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Biomedical subjects

L H Kuller

Publications and source records attributed to L H Kuller.

At least 109 records · Page 6Linked to original sources
PubMed1999

Familial resemblance of bone mineral density (BMD) and calcaneal ultrasound attenuation: the BMD in mothers and daughters study.

The familial resemblance in bone mineral density (BMD) and calcaneal broadband ultrasound attenuation (BUA) was examined in 207 mother-daughter pairs. Mothers were participants in the Study of Osteoporotic Fractures. Three groups of daughters were recruited based on their maternal history of "fracture," "low BMD" without fracture (< 0.58 g/cm2, t-score < -2.5), and "normal BMD" without fracture (> 0.67 g/cm2, t-score > -1.6). Data on other potentially heritable factors known to influence BMD and BUA were also collected. BMD was measured at the hip, spine, whole body, and calcaneus. Calcaneal BUA was assessed using the Walker-Sonix UBA 575. Total hip and femoral neck BMD were significantly lower (5.0-8.0%, p < 0.017) among daughters, in particular premenopausal daughters, of mothers with established osteoporosis ("fracture" or "low BMD") compared with daughters of mothers at lower risk of osteoporosis ("normal BMD"). BUA did not differ across daughter groups. Lifestyle characteristics (dietary calcium, smoking, physical activity) were not highly correlated in mothers and daughters. Height, weight, and body composition were significantly correlated within mother-daughter pairs and could be a potential mechanism by which BMD is inherited. Among pre- and postmenopausal daughters, heritability estimates ranged from 50-63% and 34-48%, respectively. Heritability for calcaneal BUA (53%) was evident among postmenopausal daughters only. In conclusion, familial association in BMD was strongest among premenopausal daughters. Estimates of heritability suggest that maternal BMD and BUA are important independent predictors of BMD and BUA among daughters, reinforcing the importance of prevention and early intervention among women with a positive family history of osteoporosis.

Adult↗
PubMed1999

Apolipoprotein E polymorphism: A new genetic marker of hip fracture risk--The Study of Osteoporotic Fractures.

Hip fractures are common and devastating events. The apolipoprotein E*4 (APOE) allele, associated with Alzheimer's disease, has also been associated with osteoporosis in hemodialysis patients. We prospectively studied 1750 women, age >/=65 years, who underwent measurements of hip and calcaneal bone mineral density (BMD), were typed for APOE and followed for approximately 7.0 years for the occurrence of fractures and falls. Women with at least one APOE*4 allele had an increased risk of hip fracture, relative hazard (RH) (95% confidence interval) = 1.90 (1.05-3.41) and wrist fracture, RH = 1.67 (1.01-2.77) compared with women without APOE*4, even after adjusting for age, cognitive function, falling, and BMD. The effect of APOE*4 on hip fracture was greatest among women with additional (>/=3) other risk factors. Women with an APOE*4 allele were also likely to report a maternal history of fracture. The average number of falls per year did not differ by APOE*4: 0.46 for APOE*4 women and 0.41 for women without an APOE*4 allele. Women with an APOE*4 allele experienced greater weight loss which contributed to faster rates of bone loss. We conclude that women with the APOE*4 polymorphism are at substantially increased risk of hip and wrist fracture that is not explained by bone density, impaired cognitive function, or falling. Possible alternate explanations include an effect of APOE on vitamin K, bone turnover, or weight loss. The APOE polymorphism may be a candidate gene for hip fractures among community dwelling nondemented women.

Accidental Falls↗
PubMed1999

Blood pressure levels and measurement of subclinical vascular disease.

Increased blood pressure, especially systolic blood pressure (SBP), is linearly associated with an increased risk of cardiovascular disease and stroke. The attributable risk of vascular disease due to elevated blood pressure is greater for normal and high normal blood pressures and stage 1 hypertension than for more advanced hypertension (stages 2 and 3). The development of noninvasive methods for measuring the effects of blood pressure on the vascular system help identify early vascular disease, high risk populations at similar levels of blood pressure, and successful methods of therapy. The future goals of the control of elevated blood pressure should be to prevent: (1) the rise in blood pressure associated with increasing age; (2) the development of subclinical vascular disease associated with even slightly elevated blood pressure; and (3) clinical disease. Measurement of subclinical vascular disease should be a component of both observational epidemiological studies and clinical trials. The subclinical measures should include those primarily associated with the progression of atherosclerosis and the pathophysiology of elevated blood pressure.

Blood Pressure↗
PubMed1998

Bone mineral density and risk of breast cancer: differences by family history of breast cancer. Study of Osteoporotic Fractures Research Group.

Recent studies have suggested that bone mineral density (BMD) is related to risk of breast cancer in elderly women. This study investigated whether the level of breast cancer risk associated with BMD in women with a positive family history of breast cancer is different from that in women without a family history of breast cancer. Radial and calcaneus BMD were measured at baseline (1986-1988) in 7,250 elderly white women enrolled in the Study of Osteoporotic Fractures, and initial breast cancer status was ascertained at year 1 of follow-up. After a mean of 3.2 years of additional follow-up, 104 incident breast cancer cases, 20 of which appeared in women with a family history of breast cancer, were identified and confirmed by medical record review. Modification of the BMD effect by family history status was assessed by inclusion of interaction terms in proportional hazards regression models. Among women without a family history of breast cancer, those with a proximal radius BMD in the highest tertile were at a 1.48-fold increased risk compared with women in the lowest tertile; among women with a positive family history of breast cancer, those with highest tertile BMD were at a 3.41-fold increased risk compared with women in the lowest tertile. These results suggest that the association between BMD and breast cancer may be different in subgroups of women defined by family history.

Aged↗
PubMed1998

Are menopausal symptoms associated with bone mineral density and changes in bone mineral density in premenopausal women?

BACKGROUND: The relationship between menopausal symptoms and bone mineral density (BMD) was examined in 290 premenopausal women, ages 44-50 years, participating in a randomized clinical trial of a dietary and exercise intervention: The Women's Healthy Lifestyle Project. METHODS: Information on hot flashes (presence, absence), menstrual cycles (irregular, regular) and menstrual flow per period (variable, same) over the past 6 months was collected at entry. Participants reporting at least one menopausal symptom were classified as symptomatic and compared to those having no symptoms. Bone mineral density (BMD) at the lumbar spine (L1-L4), total hip and whole-body were made at baseline and at 30 months using a dual-energy X-ray absorptiometer (Hologic QDR 2000 densitometer). RESULTS: Baseline BMD at the spine, hip and whole-body were significantly reduced in women reporting menopausal symptoms compared to asymptomatic women, after adjustment for age, weight and intervention status (all p < 0.05). Women with irregular menstrual cycles had greater annualized rates of bone loss at the spine and hip than asymptomatic women (spine, -0.77 (1.6)% per year vs. -0.19 (1.0)% per year, p = 0.0043; hip, -0.37 (1.1)% per year vs. -0.04 (1.0)% per year, p = 0.061), after adjustments for age, percent change in weight, intervention status, and baseline BMD. Similar findings were not found for whole-body BMD. CONCLUSIONS: These results suggest that menopausal symptoms are useful for the effective identification of premenopausal women at higher risk of low BMD and perhaps, of osteoporosis.

Absorptiometry, Photon↗
PubMed1998

Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women.

CONTEXT: Raloxifene is a selective estrogen receptor modulator that has estrogen-agonistic effects on bone and estrogen-antagonistic effects on breast and uterus. OBJECTIVE: To identify the effects of raloxifene on markers of cardiovascular risk in postmenopausal women, and to compare them with those induced by hormone replacement therapy (HRT). DESIGN: Double-blind, randomized, parallel trial. SETTING: Eight sites in the United States. PARTICIPANTS: 390 healthy postmenopausal women recruited by advertisement. INTERVENTION: Participants were randomized to receive 1 of 4 treatments: raloxifene, 60 mg/d; raloxifene, 120 mg/d; HRT (conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone acetate, 2.5 mg/d); or placebo. MAIN OUTCOME MEASURES: Change and percent change from baseline of lipid levels and coagulation parameters after 3 months and 6 months of treatment. RESULTS: At the last visit completed, compared with placebo, both dosages of raloxifene significantly lowered low-density lipoprotein cholesterol (LDL-C) by 12% (P < .001), similar to the 14% reduction with HRT (P < .001). Both dosages of raloxifene significantly lowered lipoprotein(a) by 7% to 8% (P < .001), less than the 19% decrease with HRT (P<.001). Raloxifene increased high-density lipoprotein-2 cholesterol (HDL2-C) by 15% to 17% (P < .05), less than the 33% increase with HRT (P < .001). Raloxifene did not significantly change high-density lipoprotein cholesterol (HDL-C), triglycerides, or plasminogen activator inhibitor-1 (PAI-1); whereas HRT increased HDL-C by 11% and triglycerides by 20%, and decreased PAI-1 by 29% (for all, P < .001). Raloxifene significantly lowered fibrinogen by 12% to 14% (P < .001), unlike HRT, which had no effect. Neither treatment changed fibrinopeptide A or prothrombin fragment 1 and 2. CONCLUSIONS: Raloxifene favorably alters biochemical markers of cardiovascular risk by decreasing LDL-C, fibrinogen, and lipoprotein(a), and by increasing HDL2-C without raising triglycerides. In contrast to HRT, raloxifene had no effect on HDL-C and PAI-1, and a lesser effect on HDL2-C and lipoprotein(a). Further clinical trials are necessary to determine whether these favorable biochemical effects are associated with protection against cardiovascular disease.

Aged↗
PubMed1998

Prospective association between lipid soluble antioxidants and coronary heart disease in men. The Multiple Risk Factor Intervention Trial.

A nested case-control study was performed using participants enrolled in the Multiple Risk Factor Intervention Trial (MRFIT). The cases involved nonfatal myocardial infarction or death from coronary heart disease. Serum samples (n = 734) obtained at baseline and frozen for approximately 20 years were analyzed for the antioxidants, carotenoids, retinol, and alpha-, gamma-, and total tocopherol. The concentrations of antioxidants were in the expected range and their association with low density lipoprotein (LDL) cholesterol reflected their absorption and transport mechanisms. Among nonsmokers, the odds ratios (95% confidence intervals (CI)) for quartile IV versus quartile I were 1.40 (0.40-4.89), 0.77 (0.20-2.96), 1.45 (0.38-5.56), 2.34 (0.56-9.81), and 2.40 (0.52-11.07) for retinol, total carotenoids, and alpha-, gamma-, and total tocopherol, respectively. The equivalent odds ratios (95% CI) for smokers were 0.90 (0.34-2.41), 0.66 (0.23-1.84), 0.67 (0.21-2.13), 2.04 (0.88-4.73), and 0.52 (0.16-1.67), respectively. This analysis of antioxidant concentrations by quartiles indicated no significant association of antioxidant levels with the risk of coronary disease death or nonfatal myocardial infarction.

Adult↗
PubMed1998

Lifetime weight cycling and psychological health in normal-weight and overweight women.

OBJECTIVE: The relationship between weight cycling history and psychological health was studied in a sample of 429 normal-weight and overweight women. METHOD: Participants were from the Healthy Women Study, a longitudinal investigation of biological and psychosocial aspects of menopause. Participants were asked to report retrospectively details on their weight cycling history in terms of the frequency and magnitude of previous weight loss episodes. Data were examined using the total cycle weight lost and the frequency of weight cycles > or = 10 lb. Self-reported measures of depression, stress, anxiety, and anger were used to evaluate psychological health. RESULTS: For both normal-weight and overweight women, the analyses revealed no adverse relationships between weight cycling history and the psychological measures. DISCUSSION: These findings suggest that a history of weight cycling regardless of weight status does not adversely impact psychological health.

Adaptation, Psychological↗
PubMed1998

Genetic variation in alpha 2HS-glycoprotein is related to calcaneal broadband ultrasound attenuation in older women.

Calcaneal broadband ultrasound attenuation (BUA) is an independent predictor of hip and vertebral fractures. BUA is under genetic control, but the specific genes contributing to BUA are not well defined. We examined the relationship between genetic variation in alpha2HS-glycoprotein (AHSG), an abundant noncollagenous protein of bone matrix, and calcaneal BUA. Genetic polymorphism in AHSG was determined in 222 Caucasian women (age 66-92) enrolled in the Pittsburgh Study of Osteoporotic Fractures clinical center by isoelectric focusing of serum samples. Calcaneal BUA and bone mineral density (BMD) were measured on the same foot with a Walker Sonix UBA 575(+) and single X-ray absorptiometry. Hip and spine BMD were determined with a Hologic QDR-1000 densitometer using dual-energy X-ray absorptiometry. AHSG polymorphism was not significantly related to hip, lumbar spine, or calcaneal BMD. Compared with the homozygous AHSG*2 women, calcaneal BUA was 13% lower in heterozygous (P < 0.05) and 16% lower in homozygous AHSG*1 women (P < 0.05). This relationship persisted after controlling for age, weight, height, walks for exercise, and calcaneal BMD. Current and self-reported height were also lowest in homozygous AHSG*1 women, intermediate in heterozygous women, and highest among homozygous AHSG*2 subjects. These results suggest that the AHSG polymorphism may contribute to the genetic influence on calcaneal BUA and stature.

Aged↗
PubMed1998

Cytokine production and bone mineral density at the lumbar spine and femoral neck in premenopausal women.

Cytokines such as interleukin-1 (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha) can influence both bone resorption and bone formation. The objective of this cross-sectional study was to examine the relationship between cytokine production by peripheral blood mononuclear cells (PBMC) and bone mineral density (BMD); the annual rate of change in BMD was examined. Subjects participating in a randomized clinical trial entitled the Women's Healthy Lifestyle Project in Allegheny County, Pennsylvania were used. They included 50 healthy premenopausal women, aged 45-52 years, who had regular menses within the past 3 months and were not on replacement estrogens. Dual-energy X-ray absorptiometry measurements at the AP lumbar spine and femoral neck were made at baseline and at the first annual exam using a Hologic QDR 2000 densitometer. Cytokine production of IL-1beta, IL-6, and TNF-alpha by PBMC was measured at the annual exam. The median values for stimulated cytokine production by PBMC were 3.92 ng/ml, 31.3 ng/ml, and 1.05 ng/ml, for IL-1beta, IL-6, and TNF-alpha, respectively. There were modest correlations between cytokine production and cross-sectional BMD, ranging from r = -0.30 to r = -0.13. Trends of greater spinal bone loss were observed in women with "high" (>/=75th percentile) cytokine production of stimulated IL-1beta and IL-6 (IL-1beta: "high" = -1.56% +/- 0.70 versus "low" (<75th percentile) = -0.56% +/- 0.35, P = 0.21). In contrast, greater annual gains in femoral neck BMD were observed in those with high cytokine production of IL-1beta and IL-6 (IL-1beta: high = 3.39% +/- 1.16 versus low = -0. 85 +/- 0.58, P = 0.002). There was no association between stimulated TNF production and annual change in BMD. In this population of healthy premenopausal women, the relationship between cytokine production by PBMC and the rate of change in BMD was significantly different for the lumbar spine and femoral neck, possibly reflecting differences in the proportion of trabecular and cortical bone at these sites.

Adult↗
PubMed1998

Do urinary oestrogen metabolites predict breast cancer? Guernsey III cohort follow-up.

This is the first prospective study of urinary measures of the two major competing pathways of oestrogen metabolism, 16alpha-hydroxyoestrone (16alpha-OHE1) and 2-hydroxyoestrone (2-OHE1), in relation to incident breast cancer risk. Experimental and case-control study results suggest that metabolism favouring the more oestrogenic 16alpha-OHE1 pathway may be linked to higher breast cancer risk. Women aged 35 and older from Guernsey (n = 5104) were surveyed in 1977-85 and have been continuously monitored for breast cancer and mortality up to the present (Guernsey III, Imperial Cancer Research Fund). Incident cases of breast cancer were matched to three control subjects for comparison of urinary oestrogen metabolite levels measured by enzyme immunoassay (EIA) in spot urine samples collected at baseline and stored frozen for up to 19 years. Consistent with case-control study results, post-menopausal (but not premenopausal) women at baseline who went on to develop breast cancer showed about a 15% lower 2:16alpha-OHE1 ratio than matched control subjects. Further, subjects with metabolite ratios in the highest tertile of 2:16alpha-OHE1 had about a 30% lower risk than women with ratios in the lowest two-thirds, although results were not statistically significant (OR = 0.71, 95% CI = 0.29-1.75). It is of potential importance that, in contrast to most risk factors for breast cancer, such as late age at first birth, oestrogen metabolism appears to be modifiable via diet and exercise, offering women the possibility of lowering breast cancer risk through non-pharmacological measures, although this remains to be tested.

Adult↗
PubMed1998

Sagittal diameter in comparison with single slice CT as a predictor of total visceral adipose tissue volume.

BACKGROUND: Abdominal obesity has an important biological and epidemiological relationship to disease. The gold standard for measurement of visceral adipose tissue (VAT) is assessment by computerized tomography (CT) or magnetic resonance imaging (MRI), but because of simplicity and ease in collection, anthropometric variables are a desirable alternative to estimate VAT. OBJECTIVE: To compare the abilities of a single slice CT scan through the L4-L5 interspace (L4-L5 VAT), sagittal diameter, and body mass index (BMI) to estimate total volume VAT. Total volume VAT (the gold standard) was measured by total abdominal CT scanning, with a mean of 42 CT slices per patient. Estimation of VAT in subjects of similar body size was emphasized. DESIGN: Retrospective study of subjects undergoing complete abdominal and pelvic CT scanning for clinical reasons. SUBJECTS: 40 subjects (20 men and 20 women) mean age 56.5y, with a balanced selection for BMI < 27 and > 27. RESULTS: In univariate regression models, L4-L5 VAT explained the largest proportion of the variance in total VAT (R2=0.87 [P<0.001]), though age (R2=0.11 [P=0.04]), BMI (R2=0.37 [P<0.001]), and sagittal diameter (R2=0.50 [P < 0.001]) were also statistically significantly related to total VAT. When limited to individuals with a BMI > or= 27 however, L4-L5 VAT explained a large proportion of the variance in total VAT (R2=0.87 [P < 0.001]) whereas sagittal diameter was only of borderline significance (R2=0.20 [P=0.06]), and BMI was not associated with total VAT (R2=0.04 [P=NS]). In multiple regression analyses, L4-L5 VAT area explained a large proportion of the variance (0.84-0.90), and once in the model, BMI, sagittal diameter, and age did not additionally contribute significantly to the explained variance in total VAT. CONCLUSIONS: Abdominal sagittal diameter is poorly correlated to total VAT for men and women with a BMI > 27. Within a 2 cm range of sagittal diameter, there is nearly a three-fold variability in total VAT.

Adipose Tissue↗
PubMed1998

John Henryism and blood pressure among Nigerian civil servants.

STUDY OBJECTIVE: Among urban Nigerian civil servants, higher socioeconomic status is related to increased blood pressure. In the United States, the relation between increased blood pressure and low socioeconomic status or low level of education has been found to be potentiated by high effort active coping (John Henryism) among African-Americans. Thus, the potentiating effect of high effort active coping as measured by the John Henryism Active Coping Scale, on socioeconomic status, as measured by job grade, was considered in relation to blood pressure in a Nigerian civil servant population. DESIGN: The influence of John Henryism on the association between educational level or socioeconomic status and increased blood pressure was examined during a comprehensive blood pressure survey. John Henryism refers to a strong behavioural predisposition to actively cope with psychosocial environmental stressors. SETTING: Benin City, Nigeria. PARTICIPANTS: Nigerian civil servant sample of 658 adults, aged 20 to 65 years. MAIN RESULTS: Among those with high John Henryism scores of upper socioeconomic status, whether measured by education level or job grade, there was a trend toward higher systolic and diastolic blood pressures, adjusted for age and body mass index, in men and women, though not statistically significant. CONCLUSIONS: This trend is consistent with recent findings of increased blood pressure among women and African-Americans with high John Henryism and high status jobs.

Adaptation, Psychological↗
PubMed1998

Relationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study.

BACKGROUND AND PURPOSE: We determined the relationship between apolipoprotein (Apo)E, MRI, and low cognitive scores. METHODS: The relationship between age, education, ApoE genotype, MRI examination of the brain, subclinical and clinical cardiovascular disease, and low (<80) score on the Modified Mini-Mental State Examination (3MSE, as modified by Teng and Chui) was evaluated for 3469 black and white participants in the Cardiovascular Health Study (CHS) in years 5 and 6 of the study. The participants were followed for up to 3 years. RESULTS: The prevalence of scores <80 in years 5 and 6 of the CHS was 8.2% for participants without and 20.4% for those with prior history of stroke. Age, race, and education were important determinants of low 3MSE scores. The prevalence of ApoE-4 (odds ratio [OR], 1.6 [1.1 to 2.1]) was directly related to scores <80, as was high ventricular volume (OR, 1.6 [1.2 to 2.3]), high white matter grade (OR, 1.4 [1.1 to 1.9]), and infarctlike lesions (OR, 1.6 [1.2 to 2.1]) on the MRI in the multivariate analysis. A five-point or greater decline in scores over up to 3 years was more often observed for participants with low 3MSE scores at year 5, at older ages, with lower education, and experiencing incident stroke (OR, 3.6 [1.2 to 10.6]), ApoE-4 genotype (OR, 1.8 [1.4 to 2.3]), and with MRI findings of high ventricular volume (OR, 2.0 [1.5 to 2.7]), and infarctlike lesions (OR, 1.2 [0.9 to 1.5]). CONCLUSIONS: These results demonstrate that vascular changes on MRI, measures of brain atrophy, ApoE-4, and age, education, and race are associated with low cognitive scores among older individuals. The MRI of the brain provides valuable information related to cognitive tests and decline over time. The potential exists for using MRI measurements to identify high-risk individuals for dementia and to test potential interventions to reduce the risk of dementia.

Aged↗
PubMed1998

Subclinical atherosclerosis in relation to hysterectomy status in black women.

BACKGROUND AND PURPOSE: This study was designed to investigate whether black women who underwent hysterectomy only (n = 59) or hysterectomy plus bilateral oophorectomy (n=25) were at increased risk of subclinical carotid atherosclerosis compared with black women who underwent natural menopause (n = 54). The effects of both surgery and menopausal status were evaluated. METHODS: Women aged 34 to 58 years were recruited from the Pittsburgh, Pa, area. Postmenopausal status was defined as a serum follicle-stimulating hormone level of >30 mIU/mL. Carotid duplex scans were performed to assess the degree of focal plaque. RESULTS: Among premenopausal women, focal plaque was present in 20% of nonhysterectomized versus 49% of hysterectomized-only women (P=.004). Among postmenopausal women, plaque was present in 69% of nonhysterectomized women, 86% of women with hysterectomy only, and 48% of women with oophorectomy and hysterectomy (P=.056). Among postmenopausal women, hormone replacement therapy was used by 23% of women who had undergone natural menopause, 0% of women with hysterectomy only, and 36% of women with oophorectomy and hysterectomy. The prevalence of plaque was 33% among hormone replacement therapy users versus 73% among nonusers (P=.014). In multivariate analysis, independent associations with the presence of at least 1 plaque were postmenopausal status and hysterectomy only. CONCLUSIONS: These data suggest that black women who undergo hysterectomy without oophorectomy may be at higher risk of subclinical carotid atherosclerosis than black women who undergo natural menopause or hysterectomy plus oophorectomy.

Adult↗