Occupation and the risk of adult glioma in the United States.

OBJECTIVE: Previous studies have observed increased glioma incidence associated with employment in the petroleum and electrical industries, and in farming. Several other occupations have also been associated with increased risk, but with inconsistent results. We evaluated associations between occupational title and glioma incidence in adults. METHODS: Cases were 489 patients with glioma diagnosed from 1994 to 1998 at three United States hospitals. Controls were 799 patients admitted to the same hospitals for non-malignant conditions. An experienced industrial hygienist grouped occupations that were expected to have similar tasks and exposures. The risk of adult glioma was evaluated for those subjects who ever worked in an occupational group for at least six months, those who worked longer than five years in the occupation, and those with more than ten years latency since starting work in the occupation. RESULTS: Several occupational groups were associated with increased glioma incidence for having ever worked in the occupation, including butchers and meat cutters (odds ratio [OR] = 2.4; 95% confidence limits [CL]: 1.0, 6.0), computer programmers and analysts (OR = 2.0; 95% CL: 1.0, 3.8), electricians (OR = 1.8; 95% CL: 0.8, 4.1), general farmers and farmworkers (OR = 2.5; 95% CL: 1.4, 4.7), inspectors, checkers, examiners, graders, and testers (OR = 1.5; 95% CL: 0.8, 2.7), investigators, examiners, adjustors, and appraisers (OR = 1.7; 95% CL: 0.8, 3.7), physicians and physician assistants (OR = 2.4; 95% CL: 0.8, 7.2), and store managers (OR = 1.6; 95% CL: 0.8, 3.1), whereas occupation as a childcare worker was associated with decreased glioma incidence (OR = 0.4; 95% CL: 0.2, 0.9). These associations generally persisted when the subjects worked longer than five years in the occupation, and for those with more than ten years latency since starting to work in the occupation. CONCLUSIONS: This is our first analysis of occupation and will guide future exposure-specific assessments.

Cellular-telephone use and brain tumors.

BACKGROUND: Concern has arisen that the use of hand-held cellular telephones might cause brain tumors. If such a risk does exist, the matter would be of considerable public health importance, given the rapid increase worldwide in the use of these devices. METHODS: We examined the use of cellular telephones in a case-control study of intracranial tumors of the nervous system conducted between 1994 and 1998. We enrolled 782 patients through hospitals in Phoenix, Arizona; Boston; and Pittsburgh; 489 had histologically confirmed glioma, 197 had meningioma, and 96 had acoustic neuroma. The 799 controls were patients admitted to the same hospitals as the patients with brain tumors for a variety of nonmalignant conditions. RESULTS: As compared with never, or very rarely, having used a cellular telephone, the relative risks associated with a cumulative use of a cellular telephone for more than 100 hours were 0.9 for glioma (95 percent confidence interval, 0.5 to 1.6), 0.7 for meningioma (95 percent confidence interval, 0.3 to 1.7), 1.4 for acoustic neuroma (95 percent confidence interval, 0.6 to 3.5), and 1.0 for all types of tumors combined (95 percent confidence interval, 0.6 to 1.5). There was no evidence that the risks were higher among persons who used cellular telephones for 60 or more minutes per day or regularly for five or more years. Tumors did not occur disproportionately often on the side of head on which the telephone was typically used. CONCLUSIONS: These data do not support the hypothesis that the recent use of hand-held cellular telephones causes brain tumors, but they are not sufficient to evaluate the risks among long-term, heavy users and for potentially long induction periods.

Treatment patterns and distribution of low-density lipoprotein cholesterol levels in treatment-eligible United States adults.

To estimate the fraction of United States (U.S.) adults who are eligible for treatment to reduce elevated low-density lipoprotein (LDL) cholesterol levels based on Adult Treatment Panel II (ATP II) guidelines and the percent reduction in LDL cholesterol required by those who qualify for treatment, we analyzed data on 7,423 respondents to Phase 2 of the third National Health and Nutrition Examination Survey (NHANES III) administered between 1991 and 1994. Approximately 28% of the U.S. adult population aged > or = 20 years is eligible for treatment based on ATP II guidelines. Eighty-two percent of adults with coronary heart disease are not at their target LDL cholesterol level of 100 mg/dl. Of those eligible for treatment, 65% report that they receive no treatment. Overall, 40% of people who qualify for drug therapy require an LDL cholesterol reduction of > 30% to meet their ATP II treatment goal. Approximately 75% of those with coronary heart disease who qualify for drug therapy require an LDL cholesterol reduction of >30%. Although elevated LDL cholesterol levels can be treated, prevalence rates in the U.S. adult population remain high. Several recent studies indicate that a considerable percentage of people treated with drug therapy do not reach their treatment goals. The findings in this study provide at least a partial explanation for why many patients receiving therapy do not reach their treatment goals: they require a larger reduction in LDL cholesterol than many therapies can provide.

Cancer incidence among an HIV-infected cohort. Pulmonary Complications of HIV Infection Study Group.

Malignancies, particularly Kaposi's sarcoma and non-Hodgkin's lymphoma (NHL), are associated with human immunodeficiency virus (HIV) infection. Cancer incidence among 1,073 asymptomatic HIV-infected individuals from the Pulmonary Complications of HIV Infection Study cohort, persons from six states followed from 1988 to 1994, was examined. Total cancer incidence was 3.99/100 person-years; for Kaposi's sarcoma, incidence was 2.64 cases/100 person-years, and for NHL, it was 1.18 cases/100 person-years. Total cancer (n = 156 cases) was higher among nonblacks than among blacks (rate ratio = 2.8, 95% confidence interval 1.3-6.1), with similar results for Kaposi's sarcoma and NHL. The rate of lung cancer (n = 5) among white, homosexual/bisexual males was 0.18 per 100 person-years, suggesting a high risk of lung cancer.

Incidence of tuberculosis in the United States among HIV-infected persons. The Pulmonary Complications of HIV Infection Study Group.

BACKGROUND: The resurgence of tuberculosis in the United States is largely linked to the human immunodeficiency virus (HIV) epidemic. Despite this link, the epidemiology of tuberculosis and preventive strategies in patients infected with HIV are not completely understood. OBJECTIVES: To determine the incidence and predictors of tuberculosis in HIV-infected persons. DESIGN: Prospective, multicenter cohort study. SETTING: Community-based cohort of persons with and without HIV infection at centers in the eastern, midwestern, and western United States. PARTICIPANTS: 1130 HIV-seropositive patients without AIDS who were followed for a median of 53 months (814 homosexual men, 261 injection drug users, and 55 women who had acquired HIV through heterosexual contact). MEASUREMENTS: Delayed hypersensitivity response to purified protein derivative (PPD) tuberculin and mumps antigen, CD4 T-lymphocyte counts, and frequency of tuberculosis. RESULTS: 31 HIV-seropositive patients developed tuberculosis (0.7 cases per 100 person-years [95% CI, 0.5 to 1.0]). The most important demographic risk factor was location (adjusted risk ratio for eastern compared with midwestern and western United States, 4.1 [CI, 2.0 to 8.4]). Tuberculosis occurred more frequently in persons with CD4 counts of less than 200 cells/mm3 (1.2 cases per 100 person-years [CI, 0.7 to 1.9]) than in those with higher counts (0.5 cases per 100 person-years [CI, 0.3 to 0.8]). The rate of tuberculosis was highest among tuberculin converters (5.4 cases per 100 person-years [CI, 1.1 to 15.7]), lower among patients who were PPD positive at first testing (4.5 cases per 100 person-years [CI, 1.6 to 9.7]), and lowest among patients who remained PPD negative (0.4 cases per 100 person-years [CI, 0.2 to 0.7]). Tuberculosis was not reported among persons who had PPD reactions of 1 to 4 mm. Compared with that of patients who tested positive for mumps, the risk for tuberculosis of those who tested negative was increased about sevenfold if they were PPD positive (P < 0.03) and fourfold if they were PPD negative (P < 0.02). CONCLUSIONS: Incidence of tuberculosis was higher in the eastern United States, in patients with CD4 counts of less than 200 cells/mm3, and in PPD-positive patients. Analysis of tuberculin reaction size supports the current interpretive criteria of the Centers for Disease Control and Prevention. Nonreactivity to mumps antigen indicated increased risk for tuberculosis independent of PPD response.

Isoniazid-related fatal hepatitis.

To describe the clinical and demographic characteristics of fatal hepatitis due to single-drug isoniazid preventive therapy for tuberculosis, we did a survey of cases from state health departments, published case reports, and reports to the Centers for Disease Control and Prevention from 1970 to 1992. Of 108 reported cases, some clinical information was available for 76. A medical review panel judged 39 of these deaths as probably due to isoniazid hepatitis and 23 deaths as possibly due to isoniazid hepatitis. Of the 62 probable and possible cases combined, 50 (81%) were female, 49 (79%) were non-Hispanic black or Hispanic, and 19 (31%) were younger than 35 years. The median duration of isoniazid preventive therapy before symptom onset was 16 weeks. Of the 60 cases with symptom information, 54 (90%) presented with jaundice. Of the 62 cases, 26 (42%) were monitored monthly in accordance with current recommendations, and 6 of the patients were younger than 35 years. We estimate that the rate of fatal isoniazid hepatitis among patients in the public sector was no greater than 4.2 per 100,000 persons beginning therapy and no greater than 7 per 100,000 persons completing therapy. Adherence to isoniazid preventive therapy guidelines apparently reduces, but does not eliminate, the risk of fatal hepatitis. Careful patient selection, education, and monitoring are critical for minimizing that risk.

A sensitive color ELISA for detecting polycyclic aromatic hydrocarbon-DNA adducts in human tissues.

Human exposure to polycyclic aromatic hydrocarbons (PAHs) has been determined by measurement of DNA adducts in human tissues. Competitive enzyme-linked immunosorbent assays (ELISAs) using antisera recognizing benzo[a]pyrenediol-epoxide-modified DNA (BPDE-I-DNA) and color of fluorescence endpoint detection have been used extensively for quantifying PAH-DNA adducts. The fluorescence ELISA (limit of detection 1 adduct/10(8) nucleotides) was previously reported to be more sensitive than the color ELISA (1/10(7)) for measuring PAH adducts (Santella et al. (1988) Carcinogenesis, 9, 1265-1269). However, the fluorescence assay has the disadvantages of greater variation among the replicates and higher background levels than the color assay. Using a newly developed antiserum against BPDE-I-DNA, we have modified the color of ELISA so that it has the same sensitivity as the fluorescence ELISA and requires only 33% of the sample quantity needed for the fluorescence ELISA. The modifications included preincubation of the antiserum with the samples, using microtiter plates with half-size, flat bottom wells, and optimizing the assay conditions. The improved color ELISA was used to analyze DNA samples from human autopsy tissues, including heart, lung, liver, kidney, spleen, pancreas and stomach from smokers and nonsmokers. With the exception of spleen and stomach, all tissues from smokers showed higher PAH-DNA adducts (ranging from 0.3 to 19.0 adducts/10(7) nucleotides) than the tissues from the nonsmokers (0.3 to 3.7 adducts/10(7) nucleotides) in two separate experiments. Among the tissues from smokers, heart showed the highest level of DNA adducts. This study demonstrates that a stable color ELISA with high sensitivity can be useful in assessing human exposure to PAH.

Bacterial pneumonia in persons infected with the human immunodeficiency virus. Pulmonary Complications of HIV Infection Study Group.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection are at increased risk for bacterial pneumonia in addition to opportunistic infection. However, the risk factors for bacterial pneumonia and its incidence in this population are not well defined. METHODS: In a multicenter, prospective, observational study, we monitored 1130 HIV-positive and 167 HIV-negative participating adults for up to 64 months for pulmonary disease. The HIV-positive group comprised 814 homosexual or bisexual men, 261 injection-drug users, and 55 female partners of HIV-infected men. RESULTS: There were 237 episodes of bacterial pneumonia among the HIV-positive participants (rate, 5.5 per 100 person-years), as compared with 6 episodes among the HIV-negative participants (rate, 0.9 per 100 person-years; P < 0.001). The rate of bacterial pneumonia increased with decreasing CD4 lymphocyte counts (2.3, 6.8, and 10.8 episodes per 100 person-years in the strata with more than 500, 200 to 500, and fewer than 200 cells per cubic millimeter, respectively; P < or = 0.022 for each comparison). Injection-drug users had a higher rate of bacterial pneumonia than did homosexual or bisexual men or female partners. In the stratum with the fewest CD4 lymphocytes, cigarette smoking was associated with an increased rate of pneumonia. Mortality was almost four times higher among participants with an episode of pneumonia than among the others. Prophylaxis with trimethoprim-sulfamethoxazole was associated with a 67 percent reduction in confirmed episodes of bacterial pneumonia (P = 0.007). CONCLUSIONS: Bacterial pneumonia is more frequent in HIV-positive persons than in seronegative controls, and the risk is highest among those with CD4 lymphocyte counts below 200 per cubic millimeter and among injection-drug users.

Population-based exposure measurements in EPA region 5: a phase I field study in support of the National Human Exposure Assessment Survey.

The National Human Exposure Assessment Survey (NHEXAS) Phase I study is designed to be part of the total NHEXAS framework developed from a series of scientific discussions and workshops conducted by the U.S. Environmental Protection Agency (EPA) during 1992 and 1993. NHEXAS examines total human exposure and is structured to include: Phase I, scoping studies; Phase II, a full national exposure survey; and Phase III, a series of highly focused characterization modules. Our research program examines the scientific issues important to Phase II, including statistical sampling, methods evaluation, media concentration measurements, formulating quality assurance goals, and identification of important pathways leading to exposure. To determine the feasibility of NHEXAS in characterizing human exposure for a representative population, a hypothesis-driven design is used to answer important questions about human exposure to specific environmental contaminants. This paper describes: (1) hypotheses to be tested; (2) contaminants selected for study; (3) strategies for measuring exposure; (4) study area and population; (5) population sampling design; (6) media sampling and analysis procedures; and (7) data analysis. The contaminants of concern in this Phase I study include selected metals and volatile organic compounds. From these classes the first-tier contaminants to be measured are lead, arsenic, benzene, chloroform, perchloroethylene, and trichloroethylene. Contaminants selected for examination may potentially be found in many media (personal-nonoccupational, personal-occupational, indoor, and outdoor residential air; dust; potable water; food/beverages; soil; blood; hair; and urine) and exposures may occur by multiple routes (inhalation, ingestion, dermal). The central hypothesis of our field study is to discover whether individual and population exposures determined by modeled or extant data are/are not significantly different from those determined directly from multipathway and multimedia measurements. In addition, there are a series of subhypotheses ranging from pollutant-specific exposure measurement and body burden hypotheses to the optimization of exposure models. In keeping with the NHEXAS framework, a probability-based population sample for total exposure and the field study will be conducted in counties located throughout EPA Region 5 (Minnesota, Wisconsin, Illinois, Indiana, Ohio, and Michigan). Sampling units will be households and an individual residing within each household. Environmental, exposure, and biological media sample collection will be performed by this consortium. Analyses of the external media and biological media samples will be completed by this consortium or Federal laboratories of the Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), or EPA. The protocols and analytical techniques selected for use represent the best available for total exposure assessment at this time.

Ultrasonographic correlates of carotid atherosclerosis in transient ischemic attack and stroke.

BACKGROUND AND PURPOSE: Atherosclerotic plaques in extracranial carotid arteries, particularly in the bifurcation of the common carotid and internal carotid arteries, may cause transient cerebral ischemia and stroke by lumen stenosis or plaque-related thromboembolism. B-mode ultrasound imaging has the capability of providing information on plaque thickness, characteristics, and location in carotid arteries. METHODS: A retrospective analysis of 242 stroke and 336 transient ischemic attack (TIA) patients, recruited for the B-Scan Ultrasound Imaging Assessment Program, was performed to determine the ultrasonographic correlates of carotid atherosclerosis and acute cerebral ischemia. A matched case-control study design was used to compare brain hemispheres with ischemic lesions ("cases") to unaffected contralateral hemispheres ("controls") with regard to the presence and characteristics of carotid artery plaques. RESULTS: The first set of analyses examined the association between the presence of carotid plaques ipsilateral to the brain lesion and the occurrence of stroke or TIA and showed an association with recent episodes of TIA and stroke (odds ratio [OR], 1.6; P = .03) but not with past episodes. In a subset (n = 232) of patients with plaques in both carotid arteries and recent cerebral ischemic events, stroke was associated with ipsilateral carotid artery occlusion (P = .02). Lumen measurements at the site of the minimum residual lumen (MRL) diameter showed a significant association between a narrower lumen diameter in the carotid artery ipsilateral to case hemisphere and stroke (difference, 1.0 mm; P = .0003). TIA patients showed an association between both hypoechoic carotid plaques (OR, 3.0; P = .005) and the presence of longitudinal lesion motion (OR, 3.0; P = .02) with ipsilateral brain involvement. Plaque thickness at the MRL was positively correlated with both ipsilateral TIA (ipsilateral side, 4.4 +/- 0.15 mm; contralateral side, 3.9 +/- 0.16 mm; P = .007) and stroke (ipsilateral side, 4.2 +/- 0.23 mm; contralateral side, 3.3 +/- 0.21 mm; P = .0006). CONCLUSIONS: These data demonstrate significant relationships between carotid artery ultrasound plaque characteristics and ischemic cerebrovascular events. These findings encourage further prospective studies in asymptomatic subjects focused on echographic carotid plaque characteristics as predictors of subsequent TIA or stroke.

Biological markers of intermediate outcomes in studies of indoor air and other complex mixtures.

Biological markers of intermediate health outcomes sometimes provide a superior alternative to traditional measures of pollutant-related disease. Some opportunities and methodologic issues associated with using markers are discussed in the context of exposures to four complex mixtures: environmental tobacco smoke and nitrogen dioxide, acid aerosols and oxidant outdoor pollution, environmental tobacco smoke and radon, and volatile organic compounds. For markers of intermediate health outcomes, the most important property is the positive predictive value for clinical outcomes of interest. Unless the marker has a known relationship with disease, a marker response conveys no information about disease risk. Most markers are nonspecific in that various exposures cause the same marker response. Although nonspecificity can be an asset in studies of complex mixtures, it leads to problems with confounding and dilution of exposure-response associations in the presence of other exposures. The timing of a marker's measurement in relation to the occurrence of exposure influences the ability to detect a response; measurements made too early or too late may underestimate the response's magnitude. Noninvasive markers, such as those measured in urine, blood, or nasal lavage fluid, are generally more useful for field studies than are invasive markers. However, invasive markers, such as those measured in bronchoalveolar lavage fluid or lung specimens from autopsies, provide the most direct evidence of pulmonary damage from exposure to air pollutants. Unfortunately, the lack of basic information about marker properties (e.g., sensitivity, variability, statistical link with disease) currently precludes the effective use of most markers in studies of complex mixtures.

Tuberculin and anergy testing in HIV-seropositive and HIV-seronegative persons. Pulmonary Complications of HIV Infection Study Group.

OBJECTIVE: To determine the prevalence and predictors of reactivity to tuberculin purified protein derivative (PPD) and skin test anergy in patients with human immunodeficiency virus (HIV) infection and in HIV-seronegative controls. DESIGN: Cross-sectional analysis of baseline data from a prospective, multicenter study of pulmonary complications of HIV infection. SETTING: Community-based cohort of persons with and without HIV infection. PATIENTS: A total of 1171 HIV-seropositive patients without AIDS (841 homosexual men, 274 intravenous drug users, and 56 women with heterosexually acquired infection); 182 HIV-seronegative persons (125 homosexual men and 57 intravenous drug users). MEASUREMENTS: Delayed-type hypersensitivity response to tuberculin PPD, trichophytin, mumps, and Candida antigens; T-lymphocyte subsets. RESULTS: The prevalence of tuberculin PPD reactivity was higher among intravenous drug users than among homosexual men, in both HIV-seronegative (19.1% compared with 6.8%, P = 0.03) and HIV-seropositive persons (15.1% compared with 2.5%, P < 0.001). Among HIV-infected patients, the prevalence of tuberculin reactivity varied directly and that of anergy inversely with the absolute CD4 lymphocyte count. Prevalences were 1% and 72%, respectively, in patients with fewer than 200 CD4 cells/mm3, and 8.4% and 25.5%, respectively, in those with 600 CD4 cells/mm3 (P < 0.001 for both comparisons). Patients with HIV infection and fewer than 400 CD4 lymphocytes/mm3 had a lower prevalence of PPD reactivity than HIV-seronegative controls (2.7% compared with 10.0%, P < 0.001). The strongest predictors of tuberculin reactivity were intravenous drug use, black race, a previous positive PPD test result, and a history of Calmette-Guérin bacillus vaccination. The strongest predictor of anergy was HIV seropositivity. CONCLUSIONS: The response to delayed-type hypersensitivity antigens depends on immune status. The value of PPD and anergy testing in HIV-seropositive patients depends on the ability of such testing to predict subsequent tuberculosis, which is imprecisely known. Until more data or better methods are available, these tests should be done as early as possible in the course of HIV infection.

Comparison of DNA adducts from exposure to complex mixtures in various human tissues and experimental systems.

DNA adducts derived from complex mixtures of polycyclic aromatic compounds emitted from tobacco smoke are compared to industrial pollution sources (e.g., coke ovens and aluminum smelters), smoky coal burning, and urban air pollution. Exposures to coke oven emissions and smoky coal, both potent rodent skin tumor initiators and lung carcinogens in humans, result in high levels of DNA adducts compared to tobacco smoke in the in vitro calf thymus DNA model system, in cultured lymphocytes, and in the mouse skin assay. Using tobacco smoke as a model in human studies, we have compared relative DNA adduct levels detected in blood lymphocytes, placental tissue, bronchoalveolar lung lavage cells, sperm, and autopsy tissues of smokers and nonsmokers. Adduct levels in DNA isolated from smokers were highest in human heart and lung tissue with smaller but detectable differences in placental tissue and lung lavage cells. Comparison of the DNA adduct levels resulting from human exposure to different complex mixtures shows that emissions from coke ovens, aluminum smelters, and smoky coal result in higher DNA adduct levels than tobacco smoke exposure. These studies suggest that humans exposed to complex combustion mixtures will have higher DNA adduct levels in target cells (e.g., lung) as compared to nontarget cells (e.g., lymphocytes) and that the adduct levels will be dependent on the genotoxic and DNA adduct-forming potency of the mixture.

Changes in plasma lipid and lipoprotein cholesterol and weight prior to the diagnosis of cancer.

Changes in lipoprotein cholesterol, total plasma cholesterol, and weight prior to the diagnosis of cancer were examined in 103 men who developed cancer in a cohort of 3805 type IIa hyperlipidemic men aged 35-59 enrolled in the Lipid Research Clinics Coronary Primary Prevention Trial. Study measurements were made bimonthly. After adjusting for the effects of the trial intervention and other determinants of lipid levels, the cholesterol levels of the cases diagnosed with nonlocalized cancer dropped below the expected level approaching diagnosis when compared to the entire study population. The decrease averaged 9.3 mg/dl and began about 2 years prior to diagnosis. Weight levels dropped an average of 1.2 kg over the same period. Weight and cholesterol were significantly lower than expected within 8 months of diagnosis (P less than 0.05). No decrease was seen for those diagnosed with localized malignancies. Patterns for low-density lipoprotein cholesterol reflected those of total cholesterol. There was no clear relationship between cancer diagnosis and patterns of change for triglycerides and high-density lipoprotein cholesterol. In the future, investigations of any relationship between a host physiological state and cancer occurrence should account for the metabolic effects of preclinical disease demonstrated here. To protect against spurious conclusions, incident cases occurring within 2 years of measurement should be analyzed separately. In studies of cancer mortality, deaths occurring within 3.5 years of the base-line measurement should be analyzed separately.

Solvent exposure and cardiovascular disease.

A review of cardiovascular disease (CVD) resulting from environmental exposures pointed out the lack of studies concerned with the cardiovascular effects of hazardous environmental exposures. A later Working Group report on CVD in the workplace recommended further occupational studies of CVD, and it identified carbon monoxide, nitrates, and organic solvents as exposures especially deserving of study. The literature lacks a detailed, critical epidemiologic overview of work on this last topic. Therefore, the following review focuses on the cardiovascular effects of solvent exposures. Some major difficulties inherent in studies of CVD and environmental exposures are brought out, and some suggested areas for future epidemiologic research are discussed.

Obesity and mortality in the Lipid Research Clinics Program Follow-up Study.

Using data from the Lipid Research Clinics Program for 1972-1983, the study presented here examined weight history and two indices of obesity: the body mass index (BMI) and the triceps skinfold (TSF) thickness. Cox regression analyses with and without adjustment for cardiovascular disease risk factors revealed a significant (p less than 0.05) quadratic association between BMI and all-causes mortality among men, but not women, after an average 8.4 years of follow-up; mortality was relatively high at both extremes of the BMI distribution. The association was stronger among smokers compared with nonsmokers, and it was apparent among male normotensives, but not hypertensives. All TSF-mortality associations and BMI associations with cancer and coronary heart disease mortality were weak and nonsignificant. Among men, per cent weight change in adulthood showed a significant inverse association with all-causes and cancer mortality. Because BMI and weight history were significantly associated with mortality after adjustment for other risk factors, they appear to be independent predictors of mortality among men.

Biological markers in epidemiologic research.

This paper identifies some of the issues relevant to the use of biological markers in epidemiologic research. Foremost among these are clarity of definitions and marker classification. Illustrations of markers in the categories of internal dose, biological effective dose, biological response, disease, and susceptibility are presented with a theoretical model for the interrelationship among these. Issues faced by epidemiologists in selecting markers for specific studies concern exposure complexity, marker specificity, marker persistence, time to appearance, and the use of target vs. surrogate biological media. Feasibility issues concern sample collection, transport, storage, and characteristics of the laboratory assay. The rationale for biological markers in epidemiologic research is strong in that markers have the potential for (1.) improving the accuracy of our "exposure variables," (2.) permitting the identification of preclinical disease and providing opportunities for prevention, (3.) allowing for more homogeneous and etiologically relevant classifications of disease, and (4.) enhancing our understanding of the biological processes leading to disease occurrence, thereby strengthening the interpretation of epidemiologic data and the theoretical framework from which we formulate research questions.

The prevalence and correlates of Rose Questionnaire angina among women and men in the Lipid Research Clinics Program Prevalence Study population.

The prevalence and correlates of Rose Questionnaire angina were investigated in a sample of 4,661 white woman and men aged 30 years and above who participated in the Lipid Research Clinics Program Prevalence Study 1972-1976. Among men, the prevalence of Rose angina increased with age from about 1% to 12%, while the prevalence among women ranged from about 3% to 6%. Young women compared with men also had a relatively high prevalence of dyspnea, which was strongly correlated with Rose angina in both sexes. For women and men younger than 50 years, the dyspnea-Rose angina odds ratio was about 6 (p less than 0.001), while older women and men had somewhat lower sand higher odds ratios, respectively. Major and minor resting electrocardiographic abnormalities and self-reported history of a heart attack were not significantly associated with Rose angina among young participants of either sex, but they did show positive associations among older participants with the exception of minor electrocardiographic abnormalities in men. A logistic regression analysis revealed a strong inverse association between high density lipoprotein cholesterol and Rose angina in both sexes. Because mortality studies consistently show an excess of coronary heart disease death among young men compared with women, the female excess of Rose angina at young ages suggests that the grouping of angina and myocardial infarction into a single endpoint in cardiovascular disease studies may be more appropriate for young men than for young women.