Disease Risk In Postmenopausal Women Research Articles

Lipid profile, cardiorespiratory function and quality of life of postmenopausal women improves with aerobic exercise

Objective: Menopause is characterized by physiological changes with increased risk of obesity, dyslipidemia and decreased quality of life (QoL). Despite the plethora of reports on the alleviating effect of exercise on climacteric symptoms, there is little documentation of this lifestyle intervention among Ghanaian menopausal women. This study examined the effect of aerobic exercise on lipid profile, cardiorespiratory function and QoL among menopausal women. Methods: Eighteen sedentary postmenopausal women between 45 to 75 years were randomly assigned to experimental (EG, n=8) and control (CG, n=10) groups. The EG received moderate intensity aerobic exercise training for eight weeks, three times a week while the CG observed normal daily activities. Blood pressure, resting heart rate, BMI, and lipid profile were measured and QoL assessed using the Utian QoL questionnaire at weeks 0 and 9. Results: After 8 weeks, the EG demonstrated significant decrease in cardiovascular risk ratio by 6.5L% and a non-significant decrease in LDL by 11.9L%. The CG showed significant increase in systolic BP by 3.2%L and a non-significant increase in LDL and cardiovascular risk by 14.9L% and 9.4L% respectively. QoL significantly improved in the EG group compared to CG after the 8 weeks. Conclusion: The health and QoL of participants in EG was significantly better than the CG at the end of the experiment. Aerobic exercise decreases cardiovascular disease risk in postmenopausal women and shows potential impact on lipid profile and health QoL. Proactively sponsored aerobic exercise programmes geared towards healthy living of postmenopausal women in Kumasi, Ghana are recommended.

Isoflavone supplementation in postmenopausal women does not affect leukocyte LDL receptor and scavenger receptor CD36 expression: A double-blind, randomized, placebo-controlled trial.

Isoflavones are discussed to improve serum lipoproteins and body composition and to reduce cardiovascular disease risk in postmenopausal women (PMW). LDL receptors (LDLR) and scavenger receptor CD36 (CD36) play a pivotal role in the regulation of plasma LDL-cholesterol concentrations (LDL-chol). We investigated the impact of isoflavones on the receptor expression of both receptors in leukocytes of PMW. A randomized, double-blind, placebo-controlled trial in parallel design was conducted to assess the effects of an isoflavone-enriched soy extract (117.4 mg/day isoflavone aglycone equivalents) for 12 weeks on serum LDL-chol, LDLR, and CD36 expression on leukocytes in 170 healthy PMW. Baseline and after 12 weeks, blood lipid concentrations, anthropometric data and body composition were determined. Receptor expression on leukocytes was measured by means of flow cytometry. After the intervention, no significant differences were found for LDLR and CD36 expression on leukocytes. A significant increase of serum LDL-chol was shown for the isoflavone group (p = 0.03) after 12 weeks. Body fat content and VAT were not affected. Isoflavone supplementation for 12 weeks did not change LDLR and CD36 expression on leukocytes of PMW and did not affect body fat content and visceral adipose tissue (VAT), but slightly increased serum LDL-chol.

Sarcopenia and Sarcopenic Obesity and Their Association with Cardiovascular Disease Risk in Postmenopausal Women: Results for the 2008-2011 Korea National Health and Nutrition Examination Survey

Objectives: This study was conducted to investigate the association between sarcopenia and sarcopenic obesity and cardiovascular disease risk in Korean postmenopausal women. Methods: We analyzed data of 2,019 postmenopausal women aged 50-64 years who participated in the Korea National Health and Nutrition Examination Survey in 2008-2011 and were free of cardiovascular disease history. Blood pressure, height, and weight were measured. We analyzed the serum concentrations of glucose, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglyceride levels. Waist circumference was used to measure obesity. Appendicular skeletal muscle mass was measured by dual-energy X- ray absorptiometry. Sarcopenia was defined as the appendicular skeletal muscle mass/body weight<1 standard deviation below the gender-specific means for healthy young adults. The estimated 10-year risk of cardiovascular disease risk was calculated by Pooled Cohort Equation. Subjects were classified as non-sarcopenia, sarcopenia, or sarcopenic obesity based on status of waist circumference and appendicular skeletal muscle mass. Results: The prevalence of sarcopenia and sarcopenic obesity was 16.3% (n=317) and 18.3% (n=369), respectively. The 10-year risk of cardiovascular disease risk in the sarcopenic obesity group was higher (3.82 ± 0.22%) than the normal group (2.73 ± 0.09%) and sarcopenia group (3.17 ± 0.22%) (p < 0.000). The odd ratios (ORs) for the ≥7.5% 10-year risk of cardiovascular disease risk were significantly higher in the sarcopenic obesity group (OR 3.609, 95% CI: 2.030-6.417) compared to the sarcopenia group (OR 2.799, 95% CI: 1.463-5.352) (p for trend < 0.000) after adjusting for independent variables (i.e., exercise, period of menopausal, alcohol use disorders identification test (AUDIT) score, income, education level, calorie intake, %fat intake and hormonal replacement therapy). Conclusions: Sarcopenia and sarcopenic obesity appear to be associated with higher risk factors predicting the 10-year risks of cardiovascular disease risk in postmenopausal women. These findings imply that maintaining normal weight and muscle mass may be important for cardiovascular disease risk prevention in postmenopausal women.

Association of Markers of Intravascular Cellular Interaction with Carotid Intima Medial Thickness in Postmenopausal Women

Objective: Increases in carotid intima medial thickness (CIMT) reflect unwanted intravascular cellular interactions and activations and increased risk of stroke. This study aimed to evaluate interactions among intravascular cells and cellular origin of microvesicles (MV) released from activated cells that might contribute to increased cardiovascular disease risk in postmenopausal women. Methods: Postmenopausal women (n=75) who completed the Kronos Early Estrogen Prevention Study (KEEPS) at Mayo Clinic, Rochester MN, were invited to participate for follow-up evaluation. Blood samples were drawn into protease inhibitors anticoagulant tubes. CIMT was evaluated by B-mode ultrasound at study baseline, years 1-4 during KEEPS and at 3 year follow-up. Intravascular cells interactions and cellular origin of MV in peripheral blood were measured by digital flow cytometer. Results: The average age and month past menopause is 60 ± 2 years and 103 ± 9 months respectively. Conventional cardiovascular risk factors were within the normative ranges. CIMT increased 9.8 ± 8.7% from year 1 to 7 and positively correlated with age (ρ = 0.36, P<0.0001) and month past menopause (ρ = 0.23, P<0.0001). CIMT also positively correlated with mean platelet volume (ρ = 0.24, P=0.02), total leukocytes-derived MV (ρ = 0.26, P=0.004), percentage of circulating lymphocytes carrying platelet antigen (ρ = 0.26, P=0.03), and endothelial antigen (ρ = 0.25, P=0.003). Conclusion These results suggest that intravascular cellular activations and interactions may contribute to vascular remodeling with age in apparently healthy postmenopausal women. Funding: Aurora Foundation and NIH AG044170.

The Association between Prolactin, High-Sensitivity C-Reactive Protein and Framingham Risk Score in Menopause

Aims: To evaluate the association between serum prolactin, high-sensitivity C-reactive protein (hs-CRP) levels and cardiovascular disease risk in postmenopausal women regarding the Framingham Risk Score (FRS). Methods: Fifty-eight menopausal women were enrolled into the cross-sectional study. All participants had 24-hour ambulatory blood pressure monitoring, echocardiography, electrocardiography, and carotid intima-media thickness measurement. Blood samples were obtained for prolactin, hs-CRP, lipid profile, fasting glucose, and insulin. Results: Among the participants, 67.24% had a FRS <10%, and 32.75% had a FRS ≥10%. Levels of prolactin and hs-CRP did not differ between the FRS groups. In the FRS <10% group, significantly higher levels of prolactin were found. Cases with hypertension have significantly higher levels of hs-CRP. Prolactin and hs-CRP were found to be associated with hypertension in the FRS <10% and ≥10% groups, respectively. Conclusions: Hypertensive postmenopausal women with low risk for cardiovascular diseases have increased levels of prolactin, suggesting a possible role in the pathogenesis of hypertension. The correlation of hs-CRP with systolic blood pressure can be interpreted as a potential effect of hypertensive heart disease reflecting a state of high-risk milieu with elevated inflammatory markers.

Characterization of Vascular Disease Risk in Postmenopausal Women and Its Association with Cognitive Performance

ObjectivesWhile global measures of cardiovascular (CV) risk are used to guide prevention and treatment decisions, these estimates fail to account for the considerable interindividual variability in pre-clinical risk status. This study investigated heterogeneity in CV risk factor profiles and its association with demographic, genetic, and cognitive variables.MethodsA latent profile analysis was applied to data from 727 recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Women were cognitively healthy, within three years of their last menstrual period, and free of current or past CV disease. Education level, apolipoprotein E ε4 allele (APOE4), ethnicity, and age were modeled as predictors of latent class membership. The association between class membership, characterizing CV risk profiles, and performance on five cognitive factors was examined. A supervised random forest algorithm with a 10-fold cross-validation estimator was used to test accuracy of CV risk classification.ResultsThe best-fitting model generated two distinct phenotypic classes of CV risk 62% of women were “low-risk” and 38% “high-risk”. Women classified as low-risk outperformed high-risk women on language and mental flexibility tasks (p = 0.008) and a global measure of cognition (p = 0.029). Women with a college degree or above were more likely to be in the low-risk class (OR = 1.595, p = 0.044). Older age and a Hispanic ethnicity increased the probability of being at high-risk (OR = 1.140, p = 0.002; OR = 2.622, p = 0.012; respectively). The prevalence rate of APOE-ε4 was higher in the high-risk class compared with rates in the low-risk class.ConclusionAmong recently menopausal women, significant heterogeneity in CV risk is associated with education level, age, ethnicity, and genetic indicators. The model-based latent classes were also associated with cognitive function. These differences may point to phenotypes for CV disease risk. Evaluating the evolution of phenotypes could in turn clarify preclinical disease, and screening and preventive strategies.ClinicalTrials.gov NCT00154180

Carvedilol Prevents Ovariectomy-Induced Myocardial Contractile Dysfunction in Female Rat

Carvedilol has beneficial effects on cardiac function in patients with heart failure but its effect on ovariectomy-induced myocardial contractile dysfunction remains unclear. Estrogen deficiency induces myocardial contractile dysfunction and increases cardiovascular disease risk in postmenopausal women. Our aim was to investigate whether carvedilol, a beta receptor blocker, would prevent ovariectomy-induced myocardial contractile dysfunction. Female rats (8 weeks old) that underwent bilateral ovariectomy were randomly assigned to receive daily treatment with carvedilol (OVX+CAR, 20 mg/kg), placebo (OVX) and SHAM for 58 days. Left ventricle papillary muscle was mounted for isometric tension recordings. The inotropic response to Ca2+ (0.62 to 3.75 mM) and isoproterenol (Iso 10−8 to 10−2 M) were assessed. Expression of calcium handling proteins was measured by western blot analysis. Carvedilol treatment in the OVX animals: prevented weight gain and slight hypertrophy, restored the reduced positive inotropic responses to Ca2+ and isoproterenol, prevented the reduction in SERCA2a expression, abolished the increase in superoxide anion production, normalized the increase in p22phox expression, and decreased serum angiotensin converting enzyme (ACE) activity. This study demonstrated that myocardial contractile dysfunction and SERCA2a down regulation were prevented by carvedilol treatment. Superoxide anion production and NADPH oxidase seem to be involved in this response.

ADRB3 and PPARγ2 gene polymorphisms and their association with cardiovascular disease risk in postmenopausal women

Objectives The contribution of heritability to the development of cardiovascular disease (CVD) is of interest as the identification of genes enhancing the susceptibility of individuals to CVD may help the design of clinical interventions optimized for the individual's genome.Methods We studied the associations of polymorphism of ADRB3 and PPARγ2 genes with obesity indices, unfavorable lipid profile parameters and insulin resistance index HOMA in 343 postmenopausal women.Results No association was found between tested polymorphisms and CVD risk factors such as total cholesterol ≥ 5.0 mmol/l, high density lipoprotein cholesterol < 1.2 mmol/l, low density lipoprotein cholesterol > 3.0 mmol/l and triacylglycerols > 1.7 mmol/l. The presence of arterial hypertension and HOMA value ≥ 1.95 were also not related to these polymorphisms. A significant association between PPARγ2 gene polymorphism and total body fat mass (odds ratio = 1.90 at p = 0.037) as well as android fat deposit mass (odds ratio = 1.82 at p = 0.048) was found.Conclusions CVD risk factors in postmenopausal women are not directly associated with the polymorphisms of PPARγ2 and ADRB3 genes. We suggest that some indirect link between PPARγ2 gene polymorphism and susceptibility of postmenopausal women to CVD may exist. This suggestion is based on our finding that high total body fat mass and high android fat deposits are associated with the presence of the Pro12Ala allele of the PPARγ2 gene.

Low-fat dietary pattern and change in body-composition traits in the Women’s Health Initiative Dietary Modification Trial

The Women's Health Initiative Dietary Modification (DM) Trial was a randomized controlled trial that compared the effects of a low-fat (≤20% of total energy) or a usual diet in relation to chronic disease risk in postmenopausal women. We characterized long-term body-composition changes associated with the DM trial and potential modifiers of these associations. In the DM trial, 48,835 women aged 50-79 y were randomly assigned to intervention (40%) or comparison (60%) groups. We studied a subset with whole-body dual-energy X-ray absorptiometry scans at baseline and during follow-up. Changes in fat mass (FM), lean mass (LM), and percentage body fat between the intervention (n = 1580) and comparison (n = 2731) groups at years 1, 3, and 6 were compared. By using generalized estimating equations, we calculated overall differences between groups and tested for interactions with age, diabetes, race-ethnicity (white, black, and Hispanic), body mass index (BMI), and hormone therapy (HT). The intervention women experienced significantly greater reductions in percentage body fat, FM, and LM at years 1 and 3 than did women in the comparison group (all P < 0.05). At year 6, only the FM change was significantly different between groups. Overall, the intervention was associated with reductions in percentage body fat (-0.8%; 95% CI: -1.0%, -0.6%), FM (-1.1 kg; 95% CI: -1.3, -0.8 kg), and LM (-0.17 kg; 95% CI: -0.28, -0.06 kg) during follow-up (all P < 0.003). Intervention associations varied by race-ethnicity, BMI, diabetes, and HT and remained significant after adjustment for physical activity. This intervention was associated with modest long-term body-composition changes; the findings were more robust in years 1 and 3. This trial was registered at clinicaltrials.gov as NCT00000611.

Effects of soy bean on serum paraoxonase 1 activity and lipoproteins in hyperlipidemic postmenopausal women

Background/aim Because of an unfavorable serum lipoprotein profile, postmenopausal women are at risk of cardiovascular disease. Soy protein may help protect against these risk factors, although its effect on paraoxonase 1 (PON1) is not clear. The aim of the present study was to determine the effects of soy protein on serum concentration of lipoproteins and PON1 activity in hypercholesterolemic postmenopausal women.Design In a double-blind randomized clinical trial with a parallel design, 52 hypercholesterolemic postmenopausal women were randomly assigned to 50 g/day soy protein containing 164 mg isoflavones or placebo, for 10 weeks. Serum lipoproteins and PON1 activity were measured at baseline and at the 10th week.Results There was significant increase in PON1 activity (P=0.029) and a significant decrease in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), LDL-C/high-density lipoprotein cholesterol (HDL-C), triacylglycerol/HDL-C and TC/HDL-C in the soy group compared with the placebo group (P=0.001, P=0.008, P=0.012, P=0.04 and P=0.029, respectively) at the end of the study. Similarly, PON1 activity was significantly increased (P=0.015) and LDL-C, TC, LDL-C/HDL-C, triacylglycerol/HDL-C and TC/HDL-C were significantly decreased (P=0.001, P=0.002, P=0.001, P=0.016 and P=0.001) at the end of the study compared with the beginning value in soy group.Conclusion Soy protein reduces the cardiovascular disease risk in postmenopausal women because of both modest reductions in serum lipoproteins and an increase in PON1 activity.

Effects of hormone therapy on soluble cell adhesion molecules in postmenopausal women with coronary artery disease.

Although observational studies showed an apparent lower ischemic coronary disease risk in postmenopausal women receiving hormone therapy (HT), randomized clinical trials in postmenopausal women showed an increase in ischemic cardiovascular events. Soluble cell adhesion molecules have been associated with cardiovascular risk factors and events. HT reduces circulating levels of soluble cell adhesion molecules in healthy postmenopausal women, but its effects in postmenopausal women with coronary artery disease are less clear. We assessed the effect of HT on soluble cell adhesion molecules in the Estrogen Replacement and Atherosclerosis trial. The Estrogen Replacement and Atherosclerosis trial was a double-blind, placebo-controlled study that randomized 309 postmenopausal women (mean age, 65.8 y) to daily unopposed estrogen (conjugated estrogens 0.625 mg), estrogen plus 2.5 mg of medroxyprogesterone acetate, or placebo, with a mean follow-up period of 3.2 years. Soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin were measured in serum obtained from participants at baseline and after 12 months of follow-up. Of the 265 women with complete data, 87 women were assigned to unopposed estrogen, 88 women to estrogen plus medroxyprogesterone acetate, and 90 women to placebo. Compared with placebo, 12 months of HT (n = 175) was associated with reductions in soluble intercellular adhesion molecule-1 (25.6 +/- 4.7 vs 10.6 +/- 6.4 ng/mL, P = 0.06), soluble vascular cell adhesion molecule-1 (80.2+/- 10.6 vs 28.8 +/- 14.7 ng/mL, P = 0.005), and E-selectin (8.8 +/- 0.9 vs -1.1 +/- 1.2 ng/mL, P < 0.001). Twelve months of HT in postmenopausal women with established coronary artery disease was associated with reductions in serum markers of endothelial cell activation/injury such as soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin.

Effect of 6 months of exercise and isoflavone supplementation on clinical cardiovascular risk factors in obese postmenopausal women

To investigate whether 6 months of exercise combined with isoflavone supplementation could improve clinical risk factors that predispose to cardiovascular disease in obese postmenopausal women. This was a randomized, double-blind, controlled trial in which 50 healthy obese postmenopausal women were divided into two groups and assigned to isoflavone supplementation (n=25) or a placebo (n=25) for 1 year. For the last 6 months, both groups participated in an exercise program (three times per week), at the end of which cardiovascular disease risk factors were compared between groups. Body composition (using dual-energy x-ray absorptiometry), metabolic profile (blood lipids, fasting insulin, fasting glucose, sex hormone-binding globulin, C-reactive protein) were determined at baseline and at 6 and 12 months. We observed a significant effect of exercise and isoflavone supplementation on body weight, total and abdominal fat mass (kilograms and percentage), body mass index, appendicular fat-free mass, fat-free mass/fat mass ratio, and sex hormone-binding globulin, but not with exercise alone. No difference was observed for other biochemical characteristics, although the quantitative insulin sensitivity check index increased equally in both groups. Conversely, although not significant, we observed a tendency for a treatment effect on body mass index (P=0.07) and on absolute (kilograms) (P=0.07) and percentage of (P=0.053) abdominal fat mass, whereas no effect of treatment was found for other variables using the Mann-Whitney test. Compared to an aerobic exercise program alone, 70 mg/day of isoflavones combined with exercise may promote significant improvements in body composition parameters that are known to influence cardiovascular disease risk in postmenopausal women.

Does Cardiorespiratory Fitness Modulate the Relationship Between CRPand Cardiovascular Disease Risk in Postmenopausal Women?

High sensitivity C reactive protein (hsCRP) has been reported to be an independent risk factor for cardiovascular disease (CVD) in postmenopausal women, however its association with cardiorespiratory fitness (CRF) and other traditional CVD risk factors post-menopause is unclear. PURPOSE This study aimed to assess the relationship between CRF (VO2peak), hsCRP and key CVD risk factors in 76 postmenopausal women (age 57.2 ± 3.6 yr, BMI 27.4 ± 4.5). METHODS: VO2peak was recorded from a Bruce treadmill protocol, body composition from skinfolds and circumferences and a fasting blood sample was analysed for hsCRP, total cholesterol (TC), high (HDL) and low (LDL) density lipoproteins, triglycerides (TG), glycosylated haemoglobin (HbA1c), insulin and glucose concentration. The cohort was divided into low, medium and high risk of CVD by hsCRP concentration (Low: <1.0 mg/L, N = 41; Medium: 1.0-2.9 mg/L, N = 18; High: >3.0 mg/L, N = 17). These groups did not differ in age or years post-menopause (P > 0.05). Group differences in VO2peak and risk factors were assessed via ANOVA and relationships between variables via correlation. Waist circumference (WC) displayed the strongest correlation with hsCRP (r = 0.58, P < 0.001) and was used as a covariate in further analysis. RESULTS WC differed between CVD risk groups (Low: 79.3 ± 8.6; Medium: 83.0 ± 9.8; High: 91.1 ± 12.4 cm), as did hip circumference, waist: hip, percentage body fat, BMI, body mass and concentrations of TG, LDL, HDL, TC, HbA1c and insulin (P < 0.05). hsCRP was correlated with VO2peak, WC, hip circumference, waist:hip, % body fat, body mass, BMI, insulin, glucose, TG, HDL and HbA1c (P < 0.05) but normalizing for WC removed these correlations. Using WC as a covariate also removed the group differences in TG, HDL and insulin but did not eliminate group differences in TC (Low: 6.13 ± 0.18, Medium: 5.94 ± 0.26; High: 5.22 ± 0.29 mmol/L), LDL (Low: 3.73 ± 0.13; Medium: 3.57 ± 0.19; High: 2.84 ± 0.21 mmol/L) and HbA1c (Low: 5.17 ± 0.06; Medium: 5.07 ± 0.08; High: 5.41 ± 0.9 %) (P <0.05). VO2peak did not differ with CVD risk group or modulate group differences in CVD risk factors (P > 0.05). CONCLUSION In postmenopausal women the relationship between hsCRP and key CVD risk factors appears to be modulated by body composition. CRF does not modulate the relationship between hsCRP and key CVD risk factors.

Soy-isoflavone-enriched foods and markers of lipid and glucose metabolism in postmenopausal women: interactions with genotype and equol production

The hypocholesterolemic effects of soy foods are well established, and it has been suggested that isoflavones are responsible for this effect. However, beneficial effects of isolated isoflavones on lipid biomarkers of cardiovascular disease risk have not yet been shown. The objective was to investigate the effects of isolated soy isoflavones on metabolic biomarkers of cardiovascular disease risk, including plasma total, HDL, and LDL cholesterol; triacylglycerols; lipoprotein(a); the percentage of small dense LDL; glucose; nonesterified fatty acids; insulin; and the homeostasis model assessment of insulin resistance. Differences with respect to single nucleotide polymorphisms in selected genes [ie, estrogen receptor alpha (XbaI and PvuII), estrogen receptor beta (AluI), and estrogen receptor beta(cx) (Tsp509I), endothelial nitric oxide synthase (Glu298Asp), apolipoprotein E (Apo E2, E3, and E4), cholesteryl ester transfer protein (TaqIB), and leptin receptor (Gln223Arg)] and with respect to equol production were investigated. Healthy postmenopausal women (n = 117) participated in a randomized, double-blind, placebo-controlled, crossover dietary intervention trial. Isoflavone-enriched (genistein-to-daidzein ratio of 2:1; 50 mg/d) or placebo cereal bars were consumed for 8 wk, with a wash-out period of 8 wk before the crossover. Isoflavones did not have a significant beneficial effect on plasma concentrations of lipids, glucose, or insulin. A significant difference between the responses of HDL cholesterol to isoflavones and to placebo was found with estrogen receptor beta(cx) Tsp509I genotype AA, but not GG or GA. Isoflavone supplementation, when provided in the form and dose used in this study, had no effect on lipid or other metabolic biomarkers of cardiovascular disease risk in postmenopausal women but may increase HDL cholesterol in an estrogen receptor beta gene-polymorphic subgroup.

Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production

Dietary isoflavones are thought to be cardioprotective because of their structural similarity to estrogen. The reduction of concentrations of circulating inflammatory markers by estrogen may be one of the mechanisms by which premenopausal women are protected against cardiovascular disease. Our aim was to investigate the effects of isolated soy isoflavones on inflammatory biomarkers [von Willebrand factor, intracellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), E-selectin, monocyte chemoattractant protein 1, C-reactive protein (CRP), and endothelin 1 concentrations]. Differences with respect to single-nucleotide polymorphisms in selected genes [estrogen receptor alpha (XbaI and PvuII), estrogen receptor beta [ERbeta (AluI) and ERbeta[cx] (Tsp509I), endothelial nitric oxide synthase (Glu298Asp), apolipoprotein E (Apo E2, E3, and E4), and cholesteryl ester transfer protein (TaqIB)] and equol production were investigated. One hundred seventeen healthy European postmenopausal women participated in this randomized, double-blind, placebo-controlled, crossover dietary intervention trial. Isoflavone-enriched (genistein-to-daidzein ratio of 2:1; 50 mg/d) or placebo cereal bars were consumed for 8 wk, with a washout period of 8 wk between the crossover. Plasma inflammatory factors were measured at 0 and 8 wk of each study arm. Isoflavones improved CRP concentrations [odds ratio (95% CI) for CRP values >1 mg/L for isoflavone compared with placebo: 0.43 (0.27, 0.69)]; no significant effects of isoflavone treatment on other plasma inflammatory markers were observed. No significant differences in the response to isoflavones were observed according to subgroups of equol production. Differences in the VCAM-1 response to isoflavones and to placebo were found with ERbeta AluI genotypes. Isoflavones have beneficial effects on CRP concentrations, but not on other inflammatory biomarkers of cardiovascular disease risk in postmenopausal women, and may improve VCAM-1 in an ERbeta gene polymorphic subgroup.

Long-term hormone replacement therapy does not cause increased platelet activation

Observational studies have shown apparently lower ischemic coronary disease risk in postmenopausal women receiving hormone replacement therapy (HRT). However, several recent studies have shown an increase in ischemic cardiac events when HRT is initiated in postmenopausal women with known coronary artery disease. It is postulated that estrogen may result in increased platelet aggregation. We evaluated platelet activation, as measured by flow cytometric analysis using P selectin and PAC1 as activation markers, and aggregation, as measured by standard platelet aggregation using platelet-rich plasma, in 27 postmenopausal women (17 HRT, 10 placebo) who were participants in 2 placebo-controlled randomized angiographic trials evaluating the effect of HRT on coronary atherosclerosis or saphenous vein graft disease. All women had received HRT or placebo for >2 years and were on aspirin therapy. The estrogen component was either conjugated equine estrogen or 17beta-estradiol. Patients on HRT and those on placebo had comparable degrees of platelet aggregation when measured using various doses of agonists (adenosine diphosphate and epinephrine). There were no significant differences in levels of platelet activation measured by flow cytometry. We conclude that long-term HRT does not appear to cause increased platelet activation and aggregation in women with coronary artery disease. There may be increased platelet activation in the early period after HRT initiation; however, this was not assessed in this study.

Oestrogen therapy increased stroke risk and decreased hip fracture risk but did not affect coronary heart disease risk in postmenopausal women with prior hysterectomy

Anderson GL, Limacher M, Assaf AR, et al . Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 2004;291:1701–12. [OpenUrl][1][CrossRef][2][PubMed][3][Web of...

Effect of tibolone on markers of cardiovascular disease risk in postmenopausal women undergoing hemodialysis: a pilot study

Objective To assess the effect of tibolone on markers of vascular risk in postmenopausal women who were receiving hemodialysis. Design One-year open-label study. Setting “Zvezdara” University Medical Center, Belgrade, Serbia. Patient(s) Twenty-eight postmenopausal women undergoing chronic hemodialysis. Intervention(s) Fifteen women received tibolone 2.5 mg three times per week; 13 other women served as controls. Main outcome measure(s) Mean arterial pressure and weight were measured at baseline and at 6 and 12 months, and blood was collected for insulin, total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, lipoprotein(a), high-sensitivity C-reactive protein (hs-CRP), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and markers of renal function. Result(s) Mean arterial pressure fell in the tibolone but not in the control group at 6 and 12 months versus baseline (mean [SD]: 93 [15] vs. 105 [11] mmHg and 94 [10] vs. 105 [11] mmHg, respectively). Weight, insulin, lipids, lipoprotein(a), hs-CRP, ET-1, VEGF, and renal function remained unchanged within each group, but high-density lipoprotein concentrations fell in the tibolone group after 12 months (1.2 [0.3] vs. 1.6 [0.6] mmol/L). Conclusion(s) The effects of tibolone on markers of vascular risk in postmenopausal women who are receiving hemodialysis and healthy women appear to differ. This should be taken into account when tailoring menopausal therapies to the specific requirements of each individual.

Detection of vascular disease risk in women by panoramic radiography.

Low bone mineral density and rapid bone loss of the skeleton are associated with mortality risk from vascular diseases in post-menopausal women. Panoramic radiographic measurements are considered as indicators of skeletal bone mineral density or bone turnover. We hypothesize that such measurements may be associated with vascular disease risk in post-menopausal women. Associations of mandibular cortical shape and width on panoramic radiographs with skeletal bone mineral density and risk factors related to vascular diseases were investigated in 87 post-menopausal women. Cortical shape was associated with skeletal bone mineral density, low-density lipoprotein cholesterol, apolipoprotein B, resting heart rate, and endothelial dysfunction. Cortical width was associated with skeletal bone mineral density, low-density lipoprotein cholesterol, and apolipoprotein A1. Dentists may be able to refer women with increased risk of vascular diseases, as well as low bone mineral density, to medical professionals for further examination by panoramic findings.

The effects of transdermal estradiol alone or with cyclical dydrogesterone on markers of cardiovascular disease risk in postmenopausal women with type 2 diabetes: a pilot study.

The objective of this open, longitudinal, controlled study was to assess the effect of transdermal estradiol alone or combined with cyclical dydrogesterone on the markers of cardiovascular disease (CVD) risk in postmenopausal women with type 2 diabetes. The control group consisted of postmenopausal diabetic women who declined menopausal hormone replacement therapy (HRT). Twenty-eight postmenopausal women (19 on HRT and 9 controls) with type 2 diabetes were followed up for 12 months. From the active treatment group 14 women with a uterus in situ had 80 microg/24 hr transdermal estradiol (Fematrix 80; Solvay Healthcare Ltd, Southampton, UK) and oral dydrogesterone 10 mg daily for the first 12 days of the calendar month, whereas 5 women with previous hysterectomy had 80 microg/24 hr transdermal estradiol (Fematrix 80) alone. CVD risk markers were measured before and at regular intervals after starting HRT. The main outcome measures were weight, systolic and diastolic blood pressure, fasting plasma glucose, glycated hemoglobin (HbA1c), glucose/insulin ratio, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, lipoprotein (a), high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and endothelin-1. Transdermal estradiol with or without dydrogesterone in women with type 2 diabetes did not adversely affect any of the measured markers of cardiovascular risk. There was a significant decrease in HbA1c, total cholesterol, and LDL cholesterol at 6 months in women receiving HRT. Some of the cardiovascular disease risk markers may improve in postmenopausal women with type 2 diabetes with transdermal estradiol. This effect may have important clinical implications and it deserves further investigation in appropriately designed trials.