Cardiovascular Disease In Postmenopausal Women Research Articles

Is Vitamin D a Crucial Molecule for Musculoskeletal and Cardiovascular Systems in Postmenopausal Women?

Vitamin D, a steroid hormone, acts via the vitamin D receptor expressed in various tissues, including bones, muscles, and the cardiovascular system and is associated with well-being of individuals and vitamin D deficiency is considered as a prevalent public health problem. Menopause is an important cornerstone for women, where the hormonal changes may lead to adverse health effects. Vitamin D deficiency during menopausal transition or in postmenopausal period may aggravate the health risks such as osteoporosis, sarcopenia, and cardiovascular diseases associated with menopause. This manuscript aims to provide a review of the complex interaction between vitamin D deficiency and the well-being of postmenopausal women, focusing on musculoskeletal and cardiovascular implications. Clinical studies highlight the importance of maintaining optimal vitamin D levels to decrease the risk of musculoskeletal disorders and cardiovascular diseases in postmenopausal women. However, conflicting findings regarding the effectiveness of vitamin D supplementation in reducing cardiovascular risk suggest the need for further research and a personalized approach for the chemical form of Vitamin D, dose, duration of deficiency, individual variations, and accompanying conditions. The use of vitamin D supplementation in well-evaluated patients is desirable, and help to optimize health status in postmenopausal women.

Adiponectin and visfatin as potential biomarkers of cardiovascular disease in postmenopausal women

Abstract Background Adiponectin and visfatin are involved in many changes associated with obesity and metabolic disorders so may be related to metabolic syndrome and cardiovascular disease. During the perimenopausal period, the risk of obesity and cardiometabolic diseases increases. Therefore, the aim of this study was to assess the relationship between cardiometabolic parameters and circulating levels of visfatin and adiponectin in perimenopausal women with regard to their obesity status. Material and methods This survey-based study was conducted among 168 perimenopausal women. It involved the use of questionnaires, anthropometric measurements, blood pressure measurements, and venous blood collection. Results Our study found that visceral adiposity index (VAI) and lipid accumulation product (LAP) were negatively correlated with adiponectin levels. Preliminary multivariate linear regression analysis revealed a positive correlation between circulating visfatin and IL-6 levels. Adiponectin was negatively correlated with HbA1C, fasting blood glucose, insulin, and triglycerides. Furthermore, circulating adiponectin was positively correlated with HDL, and negatively with HOMA-IR. Conclusions In the women studied, some adipokines may have played a significant role in the development of obesity, metabolic syndrome, and cardiometabolic diseases.

PFAS and their association with the increased risk of cardiovascular disease in postmenopausal women.

Cardiovascular diseases (CVDs) are one of the major causes of death globally. In addition to traditional risk factors such as unhealthy lifestyles (smoking, obesity, sedentary) and genetics, common environmental exposures, including persistent environmental contaminants, may also influence CVD risk. Per- and polyfluoroalkyl substances (PFASs) are a class of highly fluorinated chemicals used in household consumer and industrial products known to persist in our environment for years, causing health concerns that are now linked to endocrine disruptions and related outcomes in women, including interference of the cardiovascular and reproductive systems. In postmenopausal women, higher levels of PFAS are observed than in premenopausal women due to the cessation of menstruation, which is crucial for PFAS excretion. Because of these findings, we explored the association between perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorobutanesulfonic acid in postmenopausal women from our previously established CVD study. We used liquid chromatography with tandem mass spectrometry, supported by machine learning approaches, and the detection and quantification of serum metabolites and proteins. Here, we show that PFOS can be a good predictor of coronary artery disease, whereas PFOA can be an intermediate predictor of coronary microvascular disease. We also found that the PFAS levels in our study are significantly associated with inflammation-related proteins. Our findings may provide new insight into the potential mechanisms underlying the PFAS-induced risk of CVDs in this population. This study shows that exposure to PFOA and PFOS is associated with an increased risk of cardiovascular disease in postmenopausal women. PFOS and PFOA levels correlate with amino acids and proteins related to inflammation. These circulating biomarkers contribute to the etiology of CVD and potentially implicate a mechanistic relationship between PFAS exposure and increased risk of cardiovascular events in this population.

EFFECTS OF DIFFERENT SEX HORMONES ON CARDIOVASCULAR DISEASE: A META-ANALYSIS AND SYSTEMATIC REVIEW

Objective: Sex hormones play different roles in cardiovascular risk of male and female patients. Especially for postmenopausal women, sex hormone disorder is the main reason for their increased risk of cardiovascular disease. This study mainly explores the effects of different sex hormone levels on cardiovascular diseases in men and postmenopausal women. Design and method: This study included 16 studies with 404,474 patients, including 387,361 male patients and 17,113 female patients. Hazard ratio (HR) and 95%CI results of studies on sex hormones and cardiovascular disease risk in the included literature were extracted as research data. The main outcome events are: cardiovascular disease (CVD), heart failure (HF), cardiovascular death, major cardiovascular adverse events (MACE) and all-cause death. This paper mainly researches the effects of sex hormones on cardiovascular risk and the differences of cardiovascular events between men and women. Results: 1. DHT is a protective factor of cardiovascular risk in male patients, HR = 0.83, 95% CI (0.72, 0.96). 2. For postmenopausal women, SHBG and cFT are the risk factors of CVD in postmenopausal women, with HR 95%CI of 1.06(1.01,1.11) and 1.11 (1.04, 1.19) respectively. 3. DHEA and TT is a risk factor for heart failure in postmenopausal women, which can increase the risk by 17% (HR = 1.17, 95% CI (1.09, 1.24)) and HR = 1.07, 95% CI (1.03, 1.12), while the SHBG and DHEA had no significant effect on the occurrence of chronic heart failure. Conclusions: DHT is a protective factor of cardiovascular disease risk in men, and the increase of androgen level is an important risk factor of cardiovascular disease risk in postmenopausal women.

Number of Pregnancies and Risk of Atherosclerotic Cardiovascular Disease in Postmenopausal Women: A Cross-Sectional Study of NHANES from 1999 to 2018.

Background: Atherosclerotic cardiovascular disease (ASCVD) remains the most common cause of death in women. Pregnancy is an exposure unique to women leading to significant changes in maternal cardiovascular function. However, studies of the relationship between the number of pregnancies and ASCVD are rare. We aimed to clarify the association between the number of pregnancies and ASCVD. Methods: In this cross-sectional study, we used publicly available data from the National Health and Nutrition Examination Survey from 1999 to 2018. The number of pregnancies was divided into 0 (reference), 1, 2-3, 4-5, or ≥6, to create more stable estimates. A multiple logistic regression approach was used to examine the correlation between pregnancy and ASCVD in women aged 45 years or older who reported no menstruation in the past 12 months due to menopause, as well as in those aged 55 years or older, encompassing various age groups. We also separately estimated the association between the exposure of pregnancy and individual components of ASCVD. Results: In this study, age-adjusted data showed that women with six or more pregnancies had a doubled risk (odds ratio [OR]: 2.07) of ASCVD. The risk remained elevated at 1.69 times in women with four to five pregnancies and further increased to 1.90 times in women with six or more pregnancies, after adjusting for social factors. Similar patterns were observed when considering reproductive health and cardiovascular risk factors. Across the full population, every model that accounted for these variables consistently indicated that with an increasing number of pregnancies, we observed higher ORs for ASCVD risk (all p values <0.05). Conclusions: A higher number of pregnancies was associated with a higher risk of ASCVD after menopause, especially among women aged 45-64 years. Moreover, this association is particularly significant in the risk of stroke, cardiovascular heart disease, and heart attack.

Association between metabolic phenotypes of overweight/obesity and cardiovascular diseases in postmenopausal women

Background and aimObesity and metabolic abnormalities were associated with an increased risk of cardiovascular diseases. However, it is unclear how metabolic weight phenotypes relate to cardiovascular diseases in postmenopausal women. This study aimed to explore the relationships in postmenopausal women. Methods and resultsWe included 15,575 postmenopausal women aged 35–75 years (median age, 60.6) without cardiovascular disease at baseline from a subcohort of the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project. Metabolically unhealthy phenotype was defined as having ≥2 risk factors of metabolic syndrome: blood pressure ≥130/85 mm Hg or current use of antihypertensive drugs, fasting glucose ≥5.6 mmol/L or current use of antidiabetic agents, triglycerides ≥1.7 mmol/L, and high-density lipoprotein cholesterol <1.3 mmol/L. Cox regression analysis was used to evaluate the risks of cardiovascular diseases. Over a median follow-up period of 3.55 (interquartile range, 2.59–4.44) years, a total of 1354 cardiovascular events occurred. Compared to metabolically healthy normal weight, the multivariate-adjusted hazard ratios and their 95% confidence intervals were 1.41 (1.16–1.72) for metabolically unhealthy normal weight, 1.42 (1.16–1.73) for metabolically healthy overweight/obesity, and 1.75 (1.48–2.08) for metabolically unhealthy overweight/obesity. Subdividing overweight/obesity into separate groups revealed higher total cardiovascular disease risk only in metabolically unhealthy individuals across body mass index categories. ConclusionIn postmenopausal women, both metabolically healthy overweight/obesity and metabolically unhealthy normal weight were associated with a higher risk of cardiovascular disease compared to metabolically healthy normal weight, and the greatest risk was observed in the metabolically unhealthy overweight/obesity category.

Abstract P500: Proton Pump Inhibitor Use and Incident Cardiovascular Disease in Postmenopausal Women, Results From the Women’s Health Initiative

Introduction: Evidence from in-vitro and animal studies suggests that proton pump inhibitor (PPI) use is associated with incident cardiovascular disease (CVD). Observational studies in humans have shown conflicting results and didn’t account for relevant confounders such as diet and physical activity or confounding by indication. Methods: This study included 148,452 postmenopausal women without history of CVD at enrollment into the Women’s Health Initiative (WHI) observational study and clinical trials in 1993-1998. The primary exposure was PPI use (no, yes) determined by medication inventory conducted at baseline. The main outcome was incident primary CVD defined as a composite endpoint of physician-adjudicated myocardial infarction, coronary revascularization, stroke, and CVD mortality. Follow-up time was to September 2010. Cox proportional hazards regression was used to estimate hazards ratios (HR) and 95% confidence intervals (CI) for the association of PPI use and CVD. All models were adjusted for baseline age and stratified according to WHI study component. Additional models were further adjusted for demographics (education, income), lifestyle (smoking, alcohol, diet quality, physical activity, sleep duration), and major CVD risk factors (body mass index, family history of CVD, treated hypercholesterolemia, treated diabetes, treated hypertension). Results: Baseline prevalence of PPI use was 1.91%. After a mean follow-up of 11.3 years, there were 10,944 CVD events. PPI use was associated with a 28% higher risk of CVD compared to non-use in the age adjusted model (HR: 1.28, 95%CI: 1.13-1.45). The association was attenuated but remained significant after adjusting for potential confounders and was materially unchanged when using propensity score adjustment to better address confounding by indication (Table). Conclusions: PPI use was associated with higher risk of incident CVD in postmenopausal women. Further investigations are warranted to confirm this finding and identify potential mechanisms.

#370 : Hormone Replacement Therapy and Risk of Cardiovascular Diseases in Postmenopausal Women Aged 50-59 Years: A Systematic Review of Randomized Controlled Trials

Background and Aims: Cardiovascular diseases are the leading cause of mortality worldwide. Due to declining estrogen levels, women are at higher risk of contracting cardiovascular diseases. Although hormone replacement therapy (HRT) has the potential to prevent cardiovascular diseases, its safety and efficacy are still controversial. The window of opportunity theory suggests that initiating HRT during the early stages of menopause could have the most significant benefits. This review aims to assess available evidence on the effects of HRT in preventing cardiovascular disease in early postmenopausal women aged 50-59 years old. Method: Systematic literature searching was conducted on four databases: Pubmed, EMBASE, EBSCOhost, and ProQuest. Using previously designed keywords, we searched for randomized controlled trials assessing the association between HRT and various cardiovascular outcomes. Critical appraisal was conducted using the Cochrane Risk of Bias 2.0. Results: Six post-interventional analyses from 2 randomized controlled trials with a total of 9,838 subjects were included. The review only assessed the data from subjects aged 50-59 years old without any known comorbidities. Despite varying statistical significance among studies, we observed a relatively consistent trend that estrogen-only HRT lowers the risk of cardiovascular events, thus supporting the window of opportunity theory. However, there was also an increase in the risk of cardiovascular events in estrogen-progesterone combination compared to placebo or estrogen-only HRT. Conclusion: By taking into account aspects of patient characteristics, age during first administration, regimens, and therapy duration, hormone replacement therapy has the potential to prevent cardiovascular diseases in early postmenopausal women aged 50-59 years old.

Moderate intensity walking exercises reduce the body mass index and vascular inflammatory factors in postmenopausal women with obesity: a randomized controlled trial

Postmenopause, the secretion of female hormones changes, causing excessive fat accumulation in the body and leading to chronic inflammation, which increases the incidence of cardiovascular diseases (CVD). Walking is an easily accessible daily exercise and effective non-pharmacological treatment for reducing obesity and the incidence of CVD. The aim of this study was to investigate the effect of moderate intensity walking exercises on body composition, vascular inflammatory factors, and vascular endothelial growth factor (VEGF) in postmenopausal women with obesity. Twenty-six older postmenopausal women with obesity (ages 68–72) were randomly assigned to control (n = 12, BMI 26.06 ± 1.37) or exercise (n = 14, BMI 26.04 ± 1.94) groups. Following a 12-week moderate intensity walking exercise program, we measured the participants’ body composition with an InBody S10 analyzer and assessed blood sera using enzyme-linked immunosorbent assays. There was a significant clustering by weight (p < 0.01), body mass index (p < 0.01), percentage body fat (p < 0.001), high-sensitivity C-reactive protein (p < 0.05), interleukin-6, and tumor necrosis factor-α (p < 0.05) being significantly decreased in the exercise group. Although VEGF levels did not change significantly, a tendency to increase was observed in participants that exercised. Our results indicate that walking exercise may help prevent CVD in postmenopausal women with obesity by reducing obesity and vascular inflammatory factors.

Association between the Composite Dietary Antioxidant Index and Atherosclerotic Cardiovascular Disease in Postmenopausal Women: A Cross-Sectional Study of NHANES Data, 2013-2018.

The relationship between composite dietary antioxidant index (CDAI) levels and the risk of atherosclerotic cardiovascular disease (ASCVD) in postmenopausal women is unknown. In total, 3109 women from the National Health and Nutrition Examination Survey 2013-2018 were included in this cross-sectional study. We evaluated the association between CDAI levels and the risk of ASCVD by using three logistic regression models and restricted cubic splines. A stratified analysis and sensitivity analysis were also conducted. The restricted cubic splines exhibited an L-shaped dose-response association between CDAI levels and the ASCVD risk. Logistic regression analysis found that CDAI levels were negatively associated with the occurrence of ASCVD. The ORs associated with a per-SD increase in CDAI were 0.67 (95% CI: 0.51-0.88) for ASCVD risk. Similarly, women in the group with high CDAI levels were less likely to have ASCVD (OR = 0.71, 95% CI: 0.50-0.98) compared to those in the group with low CDAI levels. When the CDAI levels were divided into quartiles, it was found that the ORs for ASCVD with CDAI levels in Q2 (-1.04-1.11), Q3 (1.11-3.72), and Q4 (3.72-43.87) were 0.63 (0.44, 0.90), 0.64 (0.42, 0.94), and 0.51 (0.27, 0.97), respectively, compared to those with CDAI levels in Q1 (-6.83--1.04). In addition, age, high-density lipoprotein cholesterol levels, and smoking behaviors acted as potential modifiers, and ORs were more significant in women aged 40-69 years, in individuals with low high-density lipoprotein cholesterol levels, and in smokers (p for interaction <0.05). These findings may offer valuable insights into the role of CDAI levels in the development of ASCVD among postmenopausal women.

STUDY ON THE MECHANISM OF CARDIAC HYPERTROPHY INDUCED BY TESTOSTERONE THROUGH MTORC2 IN OVARIECTOMIZED FEMALE SPONTANEOUSLY HYPERTENSIVE RATS

Objective: The estrogen level of postmenopausal women decreased sharply, while the androgen level did not decrease significantly, which was characterized by the inversion of estrogen / androgen ratio. Therefore, it could be observed that relative excess androgen in the circulation of postmenopausal women, which may be one of the reasons for the increase of cardiovascular disease in postmenopausal women. In this study, the model of postmenopausal hypertension was established by bilateral ovariectomy in spontaneously hypertensive rats (SHR), and the specific mechanism of testosterone-induced myocardial hypertrophy in ovariectomized SHR was explored. Design and method: Twenty-four SHR were randomly divided into three groups: sham operation group (Sham group, n = 8), bilateral ovariectomized group (OVX group, n = 8) and testosterone propionate intervention group (OVX+T group, 2.85mg/kg Weekly, im for4 weeks, n = 8). The systolic blood pressure, diastolic blood pressure and heart rate of SHR were monitored and recorded twice a week. Western Blot was used to detect the protein expression of mTOR, p-mTOR, mTORC2 and its subunits Rictor and p-Rictor. Moreover, the expression of autophagy-related proteins LC3 and P62/SQSTM1 and Mitofusin2 (MFN2) and Dynamin related protein 1 (DRP1) in cardiac myocytes was observed. Results: 1. Testosterone could activate the expression of mTORC2 in myocardial tissue: testosterone could activate the expression of mTORC2 and the Rictor of mTORC2 in ovariectomized SHR(Figure 1). 2. Testosterone could inhibit cardiomyocyte autophagy: there was no significant difference in the expression of autophagy-related proteins LC3 and P62/SQSTM1 between Sham and OVX groups, while testosterone could decrease the expression of LC3 protein and increase the expression of P62/SQSTM1 protein in OVX+T group (Figure 2). 3. Testosterone could activate the mitochondrial cleavage of cardiomyocytes: the expression of DRP1 was increased in OVX+T group (Figure 3). Conclusions: In bilateral ovariectomized SHR, testosterone may inhibit cardiomyocyte autophagy by activating the expression of mTORC2, which leads to cardiac hypertrophy in SHR. And in cardiomyocyte mitochondria, testosterone can promote mitochondrial cleavage.

Factors Affecting the Risk of Cardiovascular Disease in Postmenopausal Women: A Postmenopausal Period-Stratified Analysis

Purpose: This study aimed to investigate the factors affecting the risk of cardiovascular disease among postmenopausal Korean women. Methods: This postmenopausal period-stratified analysis used secondary data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018. We selected 1,465 participants with all the relevant data for analysis. The Chi-square test and multiple logistic regression analysis were used to analyze the data. Results: Age, subjective health status, body mass index, and triglyceride level were the factors that influenced the risk of cardiovascular disease for women with a postmenopausal period ≤5 years, whereas age, subjective health status, household income, body mass index, and triglyceride level were the factors that influenced the risk of cardiovascular disease for women with a postmenopausal period &gt;5 years and ≤10 years. Conclusion: Planning health promotion strategies to lower the risk of cardiovascular disease in women must consider the differences among women according to the menopausal status and postmenopausal period.

Role of estrogen in the regulation of central and peripheral energy homeostasis: from a menopausal perspective.

Estrogen plays a prominent role in regulating and coordinating energy homeostasis throughout the growth, development, reproduction, and aging of women. Estrogen receptors (ERs) are widely expressed in the brain and nearly all tissues of the body. Within the brain, central estrogen via ER regulates appetite and energy expenditure and maintains cell glucose metabolism, including glucose transport, aerobic glycolysis, and mitochondrial function. In the whole body, estrogen has shown beneficial effects on weight control, fat distribution, glucose and insulin resistance, and adipokine secretion. As demonstrated by multiple in vitro and in vivo studies, menopause-related decline of circulating estrogen may induce the disturbance of metabolic signals and a significant decrease in bioenergetics, which could trigger an increased incidence of late-onset Alzheimer's disease, type 2 diabetes mellitus, hypertension, and cardiovascular diseases in postmenopausal women. In this article, we have systematically reviewed the role of estrogen and ERs in body composition and lipid/glucose profile variation occurring with menopause, which may provide a better insight into the efficacy of hormone therapy in maintaining energy metabolic homeostasis and hold a clue for development of novel therapeutic approaches for target tissue diseases.

Diosgenin Attenuates Myocardial Cell Apoptosis Triggered by Oxidative Stress through Estrogen Receptor to Activate the PI3K/Akt and ERK Axes.

Cardiovascular diseases in post-menopausal women are on a rise. Oxidative stress is the main contributing factor to the etiology and pathogenesis of cardiovascular diseases. Diosgenin, a member of steroidal sapogenin, is structurally similar to estrogen and has been shown to have antioxidant effects. Therefore, we aimed to investigate the effects of diosgenin in preventing oxidation-induced cardiomyocyte apoptosis and assessed its potential as a substitute substance for estrogen in post-menopausal women. Apoptotic pathways and mitochondrial membrane potential were measured in H9c2 cardiomyoblast cells and neonatal cardiomyocytes treated with diosgenin for 1[Formula: see text]h prior to hydrogen peroxide (H2O2) stimulation. H2O2-stimulated H9c2 cardiomyoblast cells displayed cytotoxicity and apoptosis via the activation of both Fas-dependent and mitochondria-dependent pathways. Additionally, it led to the instability of the mitochondrial membrane potential. However, the H2O2-induced H9c2 cell apoptosis was rescued by diosgenin through IGF1 survival pathway activation. This led to the recovery of the mitochondrial membrane potential by suppressing the Fas-dependent and mitochondria-dependent apoptosis. Diosgenin also inhibited H2O2-induced cytotoxicity and apoptosis through the estrogen receptor interaction with PI3K/Akt and extracellular regulated protein kinases 1/2 activation in myocardial cells. In this study, we confirmed that diosgenin attenuated H2O2-induced cytotoxicity and apoptosis through estrogen receptors-activated phosphorylation of PI3K/Akt and ERK signaling pathways in myocardial cells via estrogen receptor interaction. All results suggest that H2O2-induced myocardial damage is reduced by diosgenin due to its interaction with estrogen receptors to decrease the damage. Herein, we conclude that diosgenin might be a potential substitute substance for estrogen in post-menopausal women to prevent heart diseases.

Prevalence and major contributing factors predicting the 10-year risk for cardiovascular disease in post-menopausal women based on the Framingham Risk Score

Abstract Background: Framingham risk score (FRS) for cardiovascular disease (CVD) initiates preventive medication to reduce the future CVD risk. This study aimed to evaluate the prevalence and the significant contributors to predict the 10-year risk for CVD amongst post-menopausal women using FRS-CVD score. Methods: This cross-sectional study was designed amongst post-menopausal women (5080 years) lacking typical angina pectoris symptoms. Age, gender, systolic blood pressure (SBP), total and high-density lipoprotein (HDL)-cholesterol, smoking status, treatment for hypertension and diabetes were collected from the patients’ records. As per the FRS, risk for CVD was categorised as high (≥20%) and low/intermediate (≤19.9%). Results: Of the 50 subjects included in the study (mean age 63.8 ± 7.5 years), 30 (60%) showed low/intermediate risk and 15 (30%) showed high risk for CVD. Age (P &lt; 0.0002) and SBP (P &lt; 0.0001) were significantly different between the groups. No significant difference in total/HDL-cholesterol and diabetes mellitus was found between the groups. Of the 50 patients, 23 (46%) (13/15 in the high-risk group, P = 0.0002) were undergoing hypertension treatment. Multiple logistic regression analysis showed that age (P = 0.0058, 95% confidence intervals [CI]: 1.0638–1.4395) and hypertension (P = 0.0007, 95% CI: 5.2369- 476.8816) were independent contributing factors for 10-year CVD high risk. Conclusion: Thirty per cent of post-menopausal women showed a 10-year CVD high risk. Age and blood pressure were significant contributing factors for high risk. As the age advances, periodic check-up of blood pressure is inevitable to reduce CVD risk.

Improvement of Cardiovascular Function in Aging Females by the Prolonged Activation of G Protein-Coupled Estrogen Receptor.

Ample evidence suggests that estrogen replacement therapy is associated with beneficial effects with regard to cardiovascular diseases when the therapy is initiated temporally close to menopause but not when it is initiated later. Little is known about the complex interactions between hormone receptors after menopause. Coronary artery function and cardiac function were measured in rats that had either received no treatment or had been pretreated with an androgen receptor (AR) antagonist and/or a GPER agonist G-1. ICI 182,780 was used to block the classical estrogen receptors (ERs) to investigate their complex interactions with GPER. The beneficial effects of GPER were only observed by blocking ARs and classical ERs in aged female rats. The results demonstrate that GPER activation is a potential therapeutic target for the inhibition of age-dependent coronary artery dysfunction and cardiac dysfunction under the condition of blocking ARs and classical ERs after menopause. CLINICAL RELEVANCE: The risk of cardiovascular disease in postmenopausal women significantly increased. The role of sex hormones and their receptors during this process is still complicated. Our present study demonstrated that the imbalance of androgen and estrogen may contribute to the impairment of vascular reactivity and subsequent cardiac function. Treatment with GPER agonist G1 combined with the inhibition of ERα and ERβ could improve vascular function and reduce the myocardial ischemia reperfusion injury. These findings may provide the novel and effective strategy for the treatment of cardiovascular diseases in postmenopausal women.

The effect of ovariectomy on hemodynamic functions and the level of nitric oxide metabolites in the heart of rats

Background. A higher prevalence of cardiovascular disorders has been observed in women after menopause. This study aimed to determine the long-term effects of ovariectomy on hemodynamic functions and the level of nitric oxide metabolites (NOx) in the heart tissue of ovariectomized rats. Methods. Fourteen female Wistar rats were divided into two groups (n=7 in each group) of control and ovariectomized (OVX). OVX rat model was induced using the two dorsolateral skin incision method. Cardiac hemodynamic function indices, including the left ventricular developed pressure (LVDP), peak rate of positive changes in the left ventricular pressure (+dp/dt), and peak rate of negative changes in the left ventricular pressure (-dp/dt) were measured at the time of systole in hearts after 11 months of the ovariectomy. Serum and left ventricular levels of NOx were measured at the end of the study. Results. At the end of the study, OVX rats had lower LVDP (19%, P=0.001), +dp/dt (30%, P&lt;0.001) and -dp/dt (23%, P=0.004) than control group. In addition, the OVX group had lower serum NOx levels (30%, P=0.021) compared to the control group; heart tissue NOx was also lower by 31% in the OVX rats, but it was not statistically significant (P=0.056). Conclusion. Long-term ovariectomy disrupts cardiac hemodynamic function in ovariectomized rats, which is associated with decreased NOx levels in serum. Practical Implications. Our findings indicated impaired cardiac function following long-term estrogen deficiency in OVX rats. These results can be used to prevent and treat the cardiovascular disease in post-menopausal women. However, these results need to be confirmed in humans.

Sexual Dysfunction as a Harbinger of Cardiovascular Disease in Postmenopausal Women: How Far Are We?

BackgroundFemale sexual dysfunction (FSD) affects 40–50% of women in the general population, resulting from the interaction among organic, psychological, sociocultural and relational factors; differently from men, in women definitive clinical evidence suggesting a connection between cardiovascular (CV) diseases (CVDs) and female sexual function is still lacking. AimTo focus on the current scientific support for an association between CV diseases and/or risk factors and FSD, focused primarily on postmenopausal women. MethodsThis is a narrative review based on an extensive literature search of peer-reviewed publications on the associations between CV diseases and/or risk factors and FSD and their underlying mechanisms, which was performed using the PubMed database. OutcomesWe present a summary of the evidence from clinical and preclinical studies and discuss the possible mechanisms providing the pathophysiologic bases of vasculogenic FSD. ResultsGrowing evidence shows that female sexual function, especially arousal, is significantly affected by genital vascular impairment, which can lead to FSD. For many cardiometabolic risk factors and diseases, such as hypertension, diabetes, dyslipidemia and metabolic syndrome, an adverse impact on endothelial function as well as an association with FSD have been recognized. In this scenario, similarly to penile Doppler blood flow studies in men, clitoral Doppler ultrasound can represent an innovative and useful tool to early reveal the presence of CV risk factors and sexual dysfunction. Notably, although the prevalence of CVDs as well as of FSD increases as a function of menopause and aging, middle-aged women have shown a higher prevalence of distressing sexual problems than older and younger women. Clinical ImplicationsIt becomes clinically relevant to assess particularly postmenopausal women for FSD and CVDs, since both disorders still remain underdiagnosed and sub-optimally untreated. Clitoral Doppler ultrasound could represent a useful technique to diagnose the presence of underlying CVD, which along with risk factors could predict sexual dysfunction in women. Strengths & LimitationsThis review focuses on a very important and innovative topic, providing a context for describing, elaborating and evaluating the relevant theory that sexual dysfunction could be a harbinger for CVDs also in women. However, its narrative nature as well as the lack of specifically designed studies to assess a definitive association between FSD and CVDs represent the principle limitations of this paper. ConclusionPostmenopausal women, particularly those in the middle-age range, should be assessed for CV risk factors and FSD, so that both CVDs and sexual problems do not persist unnoticed.Cipriani S, Simon JA. Sexual Dysfunction as a Harbinger of Cardiovascular Disease in Postmenopausal Women: How Far Are We? J Sex Med 2022;19:1321–1332.

Study on the Potential Mechanism of Tonifying Kidney and Removing Dampness Formula in the Treatment of Postmenopausal Dyslipidemia Based on Network Pharmacology, Molecular Docking and Experimental Evidence.

BackgroundManagement of menopausal dyslipidemia is the main measure to reduce the incidence of cardiovascular disease in postmenopausal women. Tonifying Kidney and Removing Dampness Formula (TKRDF) is a traditional Chinese medicine (TCM) formula that ameliorates dyslipidemia in postmenopausal women. This study applied network pharmacology, molecular docking, and in vitro and in vitro experiments to investigate the underlying mechanism of TKRDF against postmenopausal dyslipidemia.MethodsNetwork pharmacology research was first conducted, and the active compounds and targets of TKRDF, as well as the targets of postmenopausal dyslipidemia, were extracted from public databases. Protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to identify the potential targets and signaling pathways of TKRDF in postmenopausal dyslipidemia. Molecular docking was then performed to evaluate the combination of active compounds with principal targets. Finally, an ovariectomized rat model was used for the in vivo experiment and alpha mouse liver 12 (AML12) cells treated with palmitic acid were used for the in vitro experiments to provide further evidence for the research.ResultsBased on network pharmacology analysis, we obtained 78 active compounds from TKRDF that acted on 222 targets of postmenopausal dyslipidemia. The analysis results indicated that IL6, TNF, VEGFA, AKT1, MAPK3, MAPK1, PPARG and PIK3CA, etc., were the potentially key targets, and the PI3K/AKT signaling pathway was the possibly crucial pathway for TKRDF to treat postmenopausal dyslipidemia. Molecular docking suggested that the active compounds have good binding activity with the core targets. The in vivo and in vitro experiments demonstrated that TKRDF ameliorates postmenopausal dyslipidemia by regulating hormone levels, inhibiting inflammation, promoting angiogenesis and inhibiting lipid synthesis, which appear to be related to TKRDF’s regulation of the ERK1/2 and PI3K/AKT signaling pathways.ConclusionThis study clarified the active ingredients, potential targets, and molecular mechanisms of TKRDF for treating postmenopausal dyslipidemia. It also provided a feasible method to uncover the scientific basis and therapeutic mechanism for prescribing TCM in the treatment of diseases.

Relationship Between the Single Nucleotide Polymorphism rs11558471 in the SLC30A8/ZnT8 Gene and Cardiometabolic Markers in Postmenopausal Women.

Postmenopausal women have more risk factors for metabolic syndrome, and genetic alterations in SLC30A8 (zinc transporter 8 [ZnT8]) are directly related to these factors. Our aim was to assess the relationship of the single nucleotide polymorphism (SNP) rs11558471 in the SLC30A8/ZnT8 gene with cardiometabolic markers in postmenopausal women. This cross-sectional study included 53 postmenopausal women divided into two groups according to the SNP genotype (AG + GG [n = 25] and AA [n = 28]). Anthropometric, dietary, and biochemical (glycemic, lipidic, hepatic, renal, and hormonal markers) variables were evaluated and compared between groups. No differences in glycemic, hepatic, renal, and hormonal markers were found between groups. However, the group with the polymorphic allele (AG + GG) had a better lipid profile than non-carriers (total cholesterol, p = 0.041; low-density lipoprotein cholesterol [LDL-c], p = 0.035; non-high-density lipoprotein cholesterol [non-HDL-c], p = 0.043). Logistic regression showed that the group with polymorphic allele had lower chances of increasing levels of LDL-c (odds ratio [OR] = 0.225, p = 0.012) and non-HDL-c (OR = 0.316, p = 0.045). After adjusting for age, body mass index, physical activity, and use of diabetes and dyslipidemia drugs, only LDL-c remained associated (OR = 0.218; p = 0.017). The variant allele of SNP rs11558471 in the SLC30A8 gene was associated with better LDL-c levels, which helps reduce the risks for cardiovascular diseases in postmenopausal women.