher than men, 1750 versus 688 (p = 0.00), respectively. Initial and maximal troponin levels did not show statistical difference compared to men. Mean serum glucose in the women's group was 193.5 mg/dl being significantly higher than men whom mean value was 156 mg/dl (p = 0.01), and this was reflected in the glycated hemoglobin, mean value in females was 7.7 (5.9-9.5)%, and mean value in man was 6.1 (5.6-7.6)% (p = 0.00) (Table 4). One hundred and sixty-six patients were taken to PS and 174 to PCI. The distribution by gender was 87.1% of male and 12.9% of female (Table 5).

Total ischemic time in the female group was 360 (214-658) min, first medical contact time was 180 (75-325) min, the door-to-needle time was 31 min (20-85), and the door-to-device time was 73 (65-93) min. In-hospital stay was similar to the male patients and the left ventricular ejection fraction was 50% for the female group without differences against the male group (Table 6).

In-hospital mortality was seen in 11 patients (6.3%) who underwent PCI and 9 patients (5.4%) who underwent PS without statistical significance (Table 7). In-hospital mortality was seen in 9.1% of the female group, corresponding to 4 patients (Table 8). In the logistic regression models, factors associated with mortality in man were serum glucose > 180 mg/dl systolic arterial pressure < 90 mmHg and a GRACE score above 126 points (Table 9). In the logistic regression model for risk factors associated with mortality in the female group, there were no predictors found (Table 10).

Discussion

Coronary artery disease in women has had little appreciation and has been left behind due to the higher prevalence of STEMI in man before the age of 50. Our study was focused on the characterization of women who suffer STEMI, to determine demographic, clinical, and laboratory data, evaluation of attention times, and in-hospital mortality compared to man. In our study, the mean age of STEMI presentation in women is similar to other parts of the world. Furthermore, our study shows that comorbidities such as diabetes mellitus, systemic arterial hypertension, dyslipidemia, and obesity are similar to other trials. However, in comparison to men, women had higher prevalence of cigarette smoking and diabetes mellitus. These two factors might explain why women have worst prognosis than man. Nevertheless, the logistic regression model did not show any association in the overall outcome, we cannot say that there is an association to mortality. We acknowledge that this might be because of the low size sample. Therefore, it is necessary to increase the sample to show statistical significance. As we confirm a low representation of women, we also confirm the fact that not finding predictors for mortality make it difficult to implement different medical treatment for the female group. About 94% of woman had Killip-Kimball Class I-II, without differences in comparison to man. Regarding the risk score scales, women had higher TIMI, GRACE, and CRUSADE scores with statistical significance but without association to mortality. Women with ischemic heart disease have worst outcome compared to men⁷,⁸.

Those women who have a STEMI before the age to 50 are 2 times more likely to die¹¹. Some explanations of why women die more than man are as explained by Bowles, most women do not attribute their symptoms to a cardiovascular cause which delays medical attention. This is reflected in our study since the first medical contact was much longer for women, who took 180 min to arrive to a medical facility, in comparison to man who took 120 min, meaning a delay of 60 min which again is reflected in longer total ischemic times for women, with a mean time of 360 min in comparison to man who had 313.5 min. Although we did not find a significant statistical difference in survival between genders, the proportion of female deaths was higher than men. This might be biased by the lack of representation of the female population.

Conclusions

Mortality in female patients who developed STEMI did not have statistical significance over men, although the proportion of female deaths was higher. They have more prevalence of diabetes mellitus, obesity, and cigarette smoking. The lack of statistical significance is probably due to the lack of representation.

The majority of women had Class Killip y Kimball I-II, have higher TIMI, GRACE, and CRUSADE scores than man, and have higher levels of NT proBNP and more serum glucose at admission than men. Most women have longer times for the first medical contact which is reflected in the higher total ischemic time.

One practical lesson for cardiologists and non cardiologists is that we should implement more registries where women are included and generate research guided by gender since the course and treatment of STEMI is different in each group. Redirecting the treatment can improve outcomes for women who have STEMI. We need more representation of women in trials regarding cardiovascular disease to identify possible associations that might have an impact in mortality.