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Biomedical subjects

E L Barrett-Connor

Publications and source records attributed to E L Barrett-Connor.

At least 19 recordsLinked to original sources

Metabolic syndrome and ischemic heart disease in elderly men and women.

Associations between metabolic syndrome components and prevalent ischemic heart disease (IHD) were investigated in a cross-sectional, community-based study of elderly men (n = 1,015) and women (n = 1,259) in Rancho Bernardo, California, in 1984-1987. In both sexes, there were significant positive associations between IHD defined by resting electrocardiogram criteria and age, systolic blood pressure, fasting and postchallenge hyperglycemia, total cholesterol/high density lipoprotein cholesterol (HDL cholesterol) ratio, and triglycerides and an inverse significant association with HDL cholesterol. High collinearity and interactions between serum insulin and metabolic syndrome variables were accounted for by uncorrelated principal components identified by factor analysis. In both men and women, three uncorrelated principal components were identified, representing a central metabolic factor (body mass index, fasting and 2-hour serum insulin, high serum triglycerides, and low HDL cholesterol), a glucose factor, and a blood pressure factor. In a multivariate model with age and sex, all three factors were significantly associated with IHD by electrocardiogram criteria; central metabolic factor (odds ratio (OR) = 1.6, p = 0.001), glucose factor (OR = 1.4, p < 0.001), blood pressure factor (OR = 1.2, p = 0.005), age (10 years) (OR = 1.8, p < 0.001), and female sex (OR = 0.5, p < 0.02). Similar results were obtained in analyses using clinically manifest IHD as the outcome. These results support the thesis that the metabolic syndrome exerts effects through different risk factors by different mechanisms.

Aged↗

Vitamin C supplement use and bone mineral density in postmenopausal women.

Vitamin C is known to stimulate procollagen, enhance collagen synthesis, and stimulate alkaline phosphatase activity, a marker for osteoblast formation. Studies of dietary vitamin C intake and the relation with bone mineral density (BMD) have been conflicting, probably because of the well-known limitations of dietary nutrient assessment questionnaires. The purpose of this study was to evaluate the independent relation of daily vitamin C supplement use with BMD in a population-based sample of postmenopausal women. Subjects were 994 women from a community-based cohort of whom 277 women were regular vitamin C supplement users. Vitamin C supplement use was validated. Daily vitamin C supplement intake ranged from 100 to 5,000 mg; the mean daily dose was 745 mg. Average duration of use was 12.4 years; 85% had taken vitamin C supplements for more than 3 years. BMD levels were measured at the ultradistal and midshaft radii, hip, and lumbar spine. After adjusting for age, body mass index (BMI), and total calcium intake, vitamin C users had BMD levels approximately 3% higher at the midshaft radius, femoral neck, and total hip (p < 0.05). In a fully adjusted model, significant differences remained at the femoral neck (p < 0.02) and marginal significance was observed at the total hip (p < 0.06). Women taking both estrogen and vitamin C had significantly higher BMD levels at all sites. Among current estrogen users, those also taking vitamin C had higher BMD levels at all sites, with marginal significance achieved at the ultradistal radius (p < 0.07), femoral neck (p < 0.07), and total hip (p < 0.09). Women who took vitamin C plus calcium and estrogen had the highest BMD at the femoral neck (p = 0.001), total hip (p = 0.05), ultradistal radius (p = 0.02), and lumbar spine. Vitamin C supplement use appears to have a beneficial effect on levels of BMD, especially among postmenopausal women using concurrent estrogen therapy and calcium supplements.

Age Factors↗

Nonsteroidal anti-inflammatory drugs and bone mineral density in older women: the Rancho Bernardo study.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to inhibit synthesis of prostaglandins and may help prevent bone loss, but no study has shown the differential association of type or dose of NSAID compound with bone mineral density (BMD). The purpose of this study was to determine the relation of NSAIDs by type and dose to BMD. Participants were 932 Caucasian, community-dwelling women aged 44-98 years from southern California. Data were collected from 1988 to 1991 through the use of standardized medical questionnaires. Medication use was validated by a nurse. BMD at the ultradistal and midshaft radii were measured using single-photon absorptiometry, and at the hip and lumbar spine using dual-energy X-ray absorptiometry. Women (mean age, 72 years) were classified into 818 nonusers and 114 regular daily users of NSAIDs, of which 84 used propionic acid NSAIDs and the remainder used acetic acid NSAIDs. Occasional NSAID users were excluded. Women who used propionic acid NSAIDs, but not acetic acid NSAIDs, had higher BMD at all five sites and significantly higher BMD at the midshaft radius and lumbar spine. These differences remained after controlling for known covariates of osteoporosis. When women with self-reported osteoarthritis were excluded from the model, significantly higher BMD in propionic acid NSAID users was also observed at the femoral neck and total hip. Those who concurrently used estrogen and propionic acid NSAIDs had the highest BMD at all sites, suggesting an additive effect. We conclude that regular daily use of propionic acid NSAIDs, with or without simultaneous use of estrogen, may be helpful in preventing bone loss in older women. However, further research is needed to confirm these results before any clinical practice guidelines can be recommended due to the increased risk of serious complications associated with NSAID use.

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Urinary N-telopeptide levels discriminate normal, osteopenic, and osteoporotic bone mineral density.

BACKGROUND: The level of urinary, type I collagen, crosslinked N-telopeptides (NTX) is a new marker of bone resorption. To our knowledge, no population-based studies of older adults have determined whether this measure can identify individuals with osteoporosis. OBJECTIVES: To measure the levels of NTX in a cross-sectional study of ambulatory, older, white adults and to evaluate whether this measure of bone resorption could identify individuals with osteoporosis. PATIENTS AND METHODS: The subjects, aged 50 to 98 years, formed 3 groups: 374 men, 223 women currently using estrogen, and 364 women not currently using estrogen. A standard medical history and validated record of medication use were obtained. Height and weight were measured. Bone mineral density (BMD) was measured at the hip and lumbar spine using dual energy x-ray absorptiometry. The levels of NTX were measured by enzyme-linked immunosorbent assay. RESULTS: Overall, the levels of NTX increased slightly with age in men and in estrogen users and more dramatically in nonestrogen users. In a model adjusted for all major risk factors for osteoporosis, there was a significant decrease in BMD levels by increasing quintiles of NTX levels at the hip and spine in women with and without estrogen use and at the hip in men. Using sex-specific, peak bone mass criteria and age-adjusted analyses, the levels of NTX discriminated between normal (< or = -1.0 SD), osteopenic (> -1.0 and < -2.5 SD), and osteoporotic (> or = -2.5 SD) BMD levels in all groups except the spine in men. CONCLUSIONS: The levels of NTX uniquely discriminated between older adults with normal, osteopenic, or osteoporotic BMD levels. If confirmed, these data suggest that NTX levels could be used to predict current osteoporosis in older men and women.

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Timing of postmenopausal estrogen for optimal bone mineral density. The Rancho Bernardo Study.

OBJECTIVE: To determine the effect of the timing of initiation and the duration of postmenopausal estrogen therapy on bone mineral density (BMD). DESIGN: Cross-sectional study. SETTING: White, middle-class to upper middle-class community-dwelling women. PARTICIPANTS: A total of 740 women aged 60 to 98 years who participated in a study of osteoporosis. MEASUREMENTS: Questionnaire, validated medication use, and height and weight. Bone mineral density at the ultradistal radius and midshaft radius using single-photon absorptiometry (SPA) and at the hip and lumbar spine using dual-energy x-ray absorptiometry (DEXA). RESULTS: Of the 740 women, 69% had used oral estrogen after menopause and 30% were current users. Five groups of estrogen use were identified: never users, past users who started at menopause, past users who started after age 60 years, current users who started after age 60 years, and current users who started at menopause. At all 4 bone sites, current users who started at menopause had the highest BMD levels, which were significantly higher than never users or past users who started at menopause (with 10 years' duration of use). These differences persisted after controlling for all major risk factors for osteoporosis. Among current users, there was no significant difference in BMD levels at any site between those who started estrogen at menopause (with 20 years of use) and those who started after age 60 years (with 9 years of use). CONCLUSIONS: Estrogen initiated in the menopausal period and continued into late life is associated with the highest bone density. Nevertheless, estrogen begun after age 60 years and continued appears to offer nearly equal bone-conserving benefit.

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Carbonated beverage consumption and bone mineral density among older women: the Rancho Bernardo Study.

OBJECTIVES: The association between carbonated beverage consumption and bone mineral density was examined in a community-based cohort of older White women. METHODS: One thousand women 44 to 98 years of age had bone mineral density measured at four sites and provided medical and behavioral histories, including type and quantity of carbonated beverages consumed. RESULTS: Bone mineral density levels were not associated with intake of any type of carbonated beverage after adjustment for age, obesity, calcium intake, exercise, and current use of tobacco and alcohol, thiazides, estrogen, or thyroid hormone. CONCLUSIONS: Modest intake of carbonated beverages does not appear to have adverse effects on bone mineral density in older women.

Adult↗

Predictors of progression from impaired glucose tolerance to NIDDM: an analysis of six prospective studies.

Risk factors associated with the progression from impaired glucose tolerance (IGT) to NIDDM were examined in data from six prospective studies. IGT and NIDDM were defined in all studies by World Health Organization (WHO) criteria, and baseline risk factors were measured at the time of first recognition of IGT. The studies varied in size from 177 to 693 participants with IGT, and included men and women followed from 2 to 27 years after the recognition of IGT. Across the six studies, the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years. Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence, incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels, but increased linearly with increasing 2-h postchallenge glucose quartiles. Incidence rates were higher among the Hispanic, Mexican-American, Pima, and Nauruan populations than among Caucasians. The effect of baseline age on NIDDM incidence rates differed among the studies; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies. In all studies, estimates of obesity (including BMI, waist-to-hip ratio, and waist circumference) were positively associated with NIDDM incidence. BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately, but not in the three studies with the highest NIDDM incidence rates. Sex and family history of diabetes were generally not related to NIDDM progression. This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements. The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention.

Adolescent↗

Thyroid hormone use and bone mineral density in elderly men.

BACKGROUND: Excessive thyroid hormone use reduces bone density in women. Thyroid hormone use is much less common in men, who also have less osteoporosis. We examined bone mineral density in a community-based sample of elderly men who reported long-term thyroid hormone use. METHODS: All 685 white men aged 50 to 98 years from a Southern California community who participated in a study of osteoporosis were examined. Medication use was validated. Height and weight were measured. Bone mineral density was measured at the ultradistal radius and midshaft radius using single photon absorptiometry and at the hip and lumbar spine using dual energy x-ray absorptiometry. RESULTS: Thirty-three men taking a mean thyroxine-equivalent dose of 130 micrograms daily for an average of 15.5 years were compared with 653 nonusers. There were no significant differences in bone density at any site between users and nonusers, before or after controlling for age, body mass index, smoking, thiazide diuretics, and oral corticosteroid use. Bone density also did not differ according to thyroid hormone type, duration of use, or use of suppressive dose adjusted for body weight. CONCLUSIONS: Long-term thyroid hormone use was not associated with adverse effects on bone mineral density in men.

Aged↗

Inhaled and oral corticosteroids: their effects on bone mineral density in older adults.

Use of oral and inhaled corticosteroids and bone mineral density were examined cross-sectionally in 1673 community-dwelling white subjects aged 56 to 91 years. Bone mineral densities at the ultradistal and midshaft radii, hip, and lumbar spine were compared in users of inhaled (n = 34) and oral (n = 44) corticosteroids and nonusers. Women who used oral corticosteroids had significantly lower bone mineral densities at the midshaft radius, hip, and spine than never users. Women who used inhaled corticosteroids had bone mineral densities at the ultradistal radius, hip, and spine that were intermediate between those of oral corticosteroid users and those of never users. Bone mineral density did not vary significantly according to corticosteroid use in men.

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Testosterone and risk factors for cardiovascular disease in men.

It has been assumed for years that male testosterone levels play a central role in worsening lipoprotein patterns and causing greater susceptibility to ischemic heart disease. Yet most clinical trials of quasi-physiologic doses of intramuscular testosterone in older men show no effect on high-density lipoprotein (HDL)-cholesterol, while cross-sectional epidemiologic studies almost uniformly find that endogenous testosterone levels are positively associated with HDL-cholesterol levels. Further work is required to determine whether and why physiologic testosterone levels in the high normal range appear to be conducive to optimal cardiovascular health for adult men.

Adult↗

Hyperinsulinemia does not increase the risk of fatal cardiovascular disease in elderly men or women without diabetes: the Rancho Bernardo Study, 1984-1991.

The relation of fasting and 2-hour serum insulin to the risk for fatal cardiovascular disease was examined in men and women without diabetes. Between 1984 and 1987, 80% of all surviving local members of the Rancho Bernardo Study cohort had measures of insulin and glucose levels obtained before and after a 75-g oral glucose tolerance test. Over the next 5 years, there were 24 cardiovascular disease deaths among 538 men and 21 cardiovascular disease deaths among 705 women. Fasting insulin was unrelated to cardiovascular disease death in men or women; 2-hour insulin was significantly lower in men (but not in women) who died from cardiovascular disease. In men, a 1-standard deviation increase in 2-hour insulin was associated with a 36% reduction in cardiovascular disease mortality (p = 0.01). The significant inverse association of 2-hour insulin with cardiovascular disease death persisted in multiply adjusted models (relative hazard = 0.68; 95% confidence interval 0.47-0.96). Patterns were similar when the analysis was repeated, including men with non-insulin-dependent diabetes mellitus or heart disease at baseline. These findings were not explained by antihypertensive drug use or cigarette smoking. Hyperinsulinemia was not a risk factor for cardiovascular disease in these older men or women. The role of insulin as a cardiovascular disease risk factor requires further investigation.

Age Factors↗

Thiazides and bone mineral density in elderly men and women.

The relation of bone mineral density of the ultradistal radius, midshaft radius, hip, and lumbar spine to thiazide use were examined in a community-based sample of 1,696 white men and women aged 44-98 years. Male thiazide users had higher age-adjusted bone mineral density levels only at the midshaft radius (p < 0.05). Among women, thiazide users had significantly higher bone mineral density levels at all four sites (p < 0.05), both before and after controlling for the effects of age, body mass index, smoking, and estrogen use. The association was explained by current thiazide use; no significant association was found between past use or duration of use and bone mineral density levels. Results were similar when hypertensive women were excluded from the analyses, suggesting the effect was drug-related and not due to hypertension or some other factor related to hypertension. At all sites, the highest bone mineral density levels were seen in women currently using both estrogen and thiazide. Overall, these findings suggest that thiazides may be useful in the prevention of osteoporosis in postmenopausal women.

Adult↗

Thyroid hormone use and bone mineral density in elderly women. Effects of estrogen.

OBJECTIVE: To determine the effect of long-term use of thyroid hormone on bone mineral density (BMD) in elderly women and the potential mitigating effects of estrogen replacement therapy. DESIGN: Cross-sectional, community-based study. SETTING: Rancho Bernardo, Calif. PARTICIPANTS: A total of 991 white women aged 50 to 98 years who participated in a study of osteoporosis. MAIN OUTCOME MEASURES: Bone mineral density at the ultradistal radius and midshaft radius using single-photon absorptiometry and at the hip and lumbar spine using dual-energy x-ray absorptiometry. RESULTS: A total of 196 women taking thyroid hormone for a mean duration of 20.4 years were compared with 795 women who were not using thyroid hormone. Women taking daily thyroxine-equivalent doses of 200 micrograms or more had significantly lower BMD levels at the midshaft radius and hip compared with those taking less than 200 micrograms. Daily doses of 1.6 micrograms/kg and greater were associated with lower bone mass at all four sites compared with nonuse, whereas doses less than 1.6 micrograms/kg were not associated with lower BMD levels. These associations were independent of age, body mass index, smoking status, and use of thiazides, corticosteroids, and estrogen. Women taking both estrogen and a thyroid hormone dose of 1.6 micrograms/kg or greater had significantly higher BMD levels at all four sites than women taking the same thyroid hormone dose alone. Women taking both thyroid hormone and estrogen had BMD levels comparable with those observed in women taking only estrogen. CONCLUSIONS: Long-term thyroid hormone use at thyroxine-equivalent doses of 1.6 micrograms/kg or greater was associated with significant osteopenia at the ultradistal radius, midshaft radius, hip, and lumbar spine. Estrogen use appears to negate thyroid hormone-associated loss of bone density in postmenopausal women.

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Sex differences in bone mineral density in 1653 men and women in the sixth through tenth decades of life: the Rancho Bernardo Study.

This cross-sectional population-based study examined the effect of age and sex on bone mineral density (BMD) in the elderly. BMD was measured at the spine and hip using dual-energy x-ray absorptiometry and at midshaft and ultradistal radius using single-photon absorptiometry in 672 men and 981 women aged 50-98 years. In both sexes, mean BMD levels decreased significantly with age at all sites except the male spine. In linear regression models, the slope of loss was significantly greater in women than in men at all sites except the ultradistal radius. The slope was steeper at most sites in women aged 50-59 years than in older women, 60-98 years. In both age groups, mean age-adjusted BMD levels were lower at all sites in women who were past or never users of replacement estrogen than in women who were current estrogen users. Current estrogen users generally had lower slopes of loss with age than never or past estrogen users; however, few of these differences were statistically significant. We conclude that BMD levels decrease in old age in both sexes. Continued bone loss in old age raises the possibility that intervention to retard further loss may still be warranted in the elderly.

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Thiazide-associated metabolic abnormalities and estrogen replacement therapy: an epidemiological analysis of postmenopausal women in Rancho Bernardo, California.

The objective of this study was to identify abnormalities in lipid and carbohydrate metabolism in women taking thiazide diuretics and determine whether these abnormalities are mitigated by concurrent postmenopausal estrogen replacement therapy. The study design was cross-sectional; its setting was Rancho Bernardo, an upper middle-class community in southern California. The subjects included 1047 white nondiabetic postmenopausal women, aged 50-89 yr, categorized by the use of thiazide diuretic, estrogen replacement therapy, both, or neither. Medical history including behavior, verified medication use, height, weight, fasting chemistry and lipid panels, and a standardized oral glucose tolerance test with fasting and 2-h plasma glucose and serum insulin levels were determined. Compared with nonusers, women taking thiazides had significantly lower high density lipoprotein cholesterol levels and significantly higher fasting triglyceride, glucose, and insulin levels. Concomitant use of thiazide and estrogen yielded lipid profiles and fasting glucose and insulin levels similar to those of subjects receiving estrogen alone, i.e. elevated high density lipoproteins, decreased low density lipoproteins, and lower levels of fasting glucose and insulin compared with those in nonusers. However, thiazide-associated postchallenge glucose and insulin elevations were not modified by estrogen. These patterns were not explained by differences in age, body mass index, exercise, smoking, alcohol use, type or dose of thiazide diuretic, type of estrogen replacement, or serum potassium levels. We conclude that postmenopausal estrogen use masks thiazide-associated dyslipidemia and fasting elevations in glucose and insulin levels, but does not improve thiazide-associated postchallenge glucose intolerance and hyperinsulinemia. Modification of most of the untoward metabolic effects of thiazides in women taking postmenopausal estrogen could provide a new incentive for the use of this traditional antihypertensive in elderly women.

Aged↗

Plasma cholesterol and depressive symptoms in older men.

In several clinical trials of interventions designed to lower plasma cholesterol, reductions in coronary heart disease mortality have been offset by an unexplained rise in suicides and other violent deaths. We have tried to find out whether depressive illness is related to low plasma cholesterol concentrations in men of 50 years and older. In 1985-87, Beck depression inventories were obtained from 1020 white men, aged 50-89 years, in the Rancho Bernardo, California, cohort. Disease history and behaviours were assessed by standard questionnaires. Plasma cholesterol and weight were measured at this time, as they had been in 1972-74. Among men aged 70 years and older, categorically defined depression was three times more common in the group with low plasma cholesterol (< 4.14 mmol/L) than in those with higher concentrations (5/31 [16%] vs 22/363 [6%]; p = 0.033). Depressive symptom scores correlated significantly and inversely with plasma cholesterol concentrations, even after adjustment for age, health status, number of chronic illnesses, number of medications, and exercise, as well as measured weight loss and change in plasma cholesterol in the previous 13 years. Our finding that low plasma cholesterol is associated with depressive symptoms in elderly men is compatible with observations that a very low total cholesterol may be related to suicide and violent death. Since cholesterol lowering in the general population is widely recommended, this observation warrants further investigation.

Aged↗

Blood pressure change and survival after age 75.

Higher diastolic pressure predicted better survival in men 75 years or older in two prior analyses in the Rancho Bernardo population. Diastolic change was implicated as a possible explanation. We studied this by assessing survival according to blood pressure change in 795 men and women aged 75 years and older at the time of a second measurement taken an average of 11 years after the first, who were then followed for 5 years. Sex-specific analyses compared participants with a diastolic decrease of 5 mm Hg or greater and participants with a systolic decrease of 10 mm Hg or greater with those whose blood pressure levels did not change or increased. In men, after adjustment for baseline pressure, a decrease in diastolic pressure of 5 mm Hg or greater was associated with higher all-cause mortality (relative risk, 2.33; 95% confidence interval, 1.39 to 3.91) and cardiovascular mortality (3.13, 1.47 to 6.66). The mortality risk was strongest in men who took antihypertensive medication and had a fall in diastolic pressure (12.33, 2.73 to 55.72) compared with treated men whose pressures did not decrease. Among men with isolated systolic hypertension, those treated whose diastolic pressure remained stable had the best survival. A systolic fall in men and a decrease in either diastolic or systolic in women was not associated with poorer survival after adjustment for baseline pressure. We conclude that a fall in diastolic pressure of 5 mm Hg was associated with poor survival in men after age 75. This risk was strongest in men who took antihypertensive medication.

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