Cardiovascular Disease In Postmenopausal Women Research Articles

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.

Effects of heavy metals on cardiovascular diseases in pre and post-menopausal women: from big data to molecular mechanism involved.

To assess the link between a mixed heavy metal (cadmium, lead, and mercury) and the 10-year risk of cardiovascular diseases (CVDs) in pre- and post-menopausal Korean women aged ≥20 years, as well as identify potential molecular mechanisms of mixed heavy metal-induced CVDs. Multivariate linear regression, weighted quantile sum (WQS) regression, quantile g-computation (gqcomp), and Bayesian kernel machine regression (BKMR) models were used to examine the effects of mixed heavy metals and the 10-year risk of CVDs. The Comparative Toxicogenomics Database, MicroRNA ENrichment TURned NETwork, and the microRNA sponge generator and tester were used as the key data-mining approaches. In our BKMR analysis, we found that the overall effect of mixed heavy metals was linked to the 10-year risk of CVDs in postmenopausal women in the upper 20th percentiles and in premenopausal women in the upper 55th percentiles. Mercury was identified as the key chemical for the 10-year risk of CVDs in pre- and postmenopausal women. In silico analysis revealed that a heavy metal mixture interacted with six genes associated with CVD development. Physical interactions (77.6%) were found to be the most common among CVD-related genes induced by the heavy metals studied. Several pathways have been identified as the main molecular mechanisms that could be affected by studied heavy metals and are implicated in the development of CVDs (e.g., lipid and lipoprotein metabolism, lipoprotein metabolism, cholesterol metabolism, and cardiovascular disease). ALB, APOE, ATF5, and CREB3L3 were the key genes and transcription factors related to CVDs induced by the mixture of the investigated heavy metals, respectively. The two miRNAs with the highest interaction and expression in the development of CVDs were hsa-miR-199a-5p and hsa-miR-199a-3p. We also designed and tested miRNA sponge sequences for these miRNAs. The cutoff thresholds for each heavy metal level linked with the 10-year risk of CVDs were described. A mixture of heavy metal exposures, especially mercury, was more strongly linked with the 10-year risk of CVDs in postmenopausal women than in premenopausal women. Early interventions in postmenopausal women should be considered to reduce CVD risks.

Sleep Disturbance and Sympathetic Reactivity in Menopausal Women

IntroductionCardiovascular disease (CVD) is the leading cause of death in women. Sleep disturbances (DS), such as insomnia or frequent nocturnal awakenings, may increase the risk of CVD. Prior work suggests that autonomic blood pressure (BP) dysregulation in postmenopausal women may exaggerate risk of hypertension (HTN) and CVD. In addition, individuals with greater BP and sympathetic neural responses to stressors, such as a cold pressor test (CPT), demonstrate future risk for HTN development. Further, when exposed to 24‐hour sleep deprivation, older women, but not older men, demonstrate greater sympathetic activity. It is unknown, however, if women who experience DS demonstrate a greater sympathetic reactivity to a CPT. The purpose of this study was to determine if postmenopausal women with DS exhibit sympathetic reactivity to a CPT compared to women without DS.MethodsEighteen women (62±1yrs old; mean±SE) participated in two study visits. Visit 1: Informed consent and medical and health questionnaires. Visit 2: DS was assessed by the Menopause‐Specific Quality of Life questionnaire. Participants were classified as having disturbed sleep (DS; n=10) or non‐disturbed sleep (NDS; n=8) based on a scale of 1 indicating ‘none’ and 2‐8 being how bothersome it is. The study was conducted in the morning after overnight fast and abstinence of alcohol, caffeine, and exercise. Muscle sympathetic nerve activity (MSNA) was measured from the peroneal nerve using microneurography. Heart rate (HR) via 3‐lead electrocardiography, MSNA, and beat‐to‐beat BP using a non‐invasive finger cuff were measured during a 10‐min quiet rest and a two‐min CPT of the left hand.ResultsMenopause onset ranged from 40‐57yrs (50±1yrs). Body mass index was similar between groups (DS=25±1kg/m2, NDS=24±2kg/m2, p=0.53). MSNA burst incidence (bursts/100 heart beats, hb) increased throughout the CPT (time effect, p<0.01), but increases were not significantly different between DS (Δ19±6b/100hb; 95% CI [7,31]) and NDS (Δ11±6b/100hb; 95% CI [‐2,24]) (time*group, p=0.36) groups. Systolic BP, Diastolic BP and HR increased similarly (p>0.05) during the CPT for both groups. Sleep difficulty score was correlated with resting diastolic BP (r=0.43, p=0.03) and trended to correlate with the age of menopause (r= ‐0.37, p=0.05).ConclusionThese findings suggest that women with DS do not demonstrate greater sympathetic reactivity to a CPT, however, we did observe that DS was linked to greater diastolic BP at rest and appeared to be more bothersome for women who completed menopause at an earlier age. These findings suggest a pathway by which disrupted sleep may contribute to the future development of HTN and CVD in postmenopausal women.

Cardiovascular Reactivity During a Fatiguing Exercise in Women: The Influence of Menopause Duration and Age

IntroductionThe risk of hypertension (HTN) and cardiovascular disease (CVD) dramatically increases following menopause, and premature and early menopause (<45yr) substantially increase this risk. Greater blood pressure (BP) reactivity to stressors such as exercise can predict future risk of developing HTN. Thus, we aimed to determine if the time since menopause completion contribute to greater BP reactivity during a fatiguing hand grip (HG). We hypothesized that women who have been postmenopausal for a longer duration would exhibit greater cardiovascular reactivity to a fatiguing HG exercise.MethodsWomen who experienced early and typical‐age (>46yr) menopause completed two visits. Visit 1: Informed consent, medical and health questionnaires. Visit 2: Participants rested in a supine position. Three maximum voluntary contractions (MVC) of their left hand were completed followed by a baseline rest (BL) of 10 minutes. Following BL, a HG test at 30% of MVC was performed until time to task failure. Non‐invasive beat‐to‐beat BP and heart rate (HR) were recorded during BL and HG test. Systolic (SAP), diastolic (DAP), mean arterial (MAP), and HR were analyzed as BL averages and in 20‐30s intervals at start, 25%, 50%, 75%, and task failure. Repeated‐measures ANOVA and independent T‐tests were used for the statistical analysis; results are presented as mean±SD.ResultsEighteen postmenopausal females completed the study and were divided into two groups: 1) postmenopause ≤10yrs (PM≤10; 8±2 yrs; body mass index (BMI): 25±3 kg/m2, n=8) and 2) postmenopause ≥11 (PM≥11; 15±5 yrs; BMI: 25±5 kg/m2, n=10). The PM≥11 group was slightly older (64±3yrs) than the PM≤10 (60±4yrs, p=0.005). BL SAP was not different between PM≤10 (133±14mmHg) and PM≥11 (128.75±14mmHg; p=0.95). DAP (85±9 vs 81±10mmHg; p=0.68) and MAP (100±10 vs 96±9mmHG; p=0.40), were not different between PM≤10 and PM≥11, respectively. During the fatiguing contraction, SAP increases were exaggerated in PM≥11 compared with PM≤10 (Δ63±25 vs Δ40±16mmHg; group × time, p=0.03). Similarly, MAP increased more in PM≥11 compared with PM≤10 (Δ49±16 vs Δ31±10mmHg; group × time, p=0.04), but not DAP (group × time, p=0.1) or HR (group × time, p=0.08). When co‐varying for age, however, the interactions were no longer significant (p>0.05, for all). In addition, peak increases in SAP (p=0.04), MAP (p=0.01), and HR (p=0.02) were greater in PM≥11 compared with PM≤10, but these observations were no longer significant when co‐varying for age (p>0.05, for all).ConclusionNovel findings from this study suggest that although the duration of menopause influences BP reactivity during a moderate intensity fatiguing contraction, this greater increase may be explained by older age. This elevated response to submaximal exercise may contribute to the increased risk of HTN and CVD in postmenopausal women.

Nutraceuticals for Age-Related Macular Degeneration: Formulation Optimization Focused on Safety

Age-related macular degeneration (AMD) is a multifactorial disease, with oxidative stress as a main pathogenetic factor in the development and progression. Large clinical trials have shown that the additional intake of vitamins and minerals in high doses reduce the risk progression to advanced wet AMD by 25 %. Some of these powerful antioxidants are not synthesized in the human body and can only be obtained with food as part of dietary supplements. However, patients with AMD, belonging to the older age group, often have comorbid conditions, for which they are used to take appropriate drug and vitamin therapy for a long time, as well as they have malnutrition of varying severity. Additional intake of high doses of ophthalmic vitamin-mineral complexes can lead to side effects due to overdose and possible disorders of drug absorption due to concomitant pathology. The article presents the results of the AREDS 2 study and a number of other clinical trials that studied long-term intake of vitamins and minerals in dosages similar to the AREDS 1 formula, containing vitamin C (500 mg), vitamin E (400 international units), beta-carotene (15 mg), zinc (80 mg as zinc oxide) and copper (2 mg as copper oxide). The cited works show that long-term intake of high dosages of some vitamins in elderly patients with severe concomitant diseases and a history of smoking can lead to undesirable consequences for the eye and other body systems. Potential side effects include an increased risk of glaucoma and cataract, an increased risk of prostate cancer in healthy men, an increased risk of lung cancer in former smokers, and an increased risk of cardiovascular disease in postmenopausal women with diabetes. Thus, high dosages of vitamins and minerals in nutraceuticals should be administered with great caution, and a reduction in dosages to the recommended intake rates when switching to long-term intake may be considered. One of the possibilities for increasing the bioavailability of active substances in the composition of dietary supplements can be a microencapsulation.

Roles of Hormone Replacement Therapy and Menopause on Osteoarthritis and Cardiovascular Disease Outcomes: A Narrative Review.

Osteoarthritis (OA) is a highly prevalent condition characterized by degradation of the joints. OA and cardiovascular disease (CVD) are leading contributors to disease burden worldwide, with a high level of overlap between the risk factors and occurrence of both conditions. Chief among the risk factors that contribute to OA and CVD are sex and age, which are both independent and interacting traits. Specifically, the prevalence of both conditions is higher in older women, which may be mediated by the occurrence of menopause. Menopause represents a significant transition in a women's life, and the rapid decline in circulating sex hormones, estrogen and progesterone, leads to complex physiological changes. Declines in hormone levels may partially explain the increase in prevalence of OA and CVD in post-menopausal women. In theory, the use of hormone therapy (HT) may buffer adverse effects of menopause; however, it is unclear whether HT offers protective effects for the onset or progression of these diseases. Studies have shown mixed results when describing the influence of HT on disease risk among post-menopausal women, which warrants further exploration. The roles that increasing age, female sex, HT, and CVD play in OA risk demonstrate that OA is a multifaceted condition. This review provides a timely consolidation of current literature and suggests aims for future research directions to bridge gaps in the understanding of how OA, CVD, and HT interact in post-menopausal women.

Effect of dehydroepiandrosterone on atherosclerosis in postmenopausal women.

In China, cardiovascular disease (CVD) has surpassed malignant tumours to become the disease with the highest mortality rate, and atherosclerosis (AS) is an important pathological cause of CVD. Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in circulating human blood and is a precursor of estrogen and androgen. DHEA is converted into a series of sex hormones in local peripheral tissues where its acts physiologically. DHEA also acts therapeutically, thereby avoiding the adverse systemic reactions to sex hormones. DHEA inhibits AS, thus inhibiting the development of CVD, and it improves the prognosis for CVD. The incidence of CVD in postmenopausal women is substantially higher than that in premenopausal women, and that incidence is believed to be related to a decrease in ovarian function. The current review analyzes the mechanisms of postmenopausal women's susceptibility to AS. They tend to have dyslipidemia, and their vascular smooth muscle cells (VSMCs) proliferate and migrate more. In addition, oxidative stress and the inflammatory response of endothelial cells (ECs) are more serious in postmenopausal women. This review also discusses how DHEA combats AS by countering these mechanisms, which include regulating the blood lipid status, protecting ECs (including coping with oxidative stress and inflammatory reactions of the vascular endothelium, inhibiting apoptosis of ECs, and inducing NO production) and inhibiting the proliferation and migration of VSMCs. As a result, DHEA has great value in preventing AS and inhibiting its progression in postmenopausal women.

Early Menopause and Cardiovascular Disease Risk in Women With or Without Type 2 Diabetes: A Pooled Analysis of 9,374 Postmenopausal Women.

OBJECTIVEEarly menopause may be associated with higher cardiovascular disease (CVD) risk. Type 2 diabetes mellitus (T2DM), coupled with early menopause, may result in even greater CVD risk in women. We examined CVD risk in women with early compared with normal-age menopause, with and without T2DM overall, and by race/ethnicity.RESEARCH DESIGN AND METHODSWe pooled data from the Atherosclerosis Risk in Communities study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. We included women with data on menopausal status, menopausal age, and T2DM, excluding pre- or perimenopausal women and those with prevalent CVD. Outcomes included incident coronary heart disease (CHD), stroke, heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD) (CHD or stroke). We estimated the risk associated with early (<45 years) compared with normal-age menopause using Cox proportional hazards models. Covariates included age, race/ethnicity, education, BMI, blood pressure, cholesterol, smoking, alcohol consumption, antihypertensive medication, lipid-lowering medication, hormone therapy use, and pregnancy history.RESULTSWe included 9,374 postmenopausal women for a median follow-up of 15 years. We observed 1,068 CHD, 659 stroke, 1,412 HF, and 1,567 ASCVD events. T2DM significantly modified the effect of early menopause on CVD risk. Adjusted hazard ratios for early menopause and the outcomes were greater in women with T2DM versus those without (CHD 1.15 [95% CI 1.00, 1.33] vs. 1.09 [1.03, 1.15]; stroke 1.21 [1.04, 1.40] vs. 1.10 [1.04, 1.16]; ASCVD 1.29 [1.09, 1.51] vs. 1.10 [1.04, 1.17]; HF 1.18 [1.00, 1.39] vs. 1.09 [1.03, 1.16]). The modifying effect of T2DM on the association between early menopause and ASCVD was only statistically significant in Black compared with White women.CONCLUSIONSEarly menopause was associated with an increased risk for CVD in postmenopausal women. T2DM may further augment the risk, particularly in Black women.

Combined Effects of Metabolic Abnormalities and Obesity on Cardiovascular Diseases among Korean Postmenopausal Women.

Combined effects of metabolic abnormalities, including metabolic syndrome and obesity, should be identified to screen postmenopausal women at risk of developing cardiovascular diseases. The purpose of this study was to identify the combined effects of metabolic abnormalities and obesity on cardiovascular diseases among postmenopausal Korean women (aged 40–83 years). Data of 5959 postmenopausal women from the Korean National Health and Nutrition Examination Survey (2015–2018) were secondarily analyzed. Using complex simple analysis procedures, logistic regression analysis was performed to identify the combined effect of metabolic abnormalities and obesity on cardiovascular diseases among postmenopausal Korean women. In combination, metabolic syndrome (more than three metabolic abnormalities) and obesity (overweight [≥23 kg/m2 and <25 kg/m2 in body mass index] and obese [>25 kg/m2 in body mass index]) increased the likelihood of developing cardiovascular diseases but combining more than one metabolic abnormality and obesity did not. Combining metabolic syndrome and non-obesity (underweight and normal weight) increased the likelihood of the prevalence of cardiovascular diseases but combining more than one metabolic abnormality and non-obesity did not. Increased cardiovascular diseases in postmenopausal women may be more commonly associated with metabolic syndrome having multiple metabolic abnormalities, but not obesity. Thus, instead of simple weight control, early management of metabolic syndrome is recommended to prevent cardiovascular disease among postmenopausal Korean women.

992-P: Early Menopause and Cardiovascular Disease Risk in Women with and without Diabetes

Background: Early menopause may be associated with higher cardiovascular disease (CVD) risk due to the early cessation of estrogens protection. The presence of diabetes (DM) coupled with early menopause may result in even greater CVD risk in postmenopausal women. We compared CVD risk in women with early vs. normal age menopause with and without DM. Methods: We pooled data from the Atherosclerosis Risk in Communities Study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. Women with data on menopausal status, age at menopause and DM (yes/no) were included. We excluded pre- or peri-menopausal women, those with hysterectomy/oophorectomy or prevalent CVD. Outcomes were incident coronary heart disease (CHD), ischemic or hemorrhagic stroke, heart failure (HF), and a composite CVD outcome (CHD, stroke or HF). Cox models examined the risk associated with early (&amp;lt;45 yrs) vs. normal age (≥45 yrs) menopause. Covariates included baseline age, race, education, BMI, blood pressure, cholesterol, smoking, alcohol consumption, and hormone therapy use. Results: During a median follow-up of 15 yrs for 5964 postmenopausal women, 684 CHD, 434 stroke, 962 HF and 1535 CVD events occurred. In adjusted models, women with early menopause had elevated risk of CHD (Hazard ratio 1.12, 95% CI 1.03-1.22), stroke (1.09, 1.01-1.18) and HF (1.09, 1.00-1.19) compared to those with normal age menopause. DM was a significant effect modifier to the relationship between early menopause and CHD, stroke or CVD (P for interaction ≤0.05). HRs for early menopause and the outcomes were greater in diabetic than nondiabetic women (CHD 1.34, 1.02-1.78 vs. 1.10, 1.00-1.20; stroke 1.26, 0.98-1.61 vs. 1.07, 0.98-1.16; CVD 1.41, 1.01-1.95 vs. 1.04, 0.94-1.14). Conclusion: Early menopause increases risk for CVD in postmenopausal women; DM places this group at even higher CVD risk. Attention to CVD risk monitoring and management in women with early menopause, with and without diabetes, should be considered. Disclosure Y. Yoshida: None. Z. Chen: None. R. L. Baudier: None. M. Krousel-wood: None. A. H. Anderson: None. V. Fonseca: Consultant; Self; Abbott Diabetes, Asahi Kasei Corporation, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Stock/Shareholder; Self; Amgen Inc., Bravo4health, Mellitus Health. F. Mauvais-jarvis: None. Funding National Institutes of Health (K12HD043451)

Abstract 030: The Association Of Hypnotics With Incident Cardiovascular Disease And Mortality Among Post-menopausal Women With Sleep Disturbances

Background: Chronic insomnia is common in post-menopausal women and is associated with higher cardiovascular disease (CVD) risk. Hypnotics are a second-line therapy after cognitive behavioral therapy for management of chronic insomnia. Among the hypnotics, nonbenzodiazepine GABA agonists (Z-drugs) are commonly prescribed. However, it is unclear whether Z-drug use and other hypnotic use is associated with risk of incident CVD and mortality in older people with sleep disturbances. Objectives: Among post-menopausal women with sleep disturbances, to evaluate the association of Z-drug use compared with use of other prescription hypnotics, and with non-use of any prescription hypnotics with CVD and mortality. Methods: The population studied were post-menopausal women from the Women’s Health Initiative (WHI) Observational Study and Clinical Trials who, at baseline, scored &gt;=9 with the WHI Insomnia Rating Scale (N=40,728). Hypnotic use was ascertained from prescription medications scanned into the Medi-Span database at baseline and first follow-up clinic visit. Frequency of use was ascertained from self-report. Participants were categorized as users of Z-drugs, users of other prescription hypnotics or non-users. Outcomes were composite CVD (congestive heart failure, stroke, and fatal/non-fatal myocardial infarction) and mortality, centrally adjudicated with review of medical records and death certificates. Hazard ratios were estimated from Cox proportional hazards regression models adjusted for demographic, medical history, and sleep measures. To address potential confounding by indication, we also adjusted for propensity to be prescribed hypnotics. Results: At the first follow-up visit 1.1% (424 of 38,979) of participants were users of Z-drugs, 4.2% (1,653 of 38,979) were users of other prescription hypnotics, 3.1% (1,187 of 38,979) had discontinued prescription hypnotic use, and 91.6% (35,715 of 38,979) were non-users at both baseline and first follow-up visit. The mean age of our cohort was 63.6 years (SD = 7.2) and mean follow-up time after the initial follow-up visit was 14.0 years (SD = 6.3). Z-drug use was significantly associated with an increased risk of composite CVD (HR= 1.35, 95%CI: 1.02-1.79) and all-cause mortality (HR= 1.38, 95%CI: 1.13-1.69). Use of other prescription hypnotics and casual use (&lt;=2 times a week) of any hypnotic were not associated with either cardiovascular disease or mortality. Conclusion: Use of Z-drugs three or more times a week was associated with an increased risk of death and cardiovascular disease in post-menopausal women being treated for insomnia. Additional research is needed to evaluate association between frequency of hypnotic use and these outcomes and to investigate possible mechanisms.

The association of hypnotics with incident cardiovascular disease and mortality in older women with sleep disturbances

Background/ObjectiveInsomnia is common in older women and is associated with higher cardiovascular disease (CVD) risk. Nonbenzodiazepine GABA agonists (Z-drugs) are the most commonly prescribed sleep aids. The study objective was to determine whether the use of Z-drugs is associated with the risk of developing CVD and mortality in older women with sleep disturbances. Patients/MethodsThe study cohort included post-menopausal women who, at baseline, scored ≥9 with the Women's Health Initiative Insomnia Rating Scale (N = 40,728). Members of the cohort were categorized as users of Z-drugs, users of other prescription hypnotics, or non-users. Outcomes were composite CVD (congestive heart failure, stroke, and fatal/non-fatal myocardial infarction) and mortality. Hazard ratios were estimated from Cox proportional hazards regression models adjusted for demographics, medical history, and sleep measures. To address potential confounding by indication, we also adjusted for propensity to be prescribed hypnotics. ResultsThe mean age of our cohort was 63.57 years (SD = 7.23) and mean follow-up time after the initial follow-up visit was 14.0 years (SD = 6.3). Z-drug use was significantly associated with an increased risk of composite CVD (HR = 1.35, 95%CI: 1.02–1.79) and all-cause mortality (HR = 1.38, 95%CI: 1.13–1.69). When groups were divided by heavy and casual use, only heavy users (≥3 times per week) had an increased risk of mortality. ConclusionsZ-drugs use was associated with an increased risk for death and CVD in post-menopausal women being treated for sleep disturbances. Additional research is needed to evaluate both frequency and duration of Z-drug use.

Pasta meal intake in relation to risks of type 2 diabetes and atherosclerotic cardiovascular disease in postmenopausal women : findings from the Women’s Health Initiative

ObjectiveTo evaluate the association between pasta meal intake and long-term risk of developing diabetes or atherosclerotic cardiovascular disease (ASCVD, including coronary heart disease (CHD) and stroke) in postmenopausal women.DesignProspective cohort...

Adipokines and Subclinical Cardiovascular Disease in Post-Menopausal Women: Study of Women's Health Across the Nation.

BackgroundThe menopausal transition is characterized by increased cardiovascular risk, weight gain, and increased adiposity for many women. The adipose‐derived secretory proteins adiponectin and leptin are associated with insulin resistance, metabolic syndrome, and cardiovascular disease but their role in subclinical atherosclerotic disease is unclear. This cross‐sectional study evaluated the associations of adiponectin and leptin with carotid artery intima‐media thickness, adventitial diameter, presence of carotid plaques, and brachial‐ankle pulse wave velocity (baPWV) in women aged 54 to 65 years.Methods and ResultsParticipants were 1399 women from SWAN (Study of Women's Health Across the Nation), a community‐based study of women transitioning through menopause. Carotid ultrasound and baPWV measures were obtained at SWAN follow‐up visits 12 or 13, when 97% of participants were post‐menopausal. Adipokines were assayed from serum specimens obtained concurrently at these visits. Linear and logistic regression models were used to evaluate adiponectin or leptin, both log‐transformed attributable to skewness, in relationship to carotid artery intima‐media thickness, adventitial diameter, baPWV, and presence of carotid plaque. Covariates included age, race, study site, smoking, alcohol use, obesity, cardiovascular disease risk factors, and menopausal status. Lower levels of adiponectin were related to greater carotid artery intima‐media thickness, wider adventitial diameter, and faster baPWV; associations were attenuated after adjusting for cardiovascular disease risk factors. Higher levels of leptin were associated with greater carotid artery intima‐media thickness and wider adventitial diameter in minimally and fully adjusted models, and contrary to expectation, with slower baPWV, particularly among women with diabetes mellitus or obesity.ConclusionsAdiponectin and leptin are 2 important inflammatory pathways that may contribute to adverse subclinical cardiovascular disease risk profiles in women at midlife.

Abstract P668: Clinically Meaningful Weight Gain Before Menopause and Risk of Stroke

Background: Obesity is an independent risk factor for stroke. Weight gain has been associated with a higher risk of cardiovascular diseases in postmenopausal women. It is unclear, however, if weight changes before menopause have similar effects. We hypothesized that clinically meaningful premenopausal weight gain, defined as Body Mass Index (BMI) change &gt;5%, would be associated with a higher stroke risk later in life. Methods: Using data from the California Teachers Study, we identified women aged &lt; 55 with no history of stroke. We used weight changes between 1995-2006 as proxy for premenopausal weight gain. We defined weight change as modest or moderate using BMI changes of 5-10% and &gt;10% respectively. Stroke outcomes were obtained from linkage to California hospitalization records. We used Cox regression models to calculate hazard ratios with 95% confidence intervals for the association of weight change and future stroke, adjusting for vascular risk factors. Results: Of 17,295 women included in the study, 113 had a stroke. In comparison to women who maintained a stable weight, women with moderate weight gain during premenopausal years had 2.0 times the risk of stroke. In the adjusted analysis, women with moderate weight gain had 89.6% higher risk of stroke, compared to the reference group. We found no significant association with stroke in women who had modest weight changes. Conclusion: Moderate premenopausal weight gain significantly increased stroke risk in women. Younger women should be educated about the effects of weight gain on future brain health. Count: 1836/1950

Protective Effects of Estrogen on Cardiovascular Disease Mediated by Oxidative Stress

Perimenopause is an important stage of female senescence. Epidemiological investigation has shown that the incidence of cardiovascular disease in premenopausal women is lower than that in men, and the incidence of cardiovascular disease in postmenopausal women is significantly higher than that in men. This phenomenon reveals that estrogen has a definite protective effect on the cardiovascular system. In the cardiovascular system, oxidative stress is considered important in the pathogenesis of atherosclerosis, myocardial dysfunction, cardiac hypertrophy, heart failure, and myocardial ischemia. From the perspective of oxidative stress, estrogen plays a regulatory role in the cardiovascular system through the estrogen receptor, providing strategies for the treatment of menopausal women with cardiovascular diseases.

Association between Thyroid Stimulating Hormone with Components of Metabolic Syndrome in Postmenopausal Women

Introduction: Metabolic Syndrome (MS) identifies a group of metabolic disorders that includes glucose intolerance, central obesity, hypertension and dyslipidaemia that place the affected individual at exaggerated risk for developing disorder, in addition as exaggerated mortality from all causes. Aim: To evaluate serum Thyroid Stimulating Hormone (TSH) levels and to determine the correlation between serum concentrations of TSH with components of MS among postmenopausal women with MS. Materials and Methods: A cross-sectional observational study was conducted for the period of four months on 100 postmenopausal women between 45-65 years who attended Outpatient Department (OPD) of Obstetrics and Gynaecology, Adichunchanagiri Institute of Medical Sciences (AIMS), Mandya, Karnataka, India. A fasting blood sample was collected from all the subjects, serum was used for estimating Fasting Plasma Glucose (FPG), Lipid profile, and Serum TSH. Results were presented on Mean±SD (Standard Deviation) (Min-Max) and in Number (%). For the comparison of means, Analysis of Variance (ANOVA) test was used. Correlation was examined by determining Pearson correlation coefficient (r-value). A p-value &lt;0.05 was taken as statistically significant. Results: Among the study population, the dysfunction in thyroid gland was found in 35 (35%). The major thyroid dysfunction was found to be hypothyroidism (32%) and only three had hyperthyroidism (3%). Waist Circumference (WC), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were 98.2±12 cm, 128.84±13.65 mmHg and 79.2±9.2 mmHg, respectively. Fasting Blood Glucose (FBS), Triglyceride (TAG), High Density Lipoprotein (HDL) cholesterol (HDL-C) and TSH were 166.7±71 mg/dL, 125.94±90.67 mg/dL, 45.46±13.13 mg/dL and 3.35±2.01 mIU/L, respectively. Statistically significant positive correlation was observed between FPG (p=0.049) and both SBP (p=0.0008) and DBP (p=0.001) and negative correlation was observed between TAG, HDL and TSH but not statistically significant in women with hypothyroidism when compared to euthyroid. A statistically negative correlation was found with WC (p=0.001) and positive correlation was found with TAG (p=0.008) and TSH among women with euthyroid condition. Conclusion: Hypothyroidism alters lipid levels and increases blood pressure leading to increased risk for cardiovascular disease (CVD). Together hypothyroidism and metabolic syndrome could increase the risk for CVD in postmenopausal women. Thus, assessing thyroid function in postmenopausal women with metabolic syndrome may aid in early detection of CVD risk and better clinical management among these patients and reduces the already existing high incidence of CVDs.

Polycystic Ovarian Syndrome and Menopause in Forty Plus Women.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age group, but it affects women's health and quality of life across the life course. During different stages of life, the PCOS phenotype can change, which requires a personalized diagnostic approach and treatment. With increasing age, the syndrome evolves from a reproductive disease to a more metabolic disorder. Along with various metabolic disturbances like insulin resistance and abnormalities of energy expenditure, PCOS is recognized as a major risk factor for the development of type 2 diabetes and cardiovascular disease (CVD) in later life. The aim of the current review was to conduct a nonsystematic review of published literature and research that has been presented so far regarding menopausal women with PCOS as well as the associated changes in hormone profile, their lipid profile, and various metabolic changes that occur. The current review may also contribute to raise awareness about the risk of hypertension and CVDs in postmenopausal women with PCOS.