Role of Gender on the Outcomes of ST-Elevation Myocardial Infarction Patients Following Primary Coronary Angioplasty

Background There are considerable differences in the prevalence of coronary artery disease (CAD) and its cardiovascular risk factors between men and women. Due to the significance of gender as a factor that potentially affects cardiovascular disorders and patient outcomes, the present study aimed to assess the baseline characteristics and outcomes of CAD patients in terms of gender distribution. Methods All consecutive patients diagnosed with ST-elevation myocardial infarction (MI) who had undergone primary percutaneous coronary intervention (PCI) in the previous two years in a comprehensive cardiology center were included. Data were retrospectively collected from the hospital record files. Color Doppler echocardiography, valvular involvement, and the type of coronary vessel involvement were also evaluated. Results In total, 557 consecutive patients (437 men and 120 women) were included with a mean age of 59.37 ± 26.23 years and 64.07 ± 11.60 years for men and women, respectively (p = 0.004). The prevalence of mitral regurgitation (MR) and tricuspid regurgitation (TR) was significantly higher among women than men. Conclusion Female patients who suffered from CAD and underwent PCI were older than men. Also, ischemic mitral regurgitation (MR) and tricuspid regurgitation (TR) were more prevalent among women, while smoking was more prevalent among men.


Introduction
ST-segment elevation myocardial infarction (STEMI) is considered the main cause of morbidity for decades worldwide [1]. Of note, ischemic heart disease has become the first cause of death and disability-adjusted life years (DALYs) during recent years in Iran [2]. Therefore, ongoing research and trials are being conducted to determine the associated risk factors for further risk management. Modifying lifestyle patterns would facilitate the path to improved cardiovascular risk profiles as well as avoiding revascularization [3].
Myocardial revascularization is the restoration of blood flow in stenosed or occluded coronary arteries through invasive strategies such as coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) [4]. Both procedures can effectively restore blood flow in the native coronary arteries, leading to the revitalization of ischemic cardiac tissues. In this context, the preferred strategy of reperfusion within 1.5-2 hours from the first medical contact is PCI (door-to-balloon time = 90 minutes) [4,5]. Although the PCI strategy has been highly successful with minimal post-procedural complications even in high-risk groups [4,6], many other factors affect the overall outcome.
In this regard, ongoing surveys are produced to determine the relevant factors and provide plenary guidelines based on individuals' characteristics. In this context, gender has shown a prominent role in the ultimate outcomes of STEMI patients who undergo PCI. The results vary in different parts of the world [7][8][9]. Herein, we investigate the risk and importance of assessing the outcomes of PCI including postinterventional ejection fraction (EF) and valvular disease for primary treatment of STEMI based on gender as a risk factor for patients in our region.

Materials And Methods
In this retrospective survey, we studied 557 consecutive patients who had undergone primary PCI following the diagnosis of STEMI in a cardiology center affiliated to Shiraz University of Medical Sciences (SUMS), Shiraz, Iran, from January 2017 to February 2018 (Al-Zahra Heart Hospital). The mentioned hospital is the main center of PCI in Shiraz. Among a total of 1328 total cases of PCI, patients with a history of previous myocardial infarction (MI), previous PCI, or incomplete records were excluded, and finally, 557 patients met all the inclusion criteria. We curated the following demographic data from the patients' hospital records: smoking history, length of hospital stay, in-hospital mortality, color Doppler echocardiography results which was obtained 48 hours after the PCI, including the valvular involvement and ejection fraction (EF), and type and number of coronary vessel involvement. The study was approved by the Ethics Committee of SUMS (Ethic code no. IR.SUMS.MED.REC.1398.069). Informed consent was waived by the ethics committee.

Statistical analysis
Descriptive analysis was used to describe the data, including mean ± standard deviation (SD) for quantitative variables and frequency (percentage) for categorical variables. The correlation between quantitative variables was assessed using Pearson's or Spearman's correlation test. To determine the gender difference in the study variables, a multivariable logistic regression model was employed. The Chi-squared test, t-test, and Mann-Whitney test were used to compare variables. For these analyses, we used IBM SPSS Statistics for Windows version 23.0 (IBM Corp., Armonk, USA). P-values below 0.05 were considered to be statistically significant.

FIGURE 4: Type of coronary vessel involvement in men and women
Procedure-related death occurred in 14 (3.2%) men and 6 (5.0%) women, where no significant difference was detected (p = 0.349) (  Gender was not a significant determinant for PCI-related death when adjusted for baseline variables (OR = 0.552, p = 0.705) ( Table 3). Also, in a multivariable linear regression model, gender was not a predictor of the length of hospital stay for PCI (beta = -0.812, p = 0.417) (

Discussion
Due to considerable differences in the overall prevalence of CAD and related cardiovascular risk factors between men and women as well as the significant effect of gender on the likelihood of cardiovascular disorders, the present study aimed to assess baseline characteristics and outcomes of patients undergoing PCI for primary treatment of STEMI using a sample of Iranian men and women. As the main findings, we found notable differences in age, current smoking rate, and prevalence of MR and TR across the two genders. However, there was no difference in the state of left ventricular function (assessed by LVEF) and in the number of coronary arteries involved between men and women. Regarding outcomes, gender did not affect the CAD-related mortality rate, need for repeated revascularization, or hospital stay. Baseline cardiovascular status and post-PCI complications were not affected by gender. The results were also confirmed by adjusting baseline characteristics. It seems that the rate of CAD complications after revascularization depends on sex, genetic, racial, and environmental factors. While some authors demonstrated similar findings to our survey, others expressed contradictory results. In general, female sex has been linked to a poorer prognosis following coronary revascularization, with a higher risk of death and MI in women undergoing PCI. This has been attributed to older age, higher prevalence of comorbidities, and stronger coronary artery disease (CAD) risk profile [10][11][12]. Although women less than 50 years of age are at lower risk for developing CAD, they may be at higher risk for adverse events once diagnosed, thereby representing a subgroup of patients at increased risk for adverse cardiovascular events [13].
It seems that the discrepancy between the two genders in the outcomes of revascularization should be adjusted for baseline variables -especially age. As indicated in our survey, the similarity between men and women remained even after adjustment for the age factor. However, some previous reports are inconsistent with our findings. In a study by Argulian et al. in 2006 [14], women were more likely to be older, with a greater prevalence of hypertension and diabetes mellitus compared with men. After adjusting for baseline characteristics and coronary artery size, the incidence of coronary vascular injury complications was higher in women than in men, particularly among the young. No significant gender differences were present in the combined endpoint of death, myocardial infarction, and emergency CABG surgery, which is completely similar to our observation. In a study by Epps et al. in 2016 [15], although procedural success rates were similar by gender, the cumulative rate of major adverse cardiovascular events was higher in young women, driven largely by higher rates of repeat revascularizations, which is contrary to our findings. In another study by Guo et al. in 2018 [16], the in-hospital mortality in male patients was significantly lower than those of females. The major adverse cardiovascular events (MACE) decreased significantly in male subjects after initial PCI compared with females. In another study by Heer et al. in 2017 [17], there were no sex-related differences in in-hospital mortality among patients undergoing PCI, but access-related complications were twice as high in women, irrespective of the indication. In a study by Cenko et al., the female sex was associated with post-procedural Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 to 2 and higher mortality [18]. In a study by Josiah et al. in 2018 [19], there was no significant gender difference in the number of vessels attempted, the mean number of lesions treated, or the mean number of stents used. On multivariate analysis, the female sex was not a predictor of death, and there was no significant gender difference in the overall incidence of unadjusted 1-year MACE. In another study by Gudnadottir et al. in 2017 [20], all in-hospital complications following PCI were more frequent among women. There was no gender difference in adjusted 30-day mortality after PCI or CABG. Finally, Worrall-Carter et al. in 2017 [21] showed that compared to men, women were older at admission, less likely to be diagnosed with STEMI, and less likely to smoke, but no gender difference was observed for severe comorbidities or the use of coronary angiography.
Well explained in the literature, there is a wide spectrum of findings between men and women in terms of age on admission, CAD severity before PCI, initial left ventricular function, and early outcomes after PCI. These variations might be due to differences in the type of study planning, study power, racial and genetic characteristics of study populations, and the time of following up.
Our study had some remarkable strengths, particularly a great number of subjects. We faced some limitations as well; the study was retrospective so we had no hand in determining the cases or interacting with the procedures. The detailed demographics of the patients (e.g. BMI, previous history of hypertension and hyperlipidemia, pack-year index, etc) were not available for the whole population, so the study was limited to the factors applicable to all the patients.

Conclusions
According to our study, women suffering from STEMI and undergoing primary treatment with PCI are older than men. Also, ischemic MR and TR are more prevalent in women as compared to men. Regarding the outcomes of PCI, there are no differences in procedural death, left ventricular systolic function, need for CABG, and length of hospital stay between the two genders. A multi-center prospective study is warranted to validate our results.