Events In Older Women Research Articles

Estrogen levels and the risk of cardiovascular events in older women

BACKGROUND: Estrogens play a crucial role in the functioning of the reproductive, cardiovascular, skeletal, and central nervous systems. However, existing literature on the correlation between estrogen levels and the risk of cardiovascular events in elderly populations is limited and contradictory. AIM: To assess the effect of estrogen levels on the incidence of myocardial infarction and stroke in older women. MATERIALS AND METHODS: The Crystal study was a population-based cross-sectional cohort study which included community-dwelling individuals aged 65 and older (n = 280). Key study parameters included survey responses and medical record analysis for non-communicable chronic diseases, alongside laboratory assessments for estradiol, thyroid-stimulating hormone, glycated hemoglobin, total protein, albumin, lipid panel, C-reactive protein, complete blood count, and creatinine levels. RESULTS: A history of stroke was recorded in 18.9% (n = 54) of participants, while myocardial infarction was reported in 11.9% (n = 34). In participants with estradiol levels in the 4th quintile (55 pmol/l), stroke incidence was 2.5 times higher (odds ratio 2.480; 95% confidence interval 1.180–5.211) and myocardial infarction incidence was 2 times higher (odds ratio 2.003; 95% confidence interval 1.088–3.687) after adjustments for age and high-density lipoprotein levels. CONCLUSIONS: An estradiol level greater than 55 pmol/l is an independent risk factor for the development of stroke and myocardial infarction in women aged 65 years and older.

Impaired muscle function, including its decline, is related to greater long-term late-life dementia risk in older women.

Impaired muscle function has been identified as a risk factor for declining cognitive function and cardiovascular health, both of which are risk factors for late-life dementia (after 80years of age). We examined whether hand grip strength and timed-up-and-go (TUG) performance, including their change over 5years, were associated with late-life dementia events in older women and whether any associations provided independent information to Apolipoprotein E ℇ 4 (APOE ℇ 4) genotype. Grip strength and TUG were assessed in community-dwelling older women (mean±SD; age 75.0±2.6years) at baseline (n=1225) and 5years (n=1052). Incident 14.5-year late-life dementia events (dementia-related hospitalization/death) were obtained from linked health records. Cardiovascular risk factors (Framingham Risk Score), APOE genotyping, prevalent atherosclerotic vascular disease and cardiovascular-related medications were evaluated at baseline. These were included in multivariable-adjusted Cox-proportional hazards models assessing the relationship between muscle function measures and late-life-dementia events. Over follow-up, 207 (16.9%) women had a late-life dementia event. Compared with women with the highest grip strength (Quartile [Q] 4, 25.8kg), those with the lowest grip strength (Q1, 16.0kg) had greater hazard for a late-life dementia event (HR 2.27 95% CI 1.54-3.35, P<0.001). For TUG, the slowest women (Q4, 12.4 vs. Q1, 7.4s) also recorded a greater hazard for a late-life dementia event (HR 2.10 95% CI 1.42-3.10, P=002). Weak hand grip (<22kg) or slow TUG (>10.2s) provided independent information to the presence of an APOE ℇ 4 allele (n=280, 22.9%). Compared with women with no weakness and no APOE ℇ 4 allele, those with weakness and APOE ℇ 4 allele had a greater hazard (HR 3.19 95% CI 2.09-4.88, P<0.001) for a late-life dementia event. Women presenting with slowness and the APOE ℇ 4 allele also recorded a greater hazard for a late-life dementia event (HR 2.59 95% CI 1.64-4.09, P<0.001). For 5-year muscle function changes, compared with women with the lowest performance decrement (Q1), those with the largest decrement (Q4) had higher hazards for a late-life dementia event (grip strength HR 1.94 95% CI 1.22-3.08, P=0.006; TUG HR 2.52 95% CI 1.59-3.98, P<0.001) over the next 9.5years. Weaker grip strength and slower TUG, and a greater decline over 5years, were significant risk factors for a late-life-dementia event in community-dwelling older women, independent of lifestyle and genetic risk factors. Incorporating muscle function measures as part of dementia screening appears useful to identify high-risk individuals who might benefit from primary prevention programmes.

SIOG2022-0180 - Comprehensive Geriatric Assessment (CGA) in the Identification of Risk Factors for Early Adverse Events in Older Women with Breast Cancer in the Northeast Region of Brazil. Prospective Cohort Study

SIOG2022-0180 - Comprehensive Geriatric Assessment (CGA) in the Identification of Risk Factors for Early Adverse Events in Older Women with Breast Cancer in the Northeast Region of Brazil. Prospective Cohort Study

Women's Health Initiative Strong and Healthy (WHISH): A pragmatic physical activity intervention trial for cardiovascular disease prevention

BackgroundNational guidelines promote physical activity to reduce cardiovascular disease (CVD); yet, no RCT has tested the effectiveness of physical activity as the sole intervention for primary CVD prevention in older adults. The Women's Health Initiative (WHI) Strong and Healthy (WHISH) trial, a pragmatic trial embedded in the WHI-Extension Study (ES), is testing whether increasing physical activity and decreasing sedentary behavior will reduce major CV events in older women. MethodsThe randomized consent design was used to assign 49,331 women (aged 68–99 years in 2015) who had consented to ongoing WHI-ES follow-up and for whom CV outcomes were available through WHI-ES procedures (N = 18,985) and/or linkage to the Centers for Medicare and Medicaid Services (N = 30,346) to a physical activity (PA) intervention designed to promote national recommendations (N = 24,657) or “usual activity” comparison (N = 24,674). Women assigned to the intervention provided passive consent to receive the intervention and provide data. A multi-component PA intervention is delivered by seasonal (quarterly) newsletters with targeted inserts (lower, middle, higher) based on self-reported levels of physical functioning (PF) and physical activity; monthly motivational telephone messages; monthly emails; a website; and contact with staff, as requested. Major CV events, myocardial infarction (MI), stroke, or CVD death, collected annually through WHI-ES, comprise the primary outcome. Hip fracture and non-CVD death are primary safety outcomes. Intention-to-treat analyses in all randomized participants will include 8 years of follow-up. ConclusionDetermining whether increased physical activity and decreased sedentary behavior reduce major CV events in older women is of major public health significance.Clinical trials registration:ClinicalTrials.govidentifier:NCT02425345

Associations between blood sex steroid concentrations and risk of major adverse cardiovascular events in healthy older women in Australia: a prospective cohort substudy of the ASPREE trial

SummaryBackgroundBlood testosterone concentrations in women decline during the reproductive years and reach a nadir in the seventh decade, after which concentrations increase and are restored to those of reproductive-aged women early in the eighth decade. We aimed to establish the association between the concentration of testosterone in the blood and risk of major adverse cardiovascular events (MACE) and all-cause mortality in healthy older women.MethodsSHOW was a prospective cohort substudy of the longitudinal randomised ASPREE trial. Eligible participants were women aged at least 70 years from Australia with unimpaired cognition, no previous MACE, and a life expectancy of at least 5 years. Participants who were receiving hormonal or steroid therapy were ineligible for inclusion. We measured serum concentrations of sex steroids with liquid chromatography–tandem mass spectrometry and of SHBG with immunoassay. We compared lower concentrations of sex hormones with higher concentrations using four quartiles. Primary endpoints were risk of MACE and all-cause mortality, the associations of which with sex steroid concentrations were assessed using Cox proportional hazards regression that included age, body-mass index, smoking status, alcohol consumption, diabetes, hypertension, dyslipidaemia, impaired renal function, and treatment allocation in the ASPREE trial (aspirin vs placebo). ASPREE is registered with ClinicalTrials.gov, NCT01038583.FindingsOf the 9180 women recruited to the ASPREE trial between March 10, 2010, and Dec 31 2014, 6358 participants provided sufficient biobank samples at baseline and 5535 were included in the final analysis. Median age at entry was 74·0 years (IQR 71·7–77·7). During a median 4·4 years of follow-up (24 553 person-years), 144 (2·6%) women had a first MACE (incidence 5·9 per 1000 person-years). During a median 4·6 years of follow-up (3·8–5·6), 200 women died (7·9 per 1000 person-years). In the fully adjusted models, higher concentrations of testosterone were associated with a lower incidence of MACE (quartile 4 vs quartile 1: hazard ratio 0·57 [95% CI 0·36–0·91]; p=0·02), as were higher concentrations of DHEA (quartile 4 vs quartile 1: 0·61 [0·38–0·97]; p=0·04). For oestrone, a lower risk of MACE was seen for concentrations in quartile 2 only, compared with quartile 1 (0·55 [0·33–0·92]; p=0·02). In fully adjusted models, no association was seen between SHBG and MACE, or between any hormone or SHBG and all-cause mortality.InterpretationBlood concentrations of testosterone and DHEA above the lowest quartile in older women were associated with a reduced risk of a first-ever MACE. Given that the physiological effects of DHEA are mediated through its steroid metabolites, if the current findings were to be replicated, trials investigating testosterone therapy for the primary prevention of ischaemic cardiovascular disease events in older women would be warranted.FundingThe National Health and Medical Research Council of Australia, US National Institute on Aging, the Victorian Cancer Agency, the Commonwealth Scientific and Industrial Research Organisation, and Monash University.

Sex-related pharmacokinetic differences with aging.

The proportion of women increases with advanced age, but older women are often underrepresented in clinical trials. Therefore, little is known about the combined effect of sex- and age-related physiological changes on drug pharmacokinetics. We compiled clinical studies, which investigated sex-related pharmacokinetic differences both in older and young women and men. The ratio women/men was calculated for various pharmacokinetic parameters across adulthood to assess sex-related differences in drug pharmacokinetics with aging. The contribution of body weight and drug characteristics to sex-related pharmacokinetic differences were explored using analysis of variance. We found 67 studies reporting the pharmacokinetics for 56 drugs both in older and young women and men. Median peak concentration (Cmax) (interquartile range (IQR)) and drug exposure (AUC) (IQR) were 22% (8-41%) and 20% (0-39%) higher in women compared with men whereas time to peak concentration (tmax), apparent volume of distribution (VdF) and elimination half-life (t1/2) were not significantly different. Body weight and the drug main elimination pathway contributed to sex-related differences in Cmax and AUC. Relative to men, women had a modest increase in Cmax with increasing age (r = 0.19, p = 0.04). Conversely, sex-related differences in AUC remained constant with increasing age. The pharmacokinetic differences between women and men were modest and, with the exception of Cmax, remained constant with increasing age. The higher plasma concentration might be correlated to more adverse events in older women and thus, drug treatment should be started on the lower recommended dosage when appropriate particularly for drugs characterized by a narrow therapeutic index.

Perioperative adverse events in women over age 65 undergoing robot-assisted sacrocolpopexy.

Pelvic floor disorders are common among and disproportionately affect older women. There are limited data regarding perioperative adverse events in older women undergoing robot-assisted sacrocolpopexy (RASC) specifically. The aim of this study was to compare the rate of perioperative adverse events in younger (age <65years) versus older (age>65years) women who underwent RASC. We conducted a retrospective cohort study of women who underwent RASC between 2013 and 2018. Postoperative adverse events were categorized according to the Clavien-Dindo classification. Our primary outcome was the rate of intraoperative adverse events and postoperative adverse events with Clavien-Dindo grade II or greater. Outcomes were compared using univariate and multivariate analysis. Of the 327 patients included in the study, 227 were <65years of age and 100 were≥65years of age. Women ≥65years of age had higher rates of hypertension, higher American Society of Anesthesiologist (ASA) class, and higher Charlson Comorbidity Index (CCI) scores compared with women <65years of age; these were not associated with increased likelihood of adverse events. The overall rate of any perioperative adverse event was 18.3%. There was no statistically significant difference in the overall rate of perioperative adverse events between younger and older women (18.5% vs 18.0%, p = 0.91). There is no difference in rate of adverse events between women ≥65years of age undergoing RASC and their younger counterparts.

Abstract 008: Poor Lower Extremity Physical Function Increases Risk for Cardiovascular Disease Events in Older Women: The OPACH Study

Background: Good lower extremity physical functioning is paramount to healthy aging as it prevents social isolation, enables civic engagement, and facilitates physical activity. Strong evidence links physical functioning with all-cause mortality, but little is known about its relationship to cardiovascular disease (CVD). Methods: Women (n=5043, mean age=79±7) with no history of myocardial infarction or stroke completed the Short Physical Performance Battery (SPPB) consisting of three timed tasks to assess standing balance, strength (5 chair stands), and gait (4m walk). Results were summarized using prespecified cutpoints yielding a score from 0 (worst) to 12 (best). Women were followed for CVD events for up to 6 years. Hazard ratios (HR) were estimated for women with poor, low, moderate, and high functioning (respective SPPB ranges for each group; 0-3, 4-6, 7-9, and 10-12) using Cox proportional hazard models adjusted for several covariates including accelerometer-measured moderate to vigorous physical activity (MVPA) and sedentary behavior. Effect modification of associations between SPPB and CVD by age, MVPA, Reynolds Risk Score, race-ethnicity, and self-rated health were tested by including multiplicative interaction terms in fully adjusted Cox models with statistical significance for interactions set to 0.10. Results: Covariate-adjusted HRs (95% CIs) for CVD [ 1.00 (ref.); 0.85 (0.62, 1.15); 0.69 (0.51, 0.93); 0.49 (0.35, 0.68)] and CVD mortality [ 1.00 (ref.); 0.72 (0.45, 1.15); 0.44 (0.27, 0.72); 0.35 (0.19, 0.62)] decreased across poor, low, moderate, and high SPPB subgroups, respectively (p-trend&lt;.001

Initial Cholinesterase Inhibitor Therapy Dose and Serious Events in Older Women and Men.

To examine dose-related prescribing and short-term serious events associated with initiation of cholinesterase inhibitor (ChEI) therapy. Retrospective, population-based cohort study. Ontario, Canada. Women (n=47,829) and men (n=32,503) aged 66 and older who initiated a ChEI between April 1, 2010, and June 30, 2016. All-cause serious events (emergency department (ED) visits, inpatient hospitalizations, death) within 30 days of ChEI initiation. Multivariable Cox proportional hazards models were used to estimate adjusted rates of serious events. Overall, 4.8% of older adults were dispensed a lower-than-recommended ChEI starting dose, 87.9% a recommended dose, and 7.3% a higher-than-recommended starting dose. Eight thousand six hundred seventy-one (10.8%) individuals experienced a serious event within 30 days of initiating therapy, primarily ED visits (8,540, 10.6%). Relative to those initiated on a recommended starting dose, those initiated on a higher dose had a significantly increased rate of serious events (women adjusted hazard ratio (aHR) 1.50, 95% confidence interval (CI) =1.38-1.63; men aHR 1.31, 95% CI=1.19-1.45). Similar patterns were found for ED visits and inpatient hospitalizations but not death. The relative effect of higher-than-recommended starting dose dispensed vs. recommended starting dose dispensed was greater in women than it was in men: the number needed to harm was 22 (95% confidence interval (CI)=18-29) for women and 36 (95% CI= 26-61) for men. Serious events immediately after initiation of ChEIs were associated with starting ChEI dose. This association was stronger in women.

Abstract 047: Sedentary Behavior Increases Risk for Cardiovascular Disease in Older Women: The Objective Physical Activity and Cardiovascular Health (OPACH) Study

Background: Evidence on sedentary behavior and cardiovascular disease (CVD) is largely based on self-reported sedentary time. Furthermore, how sedentary time is accumulated (in longer vs. shorter bouts) may be related to CVD risk but has not been tested. Methods: Women (n=5638, mean age=79±7) with no history of myocardial infarction or stroke wore accelerometers for 4-7 days and were followed for up to 4 years for incident CVD. Hazard ratios (HR) and 95% confidence intervals (CIs) for CVD and coronary heart disease (CHD) events were estimated across quartiles of sedentary time and mean sedentary bout duration using Cox proportional hazard models adjusting for covariates. Separate models evaluated associations after adding moderate-to-vigorous physical activity (MVPA) and possible mediators: body mass index, diabetes, hypertension, systolic blood pressure, fasting glucose, HDL-cholesterol, and triglycerides. We then tested whether mean bout duration was associated with increased risk for CVD and CHD among women with above median sedentary time (≥10hr/day). Results: Covariate-adjusted HRs for CVD and CHD increased across quartiles of both sedentary time and mean bout duration (Table). All CHD associations remained significant but attenuated after adjustment for possible mediators. After adjustment for MVPA, highest vs. lowest quartile HRs (CI) for CHD were 1.6 (0.7-3.4; p-trend = .08) for sedentary time and 1.8 (0.9-3.5; p-trend = .047) for mean bout duration. Among women with high sedentary time, the HRs (CI) comparing the 75 th vs. 25 th percentile of mean bout duration were 1.05 (0.95-1.15) for CVD and 1.16 (1.01-1.34) for CHD. Conclusions: Both sedentary time and mean bout duration showed independent, dose-response associations with increased risk of CVD and CHD events in older women. Among women with high sedentary time, longer mean bout duration was associated with higher CHD risk. Taken together, this provides evidence that both total sedentary time and the way it is accumulated are predictive of incident CHD.

Duration of Reproductive Years and the Risk of Cardiovascular and Cerebrovascular Events in Older Women: Insights from the National Health and Nutrition Examination Survey.

Studies have shown conflicting information regarding the association between the age at menarche and/or menopause and cardiovascular and cerebrovascular diseases in older women. This study aimed to determine whether a longer duration of reproductive years in older women in the U.S. population was associated with a lower risk of cardiovascular and cerebrovascular diseases. Women ≥60 years who participated in the National Health and Nutrition Examination Survey from 2007 to 2012 were included. Subjects provided information about the age of menarche and menopause along with the presence/absence of cardiovascular and cerebrovascular diseases. Participants were categorized into either a longer reproductive duration group (>30 years) or shorter reproductive duration group (≤30 years). Subgroup analysis for each 5-year increment in the longer reproductive duration group was conducted. Relative risk (RR) regression was performed using a generalized linear model adjusting for several confounding factors. 3081 participants were included in the analysis. A longer duration of reproductive years was associated with a lower risk of cardiovascular and cerebrovascular diseases, compared with a shorter duration (RR 0.70, 95% confidence interval [CI] 0.53-0.92). This association was due to a reduction in the risk of stroke (RR 0.53, 95% CI 0.34-0.88) and angina (RR 0.57, 95% CI 0.34-0.97). A 1 year increase in the reproductive duration was associated with a 3% reduction in the risk of events (RR 0.97, 95% CI 0.95-0.99). Among women ≥60 years, a longer duration of reproductive years was associated with lower risk of cardiovascular and cerebrovascular diseases. This association was mainly due to a reduction in the risk of stroke and angina.

Use of cardiovascular age for assessing risks and benefits of menopausal hormone therapy.

The Women's Health Initiative studies and others have suggested that menopausal hormone therapy may enhance the risk of new cardiovascular (CV) events in older women and diminish the development of coronary atherosclerosis in younger women. The underlying mechanisms to explain these findings are encapsulated in the term "Timing Hypothesis." Extensive pathophysiologic studies have provided mechanistic evidence for the dichotomous effects of estrogen on coronary artery vasculature. Early in the atherosclerotic disease process, estrogen exerts protective effects on the endothelium and retards plaque formation. Late in the process, estrogen causes plaque erosion or rupture with subsequent thrombosis and acute coronary events. Analysis of the Timing Hypothesis in women examined in the Women's Health Initiative primarily used chronologic age to assess divergent effects of estrogen. The complexity of the data underlying coronary pathophysiology has resulted in controversy whether MHT can be used in older women or those with prior CV disease. In a debate of this issue at a recent International Menopause Society meeting, the concept of using CV age rather than chronologic age was discussed as a practical method of resolving this issue and facilitating therapeutic decisions in older women. This "Personal Perspective" will review the concepts underlying CV age, describe how it is determined, provide support for its utility, and propose future studies using this parameter.

Associations of Guideline Recommended Medications for Acute Coronary Syndromes With Fall-Related Hospitalizations and Cardiovascular Events in Older Women With Ischemic Heart Disease.

Guidelines for acute coronary syndrome recommend statins, β-blockers, angiotensin-converting-enzyme inhibitors or renin-angiotensin system blockers, and antiplatelet agents for the secondary prevention of cardiovascular events. The aim was to examine associations between guideline recommended medications and fall-related hospitalizations and cardiovascular events in robust and frail older women. 2002-2011 surveys from the Australian Longitudinal Study on Women's Health linked with administrative hospital, pharmaceutical and death registry data (2003-mid-2011) were used. Eight hundred eighty-five women (82.7±2.7 years, range 76-90) had prior admission for ischemic heart disease and ≥1 claims for any of the four medication classes. Four hundred thirteen (46.7%) were robust and 472 (53.3%) were frail. Fall-related admissions; cardiovascular event-related admissions or death; and cardiovascular death were recorded. Associations between each of the exposures and outcomes were analyzed using survival analyses with noncardiovascular death as a competing risk. There were 192 fall-related admissions and 314 cardiovascular events including 82 deaths. Using four recommended classes (compared to using one) was associated with increased risks of fall-related admissions (hazard ratio [HR] = 2.57, 95% confidence interval [CI] = 1.24-5.33), but not with cardiovascular events (HR = 1.41, CI = 0.97-2.05) or cardiovascular death (HR = 0.68, CI = 0.35-1.34). Associations for fall-related admissions were stronger in frail participants (HR = 5.46, CI = 1.34-22.30) than robust (HR = 1.37, CI = 0.48-3.95). In older women with ischemic heart disease, the combination of the four recommended medication classes was associated with increased risk of falls, particularly among frail women, with no statistically significant gain in cardiovascular health. The risks of falls and consequential morbidity in women over 75 needs consideration when prescribing medications after myocardial infarction.

Plasma Neutrophil Gelatinase-Associated Lipocalin and Kidney Function Decline and Kidney Disease-Related Clinical Events in Older Women

Background: It is still unclear whether serum neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of renal tubular injury, is a prognostic marker for the progression of chronic kidney disease (CKD) in the general population. Methods: A prospective-cohort study of 1,245 women aged ≥70 from the general population. Associations between plasma NGAL and change in 5-year estimated glomerular filtration rate (eGFR), rapid renal decline and 10-year risk of acute or chronic renal disease-related hospitalisations and/or mortality were examined. Results: Compared to women with above-median plasma NGAL of 76.5 ng/l, women with below-median plasma NGAL had a 9.3% reduction in eGFR over a 5-year period. Among women with above-median plasma NGAL, there was over a 1.7-fold increased risk of rapid renal decline (eGFR decline of >3 ml/min/year) (adjusted odds ratio 1.76, 95% CI 1.003, 3.102, p = 0.049). Compared to women with baseline eGFR of <60 ml/min/1.73 m², women with above-median plasma NGAL experienced over a 2.5-fold increased risk of renal disease events at 10 years (hazard ratio 2.55, 95% CI 1.13, 5.78, p = 0.025) after adjustment of age, hypertension and diabetes. Addition of plasma NGAL in participants with eGFR of <60 ml/min/1.73 m² significantly improved the accuracy in predicting the 10-year risk of renal disease events (adjusted area-under-curve receiver operator characteristics without and with NGAL 0.64 and 0.71, respectively; p = 0.027) and reclassified 13% of women who experienced renal disease events into the higher risk categories (p = 0.03). Conclusion: Plasma NGAL is of modest clinical utility in predicting the renal function decline and risk of renal disease-related clinical events, particularly those with mild to moderate CKD.

Effects of Sex and Postmenopausal Estrogen Use on Serum Phosphorus Levels: A Cross-sectional Study of the National Health and Nutrition Examination Survey (NHANES) 2003-2006

Elevation of serum phosphorus concentrations has been associated with cardiovascular events in older women and men. Whether age, sex, or estrogen therapy is associated with different phosphorus levels is unknown. Cross-sectional study. 7,005 participants in the National Health and Nutrition Examination Survey (NHANES) 2003-2006. Demographic data; body measurement indexes; dietary intake by 24-hour dietary recall and food-frequency questionnaire; data for reproductive health, prescription medication, cardiovascular disease, osteoporosis, and diabetes mellitus obtained by questionnaire; and blood chemistry indexes. Serum phosphorus concentrations. In both males and premenopausal females, serum phosphorus levels decline progressively with age. In males, the decline continues over the entire age range of 21-85 years. In contrast, in females, serum phosphorus levels increase between ages 46-60 years (sex×age interaction; P<0.001). The increase in serum phosphorus levels in older women is independent of changes in serum parathyroid hormone levels, daily dietary phosphorus intake, and estimated glomerular filtration rate. In analysis of covariance, we show that postmenopausal women receiving estrogen therapy have significantly lower serum phosphorus levels than non-estrogen users after adjusting for age, race, body mass index, daily dietary phosphorus intake, and serum albumin, serum parathyroid hormone, and 25-hydroxyvitamin D levels (3.83 vs 3.98mg/dL; P<0.001). The study was cross-sectional in design and estrogen therapy was not randomly assigned or concealed. Important phosphorus regulatory factors such as serum fibroblast growth factor 23 and klotho were not available in the study. Estrogen status may account for the difference in serum phosphorus levels in postmenopausal women.

Abstract 18979: Early Termination of Adjuvant Trastuzumab Associated with Cardiovascular Events in Older Women with Breast Cancer

Background: Biologic therapies for breast cancer such as trastuzumab, (i.e. Herceptin© [H]) increase risk of cardiovascular (CV) events such as heart failure (HF) in clinical trials. However, it is unknown how often H therapy is terminated early (i.e. &lt; 1yr), and which CV complications are associated with early termination. Methods: Using Medicare data linked with SEER cancer registry data from 2000 through 2007, we identified women age 67-94 with stage I-III breast cancer who started H within 90 days of completing adjuvant chemotherapy. Completion of H was defined as &gt;=9 months of continuous H treatments with no delay between H treatments &gt;3 months. We assessed factors contributing to completion of H including age, race, cancer characteristics, and comorbidities. CV events occurring +/- 3 months from last H treatment were ascertained from billing claims. Results: The sample included 294 older women (mean age 71.5 years) without CV events within the year prior to initiation of H. Approximately 79.3% (233) patients completed at least 9 months of H. Early termination of H was significantly associated with any CV complications (27.9% v 8.6%, p&lt;.001), particularly HF or cardiomyopathy (6.6% v 0.4%, p&lt;.001), p=.02) and atrial fibrillation [AF] (8.2% v 2.1%, p=0.02) Conclusion: Early termination of H is common among older women, and associated with higher rates of cardiovascular events. Preventing CV complications such as AF may improve survival in patients with breast cancer by increasing the likelihood of receiving the recommended course of H therapy. Funding(This research has received full or partial funding support from the American Heart Association)

Extremes of Endogenous Testosterone Are Associated With Increased Risk of Incident Coronary Events in Older Women

Several lines of evidence suggest that high levels of testosterone are atherogenic in women. The testosterone to estrogen balance in women increases markedly at the time of menopause when central adiposity and the incidence of cardiovascular disease also increase. The view that elevated serum androgen is harmful to the female heart is also supported by the occurrence of hyperandrogenemia, an adverse coronary heart disease (CHD) risk profile, and endothelial dysfunction in young women with polycystic ovarian syndrome. However, there has been no consistent increase in CHD events and mortality in women with polycystic ovarian syndrome. Moreover, recent studies have found that women with atherosclerotic disease have low serum levels of testosterone suggesting that unlike high levels, low levels of this hormone may have beneficial effects on the female heart. This prospective, population-based study evaluated the effects of total testosterone (total T) and bioavailable T (BioT) levels on the risk of incident coronary events among 639 older community-dwelling postmenopausal women. During a median follow-up of 12.3 year, 134 women had an incident CHD event; of these, 45 were nonfatal myocardial infarctions (MIs), 10 were coronary revascularizations, and 79 were fatal MIs. Multivariate regression analysis showed that age-adjusted CHD risk estimates were similar for the four highest total T quintiles relative to the lowest; this suggests a low threshold for incident events with total T. Age-adjusted analyses showed that compared to higher levels, the lowest total T quintile (≤80 pg/mL) was associated with a significant increase in the risk of incident CHD (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.10―2.39, P = 0.017). With BioT, age-adjusted quintile analyses suggested a U-shaped association for risk of incident CHD (P for quadratic trend <0.001). Both the lowest (low BioT) and the highest (high BioT) quintiles were associated with a significantly increased age-adjusted risk of incident CHD (HR for low BioT: 1. 7 9, with a 95% CI of 1.03-3.16, P = 0.046), and HR for high BioT: 1.96, with a 95% CI of 1.13-3.41, P = 0.022). Adjustment for other variables, including lifestyle characteristics, adiposity, estradiol, and ovarian status had a minimal effect on the results. These findings show that low levels of total T and high levels of BioT are independently associated with higher risk of incident CHD events in community-dwelling postmenopausal women. The data suggest that an optimal range of testosterone may exist for cardiovascular health in older women.

Cardiovascular Effects of Endogenous Estrogen and Hormone Therapy

The incidence of cardiovascular disease is low in healthy premenopausal women and increases with age especially after the menopause; this difference has been attributed to the loss of endogenous estrogen. Atherosclerosis is a chronic inflammatory condition of the vascular wall that may result in an acute clinical event by inducing plaque rupture/erosion leading to thrombosis. A growing body of evidence suggests that the spectrum of the effects of estrogen on vascular pathophysiology is complex and may depend largely on the state of vascular pathology. In relatively healthy vessels, estrogen prevents the development and progression of atherosclerotic lesions, while in the presence of established atherosclerotic plaques, estrogen fails to inhibit the progression of atherosclerosis or may even trigger cardiovascular events. The mechanisms responsible for this are not yet fully elucidated. It is possible that postmenopausal estrogen/progestogen therapy may be beneficial in perimenopausal and early menopausal women prior to atherosclerotic plaque formation, but it may not prevent progression of atherosclerotic plaques and acute cardiovascular events in older women with cardiovascular risk factors or women with established atherosclerosis. Various formulations, doses and routes of hormone therapy administration as well as the genetic background of women should also be taken into account when considering the benefit-to-risk ratio of hormone therapy use.

Extremes of Endogenous Testosterone Are Associated with Increased Risk of Incident Coronary Events in Older Women

Few studies have examined whether endogenous testosterone is associated with the development of coronary heart disease (CHD) in women. This study tested the association of total testosterone (total T) and bioavailable T (BioT) levels with risk of incident coronary events among older community-dwelling women. This was a prospective, population-based study of 639 postmenopausal women, aged 50-91 (mean, 73.8) yr who had serum testosterone measurements at baseline (1984-87) and who were followed for incident CHD events through 2004. A total of 134 incident CHD events occurred during follow-up [45 nonfatal myocardial infarctions, 79 fatal myocardial infarctions, and 10 coronary revascularizations]. The median follow-up was 12.3 yr. Age-adjusted CHD risk estimates were similar for the four highest total T quintiles relative to the lowest, suggesting a low threshold. In age-adjusted analyses, the lowest total T quintile (</=80 pg/ml) was associated with a 1.62-fold increased risk of incident CHD [95% confidence interval (CI), 1.10-2.39] compared to higher levels. BioT showed a U-shaped association with incident CHD. Age-adjusted risk for the lowest and highest BioT quintiles relative to the third were 1.79 (95% CI, 1.03-3.16) and 1.96 (95% CI, 1.13-3.41), respectively. Additional adjustment for lifestyle, adiposity, estradiol, and ovarian status, or for CHD risk factor covariates, had minimal influence on results. An optimal range of testosterone may exist for cardiovascular health in women, with increased risk of CHD events at low levels of testosterone overall and at high levels of the bioavailable fraction of testosterone.

Polimorfismos del gen del receptor de vitamina D y riesgo de fractura de cadera en la mujer adulta mayor de la Región del Bío Bío

Osteoporotic hip fractures are devastating events in older women. There is a genetic modulation of bone phenotypic parameters including bone density (BMD) and bone fragility fractures. Vitamin D receptor (VDR) gene polymorphisms explain a small part of the genetic influence on BMD, whereas their effect on fractures remains uncertain.To examine the contributions of VDR genotypes to the susceptibility to hip fracture in elderly Chilean women.We recruited 126 women (67 with fractures and 59 without) from Bio-Bio Region, Chile, aged 65 to 94 years. Genotyping for Bsm-l, Apa-1, Taq-1 and Fok-1 VDR polymorphisms was performed using polymerase chain reaction methods. All hip fractures were confirmed by X-ray.The allele frequencies were 0.49 for B, 0.57 for A, 0.60 for T and 0.65 for F in the Bsm-l, Apa-1, Taq-1 and Fok-1 polymorphisms respectively. The prevalence of these VDR gene polymorphisms in women with fractures were 16% BB, 69% Bb, 15% bb for Bsm-l; 30% AA, 46% Aa, 14% aa for Apa-1; 17% TT, 34 Tt, 8% tt for Taq-1 and 43%FF, 41% Ff, 16% ff for Fok-1. All VDR genotype frequencies did not differ from Hardy-Weinberg expectations. Allele or genotype frequencies did not differ between women with or without fractures. These results did not change when analysis was adjusted by age weight, height or gynecologic history.The genotype frequencies of the VDR polymorphisms are in accordance with the frequencies of other Hispanic and Caucasian populations. Our results suggest that VDR polymorphisms are not associated with the risk of hip fracture in older women of this Region of Southern Chile.