Intraventricular murine Aß infusion elicits hippocampal inflammation and disrupts the consolidation, but not retrieval, of conditioned fear in C57BL6/J mice.

Although one of the defining characteristics of Alzheimer's disease is the presence of amyloid-beta (Aß) plaques, the early accumulation of soluble Aß oligomers (AßOs) may disrupt synaptic function and trigger cognitive impairments long before the appearance of plaques. Furthermore, murine models aimed at understanding how AßOs alter formation and retrieval of associative memories are conducted using human Aß species, which are more neurotoxic in the mouse brain than the native murine species. Unfortunately, there is currently a lack of attention in the literature as to what the murine version of the peptide (mAß) does to synaptic function and how it impacts the consolidation and retrieval of associative memories. In the current study, adult mice were infused with mAß 0, 2, 6, or 46 h after contextual-fear conditioning, and were tested 2-48 h later. Interestingly, only mAß infusions within 2 h of training reduced freezing behavior at test, indicating that mAß disrupted the consolidation, but not retrieval of fear memory. This consolidation deficit coincided with increased IL-1ß and reduced synaptophysin mRNA levels, without disrupting other synaptic signaling-related genes here examined. Despite differences between murine and human Aß, the deleterious functional outcomes of early-stage synaptic oligomer presence are similar. Thus, models utilizing or inducing the production of mAß in non-transgenic animals are useful in exploring the role of dysregulated synaptic plasticity and resultant learning deficits induced by Aß oligomers.

Epstein-Barr virus-associated lymphoproliferative disease in oral cavity in a renal transplant recipient: a case report.

A 10-yr-old child on long-term cyclosporin immunosuppression for a renal transplant presented with gingival swelling enlargement, in a background of gingival hyperplasia. It is tempting to assume that it is a drug-related lesion; perhaps, an area of plaque-related inflammation. An incisional biopsy revealed a monomorphic B-cell post-transplant lymphoproliferative disease (PTLD). At this stage, high Epstein-Barrr virus (EBV) titres supported a diagnosis of EBV-driven PTLD. Despite discontinuation of cyclosporin and reduction of EBV viral load to undetectable levels, there was considerable enlargement of the tumour. The patient underwent six courses of cyclophosphamide, vincristine and prednisolone chemotherapy. This resulted in a dramatic reduction in the size of the right mandibular mass with complete mucosal healing intra-orally. Her renal transplant still has good function and there is no evidence of PTLD recurrence 23 months after initial diagnosis. This case illustrates that PTLD can manifest in unusual sites and in transplant recipients on cyclosporin immunosuppression it is easy to assume that any gingival hyperplasia is drug induced; however, the differential diagnosis of gingival hyperplasia should include PTLD.

Pulse pressure and mortality in older people.

BACKGROUND: In older people, observational data are unclear concerning the relationships of systolic and diastolic blood pressure with cardiovascular and total mortality. We examined which combinations of systolic, diastolic, pulse, and mean arterial pressure best predict total and cardiovascular mortality in older adults. METHODS: In 1981, the National Institute on Aging initiated its population-based Established Populations for Epidemiologic Studies of the Elderly in 3 communities. At baseline, 9431 participants, aged 65 to 102 years, had blood pressure measurements, along with measures of medical history, use of medications, disability, and physical function. During an average follow-up of 10. 6 years among survivors, 4528 participants died, 2304 of cardiovascular causes. RESULTS: In age- and sex-adjusted survival analyses, the lowest overall death rate occurred among those with systolic pressure less than 130 mm Hg and diastolic pressure 80 to 89 mm Hg; relative to this group, the highest death rate occurred in those with systolic pressure of 160 mm Hg or more and diastolic pressure less than 70 mm Hg (relative risk, 1.90; 95% confidence interval, 1.47-2.46). Both low diastolic pressure and elevated systolic pressure independently predicted increases in cardiovascular (P<.001) and total (P<.001) mortality. Pulse pressure correlated strongly with systolic pressure (R = 0.82) but was a slightly stronger predictor of both cardiovascular and total mortality. In a model containing pulse pressure and other potentially confounding variables, diastolic pressure (P =.88) and mean arterial pressure (P =.11) had no significant association with mortality. CONCLUSIONS: Pulse pressure appears to be the best single measure of blood pressure in predicting mortality in older people and helps explain apparently discrepant results for low diastolic blood pressure.

Combining annual blood pressure measurements in childhood to improve prediction of young adult blood pressure.

Tracking correlations of blood pressure (BP) have been reported between levels measured in a single year during both childhood and adulthood. Because of the variability of BP, these correlations increase with the number of visits and measurements per visit in each year. It remains unclear, however, whether such correlations would improve further by combining BP data collected over several years. From 1978-1981, BP was measured annually in a cohort of 339 children in East Boston, MA, at four visits one week apart with three measurements per visit. Of this cohort, then aged 18-26 years, 316 were re-examined in 1989-1990 at three visits one week apart with three measures per visit. Tracking correlations were estimated from levels measured in a single year as well as means averaged over several years in childhood, adjusting for age, year of measurement, as well as smoking, alcohol and oral contraceptive use. Multivariate models were fit to estimate tracking correlations from childhood to young adulthood adjusting for within-person variability. Using a single year in childhood, these were 0.49 in boys and 0.59 in girls for systolic BP and 0.39 and 0.48 for diastolic BP (all p<0.001). Using the long-term average in childhood and adjusting for variability across years, these values were 0.55 in boys and 0.66 in girls for systolic BP and 0.47 and 0.57 for diastolic BP (all p<0.001). We observed concomitant increases in the predictive value of childhood BP for young adult BP. These results suggest that averaging BP over at least two years during childhood increases tracking correlations and improves the prediction of adult values from childhood levels.

Interactions of familial and hormonal risk factors for large bowel cancer in women.

BACKGROUND: Family history of colorectal cancer has been consistently associated with an increased personal risk of this disease. Since evidence suggests that hormones are related to colon cancer risk in women, the effect of family history on large bowel incidence may be modified according to endogenous and exogenous hormone levels. METHODS: We analysed data from a population-based case-control study of female colorectal cancer to evaluate family history and cancer risk. Cases (n = 702) were female residents of Wisconsin with a new diagnosis of colorectal cancer, identified through a statewide tumour registry. Controls (n = 2274) were randomly selected from lists of licensed drivers and from rosters of Medicare beneficiaries. All relative risks (RR) were adjusted for age, body mass index, smoking and alcohol history, education, and use of hormone replacement therapy. RESULTS: Compared with women who reported no history of cancer in a first degree relative, women with a family history had an RR of 2.07 (95% confidence interval [CI]: 1.60-2.68). Regardless of which parent was affected, risks were increased about twofold, while sibling history was associated with about a 50% increase in risk. Risk was greater if more than one family member was affected (RR 3.65, 95% CI: 1.81-7.37). The association between family history and risk was stronger for colon cancer than for rectal cancer. There were no indications that exogenous hormonal factors, notably hormone replacement use, modified these risks. There was a suggestion that high parity attenuated the risks associated with family history (P = 0.07). CONCLUSIONS: These results confirm that family history of colorectal cancer is associated with a doubling of risk for large bowel cancer in women; some histories were associated with greater risk. This relation was not substantially different among subgroups of women with varying exogenous and endogenous hormone exposures.

Misclassification and under-reporting of acute myocardial infarction by elderly persons: implications for community-based observational studies and clinical trials.

We investigated the accuracy of self-report of hospitalization for acute myocardial infarction (MI) by elderly persons in a community-based prospective study. Among 3809 persons aged 65 years or older followed up for 6 years, self-reported hospitalization for MI was validated by review of primary records and Medicare diagnoses. Among 147 who self-reported MI and for whom hospital records were available, the diagnosis was confirmed in 79 (54%). Myocardial infarction was not a reason for hospitalization among the remaining 68 participants; misclassification with other cardiovascular diagnoses was common. Medicare diagnosis correlated well with primary hospital records. Using Medicare diagnoses as the standard, the diagnosis of MI was confirmed in 53% of self-reports; the sensitivity and specificity of self-report were 51% and 98%, respectively. False-negative reporting was common because only half of hospitalizations for MI were reported. Self-report of hospitalization for MI by elderly persons in the community may be unreliable for ascertaining trends in cardiovascular diseases.

The renal effects of nonsteroidal anti-inflammatory drugs in older people: findings from the Established Populations for Epidemiologic Studies of the Elderly.

OBJECTIVE: To determine whether older people who use nonsteroidal anti-inflammatory agents (NSAIDs) have increased levels of blood urea nitrogen (BUN), serum creatinine, and BUN:serum creatinine ratio. DESIGN: Cross-sectional, secondary data analysis. SETTING: Older people living in the communities of East Boston, MA, New Haven, CT, and Washington and Iowa Counties, Iowa. PARTICIPANTS: A total of 4099 people aged 70 years or older who were participants in the National Institute on Aging's Established Populations for Epidemiologic Studies of the Elderly project, had survived to the 6-year follow-up interview and had consented to the blood drawing. MEASUREMENTS: We assessed use of the NSAIDs at the 3- and 6-year interviews through a drug inventory and visual review of medication containers. Markers of renal function assessed through analysis of blood samples drawn at the time of the interview included BUN and creatinine. RESULTS: Fifteen percent of the cohort reported use of NSAIDs during the 2 weeks preceding the 6-year interview. Controlling for age, sex, and a range of potential confounding variables, NSAID users had significant prevalence odds ratios of 1.9 (95% confidence interval (CI), 1.5-2.3) for being in the highest quartile of BUN (>23), 1.3 (CI 1.1-1.7) for the highest quartile of serum creatinine (> or =1.4), and 1.7 (CI 1.4-2.1) for the highest quartile of the BUN:creatinine ratio (> or = 19.4). Chronic NSAID users (those who reported NSAID use at both the 3-year and 6-year interviews) accounted for the increased risk of high serum creatinine levels. CONCLUSION: Community-dwelling older people who use NSAIDs tend to have higher levels of common laboratory markers of renal dysfunction. This hypothesis requires further testing in prospective cohort studies designed a priori to evaluate these issues.

Increased pulse pressure and risk of heart failure in the elderly.

CONTEXT: Arterial stiffness increases with age. Thus, pulse pressure, an index of arterial stiffening, may predict congestive heart failure (CHF) in the elderly. OBJECTIVE: To study prospectively the association between pulse pressure and risk of CHF. DESIGN: Prospective cohort study. SETTING: The community-based East Boston Senior Health Project, East Boston, Mass. PATIENTS: A total of 1621 men and women (mean [SD] age, 77.9 [5.0] years) free of CHF who had blood pressure measurements taken in 1988-1989 and were followed up for 3.8 years. MAIN OUTCOME MEASURE: Incidence of CHF as ascertained by hospital discharge diagnosis (n = 208) and death certificates (n = 13). RESULTS: After controlling for age, sex, mean arterial pressure, history of coronary heart disease, diabetes mellitus, atrial fibrillation, valvular heart disease, and antihypertensive medication use, pulse pressure was an independent predictor of CHF. For each 10-mm Hg elevation in pulse pressure, there was a 14% increase in risk of CHF (95% confidence interval, 1.05-1.24; P = .003). Those in the highest tertile of pulse pressure (>67 mm Hg) had a 55% increased risk of CHF (P=.02) compared with those in the lowest (<54 mm Hg). Pulse pressure was more predictive than systolic blood pressure alone and was independent of diastolic blood pressure. CONCLUSION: Pulse pressure, an easily measurable correlate of pulsatile hemodynamic load, is an independent predictor of risk of CHF in this elderly cohort.

Cancer occurrence in the elderly: agreement between three major data sources.

PURPOSE: To explore agreement on cancer occurrence and site among Medicare Part A, Massachusetts Cancer Registry, and death certificates. METHODS: We linked these data sources with the cohort of the population-based East Boston Senior Health Project, a component of the National Institute on Aging's Established Populations for Epidemiologic Studies of the Elderly. The cohort consists of 905 subjects dying between January 1986 and December 1990. RESULTS: We detected the following agreements on cancer occurrence: hospitalization data and death certificates (kappa = 0.70), hospitalization and cancer registry data (kappa = 0.59), and cancer registry and death certificate data (kappa = 0.50). Measures of agreement changed little when the analyses were stratified by age, sex, calendar year and place of death, autopsy performance, cigarette smoking or alcohol consumption. Site-specific agreements were higher for colorectal and respiratory tract cancer compared to breast and prostate across all three comparisons. CONCLUSIONS: The results should assist epidemiologists to better understand the strengths and limitations of these data sources.

Education and other measures of socioeconomic status and risk of incident Alzheimer disease in a defined population of older persons.

OBJECTIVE: To assess the relations of 3 measures of socioeconomic status (education, occupational prestige, and income) to risk of incident clinically diagnosed Alzheimer disease (AD). DESIGN: Cohort study with an average observation of 4.3 years. SETTING: East Boston, Mass. a geographically defined community. PARTICIPANTS: A stratified random sample of 642 community residents 65 years of age and older who were free of AD at baseline. MAIN OUTCOME MEASURE: Clinical diagnosis of probable AD according to standard criteria, using structured uniform evaluation. RESULTS: The relations of the 3 measures of socioeconomic status to risk of disease were assessed using logistic regression analyses. In individual analyses, fewer years of formal schooling, lower income, and lower occupational status each predicted risk of incident AD; risk of disease decreased by approximately 17% for each year of education. In an analysis including all 3 measures, the effect of education on risk for disease remained approximately the same, but the effects of the other 2 measures were somewhat less and did not attain formal statistical significance, compared with separate analysis of each measure. CONCLUSIONS: Markers of lower socioeconomic status predict risk of developing incident AD. The mechanism of this relation is uncertain, but the possibility that it reflects unidentified and potentially reversible risk factors for the disease deserves careful investigation.

Prediction of young adult blood pressure from childhood blood pressure, height, and weight.

To assess the ability of childhood blood pressure, height, and weight to predict young adult blood pressure, the authors examined data obtained over multiple visits for four years on 339 children aged 8-18 years in East Boston, Massachusetts. These subjects were again seen 8-12 years later when they were aged 20-26 years. Multivariate regression models were used to predict true blood pressure in young adulthood from observed childhood measurements closest to age 10 (n = 219), adjusting for within-person variability. Without adjusting for childhood blood pressure, childhood height, weight and body mass index were at least marginally associated with young adult systolic blood pressure in boys and girls, with similar coefficients for each gender. The strongest predictor was weight (beta = 0.6 mmHg/10 lbs for girls, and beta = 0.7 mmHg/10 lbs for boys), and height was no longer predictive with weight in the model. With childhood blood pressure included, neither childhood height nor weight were predictors of future systolic blood pressure. However, change in height and weight were predictors of future systolic blood pressure. Weight change was a stronger predictor in girls than boys with beta = 0.9 mmHg/10 lbs. For diastolic blood pressure, height and weight had limited predictive ability in these data. These models, which allow for both between- and within-person variability in young adulthood, may be used to estimate the predictive value for future high blood pressure of a child's current blood pressure, height and weight, as well as future change in height and weight. These data suggest that the effects of childhood height and weight on future blood pressure may be negligible given childhood blood pressure, but that later height and weight remain predictive.

Aspirin use and cognitive function in the elderly.

Decline in cognitive function in the elderly is common and represents a major clinical and public health concern. Aspirin may reduce the decline in cognitive function by influencing multi-infarct dementia, but data are sparse. The East Boston Senior Health Project is a population-based cohort study that enrolled 3,809 community-dwelling residents aged 65 years and older in 1982-1983 and followed them with home visits every 3 years until 1988-1989. Trained interviewers assessed cognitive function by using the Short Portable Mental Status Questionnaire and assessed medication use, including over-the-counter drugs. Response to the Short Portable Mental Status Questionnaire was scored as high, medium, or low, and decline was defined as transition to a lower category. Participants who used drugs containing aspirin in the 2 weeks prior to the interview were classified as aspirin users. Multiple logistic regression was used to obtain adjusted odds ratios and their 95% confidence intervals for decline of cognitive function. The estimating equation approach was used to adjust the standard errors for repeated measurements. Aspirin users had an odds ratio for cognitive decline of 0.97 (95% confidence interval 0.82-1.15). Low frequency of aspirin use (less than daily) was associated with an odds ratio of 0.87 (95% confidence interval 0.69-1.09). Although no substantial effect was observed, the data are also compatible with a modest benefit of aspirin, especially with intermittent use, on decline of cognitive function. Concern about small residual biases from self-selection or confounding suggests that randomized trials will be necessary to provide definitive data on this question.

Interrelationships of peak expiratory flow rate with physical and cognitive function in the elderly: MacArthur Foundation studies of aging.

BACKGROUND: Peak expiratory flow rate (PEFR) is correlated with several measures of health in the elderly, including physical and cognitive function. It is unclear, however, whether these relationships persist among the non-frail. METHODS: The Community-based Studies of the MacArthur Foundation Research Network on Successful Aging included measures of PEFR using a mini-Wright peak flow meter on a sample of 1,354 subjects selected from those aged 70-79 in three population samples. Subjects were chosen on the basis of simple measures of physical and cognitive function (high = 1192; medium = 80; low = 82), and were given a series of more detailed tests. RESULTS: Residual PEFR, adjusted for age, sex, height, weight, and smoking, was highly correlated (p < .001) with several physical performance measures, including number of steps in a tandem walk, number of seconds in a single leg stand, times to turn in a circle, write one's name, and walk 10 feet at a fast pace, foot-tapping (time per tap), and hand grip strength. The strongest association was evident for a combination of six physical function items. Residual PEFR was also correlated with cognitive performance, including tests of similarities, naming, spatial recognition, memory, and figure drawing. The strongest association was present for a combined measure. These associations persisted in analyses restricted to those in the "high" function group as well as with no history of previous myocardial infarction, stroke, or cancer. Residual PEFR also exhibited a strong independent association with urinary norepinephrine, as measured in 12-hour overnight urine specimens. This relation did not appear to be mediated by smoking or medication use.

Use of antihypertensive drugs and trends in blood pressure in the elderly.

BACKGROUND: During the 1980s data became available from randomized trials concerning the clear benefits of treating hypertension in the elderly. In three large communities, we examined the impact of these findings on rates of treatment, use of specific antihypertensive drugs, and rates of elevated blood pressure as well as distributions of levels. METHODS: In 1981 the National Institute on Aging initiated population-based cohort studies in the residents of three communities who were 65 years and older. East Boston, Mass; Washington and Iowa counties, Iowa; and New Haven, Conn. Participation rates ranged from 80% to 85% across sites with 10,294 community-dwelling participants in the combined cohorts. Baseline evaluation included inhome blood pressure assessment and medication inventory. Repeated in-home evaluations occurred 3 and 6 years after baseline and follow-up rates ranged from 71% to 88%. RESULTS: Use of antihypertensive drugs increased over time in all three communities: the age- and sex-adjusted rates of use were between 14% and 32% higher in 1988 and 1989 relative to 1982 and 1983. Parallel declines in the use of thiazide diuretics occurred in all three populations along with large increases in the use of angiotensin-converting enzyme inhibitors and calcium channel blockers. In East Boston and New Haven mean systolic blood pressure decreased substantially over time and the prevalence of elevated systolic pressure (> or = 160 mmHg) decreased overall as well as by age and sex. In Iowa the mean levels of systolic blood pressure were lowest at baseline and increased slightly. CONCLUSIONS: The reported evidence about the benefits of treatment for hypertension in the elderly was followed by substantial increases in treatment rates. The use of drugs with proven efficacy declined while the use of newer agents with theoretical advantages, not yet tested in clinical trials of mortality, increased. In the United States, the ongoing therapeutic efforts to lower elevated blood pressure in elderly populations may be contributing to the continuing decline in cardiovascular and stroke mortality.

CHESS (Comprehensive Health Enhancement Support System): an interactive computer system for women with breast cancer piloted with an underserved population.

The Comprehensive Health Enhancement Support System (CHESS) is an interactive computer system containing information, social support, and problem-solving tools. It was developed with intensive input from potential users through needs-assessment surveys and field testing. CHESS had previously been used by women in the middle and upper socioeconomic classes with high school and college education. This article reports on the results of a pilot study involving eight African-American women with breast cancer from impoverished neighborhoods in Chicago. CHESS was very well received; was extensively used; and produced feelings of acceptance, motivation, understanding, and relief.

Implications of small reductions in diastolic blood pressure for primary prevention.

OBJECTIVES: To estimate the impact of small reductions in the population distribution of diastolic blood pressure (DBP), such as those potentially achievable by population-wide lifestyle modification, on incidence of coronary heart disease (CHD) and stroke. DESIGN: Published data from the Framingham Heart Study, a longitudinal cohort study, and from the National Health and Nutrition Examination Survey II, a national population survey, were used to examine the impact of a population-wide strategy aimed at reducing DBP by an average of 2 mm Hg in a population including normotensive subjects. SETTING/PARTICIPANTS: White men and women aged 35 to 64 years in the United States. MAIN OUTCOME MEASURES: Incidence of CHD and stroke, including transient ischemic attacks (TIAs). RESULTS: Data from overviews of observational studies and randomized trials suggest that a 2-mm Hg reduction in DBP would result in a 17% decrease in the prevalence of hypertension as well as a 6% reduction in the risk of CHD and a 15% reduction in risk of stroke and TIAs. From an application of these results to US white men and women aged 35 to 64 years, it is estimated that a successful population intervention alone could reduce CHD incidence more than could medical treatment for all those with a DBP of 95 mm Hg or higher. It could prevent 84% of the number prevented by medical treatment for all those with a DBP of 90 mm Hg or higher. For stroke (including TIAs), a population-wide 2-mm Hg reduction could prevent 93% of events prevented by medical treatment for those with a DBP of 95 mm Hg or higher and 69% of events for treatment for those with a DBP of 90 mm Hg or higher. A combination strategy of both a population reduction in DBP and targeted medical intervention is most effective and could double or triple the impact of medical treatment alone. Adding a population-based intervention to existing levels of hypertension treatment could prevent an estimated additional 67,000 CHD events (6%) and 34,000 stroke and TIA events (13%) annually among all those aged 35 to 64 years in the United States. CONCLUSIONS: A small reduction of 2 mm Hg in DBP in the mean of the population distribution, in addition to medical treatment, could have a great public health impact on the number of CHD and stroke events prevented. Whether such DBP reductions can be achieved in the population through lifestyle interventions, in particular through sodium reduction, depends on the results of ongoing primary prevention trials as well as the cooperation of the food industry, government agencies, and health education professionals.

Difficulty with holding urine among older persons in a geographically defined community: prevalence and correlates.

OBJECTIVE: The goal of this study was to estimate the prevalence and correlates of difficulty holding urine among a population of community-dwelling older people. DESIGN: Population-based cross-sectional study. SUBJECTS: A population census identified all residents aged 65 years and older residing in East Boston, Massachusetts, in 1982. MEASURES: Data collected via in-home interviews were used to estimate the prevalence of difficulty holding urine and to provide information regarding potential correlates of urinary difficulty. RESULTS: Of the 3809 study participants (85% response rate), 28% reported having "difficulty holding urine until they can get to a toilet" at least some of the time, and 8% reported difficulty "most" or "all of the time." Difficulty was associated with age and sex; 44% of women and 34% of men reported some difficulty (P < .001), and 9% of women and 6% of men (P < .001) reported difficulty most or all of the time. For respondents aged 65 to 74 years, 40% reported some difficulty, compared with 47% of those aged 85 and older (Ptrend < .001); difficulty most or all of the time was reported by 6% of those aged 65 to 74 and 12% of those aged 85 and older (Ptrend < .001). Difficulty holding urine was associated with important health and functional measures including depression, stroke, chronic cough, night awakening, fecal incontinence, problems with activities of daily living, decreased frequency and ease in getting out of the house, and poor self-perception of health. CONCLUSIONS: Difficulty holding urine is a prevalent condition among older people living in the community and is associated highly with a number of health conditions and functional problems.

Evidence for a positive linear relation between blood pressure and mortality in elderly people.

Many studies of blood pressure in the elderly have found higher death rates in groups with the lowest blood pressure than in those with intermediate values. In a large community study, we examined whether these findings are real or artifacts of short follow-up, co-morbidity, or low blood pressure in people near death. In 1982-83, we assessed drug use, medical history, disability, physical function, and blood pressure in 3657 residents of East Boston, Massachusetts, aged 65 and older. We identified all deaths (1709) up to 1992 and followed up survivors for an average of 10.5 (range 9.5-11.0) years. After adjustment for confounding variables (including frailty and disorders such as congestive heart failure and myocardial infarction) and exclusion of deaths within the first 3 years of follow-up, higher systolic pressure predicted linear increases in cardiovascular (p < 0.0001) and total (p < 0.0007) mortality. Higher diastolic pressure predicted increases in cardiovascular (p = 0.006) but not total (p = 0.48) mortality. These results differed from those for the first 3 years, during which groups with the lowest systolic and diastolic pressures had the highest death rates. In the long term, lower blood pressure in old age, as in middle age, is associated with better survival. Short-term findings may differ because of associations of co-morbidity and frailty with blood pressure near death. Overall, the findings support recommendations to treat high blood pressure in elderly people.

Lack of blood pressure effect with calcium and magnesium supplementation in adults with high-normal blood pressure. Results from Phase I of the Trials of Hypertension Prevention (TOHP). Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

Phase I of the Trials of Hypertension Prevention (TOHP) was a randomized, multicenter investigation that included double-blind, placebo-controlled testing of calcium and magnesium supplementation among 698 healthy adults (10.5% blacks and 31% women) aged 30 to 54 years with high-normal diastolic blood pressure (DBP) (80 to 89 mm Hg). Very high compliance (94 to 96% by pill counts) with daily doses of 1 g of calcium (carbonate), 360 mg of magnesium (diglycine), or placebos was corroborated for the active supplements by significant net increases in all urine and serum compliance measures in white men and for urine compliance measures in white women. Overall, neither calcium nor magnesium produced significant changes in blood pressure at 3 and 6 months. Analyses stratified by baseline intakes of calcium, magnesium, sodium, or initial blood pressures also showed no effect of supplementation. These analyses suggested that calcium supplementation may have resulted in a DBP decrease in white women and that response modifiers in this subgroup might have included lower initial urinary calcium levels, urinary sodium levels, or lower body mass index. However, overall analyses indicated that calcium and magnesium supplements are unlikely to lower blood pressure in adults with high-normal DBP. The subgroup analyses, useful to formulate hypotheses, raise the possibility of a benefit to white women, which requires testing in future trials.

Risk factors for non-insulin-dependent diabetes mellitus requiring treatment in the elderly.

OBJECTIVE: To examine the relationship of possible modifiable risk factors, including obesity, physical activity level, alcohol consumption, blood pressure, and thiazide diuretic use with the development of non-insulin-dependent diabetes mellitus (NIDDM) requiring treatment among a large cohort of community-dwelling elderly. SETTING: The East Boston Senior Health Project, one of four components of the National Institute on Aging-sponsored Established Populations for the Epidemiologic Study of the Elderly (EPESE). PARTICIPANTS: Residents of East Boston who were 65 years of age or older. MEASUREMENTS: We performed a prospective cohort study with follow-up over two consecutive 3-year time periods beginning in 1982-1983. The main outcome measure was the occurrence of NIDDM, defined as new treatment with a hypoglycemic agent. A total of 2737 study participants contributed 4682 3-year intervals for analysis. MAIN RESULTS: NIDDM requiring hypoglycemic therapy occurred in 185 participants over the duration of the study. High body mass index (> 26 kg/m2) (adjusted odds ratio 2.4, 95% confidence interval 1.3-4.4) and low physical activity level (adjusted odds ratio 1.5, 95% confidence interval 1.0-2.1) were significant predictors of NIDDM in a multiple logistic regression model adjusting for age, sex, blood pressure, and self-report of "high blood sugar" moderate alcohol consumption (0.5-<1 ounce per day) had an inverse relation to NIDDM of borderline significance (adjusted odds ratio 0.4, 95% confidence interval 0.2-1.0). Those receiving one or more non-thiazide antihypertensive agents had a higher risk of developing NIDDM in a model including age, sex, body mass index, various antihypertensive regimens, physical activity level, alcohol consumption, blood pressure, and self-report of "high blood sugar." Thiazide diuretic therapy alone or in combination with another antihypertensive was not associated with NIDDM. CONCLUSIONS: Our findings suggest a positive relationship of obesity and low physical activity level with the development of NIDDM requiring treatment in elderly persons. The inverse association of borderline significance between moderate alcohol use and NIDDM deserves further study. Thiazide diuretic therapy conferred no excess risk for developing NIDDM in this older population although selection factors in the choice of antihypertensive therapy may partially explain the absence of a thiazide effect.