Biomedical subjects

Aaron Aragaki

Publications and source records attributed to Aaron Aragaki.

13 recordsLinked to original sources

PubMed2006

Effects of conjugated equine estrogen on stroke in the Women's Health Initiative.

BACKGROUND: The Women's Health Initiative (WHI) Estrogen Alone trial assessed the balance of benefits and risks of hormone use in healthy postmenopausal women. The trial was stopped prematurely because there was no benefit for coronary heart disease and an increased risk of stroke. This report provides a thorough analysis of the stroke finding using the final results from the completed trial database. METHODS AND RESULTS: The WHI Estrogen Alone hormone trial is a multicenter, double-blind, placebo-controlled, randomized clinical trial in 10,739 women aged 50 to 79 years who were given daily conjugated equine estrogen (CEE; 0.625 mg; n=5310) or placebo (n=5429). During an average follow-up of 7.1 years, there were 168 strokes in the CEE group and 127 in the placebo group; 80.3% of strokes were ischemic. For all stroke the intention-to-treat hazard ratio [HR] (95% CI) for CEE versus placebo was 1.37 (1.09 to 1.73). The HR (95% CI) was 1.55 (1.19 to 2.01) for ischemic stroke and 0.64 (0.35, 1.18) for hemorrhagic stroke. The HRs indicate excess risk of ischemic stroke was apparent in all categories of baseline stroke risk, including younger and more recently menopausal women and in women with prior or current use of statins or aspirin. CONCLUSIONS: CEE increases the risk of ischemic stroke in generally healthy postmenopausal women. The excess risk appeared to be present in all subgroups of women examined, including younger and more recently menopausal women. There was no convincing evidence to suggest that CEE had an effect on the risk of hemorrhagic stroke.

Aged↗

PubMed2006

Assessment of the relationship between pre-chip and post-chip quality measures for Affymetrix GeneChip expression data.

BACKGROUND: Gene expression microarray experiments are expensive to conduct and guidelines for acceptable quality control at intermediate steps before and after the samples are hybridised to chips are vague. We conducted an experiment hybridising RNA from human brain to 117 U133A Affymetrix GeneChips and used these data to explore the relationship between 4 pre-chip variables and 22 post-chip outcomes and quality control measures. RESULTS: We found that the pre-chip variables were significantly correlated with each other but that this correlation was strongest between measures of RNA quality and cRNA yield. Post-mortem interval was negatively correlated with these variables. Four principal components, reflecting array outliers, array adjustment, hybridisation noise and RNA integrity, explain about 75% of the total post-chip measure variability. Two significant canonical correlations existed between the pre-chip and post-chip variables, derived from MAS 5.0, dChip and the Bioconductor packages affy and affyPLM. The strongest (CANCOR 0.838, p < 0.0001) correlated RNA integrity and yield with post chip quality control (QC) measures indexing 3'/5' RNA ratios, bias or scaling of the chip and scaling of the variability of the signal across the chip. Post-mortem interval was relatively unimportant. We also found that the RNA integrity number (RIN) could be moderately well predicted by post-chip measures B_ACTIN35, GAPDH35 and SF. CONCLUSION: We have found that the post-chip variables having the strongest association with quantities measurable before hybridisation are those reflecting RNA integrity. Other aspects of quality, such as noise measures (reflecting the execution of the assay) or measures reflecting data quality (outlier status and array adjustment variables) are not well predicted by the variables we were able to determine ahead of time. There could be other variables measurable pre-hybridisation which may be better associated with expression data quality measures. Uncovering such connections could create savings on costly microarray experiments by eliminating poor samples before hybridisation.

Artifacts↗

PubMed2005

Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: results from the Women's Health Initiative Randomized Clinical Trial.

BACKGROUND: The Women's Health Initiative (WHI) clinical trial of conjugated equine estrogens (CEEs), involving 10,739 postmenopausal women with hysterectomy, aged 50 to 79 years, was stopped early owing to lack of overall health benefit and increased risk of stroke. Because CEE is still prescribed for treatment of menopausal symptoms and prevention of osteoporosis, it is important to understand the overall impact of this therapy on health-related quality of life (HRQOL). METHODS: All participants completed 6 specific measures of quality of life at baseline and 1 year, and a subsample (n = 1189) also completed the questions 3 years after randomization. Changes in scores were analyzed for treatment effect. RESULTS: Randomization to CEE was associated with a statistically significant but small reduction in sleep disturbance at year 1 compared with baseline (mean benefit, 0.4 points on a 20-point scale) and a statistically significant but small negative effect on social functioning (mean effect, -1.3 points on a 100-point scale). There were no significant improvements due to CEE in the areas of general health, physical functioning, pain, vitality, role functioning, mental health, depressive symptoms, cognitive function, or sexual satisfaction at year 1. A subgroup examined 3 years after baseline had no significant benefits for any HRQOL outcomes. Among women aged 50 to 54 years with moderate to severe vasomotor symptoms at baseline, CEE did not improve any of the HRQOL variables at year 1. CONCLUSION: In this trial of postmenopausal women with prior hysterectomy, oral CEE did not have a clinically meaningful effect on HRQOL.

Aged↗

PubMed2005

Significance testing for small microarray experiments.

Which significance test is carried out when the number of repeats is small in microarray experiments can dramatically influence the results. When in two sample comparisons both conditions have fewer than, say, five repeats traditional test statistics require extreme results, before a gene is considered statistically significant differentially expressed after a multiple comparisons correction. In the literature many approaches to circumvent this problem have been proposed. Some of these proposals use (empirical) Bayes arguments to moderate the variance estimates for individual genes. Other proposals try to stabilize these variance estimate by combining groups of genes or similar experiments. In this paper we compare several of these approaches, both on data sets where both experimental conditions are the same, and thus few statistically significant differentially expressed genes should be identified, and on experiments where both conditions do differ. This allows us to identify which approaches are most powerful without identifying many false positives. We conclude that after balancing the numbers of false positives and true positives an empirical Bayes approach and an approach which combines experiments perform best. Standard t-tests are inferior and offer almost no power when the sample size is small.

Animals↗

PubMed2005

Ethnicity and breast cancer: factors influencing differences in incidence and outcome.

BACKGROUND: The lower breast cancer incidence in minority women and the higher breast cancer mortality in African American women than in white women are largely unexplained. The influence of breast cancer risk factors on these differences has received little attention. METHODS: Racial/ethnic differences in breast cancer incidence and outcome were examined in 156,570 postmenopausal women participating in the Women's Health Initiative. Detailed information on breast cancer risk factors including mammography was collected, and participants were followed prospectively for breast cancer incidence, pathological breast cancer characteristics, and breast cancer mortality. Comparisons of breast cancer incidence and mortality across racial/ethnic groups were estimated as hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazard models. Tumor characteristics were compared as odds ratios (ORs) and 95% confidence intervals in logistic regression models. RESULTS: After median follow-up of 6.3 years, 3938 breast cancers were diagnosed. Age-adjusted incidences for all minority groups (i.e., African American, Hispanic, American Indian/Alaskan Native, and Asian/Pacific Islander) were lower than for white women, but adjustment for breast cancer risk factors accounted for the differences for all but African Americans (HR = 0.75, 95% CI = 0.61 to 0.92) corresponding to 29 cases and 44 cases per 10,000 person years for African American and white women, respectively. Breast cancers in African American women had unfavorable characteristics; 32% of those in African Americans but only 10% in whites were both high grade and estrogen receptor negative (adjusted OR = 4.70, 95% CI = 3.12 to 7.09). Moreover, after adjustment for prognostic factors, African American women had higher mortality after breast cancer than white women (HR = 1.79, 95% CI = 1.05 to 3.05) corresponding to nine and six deaths per 10 000 person-years from diagnosis in African American and white women, respectively. CONCLUSION: Differences in breast cancer incidence rates between most racial/ethnic groups were largely explained by risk factor distribution except in African Americans. However, breast cancers in African American women more commonly had characteristics of poor prognosis, which may contribute to their increased mortality after diagnosis.

Adult↗

PubMed2005

Effects of estrogen with and without progestin on urinary incontinence.

CONTEXT: Menopausal hormone therapy has long been credited with many benefits beyond the indications of relieving hot flashes, night sweats, and vaginal dryness, and it is often prescribed to treat urinary incontinence (UI). OBJECTIVE: To assess the effects of menopausal hormone therapy on the incidence and severity of symptoms of stress, urge, and mixed UI in healthy postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Women's Health Initiative multicenter double-blind, placebo-controlled, randomized clinical trials of menopausal hormone therapy in 27,347 postmenopausal women aged 50 to 79 years enrolled between 1993 and 1998, for whom UI symptoms were known in 23,296 participants at baseline and 1 year. INTERVENTIONS: Women were randomized based on hysterectomy status to active treatment or placebo in either the estrogen plus progestin (E + P) or estrogen alone trials. The E + P hormones were 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate (CEE + MPA); estrogen alone consisted of 0.625 mg/d of conjugated equine estrogen (CEE). There were 8506 participants who received CEE + MPA (8102 who received placebo) and 5310 who received CEE alone (5429 who received placebo). MAIN OUTCOME MEASURES: Incident UI at 1 year among women without UI at baseline and severity of UI at 1 year among women who had UI at baseline. RESULTS: Menopausal hormone therapy increased the incidence of all types of UI at 1 year among women who were continent at baseline. The risk was highest for stress UI (CEE + MPA: relative risk [RR], 1.87 [95% confidence interval {CI}, 1.61-2.18]; CEE alone: RR, 2.15 [95% CI, 1.77-2.62]), followed by mixed UI (CEE + MPA: RR, 1.49 [95% CI, 1.10-2.01]; CEE alone: RR, 1.79 [95% CI, 1.26-2.53]). The combination of CEE + MPA had no significant effect on developing urge UI (RR, 1.15; 95% CI, 0.99-1.34), but CEE alone increased the risk (RR, 1.32; 95% CI, 1.10-1.58). Among women experiencing UI at baseline, frequency worsened in both trials (CEE + MPA: RR, 1.38 [95% CI, 1.28-1.49]; CEE alone: RR, 1.47 [95% CI, 1.35-1.61]). Amount of UI worsened at 1 year in both trials (CEE + MPA: RR, 1.20 [95% CI, 1.06-1.36]; CEE alone: RR, 1.59 [95% CI, 1.39-1.82]). Women receiving menopausal hormone therapy were more likely to report that UI limited their daily activities (CEE + MPA: RR, 1.18 [95% CI, 1.06-1.32]; CEE alone: RR, 1.29 [95% CI, 1.15-1.45]) and bothered or disturbed them (CEE + MPA: RR, 1.22 [95% CI, 1.13-1.32]; CEE alone: RR, 1.50 [95% CI, 1.37-1.65]) at 1 year. CONCLUSIONS: Conjugated equine estrogen alone and CEE + MPA increased the risk of UI among continent women and worsened the characteristics of UI among symptomatic women after 1 year. Conjugated equine estrogen with or without progestin should not be prescribed for the prevention or relief of UI.

Aged↗

PubMed2005

Frailty: emergence and consequences in women aged 65 and older in the Women's Health Initiative Observational Study.

OBJECTIVES: To define frailty using simple indicators; to identify risk factors for frailty as targets for prevention; and to investigate the predictive validity of this frailty classification for death, hospitalization, hip fracture, and activity of daily living (ADL) disability. DESIGN: Prospective study, the Women's Health Initiative Observational Study. SETTING: Forty U.S. clinical centers. PARTICIPANTS: Forty thousand six hundred fifty-seven women aged 65 to 79 at baseline. MEASUREMENTS: Components of frailty included self-reported muscle weakness/impaired walking, exhaustion, low physical activity, and unintended weight loss between baseline and 3 years of follow-up. Death, hip fractures, ADL disability, and hospitalizations were ascertained during an average of 5.9 years of follow-up. RESULTS: Baseline frailty was classified in 16.3% of participants, and incident frailty at 3-years was 14.8%. Older age, chronic conditions, smoking, and depressive symptom score were positively associated with incident frailty, whereas income, moderate alcohol use, living alone, and self-reported health were inversely associated. Being underweight, overweight, or obese all carried significantly higher risk of frailty than normal weight. Baseline frailty independently predicted risk of death (hazard ratio (HR)=1.71, 95% confidence interval (CI)=1.48-1.97), hip fracture (HR=1.57, 95% CI=1.11-2.20), ADL disability (odds ratio (OR)=3.15, 95% CI=2.47-4.02), and hospitalizations (OR=1.95, 95% CI=1.72-2.22) after adjustment for demographic characteristics, health behaviors, disability, and comorbid conditions. CONCLUSION: These results support the robustness of the concept of frailty as a geriatric syndrome that predicts several poor outcomes in older women. Underweight, obesity, smoking, and depressive symptoms are strongly associated with the development of frailty and represent important targets for prevention.

Activities of Daily Living↗

PubMed2004

Association between cardiovascular outcomes and antihypertensive drug treatment in older women.

CONTEXT: Diuretic-based therapy is at least as effective as newer classes of agents for hypertension. However, many patients with hypertension require treatment with more than 1 drug class to achieve blood pressure control. The relative benefits or risks of 2-drug-class combinations are not well known. OBJECTIVE: To prospectively evaluate if there are differences in cardiovascular mortality among postmenopausal women with hypertension but no history of cardiovascular disease (CVD) treated with different classes of antihypertensive agents, singly or in combination. DESIGN, SETTING, AND PARTICIPANTS: Women with hypertension enrolled in the Women's Health Initiative Observational Study, a longitudinal multicenter cohort study of 93 676 women aged 50 to 79 years at baseline (1994-1998), assessed for a mean of 5.9 years. MAIN OUTCOME MEASURES: Relationship between baseline use of ACE inhibitors, beta-blockers, calcium channel blockers, or diuretics, or a combination of these, and incidence of coronary heart disease, stroke, and CVD mortality. RESULTS: Among 30,219 women with hypertension but no history of CVD, 19,889 were receiving pharmacological antihypertensive treatment, of whom 11,294 (57%) [corrected] were receiving monotherapy with an ACE inhibitor, beta-blocker, calcium channel blocker, or diuretic, and 4493 (23%) were treated at baseline with a combination of diuretic plus either ACE inhibitor, beta-blocker, or calcium channel blocker or ACE inhibitor plus calcium channel blocker. Monotherapy with calcium channel blockers vs diuretics was associated with greater risk of CVD death (hazard ratio, 1.55; 95% confidence interval, 1.02-2.35), controlling for multiple covariates. Women treated with a diuretic plus a calcium channel blocker had an 85% greater risk of CVD death vs those treated with a diuretic plus a beta-blocker, after adjustment for age, race, smoking, high cholesterol levels requiring medication, body mass index, physical activity, use of hormone therapy, and diabetes. After exclusion of women with diabetes the hazard ratio was 2.16 (95% confidence interval, 1.16-4.03). Analyses adjusting for propensity to be receiving a particular treatment did not change the results. For morbid events of coronary heart disease or stroke, diuretics plus ACE inhibitors or calcium channel blockers did not differ from diuretics plus beta-blockers. CONCLUSIONS: Among women with hypertension but no history of CVD, a 2-drug-class regimen of calcium channel blockers plus diuretics was associated with a higher risk of CVD mortality vs beta-blockers plus diuretics. Risks were similar for ACE inhibitors plus diuretics and beta-blockers plus diuretics. Monotherapy with diuretics was equal or superior to other monotherapy in preventing CVD complications of high blood pressure.

Adrenergic beta-Antagonists↗

PubMed2004

Predictors of angina pectoris versus myocardial infarction from the Women's Health Initiative Observational Study.

Although risk factors for acute coronary syndromes have been extensively studied, characteristics distinguishing women who will develop unstable angina rather than acute myocardial infarction (MI) are less well understood. This analysis evaluates baseline demographic, physical, and medical characteristics as predictors of angina versus MI in the Women's Health Initiative Observational Study. During a prospective 4.5-year follow-up of 92,152 postmenopausal women, 1,527 hospitalizations for angina and 797 for MI were confirmed by centrally trained physician adjudicators. In a multivariate analysis of women with incident angina or MI, high cholesterol (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.47 to 0.80; p = 0.0004) and prior coronary disease (OR 0.70, 95% CI 0.55 to 0.89; p = 0.004) independently predicted angina (referent), whereas current cigarette smoking (OR 1.60, 95% CI 1.13 to 2.26; p = 0.007) and diabetes mellitus (1.44, 95% CI 1.10 to 1.87; p = 0.007) predicted MI. Older age and hypertension were independently, but less strongly, predictive of MI. Aspirin or statin use, physical activity, body mass index, and educational levels were not independently associated with one or the other type of acute coronary syndrome. Thus, specific risk factors strongly and independently predicted whether women with an acute coronary syndrome would present with angina or with MI.

Aged↗

PubMed2004

Depression and cardiovascular sequelae in postmenopausal women. The Women's Health Initiative (WHI).

BACKGROUND: Subclinical depression, often clinically unrecognized, may pose increased risk of cardiovascular disease. Few studies have prospectively investigated cardiovascular events related to depression in older women. We describe prevalence, cardiovascular correlates, and relationship to subsequent cardiovascular events of depressive symptoms among generally healthy postmenopausal women. METHODS: The Women's Health Initiative Observational Study followed up 93 676 women for an average of 4.1 years. Depression was measured at baseline with a short form of the Center for Epidemiological Studies Depression Scale. Risks of cardiovascular disease (CVD) events were estimated from Cox proportional hazards models adjusting for multiple demographic, clinical, and risk factor covariates. RESULTS: Current depressive symptoms above the screening cutoff point were reported by 15.8% of women. Depression was significantly related to CVD risk and comorbidity (odds ratios ranging from 1.12 for hypertension to 1.60 for history of stroke or angina). Among women with no history of CVD, depression was an independent predictor of CVD death (relative risk, 1.50) and all-cause mortality (relative risk, 1.32) after adjustment for age, race, education, income, diabetes, hypertension, smoking, high cholesterol level requiring medication, body mass index, and physical activity. Taking antidepressant medications did not alter the depression-associated risks associated. CONCLUSIONS: A large proportion of older women report levels of depressive symptoms that are significantly related to increased risk of CVD death and all-cause mortality, even after controlling for established CVD risk factors. Whether early recognition and treatment of subclinical depression will lower CVD risk remains to be determined in clinical trials.

Aged↗

PubMed2003

Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial.

CONTEXT: The Women's Health Initiative (WHI) trial of estrogen plus progestin was stopped early because of adverse effects, including an increased risk of stroke in the estrogen plus progestin group. OBJECTIVE: To assess the effect of estrogen plus progestin on ischemic and hemorrhagic stroke and in subgroups, and to determine whether the effect of estrogen plus progestin was modified by baseline levels of blood biomarkers. DESIGN: Multicenter double-blind, placebo-controlled, randomized clinical trial involving 16 608 women aged 50 through 79 years with an average follow-up of 5.6 years. Baseline levels of blood-based markers of inflammation, thrombosis, and lipid levels were measured in the first 140 centrally confirmed stroke cases and 513 controls. INTERVENTIONS: Participants received 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate (n = 8506) or placebo (n = 8102). MAIN OUTCOME MEASURES: Overall strokes and stroke subtype and severity were centrally adjudicated by stroke neurologists. RESULTS: One hundred fifty-one patients (1.8%) in the estrogen plus progestin and 107 (1.3%) in the placebo groups had strokes. Overall 79.8% of strokes were ischemic. For combined ischemic and hemorrhagic strokes, the intention-to-treat hazard ratio (HR) for estrogen plus progestin vs placebo was 1.31 (95% confidence interval [CI], 1.02-1.68); with adjustment for adherence, the HR was 1.50 (95% CI, 1.08-2.08). The HR for ischemic stroke was 1.44 (95% CI, 1.09-1.90) and for hemorrhagic stroke, 0.82 (95% CI, 0.43-1.56). Point estimates of the HRs indicate that excess risk of all stroke was apparent in all age groups, in all categories of baseline stroke risk, and in women with and without hypertension, prior history of cardiovascular disease, use of hormones, statins, or aspirin. Other risk factors for stroke, including smoking, blood pressure, diabetes, lower use of vitamin C supplements, blood-based biomarkers of inflammation, higher white blood cell count, and higher hematocrit levels did not modify the effect of estrogen plus progestin on stroke risk. CONCLUSIONS: Estrogen plus progestin increases the risk of ischemic stroke in generally healthy postmenopausal women. Excess risk for all strokes attributed to estrogen plus progestin appeared to be present in all subgroups of women examined.

Aged↗

PubMed2003

The effects of widowhood on physical and mental health, health behaviors, and health outcomes: The Women's Health Initiative.

This study examined whether widowhood was associated with physical and mental health, health behaviors, and health outcomes using a cross-sectional (N=72,247) and prospective (N=55,724) design in women aged 50-79 years participating in the Women's Health Initiative observational study (85.4% White). At baseline, married women reported better physical and mental health and generally better health behaviors than widowed women. Whereas women who remained married over the 3-year period showed stability in mental health, recent widows experienced marked impairments and longer term widows showed stability or slight improvements. Both groups of widows reported more unintentional weight loss over the 3-year period. Changes in physical health and health behaviors were inconsistent, with generally small effect sizes. Findings underscore the resilience of older women and their capacity to reestablish connections, but point to the need for services that strengthen social support among women who have difficulty during this transition.

Aged↗

PubMed2002

Pelvic organ prolapse in the Women's Health Initiative: gravity and gravidity.

OBJECTIVE: The purpose of this study was to describe the prevalence of and correlates for pelvic organ prolapse. STUDY DESIGN: This was a cross-sectional analysis of women who enrolled in the Women's Health Initiative Hormone Replacement Therapy Clinical Trial (n = 27,342 women). Baseline questionnaires ascertained demographics and personal habits. A baseline pelvic examination assessed uterine prolapse, cystocele, and rectocele. Descriptive statistics and logistic regression models were used to investigate factors that were associated with pelvic organ prolapse. RESULTS: In the 16,616 women with a uterus, the rate of uterine prolapse was 14.2%; the rate of cystocele was 34.3%; and the rate of rectocele was 18.6%. For the 10,727 women who had undergone hysterectomy, the prevalence of cystocele was 32.9% and of rectocele was 18.3%. After controlling for age, body mass index, and other health/physical variables, African American women demonstrated the lowest risk for prolapse. Hispanic women had the highest risk for uterine prolapse. Parity and obesity were strongly associated with increased risk for uterine prolapse, cystocele, and rectocele. CONCLUSION: Pelvic organ prolapse is a common condition in older women. The risk for prolapse differs between ethnic groups, which suggests that the approaches to risk-factor modification and prevention may also differ. These data will help address the gynecologic needs of diverse populations.

Black or African American↗