Mortality associated with diabetes and cardiovascular disease in older women

Background Current guidelines for the prevention of cardiovascular disease (CVD) recommend diabetes as a CVD risk equivalent. However, reports that have examined the risk of diabetes in comparison to pre-existing CVD are lacking among older women. We aimed to assess whether diabetes was associated with a similar risk of total and cause-specific mortality as a history of CVD in older women. Methodology/Principal Findings We studied 9218 women aged 68 years or older enrolled in a prospective cohort study (Study of Osteoporotic Fracture) during a mean follow-up period of 11.7 years and compared all-cause, cardiovascular and coronary heart disease mortality among 4 groups: non-diabetic women with and without existing CVD, diabetic women with and without existing CVD. Mean (SD) age of the participants was 75.2 (5.3) years, 3.5% reported diabetes and 6.8% reported existing CVD. During follow-up, 5117 women died with 36% from CVD. The multivariate adjusted risk of cardiovascular mortality was increased among both non-diabetic women with CVD (hazard ratio (HR) 2.32, 95% CI: 1.97–2.74, P<0.001) and diabetic women without CVD (HR 2.06, CI: 1.62–2.64, P<0.001) compared to non-diabetic women without existing CVD. All-cause, cardiovascular and coronary mortality of non-diabetic women with CVD were not significantly different from diabetic women without CVD. Conclusions/Significance Older diabetic women without CVD have a similar risk of cardiovascular mortality compared to non-diabetic women with pre-existing CVD. The equivalence of diabetes and CVD seems to extend to older women, supporting current guidelines for cardiovascular prevention.

Osteoporosis case finding in the general practice: phalangeal radiographic absorptiometry with and without risk factors for osteoporosis to select postmenopausal women eligible for lumbar spine and hip densitometry

Mass screening for osteoporosis using DXA measurements at the spine and hip is presently not recommended by health authorities. Instead, risk factor questionnaires and peripheral bone measurements may facilitate the selection of women eligible for axial bone densitometry. The aim of this study was to validate a case finding strategy for postmenopausal women who would benefit most from subsequent DXA measurement by using phalangeal radiographic absorptiometry (RA) alone or in combination with risk factors in a general practice setting. The sensitivity and specificity of this strategy in detecting osteoporosis (T-score < or =2.5 SD at the spine and/or the hip) were compared with those of the current reimbursement criteria for DXA measurements in Switzerland. Four hundred and twenty-three postmenopausal women with one or more risk factors for osteoporosis were recruited by 90 primary care physicians who also performed the phalangeal RA measurements. All women underwent subsequent DXA measurement of the spine and the hip at the Osteoporosis Policlinic of the University Hospital of Berne. They were allocated to one of two groups depending on whether they matched with the Swiss reimbursement conditions for DXA measurement or not. Logistic regression models were used to predict the likelihood of osteoporosis versus "no osteoporosis" and to derive ROC curves for the various strategies. Differences in the areas under the ROC curves (AUC) were tested for significance. In women lacking reimbursement criteria, RA achieved a significantly larger AUC (0.81; 95% CI 0.72-0.89) than the risk factors associated with patients' age, height and weight (0.71; 95% C.I. 0.62-0.80). Furthermore, in this study, RA provided a better sensitivity and specificity in identifying women with underlying osteoporosis than the currently accepted criteria for reimbursement of DXA measurement. In the Swiss environment, RA is a valid case finding tool for patients with risk factors for osteoporosis, especially for those who do not qualify for DXA reimbursement.

Bone mineral density at distal tibia using dual-energy X-ray absorptiometry in normal women and in patients with vertebral osteoporosis or primary hyperparathyroidism

To assess the effect of age and disease on mineral distribution at the distal third of the tibia, bone mineral content (BMC) and bone mineral density (BMD) were measured at lumbar spine (spine), femoral neck (neck), and diaphysis (Dia) and distal epiphysis (Epi) of the tibia in 89 healthy control women of different age groups (20-29, n = 12; 30-39, n = 11; 40-44, n = 12; 45-49, n = 12; 50-54, n = 12; 55-59, n = 10; 60-69, n = 11; 70-79, n = 9), in 25 women with untreated vertebral osteoporosis (VOP), and in 19 women with primary hyperparathyroidism (PHPT) using dual-energy x-ray absorptiometry (DXA; Hologic QDR 1000 and standard spine software). A soft tissue simulator was used to compensate for heterogeneity of soft tissue thickness around the leg. Tibia was scanned over a length of 130 mm from the ankle joint, fibula being excluded from analysis. For BMC and BMD, 10 sections 13 mm each were analyzed separately and then pooled to define the epiphysis (Epi 13-52 mm) and diaphysis area (Dia 91-130 mm). Precision after repositioning was 1.9 and 2.1% for Epi and Dia, respectively. In the control group, at any site there was no significant difference between age groups 20-29 and 30-39, which thus were pooled to define the peak bone mass (PBM).(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents

The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p <0.01). Conversely, no differences in crude mortality rates were observed between 1 and 3 years across clinical presentations. After multivariable adjustment, STEMI was independently associated with greater risk of 3-year mortality (hazard ratio [HR] 3.45; 95% confidence interval [CI] 1.99 to 5.98; p <0.01), whereas no differences were observed between UAP or NSTEMI and SAP (HR 0.99; 95% CI 0.73 to 1.34; p = 0.94). In women with ACS, use of new-generation DES was associated with reduced risk of major adverse cardiac events (HR 0.58; 95% CI 0.34 to 0.98). The magnitude and direction of the effect with new-generation DES was uniform between women with or without ACS (pinteraction = 0.66). In conclusion, in women across the clinical spectrum of CAD, STEMI was associated with a greater risk of long-term mortality. Conversely, the adjusted risk of mortality between UAP or NSTEMI and SAP was similar. New-generation DESs provide improved long-term clinical outcomes irrespective of the clinical presentation in women.

Older Breast Cancer Survivors: Geriatric Assessment Domains Are Associated With Poor Tolerance of Treatment Adverse Effects and Predict Mortality Over 7 Years of Follow-Up

Purpose To evaluate geriatric assessment (GA) domains in relation to clinically important outcomes in older breast cancer survivors. Methods Six hundred sixty women diagnosed with primary breast cancer in four US geographic regions (Los Angeles, CA; Minnesota; North Carolina; and Rhode Island) were selected with disease stage I to IIIA, age ≥ 65 years at date of diagnosis, and permission from attending physician to contact. Data were collected over 7 years of follow-up from consenting patients' medical records, telephone interviews, physician questionnaires, and the National Death Index. Outcomes included self-reported treatment tolerance and all-cause mortality. Four GA domains were described by six individual measures, as follows: sociodemographic by adequate finances; clinical by Charlson comorbidity index (CCI) and body mass index; function by number of physical function limitations; and psychosocial by the five-item Mental Health Index (MHI5) and Medical Outcomes Study Social Support Survey (MOS-SSS). Associations were evaluated using t tests, χ2 tests, and regression analyses. Results In multivariable regression including age and stage, three measures from two domains (clinical and psychosocial) were associated with poor treatment tolerance; these were CCI ≥ 1 (odds ratio [OR] = 2.49; 95% CI, 1.18 to 5.25), MHI5 score less than 80 (OR = 2.36; 95% CI, 1.15 to 4.86), and MOS-SSS score less than 80 (OR = 3.32; 95% CI, 1.44 to 7.66). Four measures representing all four GA domains predicted mortality; these were inadequate finances (hazard ratio [HR] = 1.89; 95% CI, 1.24 to 2.88; CCI ≥ 1 (HR = 1.38; 95% CI, 1.01 to 1.88), functional limitation (HR = 1.40; 95% CI, 1.01 to 1.93), and MHI5 score less than 80 (HR = 1.34; 95% CI, 1.01 to 1.85). In addition, the proportion of women with these outcomes incrementally increased as the number of GA deficits increased. Conclusion This study provides longitudinal evidence that GA domains are associated with poor treatment tolerance and predict mortality at 7 years of follow-up, independent of age and stage of disease.

Older Breast Cancer Survivors: Factors Associated with Self-reported Symptoms of Persistent Lymphedema Over 7 years of Follow-up

Lymphedema of the arm is a common complication of breast cancer with symptoms that can persist over long periods of time. For older women (over 50% of breast cancer cases) it means living with the potential for long-term complications of persistent lymphedema in conjunction with the common diseases and disabilities of aging over survivorship. We identified women > or =65 years diagnosed with primary stage I-IIIA breast cancer. Data were collected over 7 years of follow-up from consenting patients' medical records and telephone interviews. Data collected included self-reported symptoms of persistent lymphedema, breast cancer characteristics, and selected sociodemographic and health-related characteristics. The overall prevalence of symptoms of persistent lymphedema was 36% over 7 years of follow-up. Having stage II or III (OR = 1.77, 95% CI: 1.07-2.93) breast cancer and having a BMI >30 (OR = 3.04, 95% CI: 1.69-5.45) were statistically significantly predictive of symptoms of persistent lymphedema. Women > or =80 years were less likely to report symptoms of persistent lymphedema when compared to younger women (OR = 0.44, 95% CI: 0.18-0.95). Women with symptoms of persistent lymphedema consistently reported worse general mental health and physical function. Symptoms of persistent lymphedema were common in this population of older breast cancer survivors and had a noticeable effect on both physical function and general mental health. Our findings provide evidence of the impact of symptoms of persistent lymphedema on the quality of survivorship of older women. Clinical and research efforts focused on risk factors for symptoms of persistent lymphedema in older breast cancer survivors may lead to preventative and therapeutic measures that help maintain their health and well-being over increasing periods of survivorship.

Corpus callosum index and long-term disability in multiple sclerosis patients

Prediction of long-term disability in patients with multiple sclerosis (MS) is essential. Magnetic resonance imaging (MRI) measurement of brain volume may be of predictive value but sophisticated MRI techniques are often inaccessible in clinical practice. The corpus callosum index (CCI) is a normalized measurement that reflects changes of brain volume. We investigated medical records and 533 MRI scans at diagnosis and during clinical follow-up of 169 MS patients (mean age 42 +/- 11 years, 86% relapsing-remitting MS, time since first relapse 11 +/- 9 years). CCI at diagnosis was 0.345 +/- 0.04 and correlated with duration of disease (p = 0.002; r = -0.234) and expanded disability status scale (EDSS) score at diagnosis (r = -0.428; p < 0.001). Linear regression analyses identified age, duration of disease, relapse rate and EDSS at diagnosis as independent predictors for disability after mean of 7.1 years (Nagelkerkes' R:0.56). Annual CCI decrease was 0.01 +/- 0.02 (annual tissue loss: 1.3%). In secondary progressive MS patients, CCI decrease was double compared to that in relapsing-remitting MS patients (p = 0.04). There was a trend of greater CCI decrease in untreated patients compared to those who received disease modifying drugs (p = 0.2). CCI is an easy to use MRI marker for estimating brain atrophy in patients with MS. Brain atrophy as measured with CCI was associated with disability progression but it was not an independent predictor of long-term disability.

Expression of adipokines and estrogen receptors in adipose tissue and placenta of patients with gestational diabetes mellitus

The purpose of this study was to assess the expression profile of genes with potential role in the development of insulin resistance (adipokines, cytokines/chemokines, estrogen receptors) in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placenta of pregnant women with gestational diabetes mellitus (GDM) and age-matched women with physiological pregnancy at the time of Caesarean section. qRT-PCR was used for expression analysis of the studied genes. Leptin gene expression in VAT of GDM group was significantly higher relative to control group. Gene expressions of interleukin-6 and interleukin-8 were significantly increased, whereas the expressions of genes for estrogen receptors alpha and beta were significantly reduced in SAT of GDM group relative to controls, respectively. We found no significant differences in the expression of any genes of interest (LEP, RETN, ADIPOR1, ADIPOR2, TNF-alpha, CD68, IL-6, IL-8, ER alpha, ER beta) in placentas of women with GDM relative to controls. We conclude that increased expression of leptin in visceral adipose depot together with increased expressions of proinflammatory cytokines and reduced expressions of estrogen receptors in subcutaneous fat may play a role in the etiopathogenesis of GDM.

Long-term results of International Breast Cancer Study Group Trial VIII: adjuvant chemotherapy plus goserelin compared with either therapy alone for premenopausal patients with node-negative breast cancer

The International Breast Cancer Study Group Trial VIII compared long-term efficacy of endocrine therapy (goserelin), chemotherapy [cyclophosphamide, methotrexate and fluorouracil (CMF)], and chemoendocrine therapy (CMF followed by goserelin) for pre/perimenopausal women with lymph-node-negative breast cancer.

Intravaginal practices, bacterial vaginosis, and HIV infection in women: individual participant data meta-analysis

Background Identifying modifiable factors that increase women's vulnerability to HIV is a critical step in developing effective female-initiated prevention interventions. The primary objective of this study was to pool individual participant data from prospective longitudinal studies to investigate the association between intravaginal practices and acquisition of HIV infection among women in sub-Saharan Africa. Secondary objectives were to investigate associations between intravaginal practices and disrupted vaginal flora; and between disrupted vaginal flora and HIV acquisition. Methods and Findings We conducted a meta-analysis of individual participant data from 13 prospective cohort studies involving 14,874 women, of whom 791 acquired HIV infection during 21,218 woman years of follow-up. Data were pooled using random-effects meta-analysis. The level of between-study heterogeneity was low in all analyses (I2 values 0.0%–16.1%). Intravaginal use of cloth or paper (pooled adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.18–1.83), insertion of products to dry or tighten the vagina (aHR 1.31, 95% CI 1.00–1.71), and intravaginal cleaning with soap (aHR 1.24, 95% CI 1.01–1.53) remained associated with HIV acquisition after controlling for age, marital status, and number of sex partners in the past 3 months. Intravaginal cleaning with soap was also associated with the development of intermediate vaginal flora and bacterial vaginosis in women with normal vaginal flora at baseline (pooled adjusted odds ratio [OR] 1.24, 95% CI 1.04–1.47). Use of cloth or paper was not associated with the development of disrupted vaginal flora. Intermediate vaginal flora and bacterial vaginosis were each associated with HIV acquisition in multivariable models when measured at baseline (aHR 1.54 and 1.69, p<0.001) or at the visit before the estimated date of HIV infection (aHR 1.41 and 1.53, p<0.001), respectively. Conclusions This study provides evidence to suggest that some intravaginal practices increase the risk of HIV acquisition but a direct causal pathway linking intravaginal cleaning with soap, disruption of vaginal flora, and HIV acquisition has not yet been demonstrated. More consistency in the definition and measurement of specific intravaginal practices is warranted so that the effects of specific intravaginal practices and products can be further elucidated.

Zurich Fabry study - prevalence of Fabry disease in young patients with first cryptogenic ischaemic stroke or TIA

BACKGROUND AND PURPOSE: The etiology of stroke in young patients remains undetermined in up to half of the cases. Data on prevalence of Fabry disease (FD) in young people with cryptogenic ischaemic stroke are limited and controversial. We aimed to evaluate the frequency of unrecognized FD in a cohort of stroke patients at a tertiary stroke center. METHODS: Patients suffering from first cryptogenic ischaemic stroke or transient ischaemic attack (TIA) at the age of 18-55 years were screened for the presence of FD. We measured the serum activity of α-galactosidase (α-GAL) in all patients. In addition, sequencing of α-GAL gene was performed in men with low enzyme activity and in all women. RESULTS: Between January, 2006, and October, 2009, we recruited 150 patients (102 men, 48 women) with a mean age of 43 ± 9 years at symptom onset (135 ischaemic stroke, 15 TIA). The α-GAL activity was low in nine patients (6%; six men and three women). Genetic sequencing in six men with low enzyme activity and all 48 women detected no α-GAL gene mutation. CONCLUSION: Our study suggests that the yield of screening for FD in patients with first cryptogenic ischaemic stroke or TIA is very low. Further large-scale studies are needed to investigate the importance of FD amongst patients with recurrent cryptogenic strokes.

Obesity and risk of recurrence or death after adjuvant endocrine therapy with letrozole or tamoxifen in the breast international group 1-98 trial

To examine the association of baseline body mass index (BMI) with the risk of recurrence or death in postmenopausal women with early-stage breast cancer receiving adjuvant tamoxifen or letrozole in the Breast International Group (BIG) 1-98 trial at 8.7 years of median follow-up.