Trends in Clinical Breast Density Assessment From the Breast Cancer Surveillance Consortium.

Changes to mammography practice, including revised Breast Imaging Reporting and Data System (BI-RADS) density classification guidelines and implementation of digital breast tomosynthesis (DBT), may impact clinical breast density assessment. We investigated temporal trends in clinical breast density assessment among 2 990 291 digital mammography (DM) screens and 221 063 DBT screens interpreted by 722 radiologists from 144 facilities in the Breast Cancer Surveillance Consortium. After age-standardization, 46.3% (95% CI = 44.1% to 48.6%) of DM screens were assessed as dense (heterogeneously/extremely dense) during the BI-RADS 4th edition era (2005-2013), compared to 46.5% (95% CI = 43.8% to 49.1%) during the 5th edition era (2014-2016) (P = .93 from two-sided generalized score test). Among DBT screens in the BI-RADS 5th edition era, 45.8% (95% CI = 42.0% to 49.7%) were assessed as dense (P = .77 from two-sided generalized score test) compared to 46.5% (95% CI = 43.8% to 49.1%) dense on DM in BI-RADS 5th edition era. Results were similar when examining all four density categories and age subgroups. Clinicians, researchers, and policymakers may reasonably expect stable density distributions across screened populations despite changes to the BI-RADS guidelines and implementation of DBT.

Preoperative breast MRI and mortality in older women with breast cancer.

PURPOSE: The survival benefit from detecting additional breast cancers by preoperative magnetic resonance imaging (MRI) continues to be controversial. METHODS: We followed a cohort of 4454 women diagnosed with non-metastatic breast cancer (stage I-III) from 2/2005-6/2010 in five registries of the breast cancer surveillance consortium (BCSC). BCSC clinical and registry data were linked to Medicare claims and enrollment data. We estimated the cumulative probability of breast cancer-specific and all-cause mortality. We tested the association of preoperative MRI with all-cause mortality using a Cox proportional hazards model. RESULTS: 917 (20.6%) women underwent preoperative MRI. No significant difference in the cumulative probability of breast cancer-specific mortality was found. We observed no significant difference in the hazard of all-cause mortality during the follow-up period after adjusting for sociodemographic and clinical factors among women with MRI (HR 0.90; 95% CI 0.72-1.12) compared to those without MRI. CONCLUSION: Our findings of no breast cancer-specific or all-cause mortality benefit supplement prior results that indicate a lack of improvement in surgical outcomes associated with use of preoperative MRI. In combination with other reports, the results of this analysis highlight the importance of exploring the benefit of preoperative MRI in patient-reported outcomes such as women's decision quality and confidence levels with decisions involving treatment choices.

Mammographic screening detects low-risk tumor biology breast cancers.

Overdiagnosis of breast cancer, i.e. the detection of slow-growing tumors that would never have caused symptoms or death, became more prevalent with the implementation of population-based screening. Only rough estimates have been made of the proportion of patients that are overdiagnosed and identification of those patients is difficult. Therefore, the aim of this study is to evaluate whether tumor biology can help identify patients with screen-detected tumors at such a low risk of recurrence that they are likely to be overdiagnosed. Furthermore, we wish to evaluate the impact of the transition from film-screen mammography (FSM) to the more sensitive full-field digital mammography (FFDM) on the biology of the tumors detected by each screening-modality. All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041) accrued 2007-2011, who participated in the national screening program (biennial screening ages 50-75) were included (n = 1,165). We calculated the proportions of high-, low- and among those the ultralow-risk tumors according to the 70-gene signature for patients with screen-detected (n = 775) and interval (n = 390) cancers for FSM and FFDM. Screen-detected cancers had significantly more often a low-risk tumor biology (68 %) of which 54 % even an ultralow-risk compared to interval cancers (53 % low-, of which 45 % ultralow-risk (p = 0.001) with an OR of 2.33 (p < 0.0001; 95 % CI 1.73-3.15). FFDM detected significantly more high-risk tumors (35 %) compared to FSM (27 %) (p = 0.011). Aside from favorable clinico-pathological factors, screen-detected cancers were also more likely to have a biologically low-risk or even ultralow-risk tumor. Especially for patients with screen-detected cancers the use of tools, such as the 70-gene signature, to differentiate breast cancers by risk of recurrence may minimize overtreatment. The recent transition in screening-modalities led to an increase in the detection of biologically high-risk cancers using FFDM.

Octreotide for acute esophageal variceal bleeding: a meta-analysis.

BACKGROUND & AIMS: Studies of octreotide have not demonstrated a consistent benefit in efficacy or safety compared with conventional therapies. This study statistically pooled existing trials to evaluate the safety and efficacy of octreotide for esophageal variceal hemorrhage. METHODS: We identified randomized trials of octreotide for variceal hemorrhage from computerized databases, scientific meeting abstracts, and the manufacturer of octreotide. Blinded reviewers abstracted the data, and a meta-analysis was performed. RESULTS: Octreotide improved control of esophageal variceal hemorrhage compared with all alternative therapies combined (relative risk [RR], 0.63; 95% confidence interval [CI], 0.51-0.77); vasopressin/terlipressin (RR, 0.58; 95% CI, 0.42-0.81); or no additional intervention/placebo (among patients that received initial sclerotherapy/banding before randomization) (RR, 0.46; 95% CI, 0.32-0.67). Octreotide had comparable efficacy to immediate sclerotherapy for control of bleeding (RR, 0.94; 95% CI, 0.55-1.62), fewer major complications than vasopressin/terlipessin (RR, 0.31; 95% CI, 0.11-0.87), and a complication profile comparable to no intervention/placebo (RR, 1.06; 95% CI, 0.72-1.55). No specific alternative therapy demonstrated a mortality benefit. CONCLUSIONS: These results favor octreotide over vasopressin/terlipressin in the control of esophageal variceal bleeding and suggest it is a safe and effective adjunctive therapy after variceal obliteration techniques. Trials are needed to determine the optimal dose, route, and duration of octreotide treatment.

Performance of screening mammography among women with and without a first-degree relative with breast cancer.

BACKGROUND: Although it is recommended that women with a family history of breast cancer begin screening mammography at a younger age than average-risk women, few studies have evaluated the performance of mammography in this group. OBJECTIVE: To compare the performance of screening mammography in women with a first-degree family history of breast cancer and women of similar age without such history. DESIGN: Cross-sectional. SETTING: Mammography registries in California (n = 1), New Hampshire (n = 1), New Mexico (n = 1), Vermont (n = 1), Washington State n = 2), and Colorado (n = 1). PARTICIPANTS: 389 533 women 30 to 69 years of age who were referred for screening mammography from April 1985 to November 1997. MEASUREMENTS: Risk factors for breast cancer; results of first screening examination captured for a woman by a registry; and any invasive cancer or ductal carcinoma in situ identified by linkage to a pathology database, the Surveillance, Epidemiology, and End Results program, or a state tumor registry. RESULTS: The number of cancer cases per 1000 examinations increased with age and was higher in women with a family history of breast cancer than in those without (3.2 vs. 1.6 for ages 30 to 39 years, 4.7 vs. 2.7 for ages 40 to 49 years, 6.6 vs. 4.6 for ages 50 to 59 years, and 9.3 vs. 6.9 for ages 60 to 69 years). The sensitivity of mammography increased significantly with age (P = 0.001 [chi-square test for trend]) in women with a family history and in those without (63.2% [95% CI, 41. 5% to 84.8%] vs. 69.5% [CI, 57.7% to 81.2%] for ages 30 to 39 years, 70.2% [CI, 61.0% to 79.5%] vs. 77.5% [CI, 73.3% to 81.8%] for ages 40 to 49 years, 81.3% [CI, 73.3% to 89.3%] vs. 80.2% [CI, 76.5% to 83.9%] for ages 50 to 59 years, and 83.8% [CI, 76.8% to 90.9%] vs. 87.7% [CI, 84.8% to 90.7%] for ages 60 to 69 years). Sensitivity was similar for each decade of age regardless of family history. The positive predictive value of mammography was higher in women with a family history than in those without (3.7% vs. 2.9%; P = 0.001). CONCLUSIONS: Cancer detection rates in women who had a first-degree relative with a history of breast cancer were similar to those in women a decade older without such a history. The sensitivity of screening mammography was influenced primarily by age.

The positive predictive value of cervical smears in previously screened postmenopausal women: the Heart and Estrogen/progestin Replacement Study (HERS).

BACKGROUND: The benefits and risks of performing annual cervical smears on postmenopausal women are not well defined. The independent effect of hormone replacement therapy on development of cytologic abnormalities is unknown. OBJECTIVE: To determine the positive predictive value of cervical smears in previously screened postmenopausal women and to determine the effect of oral estrogen plus progestin on incident cervical cytologic abnormalities. DESIGN: Prospective cohort study (incidence) and randomized, double-blind, placebo-controlled trial (hormone therapy). SETTING: 20 U.S. outpatient and community clinical centers. PARTICIPANTS: 2561 women with a uterus and normal cytologic characteristics at baseline. INTERVENTIONS: Annual smears; oral conjugated equine estrogens, 0. 625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or identical placebo. MEASUREMENTS: Incident cytologic abnormalities (atypical squamous cells of undetermined significance, atypical glandular cells of undetermined significance, low-grade squamous epithelial lesion, and high-grade squamous epithelial lesion) and final histologic diagnoses. RESULTS: The incidence of new cytologic abnormalities in the 2 years following a normal smear was 110 per 4895 person-years (23 per 1000 person-years [95% CI, 18 to 27 per 1000 person-years]). Among the 103 women with known histologic diagnoses, one had mild to moderate dysplasia. The positive predictive value of any smear abnormality identified 1 year after a normal smear, therefore, was 0% (CI, 0% to 5.0%) (0 of 78 women); the positive predictive value of abnormalities found within 2 years was 0.9% (CI, 0.0% to 3.0%) (1 of 110 women). In hormone-treated compared with non-hormone-treated women, the incidence of cytologic abnormalities was nonsignificantly higher (relative hazard, 1.36 [CI, 0.93 to 1.99]), largely because of a nonsignificant 58% greater incidence of atypical squamous cells of undetermined significance (relative hazard, 1.58 [CI, 0.99 to 2.52]). CONCLUSIONS: Because of a poor positive predictive value, cervical smears should not be performed within 2 years of normal cytologic results in postmenopausal women. Therapy with oral estrogen plus progestin does not significantly affect the incidence of cytologic abnormalities.

Effect of variations in operational definitions on performance estimates for screening mammography.

RATIONALE AND OBJECTIVES: The Mammography Quality Standards Act requires practices to measure limited aspects of their performance. The authors conducted this study to calculate the differences in measurements of sensitivity and specificity due only to differences in the definitions used in the analysis. This included definitions for case inclusion. MATERIALS AND METHODS: Data from the New Mexico Mammography Project for January 1991 to December 1995 on 136,540 women who underwent screening mammography were analyzed. A starting definition was created for each performance measure. The components of the definition were varied, and estimates of sensitivity and specificity for the different definitions were calculated. RESULTS: Sensitivity was lower and specificity was higher when assessed on the basis of the results of all imaging performed in the screening work-up rather than on the initial screening examination alone. Sensitivity was higher and specificity was lower in women who did not undergo rather than in women who did recently undergo a previous examination. When the definition of a positive examination included cases that were recommended for short-term follow-up, the work-up sensitivity was slightly higher and the work-up specificity was considerably lower. Longer follow-up times for determining the diagnosis of cancer were associated with decreasing sensitivity, particularly when the follow-up period extended beyond 12 months. CONCLUSION: Variations in the operational definitions for measures of mammographic performance affect these estimates. To facilitate valid comparisons, reports need to be explicit regarding the definitions and methods used.

Pharmacotherapy for hypertension in women of different races.

OBJECTIVES: To assess whether the relative and absolute benefit of hypertension treatment in women varies with age or race. SEARCH STRATEGY: Literature search of studies from 1966 to 1998 using MEDLINE, reviews, and consultation with experts. SELECTION CRITERIA: Studies were eligible if they were randomized controlled trials of pharmacological treatment of primary hypertension, with cardiovascular morbidity and mortality outcomes, and with over one hundred women enrolled. DATA COLLECTION AND ANALYSIS: The pooled population included 23,000 women. Relative risks were combined for each endpoint to form summary risk ratios (RR) using meta-analytic techniques based on a random-effects model. Summary RR's were converted to numbers needed to treat (NNT). Data were dichotomized by age to approximate menopausal status (30 to 54 years, and 55 years and older), and by race (white and African American). MAIN RESULTS: In women ages 55 years or older (90% white), hypertension treatment results in a 38% risk reduction in fatal and nonfatal cerebrovascular events (95% confidence interval (CI) 27-47%, 5 year NNT 78), a 25% reduction in fatal and nonfatal cardiovascular events (95% CI 17-33%, 5 year NNT 58), and a 17% reduction in cardiovascular mortality (95% CI 3-29%, 5 year NNT 282). In women ages 30 to 54 years (79% white), hypertension treatment results in a 41% risk reduction in fatal and nonfatal cerebrovascular events (95% CI 8-63%, 5 year NNT 264), and a 27% risk reduction in fatal and nonfatal cardiovascular events (95% CI 4-44%, 5 year NNT 259). Hypertension treatment in African American women (mean age 52 years) reduced the risk of fatal and nonfatal cerebrovascular events by 53% (95% CI 29-69%, 5 year NNT 39), fatal and nonfatal cardiovascular events by 45% (95% CI 18-63%, 5 year NNT 21), fatal and nonfatal coronary events by 33% (95% CI 6-52%, 5 year NNT 48), and all cause mortality by 34% (95% CI 14-49%, 5 year NNT 32). Analyses in white women 30 to 54 years old did not show any statistically significant treatment benefit or harm. REVIEWER'S CONCLUSIONS: Hypertension treatment lowers the relative and absolute risk of cardiovascular morbidity and mortality in women ages 55 years and older, and in African American women of all ages. A greater effort should be made to increase awareness and treatment in these groups of women. Although relative risk reductions for cerebrovascular and cardiovascular events are similar for younger and older women, the NNT of younger women is at least 4 times higher. Decisions for treatment of hypertension in younger white women should be influenced by the individual patient's absolute risk of cardiovascular disease.

Frequency of cervical smear abnormalities within 3 years of normal cytology.

OBJECTIVE: To compare cervical screening outcomes associated with age and three screening intervals, 1, 2, and 3 years. METHODS: We did a prospective cohort study comprising 128,805 women at community-based clinics throughout the United States who were screened for cervical cancer within 3 years of normal smears through the National Breast and Cervical Cancer Early Detection Program. We determined the incidence of cytologic abnormalities defined as atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (SIL), high-grade SIL, and suggestive of squamous cell cancer. RESULTS: Over the 3 years after normal smear results, the incidence of new smears interpreted as high-grade SIL or suggestive of squamous cell cancer (high-grade SIL or worse) was 66 of 10,000 for women under 30 years old, 22 of 10, 000 for those 30-49 years, 15 of 10,000 for those 50-64 years, and 10 of 10,000 for those over 65 years. Age-adjusted incidence rates of high-grade SIL or worse were similar for women screened at 9-12 months (25 of 10,000), 13-24 months (29 of 10,000), and 25-36 months (33 of 10,000) after normal smears (P =.46). Age-adjusted incidence rates of ASCUS, the most common cytologic abnormality, did not change (P =.36). Incidence of smears interpreted as low-grade SIL increased as time from the normal smear increased (P =.01). CONCLUSIONS: Within 3 years after normal cytology results, cervical smears interpreted as high-grade SIL or worse are uncommon, and the incidence rate is unrelated to the time since last normal smear. Optimal screening strategies for women with recent normal cytology results should be based on comprehensive modeling studies that incorporate the true risks and benefits of repetitive screening.

Mortality among women with ductal carcinoma in situ of the breast in the population-based surveillance, epidemiology and end results program.

BACKGROUND: Over 14% of breast cancers diagnosed in the United States annually are ductal carcinomas in situ (DCIS). There are no published population-based reports of the likelihood of breast cancer death among US women with DCIS. METHODS: We used data from the Surveillance, Epidemiology and End Results program to determine the likelihood of breast cancer death at 5 and 10 years among US women aged 40 and older diagnosed with DCIS from 1978 to 1983 (before screening mammography was common; n = 1525) and from 1984 to 1989 (when screening mammography became common; n = 5547). We also calculated standardized mortality ratios (SMRs) to compare observed deaths from breast cancer, cardiovascular disease, and all causes combined among women with DCIS with deaths expected based on general population mortality rates. RESULTS: Among women diagnosed with DCIS from 1978 to 1983, 1.5% died of breast cancer within 5 years and 3.4% within 10 years. Among women diagnosed from 1984 to 1989, 0.7% died of breast cancer within 5 years and 1.9% within 10 years. Relative to the general population, risk of breast cancer death was greater for women diagnosed from 1978 to 1983 (SMR, 3.4; 95% confidence interval [CI], 2.5-4.5) than for women diagnosed from 1984 to 1989 (10-year SMR, 1.9; 95% CI, 1.5-2.3). Women diagnosed from 1984 to 1989 were significantly less likely than women in the general population to have died of cardiovascular diseases (10-year SMR, 0.6; 95% CI, 0.5-0.7) or of all causes combined (SMR, 0.8; 95% CI, 0.7-0.8). CONCLUSIONS: Among women diagnosed with DCIS, risk of death from breast cancer was low, at least within the 10 years following diagnosis. This may reflect the effectiveness of treatment for DCIS, the "benign" nature of DCIS, or both. At 10 years, women diagnosed from 1984 to 1989 were less likely than women diagnosed from 1978 to 1983 to have died of breast cancer, and their risk of dying of all causes combined was lower than that in the general population.

Chromosomal alterations in ductal carcinomas in situ and their in situ recurrences.

BACKGROUND: Ductal carcinoma in situ (DCIS) recurs in the same breast following breast-conserving surgery in 5%-25% of patients, with the rate influenced by the presence or absence of involved surgical margins, tumor size and nuclear grade, and whether or not radiation therapy was performed. A recurrent lesion arising soon after excision of an initial DCIS may reflect residual disease, whereas in situ tumors arising after longer periods are sometimes considered to be second independent events. The purpose of this study was to determine the clonal relationship between initial DCIS lesions and their recurrences. METHODS: Comparative genomic hybridization (CGH) was used to compare chromosomal alterations in 18 initial DCIS lesions (presenting in the absence of invasive disease) and in their subsequent ipsilateral DCIS recurrences (detected from 16 months to 9.3 years later). RESULTS: Of the 18 tumor pairs, 17 showed a high concordance in their chromosomal alterations (median = 81%; range = 65%-100%), while one case showed no agreement between the paired samples (having two and 20 alterations, respectively). Morphologic characterization of the DCIS pairs showed clear similarities. The mean number of CGH changes was greater in the recurrent tumors than in the initial lesions (10.7 versus 8.8; P =.019). The most common changes in both the initial and the recurrent in situ lesions were gains involving chromosome 17q and losses involving chromosomes 8p and 17p. The degree of concordance was independent of the time interval before recurrence and of the presence of positive surgical margins. CONCLUSIONS: In this study, DCIS recurrences were clonally related to their primary lesions in most cases. This finding is consistent with treatment paradigms requiring wide surgical margins and/or postoperative radiation therapy.

Is screening mammography effective in elderly women?

PURPOSE: Screening mammography is effective in reducing breast cancer mortality in women between the ages of 50 and 69 years. We sought to determine whether older women who undergo screening mammography have a decreased risk of metastatic breast cancer. SUBJECTS AND METHODS: We studied 690,993 women aged 66 to 79 years who were California Medicare beneficiaries from January 1992 to December 1993, and who chose the fee-for-service plan. Health Care Financing Administration part B billing records were used to determine the use of screening mammography. The extent of breast cancer (in situ, local, regional, or metastatic) was ascertained for the 6,767 women who were diagnosed with the disease in 1993, using data from the California State Cancer Registry. For each type (extent) of breast cancer, the relative risk (RR) and 95% confidence (CI) of developing breast cancer was estimated by dividing the risk of its development in screened women by the risk in women who were not screened. RESULTS: A total of 46% of women had mammography during the 2-year study period. In situ, local, and regional breast cancer were more likely to be detected among women who underwent screening mammography. For example, the relative risk of detecting local breast cancer in screened women was 3.3 (95% CI: 3.1 to 3.5). The risk of detecting metastatic breast cancer, on the other hand, was significantly reduced among women aged 66 to 79 years who underwent screening mammography (RR = 0.57, 95% CI: 0.45 to 0.72). CONCLUSION: Screening mammography is associated with a decreased risk of detecting metastatic breast cancer among elderly women. Public health recommendations need to weigh the benefit of screening elderly women against the cost and potential harm from screening and treating early lesions that may have no effect on mortality.

Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials.

BACKGROUND: Previous meta-analysis of outcome trials in hypertension have not specifically focused on isolated systolic hypertension or they have explained treatment benefit mainly in function of the achieved diastolic blood pressure reduction. We therefore undertook a quantitative overview of the trials to further evaluate the risks associated with systolic blood pressure in treated and untreated older patients with isolated systolic hypertension METHODS: Patients were 60 years old or more. Systolic blood pressure was 160 mm Hg or greater and diastolic blood pressure was less than 95 mm Hg. We used non-parametric methods and Cox regression to model the risks associated with blood pressure and to correct for regression dilution bias. We calculated pooled effects of treatment from stratified 2 x 2 contingency tables after application of Zelen's test of heterogeneity. FINDINGS: In eight trials 15 693 patients with isolated systolic hypertension were followed up for 3.8 years (median). After correction for regression dilution bias, sex, age, and diastolic blood pressure, the relative hazard rates associated with a 10 mm Hg higher initial systolic blood pressure were 1.26 (p=0.0001) for total mortality, 1.22 (p=0.02) for stroke, but only 1.07 (p=0.37) for coronary events. Independent of systolic blood pressure, diastolic blood pressure was inversely correlated with total mortality, highlighting the role of pulse pressure as risk factor. Active treatment reduced total mortality by 13% (95% CI 2-22, p=0.02), cardiovascular mortality by 18%, all cardiovascular complications by 26%, stroke by 30%, and coronary events by 23%. The number of patients to treat for 5 years to prevent one major cardiovascular event was lower in men (18 vs 38), at or above age 70 (19 vs 39), and in patients with previous cardiovascular complications (16 vs 37). INTERPRETATION: Drug treatment is justified in older patients with isolated systolic hypertension whose systolic blood pressure is 160 mm Hg or higher. Absolute benefit is larger in men, in patients aged 70 or more and in those with previous cardiovascular complications or wider pulse pressure. Treatment prevented stroke more effectively than coronary events. However, the absence of a relation between coronary events and systolic blood pressure in untreated patients suggests that the coronary protection may have been underestimated.

Continuing screening mammography in women aged 70 to 79 years: impact on life expectancy and cost-effectiveness.

CONTEXT: Mammography is recommended and is cost-effective for women aged 50 to 69 years, but the value of continuing screening mammography after age 69 years is not known. In particular, older women with low bone mineral density (BMD) have a lower risk of breast cancer and may benefit less from continued screening. OBJECTIVE: To compare life expectancy and cost-effectiveness of screening mammography in elderly women based on 3 screening strategies. DESIGN: Decision analysis and cost-effectiveness analysis using a Markov model. PATIENTS: General population of women aged 65 years or older. INTERVENTIONS: The analysis compared 3 strategies: (1) Undergoing biennial mammography from age 65 to 69 years; (2) undergoing biennial mammography from age 65 to 69 years, measurement of distal radial BMD at age 65 years, discontinuing screening at age 69 years in women in the lowest BMD quartile for age, and continuing biennial mammography to age 79 years in those in the top 3 quartiles of distal radius BMD; and (3) undergoing biennial mammography from age 65 to 79 years. MAIN OUTCOME MEASURES: Deaths due to breast cancer averted, life expectancy, and incremental cost-effectiveness ratios. RESULTS: Compared with discontinuing mammography screening at age 69 years, measuring BMD at age 65 years in 10000 women and continuing mammography to age 79 years only in women with BMD in the top 3 quartiles would prevent 9.4 deaths and add, on average, 2.1 days to life expectancy at an incremental cost of $66773 per year of life saved. Continuing mammography to age 79 years in all 10000 elderly women would prevent 1.4 additional breast cancer deaths and add only 7.2 hours to life expectancy at an incremental cost of $117689 per year of life saved compared with only continuing mammography to age 79 years in women with BMD in the top 3 quartiles. CONCLUSIONS: This analysis suggests that continuing mammography screening after age 69 years results in a small gain in life expectancy and is moderately cost-effective in those with high BMD and more costly in those with low BMD. Women's preferences for a small gain in life expectancy and the potential harms of screening mammography should play an important role when elderly women are deciding about screening.

Identification of risk factors in hypertensive patients: contribution of randomized controlled trials through an individual patient database.

BACKGROUND: Predicting individual risk is needed to target preventive interventions toward people with the highest probability of benefit over a given time period. We assessed which prognostic factors should be used in predicting risk for hypertensive patients and in searching for treatment modifiers. METHODS AND RESULTS: Data from 24 390 hypertensive participants who constituted the control groups from 8 controlled trials (1726 deaths over 5 years) were analyzed in multivariate survival models. Outcomes were coronary heart disease death, stroke death, and cardiovascular death. We explored systematically the heterogeneity of results between trials. Left ventricular hypertrophy was electrocardiographically confirmed to be a powerful risk factor and should be included in risk scoring. Height, glomerular filtration rate, and serum uric acid deserve further exploration. Body mass index and heart rate were not confirmed as independent cardiovascular risk factors in this population. The association between male sex and coronary heart disease death was significantly stronger in British cohorts. The lack of prognostic value of diastolic blood pressure was explained by an interaction with age, with a positive association before 65 years and a negative association thereafter. Previous antihypertensive treatment was a significant risk factor. CONCLUSIONS: Clinical trials provide valuable information for risk prediction. Carefully exploring the heterogeneity among trials is a way to assess the generalizability of findings. This approach, if systematically performed, should increase the ability to identify risk modifiers and to predict individual therapeutic benefit.

Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. INDANA Group.

BACKGROUND: Beneficial clinical effects of treatment with antihypertensive drugs have been shown in middle-aged patients and in those hypertensive patients over 60 years old, but whether treatment is beneficial in patients over 80 years old is not known. METHODS: We collected data from all participants aged 80 years and over in randomised controlled trials of antihypertensive drugs through direct contact with study investigators. Our primary outcome was fatal and non-fatal stroke. Secondary outcomes were death from all causes, cardiovascular death, fatal and non-fatal major coronary and cardiovascular events, and heart failure. FINDINGS: There were 57 strokes and 34 deaths among 874 actively treated patients, compared with 77 strokes and 28 stroke deaths among 796 controls, representing 1 non-fatal stroke prevented for about 100 patients treated each year. The meta-analysis of data from 1670 participants aged 80 years or older suggested that treatment prevented 34% (95% CI 8-52) of strokes. Rates of major cardiovascular events and heart failure were significantly decreased, by 22% and 39%, respectively. However, there was no treatment benefit for cardiovascular death, and a non-significant 6% (-5 to 18) relative excess of death from all causes. INTERPRETATIONS: The inconclusive findings for mortality contrast with the benefit of treatment for non-fatal events. Results of a large-scale specific trial are needed for definite conclusion that antihypertensive treatment is beneficial in very elderly hypertensive patients. Meanwhile, an age threshold beyond which hypertension should not be treated cannot be justified.

Efficacy of treating hypertension in women.

OBJECTIVE: To assess whether the relative and absolute benefit of hypertension treatment in women varies with age or race. DESIGN: Systematic review of studies from 1966 to 1998 using MEDLINE, reviews, and consultation with experts. Eleven randomized controlled trials of pharmacologic treatment of prJgiary hypertension with cardiovascular morbidity and mortality outcomes were selected, with a pooled population of 23,000 women. Relative risks were combined for each end point to form a summary risk ratio using meta-analytic techniques based on a random-effects model. Summary risk ratios were converted to numbers needed to treat (NNTs). Data were dichotomized by age to approxJgiate menopausal status (30 to 54 years, and 55 years and older), and by race (white and African American). MAIN RESULTS: In women aged 55 years or older (90% white), hypertension treatment resulted in a 38% risk reduction in fatal and nonfatal cerebrovascular events (95% confidence interval [CI] 27%, 47%; 5-year NNT 78), a 25% reduction in fatal and nonfatal cardiovascular events (95% CI 17%, 33%; 5-year NNT 58), and a 17% reduction in cardiovascular mortality (95% CI 3%, 29%; 5-year NNT 282). In women aged 30 to 54 years (79% white), hypertension treatment resulted in a 41% risk reduction in fatal and nonfatal cerebrovascular events (95% CI 8%, 63%; 5-year NNT 264), and a 27% risk reduction in fatal and nonfatal cardiovascular events (95% CI 4%, 44%; 5-year NNT 259). Hypertension treatment in African-American women (mean age, 52 years) reduced the risk of fatal and nonfatal cerebrovascular events by 53% (95% CI 29%, 69%; 5-year NNT 39), fatal and nonfatal cardiovascular events by 45% (95% CI 18%, 63%; 5-year NNT 21), fatal and nonfatal coronary events by 33% (95% CI 6%, 52%; 5-year NNT 48), and all-cause mortality by 34% (95% CI 14%, 49%; 5-year NNT 32). Analyses in white women aged 30 to 54 years did not show any statistically significant treatment benefit or harm. CONCLUSIONS: Hypertension treatment lowers the relative and absolute risk of cardiovascular morbidity and mortality in women aged 55 years and older and in African-American women of all ages. A greater effort should be made to increase awareness and treatment in these groups of women. Although relative risk reductions for cerebrovascular and cardiovascular events are sJgiilar for younger and older women, the NNT of younger women is at least 4 tJgies higher. Decisions about treatment of hypertension in younger white women should be influenced by the individual patient's absolute risk of cardiovascular disease.