Authors

• Afrasyab Altaf — Rehman medicinski institut, Peshawar, Pakistan — ORCID: 0000-0002-4292-5541
• Hammad Shah — Rehman medicinski institut, Peshawar, Pakistan — ORCID: 0000-0002-2956-397X

Abstract

Previous gender-related studies on ejection fraction (EF) were single vessel specific and considered only patients with ST-segment elevation myocardial infarction (STEMI). This study evaluated the effect of gender on EF in acute coronary syndrome, including STEMI and non-ST-segment elevation myocardial infarction (NSTEMI) as well as all blood vessels, since they can affect left ventricular function. 480 patients with acute coronary syndrome (STEMI and NSTEMI) were enrolled. All baseline characteristics along with EF were noted. All patients received reperfusion therapy as per international guidelines. Patients were followed up for one year, after which EF was reassessed. Women were significantly older than men (P<0.05). There was significant difference between EF the between female and male groups (P<0.05). No significant change was seen in EF in the female group during follow-up (P>0.05). Age and female gender were found to be independent predictors of change in EF. Female gender is an independent predictor of recovery of EF in patients with acute coronary syndrome (STEMI and NSTEMI).

Keywords

ejection fraction, women, acute coronary syndrome, percutaneous coronary intervention

DOI

Full Text

## Introduction Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide, and percutaneous coronary intervention (PCI) plays a vital role in its management. (1, 2) Despite the fact that women are affected less often than men, their mortality rates have been shown to be much higher. (3) Myocardial infarction resulting in necrosis causes left ventricular (LV) dilatation and dysfunction. Impaired LV systolic function has been proven to be associated with poor outcomes, so left ventricular ejection fraction (LVEF) is regarded as an important factor for short and long-term outcomes. (4-8) Currently, the optimum strategy in treatment of patients with MI is revascularization of the culprit vessel with PCI. (9, 10) In spite of the well-established role of PCI in protecting viable myocardium and improvement in the overall LV function, variable outcomes have been reported based on gender differences. (11, 12) As compared with men, women have been reported to have higher mortality after PCI. This may be due to higher risk in women at the time of PCI. (13, 14) However, differences based on gender with regard to LVEF in patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) receiving PCI have not been extensively studied apart from very few studies that only examined patients with anterior wall MI (STEMI). The LV is mainly supplied by the left anterior descending (LAD) branch of the left main coronary vessel. (15) Ejection fraction is also affected by infarctions other than the ones associated with the LAD artery such as right ventricular infarction and the dominant circumflex artery with the major obtuse marginal branch. Therefore, in this study we enrolled patients (STEMI and NSTEMI) irrespective of the vessel involved and assessed the effect of gender on recovery of LVEF. ## Patients and Methods Patients admitted to our hospital who fulfilled the following criteria were enrolled in the study: (**a**) age between 40 and 70 years; (**b**) patients with acute myocardial infarction and no previous history of ischemic heart disease; (**c**) patients giving written and informed consent. Patients who did not give consent or who could not afford to undergo percutaneous revascularization due to financial constraints were excluded from the study. At presentation, all baseline characteristics such as age, gender, diabetes, hypertension, smoking, LVEF, family history of coronary artery disease (CAD), and interval from onset of chest pain to PCI were noted. During coronary angiography, assessment of severity of coronary stenosis and TIMI flow was performed by three consultant cardiologists. Echocardiography was carried out at baseline (before PCI) and after one year by experienced operators who were blinded to patient information. Ejection fraction was estimated with biplane Simpson’s rule using GE Vivid S5 system. (16) Continuous variables were described as mean ± SD (standard deviation) and Student t-test was used for comparison. Categorical variables were described as frequencies and percentages, and Pearson’s chi square test was used for comparisons. Rank-sum test and multiple linear regression analysis were used to assess the effect of gender and various other variables on the change in LVEF one year after PCI. A P value of less than 0.05 was considered significant. All analyses were carried out using SPSS (version 20.0; SPSS, Chicago, Illinois, USA). Informed consent was obtained from all subjects included in the study. The study protocol was approved by the Ethics Committee of Rehman Medical Institute and the study abided by the Declaration of Helsinki. ## Results A total of 480 patients were enrolled in this study, out of which 280 (58.3%) were men and 200 (42.6%) were women. The baseline characteristics of the study group are shown in **Table 1**. Women were significantly older compared with men (65.9±8.01 vs. 55±9.38, P0.05). Patients in the male and female groups received similar medications at admission, which included aspirin, clopidogrel, beta-blockers, angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and statins. Patients were given diuretics when indicated. ### TABLE 1: Baseline characteristics of study groups. | **Variable** | **Women** | **Men** | | --- | --- | --- | | | **(n=200)** | **(n=280)** | | Age (years) | 65±8.01 | 55±9.38* | | Left ventricular ejection fraction (%) | 40.26±9.09 | 47.85±10.73* | | Diabetes | 64 (32%) | 81 (29%) | | Hypertension | 62 (31%) | 84 (30%) | | Family history of CADa | 26 (13%) | 42 (15%) | | Hyperlipidemia | 42 (21%) | 70 (25%) | | Renal failure | 18 (9%) | 28 (10%) | | Obesityb | 44 (22%) | 70 (25%) | | Smoking | 34 (17%) | 59 (21%) | | Aspirin | 200 (100%) | 280 (100%) | | Clopidogrel | 198 (99%) | 280 (100%) | | Beta blocker | 194 (97%) | 266 (95%) | | ACEIc / ARBd | 180 (90%) | 260 (93%) | | Nitrates | 196 (98%) | 269 (96%) | | Diuretics | 70 (35%) | 84 (30%) | | Lipid lowering agents | 140 (70%) | 210 (75%) | [†] a Coronary Artery Disease b Obesity is BMI above 30 c Angiotensin Converting Enzyme Inhibitor d Angiotensin Receptor Blocker *P ≤ 0.05 Coronary angiography followed by a revascularization procedure (PCI) were performed in all patients. Multi-vessel disease as well as the type of vessel involved were similar in both men and women (P>0.05). There was no significant difference between the two groups as far as re-infarction and mortality were concerned (**Table 2**). ### TABLE 2: Angiographic variables and procedural outcomes based on gender. | **Variable** | **Variable** | **Women** | **Men** | | --- | --- | --- | --- | | | | **(n/%)** | **(n/%)** | | Multi-vessel disease | | 76 / (38%) | 98 / (35%) | | LADa | | 120 / (60%) | 140 / (50%) | | LCXb | | 98 / (49%) | 122 / (43%) | | RCAc | | 80 / (40%) | 98 / (35%) | | STEMId | | 80 / (40%) | 120 / (43%) | | NSTEMIe | | 120 / (60%) | 160 / (57%) | | Pain onset to reperfusion time (hours) | | 14.56±10.05 | 12±14.30 | | Re-Infarction | | 3 / (1.50%) | 5 / (1.78%) | | Decompensated Cardiac Failure | | 8 / (4.0%) | 7 / (2.5%) | | Mortality | | 4 / (2.00%) | 6 / (2.14%) | | **PCI Procedure** Single (Culprit) Vessel | | 198 (99%) | 277 | | Multi-vessel | | 2 (1%) | 3 (1%) | | TIMI flow | | 3 | 3 | | Complications – No Flow | | 3 (1.5%) | 4 (2.0%) | | Dissection | | 2 (1%) | 3 (1%) | [†] a.Left Anterior Descending artery b.Left Circumflex Artery c.Right Coronary artery d.ST-segment Elevation Myocardial Infarction e.Non-ST-segment Elevation Myocardial Infarction. At baseline the LVEF in the female group was found to be lower than in the male group, and the difference was statistically significant (40.26±9.07 vs. 47.85±10.73, P0.05) (**Table 3**). At follow-up, LVEF was significantly lower in women as compared with men, which was analyzed with a rank sum test (mean rank 65.62 vs. 115.18, P<0.05). ### TABLE 3: Left ventricular ejection fraction in study groups at baseline and follow-up. | **Variable** | **Female** | **Male** | | --- | --- | --- | | Baseline LVEF (%) | 40.26±9.07 | 47.85±10.73* | | Follow-up LVEF (%) | 41.73±8.85 | 53.01±9.10* | [†] * P ≤ 0.05 LVEF = left ventricular ejection fraction. Multivariable linear regression analyses was used for assessment of the effect of gender on LVEF. Indices such as gender, age, smoking, diabetes, hypertension, total cholesterol, body mass index (BMI), creatinine, family history of CAD, multi-vessel disease, baseline LVEF, time interval from pain onset to reperfusion, and troponin were included in the model for analysis. The regression analysis showed that female gender and age were independent predictors of LVEF recovery (P<0.001) (**Table 4**). ### TABLE 4: Multivariable regression analysis for predictors of change in left ventricular ejection fraction. | | **Multivariable analysis** | **Multivariable analysis** | **Multivariable analysis** | | --- | --- | --- | --- | | | | **HR (95% CI)** | **P value** | | Gender | | 1.121 (1.102-1.251) | **0.04** | | Age | | 1.299 (1.102-1.611) | **0.03** | | Diabetes Mellitus | | 0.125 (0.101-1.812) | 0.15 | | Hypertension | | 2.556 (0.112-56.497) | 0.59 | | Body Mass Index | | 0.691 (0.359-1.299) | 0.30 | | Smoking | | 1.894 (0.061-65.155) | 0.69 | | Left Ventricular Ejection Fraction | | 1.112 (0.723-1.587) | 0.59 | | Creatinine | | 0.892 (0.791-1.056) | 0.10 | | Family History of Coronary Artery Disease | | 0.985 (0.899-1.010) | 0.49 | | Chest Pain (Time of Onset) | | 2.451(0.103-13.638) | 0.45 | | Total Cholesterol | | 1.165 (0.186-6.383) | 0.79 | | Multi Vessel Disease | | 0.198 (0.010-69.442) | 0.59 | | Troponins | | 0.114 (0.015-1.895) | 0.13 | ## Discussion The results of this study showed that the recovery of LVEF one year after PCI for acute MI was worse in women than men. This effect on LVEF can be explained on the basis of our study in conjunction with another study which considered patients with anterior wall myocardial infarction (STEMI) only. (4) Multiple factors may be responsible for such results, which include older age at the time of presentation and more comorbidities at the time of presentation in women. The importance of such factors can be supported by various other studies. (4, 13, 14) Women were of older age as compared to men. Based on established facts, the cardio-protective effect of estrogen is responsible for the delay in the onset of cardiovascular disease in women, which translates into the fact that CAD would present at an older age in women. (17) As comorbidities are more common in old age, women with onset at an older age tend to have higher incidence of comorbidities. Moreover, the prevalence of other diseases such as diabetes has been established to be more common in women, which can present as multi-vessel disease on coronary angiography. (11, 18-23) Findings in the current study did not show such a trend in multi-vessel disease in women, which can be attributed the fact that the number of patients with diabetes was similar in both groups. This study included patients with STEMI as well as NSTEMI. The reason for the inclusion of NSTEMI patients was that LVEF is an important predictor of mortality in NSTEMI patients as well. Moreover, previous studies of the role of gender in LVEF included only patients with STEMI in the study samples. There is no data of such studies in patients with NSTEMI. (24) Dreyer et al. (17) also demonstrated that the time from onset of chest pain to hospital admission was longer in women as compared with men. One of the main reasons suggested is that women have a lack of awareness of MI symptoms. (19) A prolonged time interval from onset of symptoms to presentation at a hospital leads to severe myocardial damage and hence impaired function. In this study, the role of such confounding variables was ruled out by including patients presenting with similar duration of chest pain. Studies have demonstrated that being female is an independent predictor of morbidity and mortality in patients with MI after PCI, (13, 14, 25, 26) which was also reflected in the results from our study. The present study had a few limitations. First, the sample size was moderate, which is due to a number of factors such as not giving consent for inclusion in the study and financial constraints. Second, the follow-up period was relatively short. We believe that the results would be more pronounced with a larger sample and longer follow-up period. ## Conclusion In this study, we found that women had a poorer recovery of LVEF as compared with men after PCI. This gender-specific effect was present in both STEMI and NSTEMI patients and is not related to the coronary vessel involved. ## Acknowledgments We thank the physicians of the echocardiography department and coronary care units as well as the staff of catheterization laboratory of our hospital.

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