Subclinical Atherosclerosis In Postmenopausal Women Research Articles

Dietary patterns are associated with arterial stiffness and carotid atherosclerosis in postmenopausal women.

PurposeThe increase in cardiovascular risk after the menopausal transition remains partly explained until today. Further research is needed to identify risk factors potentially modifiable by primary prevention practices. This cross-sectional study, part of a larger prospective project, aims to investigate possible associations between dietary patterns and indices of vascular structure and function among healthy postmenopausal women.MethodsPostmenopausal women (n = 310) without clinically overt cardiovascular disease were recruited consecutively from a University Menopause Clinic over three years. Dietary intake was assessed by a validated food frequency questionnaire and the MedDietScore. In addition, we assessed anthropometric/biochemical parameters, including the Triglyceride-glucose index (TyG-Index), body fat distribution [triceps skinfold (TSF), mid-upper arm circumference (MUAC)] and physical activity. The vascular assessment included carotid-femoral pulse wave velocity (PWV), carotid and femoral-artery intima-media thickness (IMT) and atheromatous plaques presence.ResultsConsumption of non-refined cereals was associated with carotid-bulb IMT (R2 = 5.5% b-coefficient = −0.142; p = 0.011), adjusting for age, physical activity, lipids, systolic blood pressure, smoking, body mass index, insulin resistance, and daily energy intake. PWV was associated with the intake of total dairy products (R2 = 27.3%, b-coefficient = −0.117; p = 0.017). Higher red meat consumption was related to a greater TyG-index (Model 1, R2 = 14.3%, b-coefficient=0.121; p = 0.048), an association mediated by total daily energy intake. Higher consumption of alcohol, as well as the MedDietScore, were inversely associated with TSF measurements, significant after Bonferroni correction.ConclusionDietary patterns are associated with metabolic indices and subclinical atherosclerosis in postmenopausal women independently of traditional cardiovascular risk factors, total energy intake or physical activity.

Breastfeeding is associated with lower subclinical atherosclerosis in postmenopausal women

Objective: To evaluate the association between a personal history of lactation and indices of subclinical atherosclerosis in postmenopausal women.Methods: We evaluated the association between a history of breastfeeding and indices of subclinical atherosclerosis (pulse wave velocity, PWV; intima-media thickness [IMT]; atherosclerotic plaque presence) in 197 parous postmenopausal women with history of breastfeeding.Results: Women who reported breastfeeding ≥6 months when compared with women who reported breastfeeding for 1–5 months exhibited significantly lower values of common carotid artery IMT (Model R2=15.7%, b-coefficient = −0.170, 95% CI: −0.208—0.001, p-value = .019) and lower odds of subclinical atherosclerosis (Model X2=28.127, OR = 0.491, 95% CI 0.318–0.999, p-value = .049), adjusting for traditional cardiovascular risk factors.Conclusions: Postmenopausal women with a history of breastfeeding for at least 6 months have a lower prevalence of subclinical atherosclerosis, independently of traditional cardiovascular risk factors. A longer duration of breastfeeding may have a beneficial effect on subclinical atherosclerosis later in life.

P2541Plasma levels of amyloid beta 1-40 are associated with the rate of progression of carotid subclinical atherosclerosis in postmenopausal women

Abstract Background There is increasingly recognized undetected residual cardiovascular (CV) risk in postmenopausal women, suggesting the need for new risk biomarkers in this population. We have previously shown that amyloid-beta (1–40) (Aβ1–40), a proinflammatory and pro-atherosclerotic peptide, is associated with concurrent subclinical cardiovascular disease (CVD) in the general population and with major adverse cardiac events in patients with established cardiac disease. However, the clinical value of Aβ1–40 in menopause or whether this peptide is linked with an increased rate of progression of atherosclerotic disease is unknown. Purpose To examine the association of Aβ1–40 levels with the rate of progression of carotid intima-media thickness (IMT) in postmenopausal women. Methods In the settings of a Menopause Clinic, postmenopausal women (n=140) without clinically overt CVD or diabetes were consecutively recruited and re-evaluated after a median follow-up period of 24 months. IMT in the carotid arteries was measured by ultrasonography. The average of maximal IMT (mean cIMT) measured at both left and right common carotid, carotid bulb (cb)and internal carotid (ic) artery were used as the main end-point of the analysis. Aβ1–40 was measured in plasma samples at baseline and follow up. Fasting insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Results Women with increased plasma levels Aβ1–40 in the highest tertile presented the highest probability to have increased mean cIMT (adjusted OR=2.97, 95% CI 1.18–7.52, p=0.021) independently of age, smoke, hypertension, and hyperlipidemia. After adjustment for HOMA-IR, this association remained significant. Similarly, Aβ1–40 levels were associated with increased mean cb and icIMT (adjusted OR=3.34 for highest versus lower tertile, 95% CI 1.27–8.81, p=0.015). Mean cIMT significantly increased across the follow up period (0.73mm (0.065–0.08) to 0.77mm (0.07–0.089), median increase rate per year 0.024mm, p<0.001). By multi-level linear mixed model analysis, changes in Aβ1–40 levels were associated with increased rate of progression of mean cIMT (4.1% increase per 1-SD increase, p<0.001) after adjustment for differences in follow-up duration and age, hypertension, hyperlipidemia, and smoking. When repeated measurements of HOMA-IR were also considered, this association did not materially change (p=0.021). Similarly, longitudinal changes in Aβ1–40 correlated with the progression of mean cb and icIMT (3.9% increase per 1-SD increase, p=0.001), independently of time to re-evaluation and cardiovascular risk factors. Conclusion Aβ1–40 is an independent predictor of the rate of progression of subclinical carotid atherosclerosis in menopausal women. This finding supports the clinical value of Aβ1–40 in menopause and warrants further investigation for its prognostic role in this population.

Is bioelectrical impedance analysis beneficial to estimate subclinical atherosclerosis in menopause? Prospective case-control study

Aim: To evaluate body composition and basal metabolic rate in premenopausal and postmenopausal women, using the bioelectrical impedance analysis method, and to investigate its relationship with carotid intima media thickness (CIMT). Materials and Methods: The study was conducted in 40 premenopausal and 40 postmenopausal women who had been followed up in an obstetrics and gynecology outpatient clinic between January 2009 and September 2009, and data were obtained using the hospital’s database. Body composition parameters and basal metabolic rate were measured via bioelectrical impedance analysis. CIMT was measured using the Doppler ultrasound method. Results: The mean CIMT of the postmenopausal group was statistically significantly higher than that of the premenopausal group (p < 0.001). There was a statistically significant negative correlation between basal metabolic rate and both right (p = 0.015, r = - 0.381) and left (p = 0.025, r = -0.354) CIMT in the postmenopausal group. Conclusion: Bioelectrical impedance analysis may be a useful adjunctive tool for early detection of subclinical atherosclerosis in postmenopausal women.

Effect of ApoE4 Genotype on the Association Between Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Women

Metabolic profile and ApoE4 genotype have effects on coronary heart disease. We examined the interaction between these factors on subclinical atherosclerosis in postmenopausal women from the Early versus Late Intervention Trial with Estradiol (n = 497). Based on nine metabolic biomarkers (fasting blood glucose, insulin sensitivity, ketones, triglycerides, high-density lipoprotein, low-density lipoprotein, hemoglobin A1c, and blood pressure), K-means clustering categorized women into three distinct phenotypes: healthy, high blood pressure, and poor metabolic. ApoE4 genotype was classified as either ApoE4+ or ApoE4-. General linear models tested whether the cross-sectional association between metabolic phenotypes and common carotid intima media thickness (CIMT) differed by ApoE4 genotype. Mixed effects linear models evaluated the modifying role of ApoE4 genotype on the association of metabolic phenotype with CIMT progression over a median follow-up of 4.8 years. In cross-sectional analysis, ApoE4+ women with poor metabolic phenotype had the highest CIMT compared with all other groups. In ApoE4- women, CIMT was significantly lower in those classified as healthy compared with high blood pressure phenotype (p = 0.004). In ApoE4+ women, CIMT was significantly higher in those with poor metabolic phenotype compared with healthy (p = 0.0003) and high blood pressure (p = 0.001) phenotypes. These results indicate that metabolic phenotype had a negative effect on CIMT in women with ApoE4+ but not ApoE4- (interaction p = 0.001). These effects were not observed on CIMT progression in longitudinal analysis. In conclusion, ApoE4+ women are more likely to have higher levels of subclinical atherosclerosis if their metabolic phenotype is poor compared with ApoE4+ women without poor metabolic profile and ApoE4- women.

Breastfeeding is inversely associated with subclinical atherosclerosis in postmenopausal women

Breastfeeding is inversely associated with subclinical atherosclerosis in postmenopausal women

CORRIGENDUM FOR "Hemodynamic Markers and Subclinical Atherosclerosis in Postmenopausal Women With Primary Hyperparathyroidism".

CORRIGENDUM FOR "Hemodynamic Markers and Subclinical Atherosclerosis in Postmenopausal Women With Primary Hyperparathyroidism".

Characterization of intravascular cellular activation in relationship to subclinical atherosclerosis in postmenopausal women.

ObjectiveMechanisms and interactions among intravascular cells contributing to development of subclinical atherosclerosis are poorly understood. In women, both menopausal status and pregnancy history influence progression of atherosclerosis. This study examined activation and interactions among blood elements with subclinical atherosclerosis in menopausal women with known pregnancy histories.MethodsCarotid intima-media thickness (CIMT), as a marker of subclinical atherosclerosis, was measured using B-mode ultrasound in age- and parity-matched women [40 with and 40 without a history of preeclampsia] 35 years after the index pregnancy. Interactions among intravascular cells (38 parameters) were measured by flow cytometry in venous blood. Data analysis was by principal component which retained 7 independent dimensions accounting for 63% of the variability among 38 parameters.ResultsCIMT was significantly greater in women with a history of preeclampsia (P = 0.004). Platelet aggregation and platelet interactions with granulocytes and monocytes positively associated with CIMT in postmenopausal women independent of their pregnancy history (ρ = 0.258, P< 0.05). However, the association of the number of platelets, platelet activation and monocyte-platelet interactions with CIMT differed significantly depending upon pregnancy history (test for interaction, P<0.001).ConclusionInteractions among actived intravascular cells and their association with subclinical atherosclerosis differ in women depending upon their pregnancy histories.

Association of Mild-to-Moderate Reduction in Glomerular Filtration Rate with Subclinical Atherosclerosis in Postmenopausal Women.

Due to loss of hormonal protective effects, postmenopausal women have an increased cardiovascular (CV) risk. Chronic kidney disease (CKD) is a well-established risk factor for CV disease, but little is known whether mild-to-moderate kidney dysfunction is associated with atherosclerosis burden in the postmenopausal asymptomatic women. Subclinical atherosclerosis was evaluated in 125 postmenopausal women with no clinical form of atherosclerosis, by carotid and femoral ultrasonography, ankle-brachial index (ABI), and flow-mediated dilation (FMD). Carotid and femoral atherosclerosis were defined as increased intima-media thickness (IMT) and/or the presence of plaques. Endothelial function was assessed by endothelial dependent (flow-mediated dilation at 1 minute [FMD1]) and independent (flow-mediated dilation after nitroglycerin [FMDNTG]) vasodilation. Classical CV risk factors (age, smoking, obesity, diabetes, blood pressure, and lipids) were evaluated. Kidney function was evaluated in terms of estimated glomerular filtration rate (eGFR) calculated by the CKD-EPI formula. Univariate linear regression and multivariate logistic regressions were used to evaluate the independent associations between kidney function and markers of subclinical atherosclerosis. In the unadjusted linear analysis, eGFR showed a significant negative association with markers of subclinical atherosclerosis: carotid IMT (R2 = 0.305; p < 0.001), femoral IMT (R2 = 0.19, p < 0.001), carotid plaques (R2 = 0.22; p < 0.001), femoral plaques (R2 = 0.09; p = 0.0005), ABI (R2 = 0.05; p = 0.01), FMD1 (R2 = 0.45; p < 0.001), and FMDNTG (R2 = 0.205, p < 0.001). After adjustment for classical CV risk factors the association remained significant. Mild-to-moderate reduced eGFR is related to subclinical atherosclerosis, independent of traditional CV risk factors. It is important to detect renal function decline, even if it is mild, to improve risk stratification of subclinical atherosclerosis in postmenopausal women.

Hemodynamic markers and subclinical atherosclerosis in postmenopausal women with primary hyperparathyroidism.

Recent evidence suggests that primary hyperparathyroidism (pHPT) is linked with hypertension and subclinical atherosclerosis. These associations have not been examined in postmenopausal women, in whom cardiovascular risk steeply rises after menopausal transition. The objective of the study was to assess whether pHPT is associated with hemodynamic markers and subclinical atherosclerosis in postmenopausal women under a cross-sectional case-control design. One hundred two postmenopausal women with pHPT and 102 women matched 1:1 for age and menopausal status were consecutively recruited. In all patients, flow-mediated dilatation, carotid-femoral pulse wave velocity, reflected waves, aortic blood pressures (BP), intima-media thickness, and the presence of plaques in the carotid and common femoral arteries were measured. Women with pHPT had higher aortic and peripheral BP (P < .05 for all), but no correlation was observed with subclinical atherosclerosis. After adjusting for possible confounders, pHPT was an independent determinant of peripheral and aortic diastolic BP (P < .05 for all). The association with systolic BP was lost after adjusting for C-reactive protein. Further adjustment for PTH and 25-hydroxyvitamin D levels revealed that PTH but not 25-hydroxyvitamin D was an independent determinant of all BP parameters. Both peripheral and aortic BP increased across PTH tertiles as compared with the control group, but this association lost significance after adjustment for C-reactive protein. These results suggest that pHPT may increase peripheral and aortic BP through PTH and inflammatory-mediated mechanisms. A direct impact of the disease on the arterial wall cannot be implicated despite the large number of markers of subclinical atherosclerosis measured in this study.

Collagen cross-links as a marker for subclinical atherosclerosis in postmenopausal women

This study aimed to examine the utility of pyridinoline (Pyd) and deoxypyridinoline (Dpd) cross-links in the detection of subclinical atherosclerosis in postmenopausal women with or without osteoporosis. We measured Pyd, Dpd, carotid intima-media thickness (CIMT), fasting total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and blood pressure in 59 healthy postmenopausal women: 30 had normal bone mineral density (group I) and the remaining 29 had osteoporosis or osteopenia (group II) according to World Health Organization criteria. There were no statistically significant differences in age, duration of menopause, age at menopause, lipid profile, body mass index, Pyd level, Dpd level, and Pyd-to-Dpd ratio between the groups (P > 0.05). No significant difference in CIMT was found when groups I and II were compared (P = 0.538). No statistically significant differences in Pyd level, Dpd level, and Pyd-to-Dpd ratio were found when women with CIMT higher than 5 mm and women with CIMT of 5 mm or less were compared in groups I and II (P > 0.05). However, significantly declined Dpd level and increased Pyd-to-Dpd ratio were found in women with CIMT higher than 5 mm when compared with women with CIMT of 5 mm or less. CIMT was found to be negatively correlated with Dpd level (r = -0.346, P = 0.007) and to be positively correlated with the Pyd-to-Dpd ratio (r = 0.702, P < 0.001). The increase in the Pyd-to-Dpd ratio, irrespective of the participants' bone mineral density, may have predictive value in the determination of subclinical atherosclerosis in postmenopausal women.

Relationship between decreased bone mineral density and subclinical atherosclerosis in postmenopausal women

Objectives The study aimed to compare measurements of coronary artery calcification (CAC) and bone mineral density (BMD) in postmenopausal women.Methods The CAC of the women was measured with electron beam tomography using a GE Imatron C150 XP EBT scanner. Subjects with calcium scores above 0 were classified as CAC(+); those without detectable coronary calcium were classified as CAC(−). BMD was measured by dual-energy X-ray absorptiometry (DEXA). Patients were divided into two groups, depending on the T scores of their lumbar spine, into those with normal bone and those with osteopenia-osteoporosis.Results The proportions of patients classified as CAC(+) were 20% in the normal group and 60% in the osteopenia-osteoporosis group (p = 0.037). BMD values in L1–4 were 1.13 ± 2.29 and 0.98 ± 2.79 g/cm2 in the normal group and osteopenia-osteoporosis group, respectively and the mean total CAC scores were 1.34 ± 1.2 and 69.0 ± 20.5, respectively. The CAC scores of patients with osteopenia-osteoporosis were significantly higher compared with those of the normal group (p = 0.014).Conclusion The study shows that postmenopausal women with decreased bone mineral density may have higher risk of subclinical coronary atherosclerosis.

Relationship between decreased bone mineral density and subclinical atherosclerosis in postmenopausal women

Relationship between decreased bone mineral density and subclinical atherosclerosis in postmenopausal women

CYP A-204C polymorphism is associated with subclinical atherosclerosis in postmenopausal women

To assess the association of common polymorphisms involved in lipoprotein oxidation, platelet activation, and cholesterol and homocysteine metabolism with subclinical atherosclerosis and indices of endothelial function and arterial elasticity in healthy postmenopausal women. The study investigated 84 healthy postmenopausal women recruited from the Menopause Clinic of the 2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital. The following polymorphisms were genotyped: apolipoprotein B 3500, apolipoprotein E (E2/E3/E4), cholesterol 7 alpha-hydroxylase A-204C (CYP A-204C), cholesterol ester transfer protein B1/B2, glycoprotein IIIa leu33pro, integrin beta 3 PLA1/PLA2, plasminogen activator inhibitor 1 4G/5G, paraoxonase 1 gln192 arg, and methylenetetrahydrofolate reductase ala222val. Ultrasound examination aimed to assess the presence of atherosclerotic plaque and to measure intima-media thickness in the carotid and femoral arteries and to estimate the augmentation index, brachial flow-mediated dilatation, and radial and femoral pulse-wave velocity. The cholesterol 7 alpha-hydroxylase A-204C polymorphism was positively associated with the presence of atherosclerotic plaque (P = 0.004) and carotid and femoral intima-media thickness (P = 0.047 and P = 0.025, respectively). The CYP A-204C polymorphism was positively associated with subclinical atherosclerosis in healthy postmenopausal women. It remains to be clarified whether the presence of these polymorphisms may be valuable in assessing the inherent risk among postmenopausal women.

Sex hormone levels and subclinical atherosclerosis in postmenopausal women: The Multi-Ethnic Study of Atherosclerosis

We examined cross-sectional associations between sex hormones and carotid artery intimal-medial thickness (cIMT) and coronary artery calcium in women in the Multi-Ethnic Study of Atherosclerosis. Serum testosterone, estradiol, sex hormone binding globulin (SHBG), and dehydroepiandrosterone levels were measured in 1947 postmenopausal women aged 45–84 years (30% White, 14% Chinese-American, 31% Black, and 25% Hispanic) and not on hormone therapy. Using multiple linear regression we evaluated associations between log(sex hormone) levels and log(cIMT) adjusted for age, ethnicity, body mass index (BMI) and cardiac risk factors. Associations between sex hormone levels and the presence and extent of coronary calcium were evaluated. Total and bioavailable testosterone were positively associated with common cIMT independent of age, BMI, hypertension, smoking, HDL-cholesterol, LDL-cholesterol and insulin sensitivity ( p = 0.009 and p = 0.002, respectively). SHBG was negatively associated with common cIMT ( p = 0.001) but further adjustment for BMI, cardiovascular risk factors, and LDL- and HDL-cholesterol removed significance. Estradiol and dehydroepiandrosterone were not associated with common cIMT. Sex hormones were not associated with presence of coronary calcium. Among women with measurable coronary calcium, higher SHBG ( p = 0.012) and lower bioavailable testosterone ( p = 0.007) were associated with greater coronary calcium score. No heterogeneity by ethnicity was found. In postmenopausal women, testosterone is independently associated with greater common cIMT. SHBG is negatively associated and this may be mediated by LDL- and HDL-cholesterol. In contrast, SHBG and testosterone were associated with extent of coronary calcium but in the opposite direction compared to carotid intimal-medial thickness. These differences warrant further evaluation.

Relationship between Serum Levels of Sex Hormones and Progression of Subclinical Atherosclerosis in Postmenopausal Women

Postmenopausal hormone therapy has been examined extensively in relation to cardiovascular disease. However, research relating serum levels of sex hormones to cardiovascular disease is sparse, and the results are inconclusive. We measured sex hormones in longitudinally collected samples of 180 postmenopausal women, 91 randomized to 17beta-estradiol and 89 to placebo, in the Estrogen in the Prevention of Atherosclerosis Trial. Repeated measures of sex hormone levels were tested for an association with carotid artery intima-media thickness (CIMT), which was also assessed longitudinally over 2 yr. In all women, changes in serum estrone (P = 0.02), total estradiol (P = 0.01), free estradiol (P = 0.02), and SHBG (P = 0.005) were significantly inversely associated with CIMT progression, controlling for age and body mass index. All the estrogen compounds and SHBG were significantly inversely related with low-density lipoprotein cholesterol and positively associated with high-density lipoprotein cholesterol (all P < 0.0001), whereas free testosterone was positively related with low-density lipoprotein cholesterol and inversely associated with high-density lipoprotein cholesterol (P < 0.003). Despite an increase in serum-free estradiol with estradiol therapy, women with unchanged SHBG and free testosterone levels had an average (se) progression in CIMT of 8.53 (4.72) microm/yr, whereas women with increased free estradiol and SHBG and decreased free testosterone had the largest reduction in CIMT progression [-5.45 (2.77) microm/yr; trend P = 0.03]. Estrogen and SHBG are associated with reduced subclinical atherosclerosis progression in healthy postmenopausal women. These associations are partially mediated by their beneficial effects on lipids. Among women taking estradiol, the most beneficial hormone profile for CIMT progression was increased free estradiol and SHBG with concomitant decreased free testosterone.

Effects of Hormone Replacement on Progression of Coronary Calcium as Measured by Electron Beam Tomography

The recent Women's Health Initiative (WHI) results have demonstrated that combined estrogen plus progestin imparts a small but significant increase in cardiovascular risk and breast cancer among asymptomatic women. However, the effect and potential benefit of unopposed estrogen is not as clear. We sought to evaluate the progression of subclinical atherosclerosis in postmenopausal women using no hormone replacement therapy (HRT), combined therapy, and estrogen alone in an observational study. Postmenopausal women without symptoms or known coronary heart disease (CHD) were evaluated at our center for follow-up of coronary calcification. Patients were physician referred and underwent two consecutive electron beam tomography scans at least 1 year apart. All women fitting the study criteria were asked to participate, and those who consented were included. Demographic data, risk factors for CHD, HRT, and other medication use were collected by interview. The study included 177 asymptomatic women. Calcium progression was 14.6%+/-21% in women taking any hormone therapy (n=97). Annual calcium progression rates in nonusers (n=80) was 22.3%+/-32%. Relative to the nonuser group, HRT treatment inhibited the progression of atherosclerosis by 35% (p=0.01). This effect was independent of age, risk, cardiovascular factors, statin use, or baseline CAC score. Thirty-five of the 97 women (36%) were taking estrogen plus progestin, with an annual increase in calcium scores of 24%+/-23%, similar to the non-HRT women (22%). Those women taking estrogen replacement only (n=62) was 63% lower (9%+/-22%). This is an observational study, and the results are in accordance with the recently published WHI study, demonstrating no benefit of estrogen plus progestin compared with no therapy. However, women taking unopposed estrogen demonstrated a significant slowing of subclinical atherosclerosis compared with non-HRT and estrogen plus progestin.