Current Pharmaceutical Design - Volume 27, Issue 29, 2021

The gender effects in arterial hypertension (HT) epidemiology remain poorly clarified to date. We present an up-to-date review of the data regarding gender disparities in HT’s prevalence, awareness, treatment, and control. Based on the data from three consecutive national-representative SEPHAR (Study for the Evaluation of Prevalence of Hypertension and Cardiovascular Risk in Romania) surveys conducted between 2005 and 2016, we provide insights into gender differences in HT’s epidemiology and their 11- years the evolutionary trend in a high-CV risk European country. Our data displays gender effects in different age-dependent epidemiological patterns in terms of hypertension prevalence, awareness, treatment, and control, mainly due to hormonal status. Hypertension’s prevalence is higher in younger men and older women. Although women are more often aware of their hypertensive condition and receive more often antihypertensive treatment, BP control is lower in older women compared to men of the same age, mainly due to a higher treatment side-effect rate. There is no solid evidence that different antihypertensive drugs exhibit different effects in lowering BP values between genders. In high CV risk European countries like Romania, if all the influencing conditions remain similar to those in the past 11 years, gender discrepancies in terms of HT's prevalence will diminish over time, awareness and treatment of hypertension will continue to be higher in females than in men, with an upward trend of BP control predicted only for women, while in men HT treatment control rate is expected to stagnate.

Potential sex-related differences in the periprocedural and long-term postprocedural outcomes of coronary angioplasty in patients with stable coronary artery disease have been studied thoroughly over the last few decades, to determine whether female sex should be regarded as an independent risk factor that affects clinical outcomes. Based on a significant number of observational studies and meta-analyses, sex has not yet emerged as an independent risk factor for either mortality or major cardiac and cerebrovascular events, despite the fact that in the early 1980s, for several reasons, female sex was associated with unfavourable outcomes. Therefore, it remains debatable whether the female sex should be considered as an independent risk factor for periprocedural and long-term bleeding events. The pharmacological and technological advancements that support current coronary angioplasty procedures, as well as the non-delayed treatment of coronary artery disease in females, have certainly lessened the outcome differences between the two sexes. However, females show fluctuations in blood coagulability through their lifetime and a higher prevalence of bleeding episodes associated with the antithrombotic treatment following transcatheter coronary reperfusion interventions. In conclusion, the clinical results of percutaneous coronary intervention in patients with stable coronary artery disease, during the periprocedural and long-term postprocedural periods, appear to show no significant differences between the two sexes, except for bleeding rates, which seem to be higher in females, a difference that mandates further systematic research.

Cardiovascular diseases (CVD) remain the world's leading cause of death and disability in both men and women, but with different prognostics and outcomes between sexes. Although the burden of CVD is generally related to the conventional risk factors, the relevance of non-traditional risk factors is increasingly being recognized to explain the so-called “residual risk”. Men and women share many similarities regarding classical cardiovascular risk factors but have different disease pathophysiology, clinical presentations, prevalence, and outcomes of CVDs. How sex-specificities regarding the effects of non-traditional risk factors may contribute to the evolution of atherosclerosis and its clinical manifestations in males and females remain largely underanalyzed. The present review summarizes the current knowledge for sex differences in atherosclerotic plaque composition and clinical evolution in association with risk factors, such as inflammation, lipoprotein(a), hemostasis, intraplaque calcification, and depression. We further discuss the potential sex-differential impact of chronic infectious diseases, gut microbiome and, epigenetic gene expression regulation for atherosclerosis and the effect of female-specific disorders in CVD.

Subjects affected by ischemic heart disease with non-obstructive coronary arteries constitute a population that has received increasing attention over the past two decades. Since the first studies with coronary angiography, female patients have been reported to have non-obstructive coronary artery disease more frequently than their male counterparts, both in stable and acute clinical settings. Although traditionally considered a relatively infrequent and low-risk form of myocardial ischemia, its impact on clinical practice is undeniable, especially when it comes to infarction, where the prognosis is not as benign as previously assumed. Unfortunately, despite increasing awareness, there are still several questions left unanswered regarding diagnosis, risk stratification and treatment. The purpose of this review is to provide state of the art update on the current evidence available on gender differences in clinical characteristics, management and prognosis of ischemic heart disease with non-obstructive coronary arteries, both in the acute and stable clinical settings.

Mortality decline in women to a lesser extent than in men with coronary artery disease (CAD) has provoked a bigger interest in some already existing dilemmas and questions. Many studies carried out in the past three decades did not provide us with precise conclusions. Moreover, various challenges in the prevention, diagnosis, treatment and outcome of CAD in women are still remaining. The meta-analysis and the systematic review conducted in the last years have offered novel approaches to understanding CAD gender disparities in access to care and coronary disease management in women, but women are more likely to experience less favorable short- and long-term outcomes than men do. The reasons for these findings should lie in several known segments in the CAD pathophysiological mechanisms different in women and ultimately leading to a lower quality of care. Clinical presentation in women, which is often characterized by atypical chest pain and a higher prevalence of non-obstructive CAD when evaluated invasively, places women to the false-negative diagnosis of CAD and influences inadequate access to care. Clinical presentation and diagnostic methods, as well as the appropriate treatment options insufficiently examined in women, need to be better defined. The traditional CAD risk factors have a greater impact on women than on men. Unique CAD risk factors only seen in women, have recently been recognized with more attention. However, it is important to note that even in women with obstructive CAD and typical clinical presentation, invasive therapy and pharmacologic therapy are not always implemented as recommended by guidelines as in men. Women are underrepresented in CAD trials, and in current guidelines, gender differences in CAD management have not yet been justified. The underestimation of the risk of CAD in women, followed by its underdiagnosis and undertreatment, might be one of the reasons for a worse prognosis in women in comparison with men.

Background: Accelerated atherosclerosis is widely present in patients with systemic lupus erythematosus. Objective: The aim of this review was to analyze the relationship between systemic lupus erythematosus and cardiovascular diseases, with the emphasis on acute myocardial infarction. Methods: We conducted a literature review through PubMed and Cochrane, using keywords: SLE, atherosclerosis, atherothrombosis, coronary artery disease, myocardial infarction, prognosis, sex specifics. Results: Various molecular mechanisms triggered by infection/inflammation are responsible for endothelial dysfunction and the development of atherosclerosis at an earlier age. A contributing factor is the cumulative effect of traditional cardiovascular risk factors interaction with disease-related characteristics. Myocardial infarction rates are 2- to 10-fold higher compared to the general population. Young women have the highest relative risk, however, men carry at least 3-fold higher risk than women. Coronary involvement varies from normal coronary artery with thrombosis, coronary microartery vasculitis, coronary arteritis, and coronary atherosclerosis. Typical clinical presentation is observed in men and older women, while atypical is more frequent in young women. Treatment is guided by the underlying mechanism, engaging invasive procedures alone, or accompanied with immunosuppressive and/or anti-inflammatory therapy. There are significant gender differences in pathophysiology and clinical presentation. However, they receive the same therapeutic treatments. Conclusion: Systemic lupus erythematosus is a major contributor to atherosclerotic and non-atherosclerotic mechanisms involved in the development of myocardial infarction, which should be taken into account during therapeutic treatment. Although systemic lupus erythematosus per se is a “female” disease, males are at increased cardiovascular risk and worse outcomes.

Office white-coat effect tail (OWCET) is defined as a decrease of ≥10 mmHg in systolic blood pressure (SBP) between successive measurements after its waxing during an office visit. The influence of sex on the incidence of long-term major fatal and non-fatal cardiovascular events was studied in two Italian populational cohorts [from the Gubbio Study and the Italian Rural Areas of the Seven Countries Study (IRA)]. OWCET increased risk of cardiovascular disease (CVD) [HR: 1.591 (95% CI: 1.204-2.103)], coronary heart disease (CHD) [HR: 1.614 (95% CI: 1.037-2.512)] and stroke (STR) [HR: 1.696 (95% CI: 1.123-2.563)] events independently of age, serum and high density lipoprotein (HDL) cholesterol, cigarettes, body mass index (BMI) and SBP in women included in Gubbio study over an almost 20-year follow-up. However, risks of CVD, CHD or STR increased in men with OWCET neither in the Gubbio 20-year follow-up nor in the IRA 50-year follow-up. The correction of the regression dilutions bias between the first and the subsequent SBP measurements did not significantly change these outcomes. Primary care physicians should evaluate OWCET, especially in women, to improve stratification of long-term CVD, CHD and STR risks.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common reasons for the increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Moreover, liver- associated death is approximately 10 times higher in patients with NAFLD than in common individuals. In theory, NAFLD is a kind of metabolic syndrome that manifests in the liver, and insulin resistance plays an important role in it. Therefore, drugs that improve insulin sensitivity may be effective for NAFLD. Objective: The aim of this study was to evaluate the effect of metformin treatment on aminotransferase levels, metabolic parameters and body mass index in NAFLD patients via a meta-analysis of clinical trials. Methods: A comprehensive search on PubMed, EMBASE, the Web of Science and the Cochrane Central Register of Controlled Trials was performed for randomized controlled trials (RCTs) on the effect of metformin treatment on aminotransferase levels, metabolic parameters and body mass index in NAFLD patients. Serum hepatic enzyme, lipid, glucose and insulin levels, homeostasis model assessment-insulin resistance (HOMA-IR) index and body mass index (BMI) at different follow-up points exhibited desirable outcomes. The final search was performed in January, 2021. Results: In total, 10 RCTs with 459 patients were included. Compared with controls, metformin could effectively reduce serum fasting glucose and insulin levels and the HOMA-IR index in NAFLD patients at the 6-month follow-up. In addition, metformin could clearly reduce the serum ALT and HOMA-IR index at the 12-month follow-up. Although metformin was found to be effective in managing lipid metabolism and controlling BMI in NAFLD patients compared with that at baseline, the effect was similar to that in controls. In addition, the speed of metformin treatment seemed to be slower than that of controls. Conclusion: Compared to the controls, metformin could effectively reduce the serum fasting glucose and insulin levels and the HOMA-IR index in NAFLD patients at the 6-month follow-up and ALT and the HOMA-IR index at the 12-month follow-up.

Background: As one of the most common cancers globally, hepatocellular carcinoma (HCC) usually has a poor prognosis. Many HCC patients are usually diagnosed at advanced stages. Therefore, new potential biomarkers for the diagnosis and prognosis of HCC are urgently needed. More and more studies have shown that miR-92a-3p can regulate the occurrence and development of various cancers, but its clinical significance and molecular mechanism in HCC are still elusive. Here, we tried to clarify the regulatory mechanism of miR-92a-3p in HCC.

Methods: In this study, we conducted qRT-PCR and revealed that miR-92a-3p was notably upregulated in HCC cells. MTT, flow cytometry, wound healing, Transwell invasion assays and western blot were conducted to uncover that overexpressed miR-92a-3p could boost the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells while inhibiting cell apoptosis. In addition, the proteins associated with the PI3K/AKT/mTOR pathway were also detected by western blot.

Results: It was suggested that miR-92a-3p could activate the PI3K/AKT/mTOR signaling pathway.

Conclusion: These results suggest that miR-92a-3p plays a tumor-promoting role in HCC and may be a potential biomarker for the diagnosis and prognosis of HCC.