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Biomedical subjects

L H Kuller

Publications and source records attributed to L H Kuller.

At least 145 records · Page 8Linked to original sources
PubMed1997

Apolipoprotein E phenotype, arterial disease, and mortality among older women: the study of osteoporotic fractures.

This study is an investigation of the relationship between apolipoprotein E (apoE) phenotype, arterial disease, and mortality in a group of women (n = 1,751) aged 65 years and older enrolled in the Study of Osteoporotic Fractures. Crude mortality rates were highest among women with the 4-3 and 4-4 phenotypes but age-adjusted mortality showed no statistically significant variations across the phenotype groups. Using multivariate analysis, the mortality experience of women with 4-3 or 4-4 apoE phenotypes was compared to that of women with the 3-3 phenotype: no significant excess total mortality was found [relative risk (RR) = 1.2, 95% confidence interval (CI) 0.8, 1.8] among women with the epsilon 4 allele. Similarly, neither cardiovascular (RR = 0.9. 95% CI 0.5, 1.8) nor cancer (RR = 1.5, 95% CI 0.8, 2.8) mortality rates were significantly different in this group of women. Inclusion of cholesterol levels in the regression models did not change the relative mortality risks. Among women 65-69 year of age epsilon 4 was associated with an approximate doubling of RR for death due to both cardiovascular disease and cancer. No association was found between apoE phenotype and the presence of lower extremity arterial disease (defined as an ankle/arm index of 0.9 or less). These results suggest that women with the epsilon 4 who survive to age 70 years or beyond have a life expectancy that is similar to that for women homozygous for the 3 allele who comprise the majority of the population.

Aged↗
PubMed1997

The epidemiology of quantitative ultrasound: a review of the relationships with bone mass, osteoporosis and fracture risk.

Quantitative ultrasound (QUS) is a simple, inexpensive and non-invasive measure of bone which has been used in research settings for the prediction of osteoporosis. This review summarizes the current status of the epidemiology of QUS analysis, including its relationship with bone mineral density (BMD), risk of osteoporotic fracture and risk factors for osteoporosis. Although only moderately correlated with BMD, QUS appears to be as strong a predictor of osteoporotic fracture as BMD and may predict fracture independent of BMD. Risk factors for low QUS, including age, menopause, body composition and physical inactivity, seem to parallel those of low BMD. More longitudinal research is needed to confirm the clinical utility of QUS and more experimental and population-based studies are needed to determine whether the etiology of low QUS values is different from that of low bone mass.

Bone Density↗
PubMed1997

Dietary fat and chronic diseases: epidemiologic overview.

The association between dietary fat consumption and risk of cancer, especially colon, breast, prostate, and ovary cancer, has been debated for many years. Ecologic studies over the past 30 years have demonstrated the correlation of greater dietary fat intake with higher mortality due to various cancers. Migrant studies also have shown that increased fat consumption may be associated with increased risk of cancer. Specific saturated fatty acids raise blood cholesterol levels and, thereby, increase the risk of atherosclerosis. Greater fat, intake is a major cause of obesity and hypertension, diabetes, and gallbladder disease. Higher fat intake may heighten the risk of breast cancer directly through increased blood estrogen levels and/or secondarily through increased obesity. The critical experimental studies to determine the effects of a low-fat diet on disease risk have not been completed, but reducing fat in the US diet has the potential to decrease morbidity and mortality substantially.

Animals↗
PubMed1997

Molecular epidemiology of hematological neoplasms--present status and future directions.

The field of molecular epidemiology, using modern epidemiological approaches and taking the advantage of the advances in molecular biology can provide new tools for the exploration of etiological determinants, either environmental or hereditary, in the development of hematological neoplasms. It is now possible to identify some host susceptibility characteristics, to measure the effective dose of exposure, and to identify early, pre-clinical biological effects, using sensitive and specific biomarkers. The significant variation in the incidence of hematological neoplasms in different geographical areas, races, and age groups, the high rates of familial aggregation in certain populations, the involvement of protooncogenes and tumor suppressor genes in the development of hematological neoplasms, as well as of many environmental agents such as chemicals, radiation, and viruses, support the important role of molecular epidemiology in the investigation of the development of hematological neoplasms.

Animals↗
PubMed1997

The next stage: molecular epidemiology.

The traditional approach in epidemiology of relating exposure to an environmental agent such as a drug or infective agent has been to measure an overall risk (i.e., average and then "adjust risk for demographic variables and other confounders"). An attempt is sometimes made to define a "susceptible" subgroup. The analyses are usually based on good statistical methodology rather than an understanding of the interaction of body of host and agent. A twofold risk for 1000 exposed versus nonexposed people could be an average twofold risk for all 1000 exposed or a 20-fold risk for 100 exposed individuals (i.e., a drug-host interaction). Clearly, finding the 100 individuals with a 20-fold risk has much greater clinical importance than a twofold risk for 1000 people. The world of epidemiology may be changing-we may soon be able to define risk based on genetic susceptibility, at least sometimes.

Apolipoproteins E↗
PubMed1997

Lung cancer mortality after 16 years in MRFIT participants in intervention and usual-care groups. Multiple Risk Factor Intervention Trial.

PURPOSE: The Multiple Risk Factor Intervention Trial (MRFIT), a randomized clinical trial for the primary prevention of coronary heart disease, enrolled 12,866 men (including 8194 cigarette smokers) aged 35-57 years at 22 clinical centers across the United States. Participants were randomized either to special intervention (SI), which included an intensive smoking cessation program, or to usual care (UC). After 16 years of follow-up, lung cancer mortality rates were higher in the SI than in the UC group. Since rates of smoking cessation in SI were higher than those for UC for the 6 years of the trial, and since risk of lung cancer mortality is known to decline with smoking cessation, these results were unexpected. The purpose of the present study was to investigate hypotheses that could explain the higher observed lung cancer mortality rates in the SI as compared with the UC group. METHODS: Analytic methods were employed to determine whether SI and UC participants differed either in baseline characteristics or in characteristics that changed during the trial and to determine whether these differences could explain the higher rates of lung cancer mortality among SI as compared to UC participants. Rates of mortality from coronary heart (CHD) were examined to explore the possibility that prevention of CHD death may have contributed to greater mortality due to lung cancer in the SI group. RESULTS: From randomization through December 1990, 135 SI and 117 UC participants died from lung cancer. The relative difference between the SI and U groups adjusted for age and number of cigarettes smoked per day, was 1.17 (95% CI:0.92-1.51). The greatest difference between the SI and UC groups in lung cancer mortality rates occurred among the heaviest smokers at baseline who did not achieve sustained smoking cessation by year 2. In this group the rates of death from CHD were approximately the same among the SI and UC subjects. No differences in baseline characteristics were found between SI and UC smokers who did not achieve sustained cessation by year 2, and there were no differences in follow-up characteristics between the two study groups that could explain the difference in lung cancer mortality. CONCLUSIONS: None of the hypotheses proposed to explain the unexpected higher rates of lung cancer mortality among SI as compared with UC subjects were sustained by the data. Thus we conclude that the difference observed is due to chance, and that a longer period of sustained smoking cessation plus follow-up is necessary to detect a reduction in lung cancer mortality as a result of smoking cessation intervention in a randomized clinical trial.

Adult↗
PubMed1997

Trp64Arg substitution in the beta 3-adrenergic receptor does not relate to body weight in healthy, premenopausal women.

OBJECTIVE: To examine the contribution of the substitution of arginine for tryptophan at amino acid position 64 (Trp64Arg) of the beta 3-adrenergic receptor to body weight and weight-related factors in healthy, premenopausal women. SUBJECTS: Five hundred and five healthy, premenopausal women 44-50 y, body mass index (BMI) 20-40 kg/m2. MEASUREMENTS: Subjects were genotyped for the Trp64Arg substitution using restriction fragment length polymorphism (RFLP) analysis. Measurements for weight and weight-related factors (for example, weight, waist-hip ratio, lipid levels) were also taken. RESULTS: Two women were homozygous Arg/Arg, 75 women were heterozygous Trp/Arg, and 428 women were homozygous Trp/Trp. The frequency of the Arg substitution was 0.078. When subjects with and without the arginine substitution were compared, no significant differences were found on measures of weight or weight-related risk factors. CONCLUSION: The results confirm previous studies suggesting that the Trp64Arg substitution of the beta 3-adrenergic receptor is not related to weight or weight-related phenotypes in healthy, premenopausal women.

Alleles↗
PubMed1997

Are life stress and social support related to parity in women?

Although an increased risk of coronary heart disease has been demonstrated among women with high gravidity/parity, the mechanism by which this association may be mediated is unclear. One possible pathway that has been suggested is that pregnancy and child rearing may result in changes in factors such as stress or lifestyle. This hypothesis was tested in a sample of 541 middle-aged women who participated in a prospective study of the effects of menopause on behavioral and biological cardiovascular risk factors. Married women generally reported less chronic stress, less perceived stress, and more structural support than did unmarried women. However, the findings in this study indicated no consistent relationship between parity and stress or parity and social support in this group of middle-aged women. Only unmarried women with more children reported a higher number of life events than did women with fewer children.

Adult↗
PubMed1997

Women's health as a paradigm for understanding factors that mediate disease.

Women's health research provides an opportunity to focus on the mechanisms underlying health and disease in both men and women. We propose that differences in risk between men and women and among individual women are primarily determined by biologic factors, such as sex steroid hormone metabolism, anatomy, immunologic function, genetic influences, and the effects of reproduction, interacting with external influences, such as psychologic development, sociocultural environment, and economic status. We provide examples whereby a comparison of disease frequencies between men and women and among women allows a focus on underlying mechanisms of disease. We then demonstrate the importance of posing questions about the genesis of differences in disease frequency.

Breast Neoplasms↗
PubMed1997

Thyroid function and perimenopausal lipid and weight changes: the Thyroid Study in Healthy Women (TSH-W).

We designed a prospective observational trial to study the relationship of thyroid function to cholesterol and weight changes at menopause. Subjects were participants in the ongoing Healthy Women Study, a prospective study of cardiovascular risk factor change through menopause. Healthy premenopausal women were recruited from a random sample of licensed drivers in selected ZIP codes of Allegheny County, Pennsylvania. Participants had to be 42-50 years of age, have menstruated within the last 3 months, not have had surgical menopause, have diastolic blood pressure < 100 mm Hg, and not be taking medications (including insulin, estrogen, lipid-lowering drugs, or thyroid or antihypertensive medications) at the baseline examination. The substudy included three groups of women who were premenopausal at baseline and were categorized according to change noted at follow-up regarding menopausal status and use of hormone replacement therapy (HRT). The groups comprised 95 women who remained premenopausal, 96 postmenopausal women not on HRT, and 61 postmenopausal women using HRT. The main outcome measures were baseline and follow-up measurements for serum levels of thyroid-stimulating hormone (TSH), thyroid peroxidase, and thyroglobulin, as well as serum cholesterol, total high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol, height, and weight. Covariates included cigarette smoking and alcohol intake. The prevalence of thyroid antibodies in this healthy population was high at both time points (range 27%-31%) and did not differ by menopausal status. The presence of thyroid antibodies was associated with increased TSH concentration. Women with antibodies at both time points had lower levels of total and LDL cholesterol compared with those with no antibodies, significant only for those women who remained premenopausal during the follow-up period. Thyroid function during menopause in this healthy population is unlikely to account for the observed changes in levels of serum lipoprotein and body weight. The presence of thyroid antibodies may be associated with lower total and LDL cholesterol, possibly through an underlying inflammatory disorder.

Adult↗
PubMed1997

Efficacy of nonpharmacologic interventions in adults with high-normal blood pressure: results from phase 1 of the Trials of Hypertension Prevention. Trials of Hypertension Prevention Collaborative Research Group.

Phase 1 of the Trials of Hypertension Prevention was conducted in 2182 adults, aged 35-54 y, with diastolic blood pressure of 80-89 mm Hg to test the feasibility and blood pressure-lowering effects of seven nonpharmacologic interventions (weight loss, sodium reduction, stress management, and supplementation with calcium, magnesium, potassium, and fish oil). At 6 and 18 mo, weight loss and sodium reduction were well-tolerated and produced significant declines in systolic and diastolic blood pressures (-2.9/-2.4 and -2.1/-1.2 mm Hg for weight loss and sodium reduction, respectively, at 18 mo). None of the other interventions lowered blood pressure significantly at either the 6- or 18-mo follow-up visits. These results suggest that both weight loss and sodium reduction provide an effective means to prevent hypertension. The long-term effects of both of these interventions are being tested in phase 2 of the trial.

Adult↗
PubMed1997

The importance of pulsatile components of hypertension in predicting carotid stenosis in older adults.

OBJECTIVE: To evaluate pulsatile components of the blood pressure as risk markers for carotid stenosis in isolated systolic hypertension. DESIGN: Duplex scans with Doppler measures of the blood flow velocity were used to diagnose carotid stenosis in 187 participants in the Systolic Hypertension in the Elderly Program and in 187 normotensive and mildly hypertensive control subjects. METHODS: The systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure, and mean arterial pressure (MAP) were selected as independent variables. A logistic regression model for carotid stenosis was used to adjust for potentially confounding risk factors. Serial models, each containing single or double blood pressure variables, were run to compare risk markers for carotid stenosis. Receiver operating characteristic curves were compared to assess the predictive value of each model. RESULTS: In the multivariate analysis, both the SBP (P = 0.005) and the pulse pressure (P < 0.001) were predictive of carotid stenosis, but the DBP and MAP were not. However, when either the SBP or the pulse pressure was included in the model, the DBP was associated negatively with carotid stenosis (P < 0.001 and P = 0.023, respectively). An increased pulse pressure and a decreased DBP were independent risk markers for carotid stenosis. Comparison of receiver operating characteristic curves indicated that the pulse pressure had superior predictive value to the SBP (P = 0.034). CONCLUSIONS: The pulse pressure is the single best predictor of carotid stenosis. There is a negative correlation between the DBP and carotid stenosis for subjects with isolated systolic hypertension, but this can be demonstrated only after one has stratified for the SBP or for the pulse pressure. Thus, the pulsatile components of the blood pressure, increased pulse pressure and decreased DBP, are the most sensitive risk markers for the diagnoses of carotid stenosis.

Adult↗
PubMed1997

Mortality over four years in SHEP participants with a low ankle-arm index.

OBJECTIVES: To assess the risk of total and cardiovascular mortality in older adults with systolic hypertension and with a low ankle-arm index (AAI) as a marker of subclinical peripheral arterial disease (PAD). DESIGN: Prospective observational study PARTICIPANTS: A subgroup of 1537 participants in the Systolic Hypertension in the Elderly Program (SHEP) were screened for lower extremity arterial disease using the AAI. Participants were evaluated at 4 years to determine vital status and cause of death. Total and cardiovascular disease (CVD) mortality rates were assessed in relationship to clinical CVD at baseline, cardiovascular risk factors and the presence of a low AAI (subclinical PAD). RESULTS: Total mortality rates increased as the AAI decreased in those with and without clinical CVD at baseline. In those without clinical CVD at baseline, the presence of an AAI < or = .9 was associated with an age-adjusted relative risk (RR) of 3.00 for total mortality in men and 2.67 in women. Results were similar for CVD mortality and persisted after adjustment for cardiovascular risk factors including the presence of an abnormal electrocardiogram. CONCLUSIONS: A low ankle arm-index predicted a two to three-fold increase in total and cardiovascular mortality in older adults with systolic hypertension of risk for incident cardiovascular disease. In this study of older adults with systolic hypertension, 19.7% of the participants had subclinical PAD. Risk factor modification could be targeted to older adults based on markers of asymptomatic atherosclerosis.

Aged↗
PubMed1997

Homocyst(e)ine and risk of cardiovascular disease in the Multiple Risk Factor Intervention Trial.

A nested case-control study was undertaken involving men participating in the Multiple Risk Factor Intervention Trial (MRFIT). Serum samples from 712 men, stored for up to 20 years, were analyzed for homocyst(e)ine. Cases involved nonfatal myocardial infarctions (MIs), identified through the active phase of the study, which ended on February 28, 1982, and deaths due to coronary heart disease (CHD), monitored through 1990. The nonfatal MIs occurred within 7 years of sample collection, whereas the majority of CHD deaths occurred more than 11 years after sample collection. Mean homocyst(e)ine concentrations were in the expected range and did not differ significantly between case patients and control subjects: MI cases, 12.6 mumol/L; MI controls, 13.1 mumol/L; CHD death cases, 12.8 mumol/L; and CHD controls, 12.7 mumol/L. Odds ratios versus quartile 1 for CHD deaths and MIs combined were as follows: quartile 2, 1.03; quartile 3, 0.84; and quartile 4, 0.92. Thus, in this prospective study, no association of homocyst(e)ine concentration with heart disease was detected. Homocyst(e)ine levels were weakly associated with the acute-phase protein (C-reactive protein). These results are discussed with respect to the suggestion that homocyst(e)ine is an independent risk factor for heart disease.

Adult↗
PubMed1997

Lifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects.

Blood levels of C-reactive protein (CRP), a marker of inflammation, are related to cardiovascular disease risk. To determine cross-sectional correlates in the elderly, we measured CRP in 400 men and women older than 65 years and free of clinical cardiovascular disease at baseline as part of the Cardiovascular Health Study. Only 2% of the values were greater than 10 mg/L, the cut-point usually used to identify inflammation. CRP levels appeared tightly regulated, since there were strong bivariate correlations between CRP and the following: inflammation-sensitive proteins such as fibrinogen (r = .52); measures of fibrinolysis such as plasmin-antiplasmin complex (r = .23); pack-years of smoking (r = .30); and body mass index (r = .24; all P values < or = .001). The association with pack-years was independent of the length of time since cessation of smoking. CRP levels were also associated with coagulation factors VIIc, IXc, and Xc; HDL cholesterol (negative) and triglyceride; diabetes status; diuretic use; ECG abnormalities; and level of exercise. Because of effect modification, two multiple linear regression prediction models were developed for CRP, one each for never smokers and ever smokers. An a priori physiologic model was used to guide these analyses, which disallowed the use of other inflammation-sensitive variables such as fibrinogen. In never smokers, the independent predictors were body mass index (+), diabetes status (+), plasmin-antiplasmin complex (+), and the presence of ECG abnormalities (+); this model predicted 15% of the CRP population variance. In ever smokers, the predictors were body mass index (+), plasmin-antiplasmin complex (+), pack-years of smoking (+), HDL cholesterol (-), and ankle-arm blood pressure index (-); this model predicted 42% of the population variance. We conclude that levels of CRP in the healthy elderly are tightly regulated and reflect lifetime exposure to smoking as well as level of obesity, ongoing level of fibrinolysis, diabetes status, and level of subclinical atherothrombotic disease. Moreover, exposure to smoking affects the relation of CRP to these other factors.

Aged↗
PubMed1997

Relationship of C-reactive protein to risk of cardiovascular disease in the elderly. Results from the Cardiovascular Health Study and the Rural Health Promotion Project.

Markers of inflammation, such as C-reactive protein (CRP), are related to risk of cardiovascular disease (CVD) events in those with angina, but little is known about individuals without prevalent clinical CVD. We performed a prospective, nested case-control study in the Cardiovascular Health Study (CHS; 5201 healthy elderly men and women). Case subjects (n = 146 men and women with incident CVD events including angina, myocardial infarction, and death) and control subjects (n = 146) were matched on the basis of sex and the presence or absence of significant subclinical CVD at baseline (average follow-up, 2.4 years). In women but not men, the mean CRP level was higher for case subjects than for control subjects (P < or = .05). In general, CRP was higher in those with subclinical disease. Most of the association of CRP with female case subjects versus control subjects was in the subgroup with subclinical disease; 3.33 versus 1.90 mg/L, P < .05, adjusted for age and time of follow-up. Case-control differences were greatest when the time between baseline and the CVD event was shortest. The strongest associations were with myocardial infarction, and there was an overall odds ratio for incident myocardial infarction for men and women with subclinical disease (upper quartile versus lower three quartiles) of 2.67 (confidence interval [CI] = 1.04 to 6.81), with the relationship being stronger in women (4.50 [CI = 0.97 to 20.8]) than in men (1.75 [CI = 0.51 to 5.98]). We performed a similar study in the Rural Health Promotion Project, in which mean values of CRP were higher for female case subjects than for female control subjects, but no differences were apparent for men. Comparing the upper quintile with the lower four, the odds ratio for CVD case subjects was 2.7 (CI = 1.10 to 6.60). In conclusion, CRP was associated with incident events in the elderly, especially in those with subclinical disease at baseline.

Aged↗
PubMed1997

Prevalence and determinants of carotid atherosclerosis in healthy postmenopausal women.

BACKGROUND AND PURPOSE: Subclinical atherosclerosis in the carotid arteries can be assessed noninvasively with B-mode ultrasound. Few studies have included enough younger postmenopausal women to examine risk factors specific to this group that were related to subclinical carotid atherosclerosis. METHODS: A subgroup of 200 participants of the Healthy Women Study underwent B-mode ultrasound of the carotid arteries. Intima-media thickness (IMT) and focal plaque were assessed in each carotid artery. Data regarding risk factors, including blood pressure parameters, lipid values, body mass index, smoking history, and hormone status, were collected at three separate time points (before menopause, 1 year after menopause, and 5 or 8 years after menopause). RESULTS: The mean IMT was 0.76+/-0.11 mm, and 50% of the population had at least one focal plaque. Smoking had the strongest association with the presence of plaque. Women who smoked at the time of the ultrasound evaluation had five times the odds of having at least one focal plaque compared with women who had never smoked (95% confidence interval, 2.0 to 13.0; P < .01). After we controlled for age and years after menopause, premenopausal values of pulse pressure (P < or = .05), LDL cholesterol (P < or = .05), and a history of smoking (P < or = .01) were independently predictive of plaque. Premenopausal values of triglycerides, pulse pressure, and ever smoking were independently related to average IMT after we controlled for age and years after menopause. CONCLUSIONS: This study has provided valuable information about the prevalence of carotid atherosclerosis and the risk factors related to carotid atherosclerosis in a group of healthy postmenopausal women.

Arteriosclerosis↗