Stroke In Postmenopausal Women Research Articles

Associations of reproductive factors with incidence of myocardial infarction and ischemic stroke in postmenopausal women: a cohort study

BackgroundTo assess the association between the reproductive factors of age at menarche, age at menopause, and reproductive span and the incidence of myocardial infarction (MI) and ischemic stroke (IS).MethodsWe used a population-based retrospective cohort study from the National Health Insurance Service database of Korea including a total of 1,224,547 postmenopausal women. Associations between age at menarche (≤ 12, 13–14 [reference], 15, 16, and ≥ 17 years), age at menopause (< 40, 40–45, 46–50, 51–54 [reference], and ≥ 55 years), and reproductive span (< 30, 30–33, 34–36, 37–40 [reference], and ≥ 41 years) and the incidence of MI and IS were assessed by Cox proportional hazard models with adjustment for traditional cardiovascular risk factors and various reproductive factors.ResultsDuring a median follow-up of 8.4 years, 25,181 MI and 38,996 IS cases were identified. Late menarche (≥ 16 years), early menopause (≤ 50 years), and short reproductive span (≤ 36 years) were linearly associated with a 6%, 12–40%, and 12–32% higher risk of MI, respectively. Meanwhile, a U-shaped association between age at menarche and risk of IS was found, with a 16% higher risk in early menarche (≤ 12 years) and a 7–9% higher risk in late menarche (≥ 16 years). Short reproductive span was linearly associated with an increased risk of MI, whereas both shorter and longer reproductive spans were associated with an increased risk of IS.ConclusionsThis study demonstrated different patterns of association between age at menarche and incidence of MI and IS: a linear association for MI versus a U-shaped association for IS. Female reproductive factors in addition to traditional cardiovascular risk factors should be considered when assessing overall cardiovascular risk in postmenopausal women.

Association between metabolically obese but normal weight and cardiovascular diseases in Korean menopausal women.

The aim of this study was to present useful data for developing effective health management strategies for cardiovascular disease (CVD) prevention in postmenopausal women by investigating health-related behaviors and the prevalence of CVD for different types of obesity classified according to metabolic health status and body mass index criteria. Using the 2016 Korean National Health and Nutrition Examination Survey VII-1 data, 1,190 menopausal women aged 50 years or older were analyzed in this cross-sectional study. The participants were divided into four groups as follows: metabolically healthy and normal weight (MHNW), metabolically obese but normal weight (MONW), metabolically healthy but obese, and metabolically obese and obese. Complex-samples general linear analysis, t tests, and logistic regression analysis were used to compare the differences in health-related behaviors and the risk of CVD among the four groups. The risk for stroke was 3.61 times higher (95% CI, 1.18-11.03) in the MONW group than in the MHNW group. We found a strong association between the MONW group of obesity and the risk for CVD, particularly stroke, in postmenopausal women. These findings would serve as valuable evidence for developing and implementing interventions to prevent stroke in postmenopausal women in the MONW group.

Calcium and magnesium in drinking water and risk of myocardial infarction and stroke—a population-based cohort study

ABSTRACTBackgroundThe implication of calcium and magnesium in drinking water for cardiovascular disease is unclear.ObjectivesTo assess the association of the concentration of calcium and magnesium in drinking water with incidence of myocardial infarction and stroke, accounting for dietary mineral intake.MethodsWe linked drinking water monitoring data to residential information of 26,733 women from the population-based Swedish Mammography Cohort, who completed a 96-item FFQ at baseline. Drinking water was categorized into low (magnesium <10 mg/L and calcium <50 mg/L) or high (magnesium ≥10 mg/L or calcium ≥50 mg/L) mineral concentration. Incident cases of myocardial infarction and stroke types were ascertained 1998–2019 using the National Patient Register.ResultsThe mean ± SD concentration of calcium and magnesium in drinking water was 29 ± 7 mg/L and 5 ± 1 mg/L in the low-exposed area and 52 ± 20 mg/L and 10 ± 3 mg/L in the high-exposed area, respectively. During 16 years of follow-up, we ascertained 2023, 2279, and 452 cases of myocardial infarction, ischemic stroke, and hemorrhagic stroke, respectively. High drinking water calcium and magnesium was associated with lower risk of ischemic and hemorrhagic stroke HRs of 0.87 (95% CI: 0.80, 0.95) and 0.78 (95% CI: 0.65, 0.95), whereas the HR for myocardial infarction was 0.93 (95% CI: 0.85, 1.02). In separate analyses, only drinking water magnesium, not calcium, remained associated with ischemic stroke (HR: 0.69; 95% CI: 0.54, 0.88).ConclusionsDrinking water with a high concentration of calcium and magnesium, particularly magnesium, may lower the risk of stroke in postmenopausal women.

An Artificial Neural Network Approach to Predicting Stroke in Postmenopausal Women.

The article's abstract is not available.

Age at menarche, age at menopause, reproductive years and risk of fatal stroke occurrence among Chinese women: the Guangzhou Biobank Cohort Study

BackgroundThe relationship between women’s reproductive characteristics and stroke events is unclear. We aimed to investigate age at menarche, age at menopause and number of reproductive years in relation to fatal stroke occurrence in the Guangzhou Biobank Cohort Study.MethodsIn total, 16,504 postmenopausal women without stroke, heart disease or a cancer history at baseline were included and followed up for a median of 12.0 years. After review of available records, 222 stroke deaths were recorded. Cox proportional hazards regression was used to assess the associations between the risk of fatal stroke occurrence and age at menarche, age at menopause and number of reproductive years.ResultsIn the whole cohort, compared with those aged 15 years at menarche, an increased risk of fatal stroke among women at menarche showed respectively in those aged 12 years (aHR (adjusted hazard ratio) = 1.86, 95% confidence interval (CI) 0.96–3.60), aged 13 years (aHR = 1.69, 95% CI 0.98–2.92), aged 17 years (aHR = 1.83, 95% CI 1.10–3.05) and aged ≥ 18 years (aHR = 1.66, 95% CI 1.03–2.70), wherein the associations revealed an atypically U-shaped; similar U-shaped association to the cohort of postmenopausal women born before 1940 released a range of incremental risks of fatal stroke in women at menarche aged ≤ 12 years (aHR = 3.68, 95% CI 1.68–8.05), aged 13 years (aHR = 2.11, 95% CI 1.02–4.34), aged 14 years (aHR = 2.07, 95% CI 1.04), aged 17 years (aHR = 2.30, 95% CI 1.20–4.39) and aged 18 years (aHR = 2.50, 95% CI 1.37–4.57), respectively. Compared with menopausal women aged 51–52 years, those aged < 43 years at menopause had an increased risk for fatal stroke among postmenopausal women born in and after 1940 (aHR = 1.64, 95% CI 0.97–2.78) and postmenopausal women born before 1940 (aHR = 1.97, 95% CI 1.05–3.69). Additionally, compared with those with 32–34 reproductive years, women with ≤ 28 reproductive years had an increased risk for fatal stroke in the whole cohort (aHR = 1.91, 95% CI 1.28–2.86) and the cohort of postmenopausal women born before 1940 (aHR = 1.79, 95% CI 1.15–2.80).ConclusionsYounger and older age at menarche, younger age at menopause and fewer reproductive ages were related to an increased risk of fatal stroke in postmenopausal women.

Computational binding analysis and toxicity evaluation of estrogen receptor with estradiol and the approved SERMs raloxifene, tamoxifen, and toremifene

Estrogen receptor is a key feature of many complex disorders. Natural estrogen ligand, estradiol has been investigated in the pharmaceutical aspect of breast cancer, Parkinson’s, Alzheimer’s, risk of stroke in postmenopausal women, and dementia. From the similar manner, synthetic selective estrogen receptor modulators (SERMs) have been investigated, and their pharmaceutical effects have been evaluated in compared to the natural ligand, estradiol, in literature. To design better alternatives to the approved SERMs and to improve the clinical observations, it is crucial to understand the molecular basis of drug-target interactions of estrogen receptor with the natural and synthetic ligands in a comparative manner. We used molecular modeling softwares PyRX, Avogadro, and Arguslab for in silico calculations. The results were analyzed using PyMol. We, in this study, provided a computational binding analysis of the estrogen receptor with the endogenous ligand estradiol and the FDA approved SERMs raloxifene, tamoxifen, and toremifene. We investigated the toxicity profile of the SERMs and estradiol and interpreted the results according to the reported clinical observations. We found that designing new molecules based on the estradiol structure instead of the approved tamoxifen analogs could result in better clinical observations for future estrogen targeting therapeutics.

Association of the length of oestrogen exposure with risk of incident stroke in postmenopausal women: Insights from a 20-year prospective study

BackgroundTo examine the relationship between the length of oestrogen exposure and risk of incident stroke. Also, the additive value of each model was compared for assessing oestrogen exposure and stroke risk in postmenopausal women. Study design and settingProspective study of 5632 post-menopausal women without a prior history of stroke from 1996 through 2016 in Australian Longitudinal Study on Women's Health. Data on surrogate measures of oestrogen exposure were used to derive five indices of oestrogen exposure including reproductive lifespan (RLS) (age at menopause-age at menarche), endogenous oestrogen and total oestrogen exposure (which included menopausal hormone therapy (MHT use)). The relationships between the length of oestrogen exposure (quartiles) and incident stroke events were examined using multivariable adjusted Cox proportional hazard regression and their predictive accuracy were compared using area under the Receiver Operating Characteristic Curve. ResultsThe mean (SD) for RLS was 37.9(4.3) years. A shorter RLS (≤34 years) was associated with a higher risk of incident stroke after adjustment (HR: 1.85, 95%CI: 1.08, 3.15), compared with 38–40 years. There was 7% decrease in risk of stroke per 1-year increase in RLS (HR: 0.93, 95%CI: 0.89, 0.97). Even though the combination of endogenous oestrogen and exogenous hormones aimed to provide more accurate length of oestrogen exposure, the results showed that each model had similar goodness of fit and did not improve the model of just using RLS as a predictor of incident stroke. ConclusionsA shorter RLS (≤34 years) was associated with higher risk of incident stroke compared to medium RLS. Endogenous oestrogen and of total oestrogen exposure (which included MHT use) did not improve the model of just using RLS as a predictor of incident stroke.

Genistein Attenuates Acute Cerebral Ischemic Damage by Inhibiting the NLRP3 Inflammasome in Reproductively Senescent Mice.

Postmenopausal women have a higher incidence of stroke compared to the age-matched males, and the estrogen was thought to be the main cause of such difference. However, estrogen replacement therapy for the prevention of postmenopausal stroke shows controversial results and is widely disputed because of its serious side effects after chronic administration. Genistein (Gen), a natural phytestrogen with fewer side effects, has a protective effect against cerebral ischemia damage. However, whether Gen could effectively prevent postmenopausal stroke has not been elucidated. In the current study, reproductively senescent mice were treated with Gen (10 mg/kg) for 2 weeks before having transient cerebral ischemia insults. Neurological scores, infarct volumes, and cell apoptosis were evaluated 24 h after reperfusion. The levels of inflammatory factors and nod-like receptor protein 3 (NLRP3) inflammasome-related proteins were also examined. The results showed that Gen treatment reduced infarct volumes, improved neurological scores, attenuated apoptosis, and decreased inflammatory factor release. The expression of NLRP3 inflammasome-related proteins in microglia was downregulated by Gen. However, the overexpression of NLRP3 in microglia abrogated the Gen-induced inhibition of inflammatory factor release and reversed the neuroprotective effect of Gen. Taken together, the results suggest that Gen treatment could attenuate the acute injury induced by cerebral ischemia in reproductively senescent mice via the inhibition of the NLRP3 inflammasome in microglia, indicating that Gen could be a candidate drug for the treatment of stroke in postmenopausal women.

Plasma Estradiol and Testosterone Levels and Ischemic Stroke in Postmenopausal Women.

Background and Purpose- Although exogenous hormone therapy (HT) use has been associated with increased risk of ischemic stroke in postmenopausal women, it remains unknown whether sex hormone levels contribute to ischemic stroke risk. We aimed to estimate associations between plasma sex hormone levels and ischemic stroke risk, by HT status, in a nested case-control study of postmenopausal women from the NHS (Nurses' Health Study). Methods- Women with confirmed incident ischemic stroke (n=419) were matched with controls (n=419) by age, HT use, and other factors. Plasma estradiol and testosterone levels were measured using liquid chromatography tandem mass spectrometry; SHBG (sex hormone-binding globulin) was assayed by electrochemiluminescence immunoassay. Associations of total and free estradiol and testosterone, the estradiol/testosterone ratio, and SHBG with ischemic stroke were estimated using conditional logistic regressions stratified by HT status with adjustment for matching and cardiovascular risk factors. Results- Current HT users had different hormone profiles from never/past users. No clear linear trends were observed between estradiol (total or free) levels or the estradiol/testosterone ratio and ischemic stroke risk among either current users (Ptrend>0.1) or never/past users (Ptrend>0.6). For both current and never/past users, the associations between some of the sex hormones and ischemic stroke differed by body mass index categories (Pinteraction≤0.04). For women with a body mass index <25 kg/m2, a higher estradiol/testosterone ratio was associated with significantly elevated ischemic stroke risk among current users (Ptrend=0.01), and higher levels of total and free estradiol were significantly associated with higher ischemic stroke risk among never/past users (Ptrend≤0.04). Testosterone and SHBG were not associated with ischemic stroke in either current or never/past users. Conclusions- Our findings do not support a role of sex hormone levels in mediating ischemic stroke risk among postmenopausal women. Replications in additional larger studies are required.

An observational study to predict the risk of stroke in post-menopausal women using hs-crp and qstroke

An observational study to predict the risk of stroke in post-menopausal women using hs-crp and qstroke

Genistein attenuates brain damage induced by transient cerebral ischemia through up-regulation of Nrf2 expression in ovariectomized rats

Objective: Postmenopausal women possess higher incidence of stroke and worse prognosis. Although estrogen replacement therapy has obvious neuroprotective effects against stroke, it is always accompanied with several adverse effects and undesired outcomes. Genistein, a natural phytoestrogen, has been indicated to be a potential neuroprotective alternative for postmenopausal women against stroke. However, the role and mechanism of genistein’s neuroprotective effects against stroke in ovariectomized rats have rarely been explored.Methods: In this study, ovariectomized rats were treated with genistein (10 mg/kg) or vehicle daily for two weeks before they received middle cerebral artery occlusion (MCAO) and reperfusion. After 72 hours of reperfusion, the neurological function was evaluated by Garcia test, infarct volume was detected by 2,3,5-triphenyltetrazolium chloride staining, and neuronal damage was detected by Nissl staining. In addition, ROS production and the expression of Nrf2, NQO1 and cleaved-Caspase3 in the ischemic penumbra were detected.Results: The results showed that genistein treatment significantly improved the neurological outcome, reduced infarct volume, increased Nrf2 and NQO1 expression, and reduced ROS production and cleaved-Caspase3 expression in ovariectomized rats. Discussion: Our findings indicated that treatment with genistein could alleviated oxidative stress injury induced by cerebral ischemia in ovariectomized rats via promoting Nrf2 and NQO1 expression, which provide a new molecular mechanism for the neuroprotective effects of genistein against stroke in postmenopausal women.

Abstract TP208: Incidence and Outcome of Iatrogenic Stroke in Post-Menopausal Women

Object: The incidence of iatrogenic stroke has not been determined in cohort studies. We determine the incidence of iatrogenic stroke in a large cohort of post-menopausal women. Methods: We analyzed the data for 93,676 women aged 50-79 years who were enrolled in the observational arm of the Women’s Health Initiative Study. We calculated crude and standardized incidence rates over a mean period (±SD) of 12±1 years. We calculated the incidences of iatrogenic and non-iatrogenic stroke adjusted for age and sex based on the 2010 US census. We compared the incidence of using standardized incidence ratio (SIR) with 95% confidence interval (CI). We estimated the 30-day case-fatality rates. Results: We identified 150 iatrogenic (141 ischemic and 9 hemorrhagic) and 2425 non-iatrogenic (1993 ischemic and 431 hemorrhagic) strokes. Age-standardized incidence rate per 100 000 was 48.9 (95% CI, 37.1- 6.25) for iatrogenic stroke and 741.9 (95% CI, 690.5 - 795.3) for non-iatrogenic strokes (SIR of 0.07). For ischemic stroke, the age adjusted incidence was 50.2 (95% CI, 38.8-64.8) for iatrogenic and 709.0 (95% CI, 658.2-762.6) for non iatrogenic stroke (SIR of 0.07). Thirty-day case-fatality rate was 9.3% (95% CI, 5.2-15) for iatrogenic stroke and 17.3% (95% CI, 15.7-19.0) for non iatrogenic stroke. Conclusions: The incidence of iatrogenic stroke was higher than previously anticipated and 1 of every 15 stokes in post menopausal women was iatrogenic in etiology

Pregnancy in advanced age and the risk of stroke in postmenopausal women: analysis of Women’s Health Initiative Study

The incidence of pregnancy in advanced age among women is increasing because of the availability of assisted reproduction, although the long-term health consequences are not known. The purpose of this study was to determine the effect of pregnancy in advanced age on the occurrence of cardiovascular events in a large cohort of postmenopausal women. We analyzed the data for 72,221 women aged 50-79 years who were enrolled in the observational arm of the Women's Health Initiative study. We determined the effect of pregnancy in advanced age (last pregnancy at age ≥40 year) on the risk of ischemic stroke, hemorrhagic stroke, myocardial infarction, and cardiovascular death over a mean period (±standard deviation) of 12±1 years using Cox Proportional Hazards analysis after adjusting for potential confounders. A total of 3306 of the 72,221 participants (4.6%) reported pregnancy in advanced age. Compared with pregnancy in normal age, the rates of ischemic stroke (3.8% vs 2.4%), hemorrhagic stroke (1.0% vs 0.5%), and cardiovascular death (3.9% vs 2.3%) were significantly higher among women with pregnancy in advanced age. In multivariate analysis, women with pregnancy in advanced age were 50% more likely to experience a hemorrhagic stroke (hazard ratio, 1.5; 95% confidence interval, 1.0-2.1) after adjustment for age, race/ethnicity, congestive heart failure, systolic blood pressure, atrial fibrillation, alcohol use, and cigarette smoking. There was no significant difference in the risk of ischemic stroke, myocardial infarction, and cardiovascular death among women with pregnancy in advanced age after adjustment for potential confounders. Women with pregnancy at an advanced age have a higher risk for hemorrhagic stroke in the postmenopausal period.

Pregnancy in Advanced Age Increases the Risk of Hemorrhagic Stroke in Post-Menopausal Women. Analysis of Women's Health Initiative Study (P6.005)

Pregnancy in Advanced Age Increases the Risk of Hemorrhagic Stroke in Post-Menopausal Women. Analysis of Women's Health Initiative Study (P6.005)

Abstract WMP50: Pregnancy in Advanced Age Increases the Risk of Hemorrhagic Stroke in Post-menopausal Women. Analysis of Women's Health Initiative Study

Background: The incidence of pregnancy in advanced age among women is increasing due to availability of assisted reproduction although the complication rates associated with pregnancy are higher. The long-term health consequences in women with pregnancy in advanced age is not known. We determine the effect of pregnancy in advanced age on occurrence of cardiovascular events in a large cohort of post-menopausal women. Methods: We analyzed the data for 72,221 women aged 50-79 years who were enrolled in the observational arm of the Women's Health Initiative Study. We determined the effect of pregnancy in advanced age (last pregnancy at age≥40 year) on risk of ischemic stroke, hemorrhagic stroke, myocardial infarction, and cardiovascular death over a mean period (± standard deviation [SD]) of 12±1 years using Cox Proportional Hazards analysis after adjusting for potential confounders. Results: A total of 3306 (4.6%) of the 72,221 participants reported pregnancy in advanced age. Compared with pregnancy in normal age, the rate of ischemic stroke (2.4% versus 3.8%, p&lt;0.0001), hemorrhagic stroke (0.5% versus 1.0%, p&lt;0.0001), myocardial infarction (2.5% versus 3.0%, p&lt;0.0001), and cardiovascular death (2.3% versus 3.9%, p&lt;0.0001) was significantly higher among women with pregnancy in advanced age. In multivariate analysis, women with pregnancy in advanced age were 60% more likely to experience a hemorrhagic stroke (Hazards ratio [HR] 1.6, 95% confidence interval [CI] 1.1-2.4) after adjusting for age, race/ethnicity, congestive heart failure, systolic blood pressure, atrial fibrillation, alcohol use and cigarette smoking. There was no significant difference in the risk of ischemic stroke, myocardial infarction, and cardiovascular death among women with pregnancy in advanced age after adjusting for potential confounders. Conclusions: Women with pregnancy in advanced age have a higher risk for hemorrhagic stroke in post-menopausal period.

Activation of classical estrogen receptor subtypes reduces tight junction disruption of brain endothelial cells under ischemia/reperfusion injury

Ischemic stroke, which induces oxidative stress in the brain, disrupts tight junctions (TJs) between brain endothelial cells, resulting in blood–brain barrier (BBB) breakdown and brain edema. Estrogen reduces oxidative stress and protects brain endothelial cells from ischemic insult. The aim of this study was to determine the protective effects of estrogen on TJ disruption and to examine the roles of classical estrogen receptor (ER) subtypes, ERα- and ERβ, in estrogen effects in brain endothelial cells (bEnd.3) exposed to oxygen-glucose deprivation/reperfusion (OGD/R) injury. Estrogen pretreatment prevented OGD/R-induced decreases in cell viability and TJ protein levels. ERα- and ERβ-specific agonists also reduced TJ disruption. Knockdown of ERα or ERβ expression partially inhibited the effects of estrogen, but completely reversed the effects of corresponding ER subtype-specific agonists on the outcomes of OGD/R. During the early reperfusion period, activation of extracellular signal-regulated kinase1/2 and hypoxia-inducible factor 1α/vascular endothelial growth factor was associated with decreased expression of occludin and claudin-5, respectively, and these changes in TJ protein levels were differentially regulated by ER subtype-specific agonists. Our results suggest that ERα and ERβ activation reduce TJ disruption via inhibition of signaling molecules after ischemic injury and that targeting each ER subtype can be a useful strategy for protecting the BBB from ischemic stroke in postmenopausal women.

Abstract P073: Urinary Isoflavonoids And Risk Of Ischemic Stroke In Postmenopausal Women

Background: Postmenopausal hormone therapy has been shown to increase stroke risk. It is unclear whether high exposure to pytoestrogens, such as soy isoflavones, may confer the same risk of stroke. Objective: To examine associations of urinary isoflavonoids, which reflect isoflavones intake, absorption, and metabolism, with risk of ischemic stroke in postmenopausal Chinese women. Design: A nested case-control study. Method: We identified 1438 incident cases of ischemic stroke druing 1997-2010 and individually matched them to 1438 controls on age, date and time of sample collection, time since last meal, and recent use of antibiotics. All subjects were postmenopausal women who had never used hormone therapy and had no history of CVD or cancer at baseline. Seven isoflavonoids were measured by LC-MS and standardized by urinary creatinine. Results: We found no significant difference between case-control pairs in mean levels of total or individual urinary isoflavonoids, including 3 parent compounds (daidzein, genistein, and glycitein) and 4 metabolites derived from intestinal bacteria (dihydrogenistein, dihydrodaidzein, O-desmethylangolensin, and equol). Multivariate analyses revealed that women in the highest quintile of equol concentration had a lower risk of ischemic stroke (OR=0.77, 95%CI=0.60-0.98). Analyses stratified by equol producing status showed a significant inverse association between isoflavone bacterial metabolites and stroke risk in equol producers (31.8% of the study population, OR=0.40 across extreme quartiles, 95%CI=0.18-0.87, Ptrend=0.002), but no association in equol non-producers. Conclusion: Overall, this large prospective study suggests that urinary isoflavonoids are not associated with risk of ischemic stroke in postmenopausal Chinese women. High level of bacteria-derived metabolites of isoflavones, however, was associated with a reduced risk in equol producers, suggesting a possible interaction between gut microbiome and soy foods in the pathogenesis of ischemic stroke.

Potassium-rich diet reduces risk of stroke in postmenopausal women

Potassium-rich diet reduces risk of stroke in postmenopausal women

Association between annual visit-to-visit blood pressure variability and stroke in postmenopausal women: data from the Women's Health Initiative.

Accumulating evidence suggests that increased visit-to-visit variability (VVV) of blood pressure is associated with stroke. No study has examined the association between VVV of blood pressure and stroke in postmenopausal women, and scarce data exist as to whether this relation is independent of the temporal trend of blood pressure. We examined the association of VVV of blood pressure with stroke in 58,228 postmenopausal women enrolled in the Women's Health Initiative. Duplicate blood pressure readings, which were averaged, were taken at baseline and at each annual visit. VVV was defined as the SD for the participant's mean systolic blood pressure (SBP) across visits (SD) and about the participant's regression line with SBP regressed across visits (SDreg). Over a median follow-up of 5.4 years, 997 strokes occurred. In an adjusted model including mean SBP over time, the hazard ratios (95% CI) of stroke for higher quartiles of SD of SBP compared with the lowest quartile (referent) were 1.39 (1.03-1.89) for quartile 2, 1.52 (1.13-2.03) for quartile 3, and 1.72 (1.28-2.32) for quartile 4 (P trend <0.001). The relation was similar for SDreg of SBP quartiles in a model that additionally adjusted for the temporal trend in SBP (P trend <0.001). The associations did not differ by stroke type (ischemic versus hemorrhagic). There was a significant interaction between mean SBP and SDreg on stroke with the strongest association seen below 120 mmHg. In postmenopausal women, greater VVV of SBP was associated with increased risk of stroke, particularly in the lowest range of mean SBP.

Recommendations for raloxifene use in daily clinical practice in the Swiss setting

Raloxifene is the first selective estrogen receptor modulator that has been approved for the treatment and prevention of osteoporosis in postmenopausal women in Europe and in the US. Although raloxifene reduces the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer, it is approved in that indication in the US but not in the EU. The aim was to characterize the clinical profiles of postmenopausal women expected to benefit most from therapy with raloxifene based on published scientific evidence to date. Key individual patient characteristics relevant to the prescription of raloxifene in daily practice were defined by a board of Swiss experts in the fields of menopause and metabolic bone diseases and linked to published scientific evidence. Consensus was reached about translating these insights into daily practice. Through estrogen agonistic effects on bone, raloxifene reduces biochemical markers of bone turnover to premenopausal levels, increases bone mineral density (BMD) at the lumbar spine, proximal femur, and total body, and reduces vertebral fracture risk in women with osteopenia or osteoporosis with and without prevalent vertebral fracture. Through estrogen antagonistic effects on breast tissue, raloxifene reduces the risk of invasive estrogen-receptor positive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer. Finally, raloxifene increases the incidence of hot flushes, the risk of venous thromboembolic events, and the risk of fatal stroke in postmenopausal women at increased risk for coronary heart disease. Postmenopausal women in whom the use of raloxifene is considered can be categorized in a 2 × 2 matrix reflecting their bone status (osteopenic or osteoporotic based on their BMD T-score by dual energy X-ray absorptiometry) and their breast cancer risk (low or high based on the modified Gail model). Women at high risk of breast cancer should be considered for treatment with raloxifene. Postmenopausal women between 50 and 70 years of age without climacteric symptoms with either osteopenia or osteoporosis should be evaluated with regard to their breast cancer risk and considered for treatment with raloxifene within the framework of its contraindications and precautions.