**3. Related factors of gender differences**

#### **3.1 Risk factors**

*Cardiac Diseases - Novel Aspects of Cardiac Risk, Cardiorenal Pathology and Cardiac Interventions*

patients with or without ST elevation acute coronary syndromes [2–4]. In the past two decades, with the emergence of drug-eluting stent, the indication of PCI in high-risk patients with coronary artery disease has been tremendously broadened. In recent years, the progress of interventional techniques has also fundamentally changed the treatment of coronary artery disease. Moreover, since balloon angioplasty has been used in patients with coronary artery disease, the influence of gender on clinical outcomes after PCI has been continuously investigated. In particular, previous studies have reported that the incidence of adverse outcomes in female patients with coronary artery disease after PCI is higher than that in male patients with those after PCI, including short- and long-term mortality, major adverse cardiovascular events (MACE), and revascularization. On the one hand, some studies have shown that gender differences in clinical outcomes persist after adjusting for multivariate factors, such as age, prior peripheral vascular disease, prior myocardial infarction, prior PCI, and chronic renal failure [5–8]. On the other hand, other studies have demonstrated that gender is not an independent factor in the clinical outcome [9–11]. Due to the protection of estrogen, a large number of studies have revealed that the onset age of female patients with coronary artery disease is approximately 5–10 years later than that of male patients with those. Additionally, the prevalence of hypertension, diabetes mellitus, and hyperlipidemia was higher in female individual than that in male individual, while the prevalence of former or current smokers was more in male individual. Therefore, the purpose of the present review is to summarize the gender differences in clinical studies of patients with coronary artery disease after PCI and to put forward suggestions for

improving primary and secondary prevention strategies.

death and ischemic cardiac and cerebrovascular events [8].

In a Japanese observational study including 43,231 patients with non-STsegment elevation acute coronary syndrome who underwent PCI from January 2014 to December 2014, the authors concluded that female patients had a higher risk of hospital complications than male patients, especially bleeding [5]. Another largescale cohort study involving 95,030 male and 35,955 female patients from a clinical registry of PCI procedures revealed that female gender remained as an independent predictor for mortality of patients with coronary artery disease underwent PCI after multivariable adjustment from January 2006 to February 2011 [6]. A multicenter study from the United Kingdom and Sweden, which included 338,462 male and 119,799 female patients, indicated that female patients with coronary artery disease after PCI had a higher all-cause mortality than male patients with those and the age was also a strong predictor of mortality [7]. Moreover, a retrospective cohort study from Germany showed that female patients with ST-segment elevation myocardial infarction undergoing PCI harbored a 20% higher age-adjusted risk of

A systematic review involving 21 studies with 21,666 patients from the Netherlands showed that crude short- and long-term mortality was higher in female patients with ST-segment elevation myocardial infarction than that in male patients with those. However, the abovementioned gender differences generally disappeared after adjusting for baseline characteristics [12]. A comprehensive meta-analysis from the United States reported that there were gender differences in patients with coronary artery disease who underwent PCI, including short- and long-term mortality. Nevertheless, these differences were also gradually weakened after adjusting for the clinical differences and/or hospitalization course [13]. Although there were no significant gender differences in long-term mortality after adjustment, the

**2. Representative researches**

**66**

It is clear that the elderly patients not only have a higher risk of cardiovascular disease but also have a higher risk of mortality. The major reason for the delayed onset of female patients with coronary artery disease is the protective effect of estrogen, which can be delayed to female patients with postmenopause. Estrogen can directly protect myocardial cells, reduce myocardial apoptosis, and prevent plaque rupture through sarcKATP channels and β-estrogen receptor [16, 17]. Nevertheless, female patients with coronary artery disease were facing the same risk factors as male patients with those. Female patients with coronary artery disease frequently had hypertension in clinical practice, which can damage endothelial cells, lead to endothelial dysfunction, and accelerate atherosclerosis. Meanwhile, hypertension is associated with chronic alterations of renin-angiotensin-aldosterone system and overexpression of angiotensin II receptor 1/renin-angiotensin-aldosterone system, which can increase myocardial fibrosis, cardiomegaly, extracellular matrix, and diastolic dysfunction. Besides, elevated blood pressure can also increase infarct size of patients with myocardial infarction [18]. In addition, previous studies have shown that more female patients with cardiovascular disease had diabetes mellitus and dyslipidemia, which can impair the endothelial cells of coronary artery and strengthen the functions of coagulation factor VIII and platelets, which can thereby further accelerate the occlusion of the coronary artery and arteriosclerosis. It has been shown that hyperuricemia and hyperhomocysteinemia are independent predictors of female patients with coronary artery disease. Uric acid crystals can deposit on the vessel wall, which can promote inflammation and atherosclerosis [19]. Hyperhomocysteinemia can affect the functions of vascular endothelial cells and lipid metabolism and increase platelet aggregation and adhesion [20, 21]. All of these risk factors may contribute to the occurrence of adverse prognosis events in female patients with coronary artery disease after PCI.
