Why is low blood cholesterol associated with risk of nonatherosclerotic disease death?
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Arteriosclerosis↗
Biomedical subjects
D R Jacobs
Publications and source records attributed to D R Jacobs.
Vitamin E, LDL, and endothelium. Brief oral vitamin supplementation prevents oxidized LDL-mediated vascular injury in vitro.
In previously reported in vitro studies, we found that heme, a physiologically widespread hydrophobic iron compound, can rapidly generate oxidized low-density lipoprotein (LDL), which then becomes cytotoxic to cultured vascular endothelial cells; both LDL oxidation and endothelial cytotoxicity were inhibited by incubation with exogenous alpha-tocopherol (vitamin E) or ascorbic acid (vitamin C). Seeking relevance to in vivo conditions, we performed a study in which 10 human volunteers were given daily antioxidant supplements of 800 IU of DL-alpha-tocopherol acetate alone or in combination with 1000 mg of ascorbic acid for 2 weeks. LDL resistance to heme oxidation ex vivo, as measured by the lag time for conjugated-diene formation, increased by as much as threefold from a mean +/- SD of 58 +/- 11 to 104 +/- 18 minutes (P < .001); LDL alpha-tocopherol increased from 11 +/- 2 to 26 +/- 6 molecules per LDL particle (P < .001); and most impressively, cytotoxicity to porcine aortic endothelial cells incubated with LDL conditioned with heme plus H2O2 or with copper was completely prevented (cytotoxicity before supplementation was 42 +/- 12%, decreasing after supplementation to 3 +/- 2%, P < .001). These measurements reverted to their presupplement levels within 2 weeks after participants stopped taking antioxidant supplements and were reproduced in 4 subjects taking 800 IU of DL-alpha-tocopherol acetate supplements alone but not in the same subjects taking 1000 mg ascorbic acid supplements alone. In conclusion, oral vitamin E supplementation increases LDL alpha-tocopherol content, increases LDL resistance to oxidation, and decreases the cytotoxicity of oxidized LDL to cultured vascular endothelial cells.
Adult↗
Lipoprotein[a] concentrations and apolipoprotein[a] phenotypes in Caucasians and African Americans. The CARDIA study.
Little is known about racial differences in lipoprotein[a] (Lp[a]) concentrations and apolipoprotein[a] (apo[a]) phenotypes. Lp[a] protein concentrations were determined by a double monoclonal antibody enzyme-linked immunosorbent assay method in 4165 Caucasian and African American men and women from four US communities. Apo[a] phenotypes were determined by polyacrylamide gel electrophoresis and immunoblotting on a random subset of these participants (n = 690). The distribution of Lp[a] protein levels in Caucasians was highly skewed (mean, 6.9 mg/dL; median, 3.7 mg/dL). In contrast, the distribution in African Americans was less skewed (mean, 13.0 mg/dL; median, 11.6 mg/dL), and Lp[a] protein levels were approximately double those in Caucasians within most apo[a] phenotypes. The previously described inverse relationship between apo[a] size and Lp[a] concentration was generally confirmed in Caucasians, but the B phenotype had lower Lp[a] levels than the S1 or S2 phenotype. In African Americans, both the B and S1 phenotypes had lower Lp[a] levels than the S2 phenotype. The frequencies of the apo[a] phenotypes in African Americans differed from those in Caucasians (P < .001) and also differed from the frequencies reported in a Sudanese population (P < .002). African Americans had a lower frequency of the S2 phenotype than Caucasians (8% vs 18%; P < .01) and a higher frequency of S3 (36% vs 25%; P < .01). As compared with the data reported in Sudanese, African Americans also had a higher frequency of the S3 phenotype (36% vs 14%; P < .001) and a lower frequency of S4 (29% vs 44%; P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Models of effects of low blood cholesterol on the public health. Implications for practice and policy.
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Adult↗
Associations of serum total cholesterol, different types of stroke, and stenosis distribution of cerebral arteries. The Akita Pathology Study.
BACKGROUND AND PURPOSE: The relation between serum total cholesterol levels and stroke is controversial. The Akita Pathology Study provides data on the association of serum total cholesterol, different types of stroke, and distribution of stenosis in cerebral arteries. METHODS: The data are based on 750 autopsied men aged 30 years and older who were admitted to a local hospital in northeast Japan between 1966 and 1984. The overall autopsy rate was 88%. The grade of stenosis in the cerebral arteries was determined blindly by one pathologist using Baker's method for basal cerebral arteries (atherosclerosis scores) and using microscopic examination of a single basal ganglion slide for the intracerebral penetrating arteries (arteriolosclerosis scores). RESULTS: The age-adjusted mean value of serum total cholesterol concentration was 164 mg/dL for cerebral hemorrhage, 177 mg/dL for infarction in penetrating artery regions, and 200 mg/dL for infarction in cortical artery regions. Mean serum cholesterol was lower in deaths caused by cerebral hemorrhage than in those caused by myocardial infarction and other cardiovascular disease. Mean atherosclerosis score of basal cerebral arteries was low for cerebral hemorrhage, intermediate for penetrating artery infarction, and high for cortical artery infarction. Stenosis of both basal and penetrating arteries was minimum or absent in cases of cerebral hemorrhage. Only the basal arteries were stenotic in cases of cortical artery infarction, whereas both basal and penetrating arteries were stenosed in cases of penetrating artery infarction. There were positive associations of serum cholesterol with stenosis of basal and penetrating arteries. Among cases of cerebral hemorrhage, serum total cholesterol levels were even lower in men with no significant stenosis in either basal or penetrating arteries than in men with stenosis in either type of artery. CONCLUSIONS: The association of serum cholesterol with pathogenesis varies among stroke types. Elevated serum cholesterol levels were associated with the presence of cortical artery infarction, while low serum cholesterol levels were associated with cerebral hemorrhage.
Adult↗
Compendium of physical activities: classification of energy costs of human physical activities.
A coding scheme is presented for classifying physical activity by rate of energy expenditure, i.e., by intensity. Energy cost was established by a review of published and unpublished data. This coding scheme employs five digits that classify activity by purpose (i.e., sports, occupation, self-care), the specific type of activity, and its intensity as the ratio of work metabolic rate to resting metabolic rate (METs). Energy expenditure in kilocalories or kilocalories per kilogram body weight can be estimated for all activities, specific activities, or activity types. General use of this coding system would enhance the comparability of results across studies using self reports of physical activity.
Energy Metabolism↗
A simultaneous evaluation of 10 commonly used physical activity questionnaires.
Ten commonly used physical activity questionnaires were evaluated for reliability and validity in 78 men and women aged 20-59, with varying physical activity habits. One month reliability was found to be high for all questionnaires except those pertaining only to the last week or month. Longer term test-retest reliability tended to be lower. Validity was studied in relation to treadmill exercise performance, vital capacity, body fatness, the average of 14 4-wk physical activity histories and the average of 14 2-d accelerometer readings. No questionnaire measure was correlated with the accelerometer reading, and correlations with vital capacity were generally low. Only the Minnesota Leisure Time Physical Activity Questionnaire household chores measure was correlated with habitual performance of household chores. Most questionnaires, even very simple ones, were related to performance of heavy intensity physical activity and treadmill performance; these same questionnaires tended to be related to percent body fat. Fewer questionnaires related to performance of light or moderate activity. Occupational activity was unrelated to any of the validation measures. It is concluded that there are multiple, nonoverlapping dimensions of physical activity, reflected in multiple nonoverlapping validation realms. More important than the length or attention to detail of a questionnaire seems to be the logic of its questions. Important areas of physical activity that should be addressed in future questionnaires include sleep, light, moderate and heavy intensity leisure activities, household chores, and occupational activity. Recent versus habitual activity should also be considered.
Adult↗
Validity and reliability of self-reported physical activity status: the Lipid Research Clinics questionnaire.
We assessed the validity and reliability of the Lipid Research Clinics (LRC) physical activity (PA) questionnaire against measures of PA and physical fitness, and compared a new scoring system (four-point) with the method used in the LRC studies (two-point) in 28 men and 50 women. The two-point method classified participants as inactive or active based one question about regular, strenuous exercise habits. The four-point method classified participants as very low, low, moderate, and high active based on two questions; regular, strenuous exercise and self-rating of PA relative to peers. After adjusting for age and gender, the four-point method explained 17-29% of the variation in VO2max, percent body fat, and heavy-and light-intensity kcal.d-1 measured by the 4 wk history questionnaire (FWH). No association was found between the LRC ratings and Caltrac kcal and activity units and FWH total, moderate-intensity, and household PA kcal.d-1. Test-retest reliability was high (two-point, r = 0.85; four-point, r = 0.88). The LRC PA questionnaire is a relatively valid and reliable indicator of heavy PA in adults. The four-point method increases the ability to show graded associations between measures of cardiorespiratory fitness, body fatness, and leisure time PA.
Adult↗
The Healthy Worker Project: a work-site intervention for weight control and smoking cessation.
OBJECTIVES: A randomized trial was conducted to evaluate the effectiveness of a work-site health promotion program in reducing obesity and the prevalence of cigarette smoking. METHODS: Thirty-two work sites were randomized to treatment or no treatment for 2 years. Treatment consisted of health education classes combined with a payroll-based incentive system. Evaluation was based on cohort and cross-sectional surveys. RESULTS: Of 10,000 total employees in treatment work sites, 2041 and 270 participated in weight control and smoking cessation programs, respectively. Weight losses averaged 4.8 lbs, and 43% of smoking participants quit. Net 2-year reductions in smoking prevalence in treatment vs control work sites were 4.0% and 2.1% in cross-sectional and cohort surveys, respectively. No treatment effect was found for weight. Treatment effects for smoking prevalence and weight were both positively correlated with participation rates in the intervention programs (r = .45 for smoking and r = .55 for weight). CONCLUSIONS: This work-site health promotion program was effective in reducing smoking prevalence at a cost that is believed to make the investment worthwhile.
Adult↗
Assessment of the accuracy of physical activity questionnaire occupational data.
The validity and reliability of occupational physical activity data from survey instruments were determined in 75 men and women (age 23 to 59 years) in white-collar jobs. Data were validated against measures of cardiorespiratory fitness, body fatness, motion detection, pulmonary function, and 12 days of occupational physical activity records. More than 90% of occupational physical activity was spent in light-intensity sitting, standing, and walking. Test-retest reliability was high for most occupational questions (r > or = .63, P < .05). Correlation coefficients between questionnaire data and validation criteria that reflect heavy-intensity physical activity were low (r < .17, P > .05). The modified Tecumseh Occupational Questionnaire and Seven-Day Recall, which classified occupational physical activity in hours per week worked and average level of ratio of associated metabolic rate for a specific activity divided by the resting metabolic rate, on the job, correlated best with physical activity records (r = .11 to .47). Validation of these self-administered questionnaires in populations with a greater diversity of jobs and occupational energy requirements is needed.
Activities of Daily Living↗
Cigarette smoking and submaximal exercise test duration in a biracial population of young adults: the CARDIA study.
Symptom-limited, graded exercise treadmill testing was performed by 4,968 white and black adults, ages 18-30 yr, during the baseline examination for the Coronary Artery Risk Development in Young Adults (CARDIA) study. Compared with nonsmokers, the mean exercise test duration of smokers was 29-64 s shorter depending on race/gender group (all P < 0.001), but mean duration to heart rate 130 (beats.min-1) ranged from 20-50 s longer (P < 0.05). In each race/gender group, test duration to heart rates up to 150 was 15-35 s longer (P < 0.05) in smokers than in nonsmokers after adjustment for age, sum of skinfolds, hemoglobin, and physical activity score. The mean maximum heart rate was lower in smokers than in nonsmokers (difference ranging from 6.7 beats.min-1 in white men to 11.2 beats.min-1 lower in black women, P < 0.001), although maximum rating of perceived exertion was nearly identical in smokers and nonsmokers. Chronic smoking appears to blunt the heart rate response to exercise, so that exercise duration to submaximal heart rates is increased even though maximal performance is impaired. This may result from downloading of beta-receptors caused by smoking. Smoking status should be considered in the evaluation of physical fitness data utilizing submaximal test protocols, or else the fitness of smokers relative to nonsmokers is likely to be overestimated.
Adolescent↗
Psychosocial correlates of body fat distribution in black and white young adults.
We examined the association of fat distribution with a number of personality attributes and behaviours in a sample of 5115 young blacks and whites. Body fat distribution, measured by the ratio of waist-to-hip circumferences (WHR), was significantly and positively associated with cigarette smoking and negatively associated with education in all of the race and sex groups. WHR was positively associated with alcohol consumption in men and black women and with marijuana use in women. A number of psychosocial factors assessing personality attributes and behaviours were also examined, including the Cook-Medley hostility score, type A/B behaviour pattern, life events, social support, financial situation, and diagnosis of a nervous, emotional or mental disorder. In age- and BMI-adjusted analyses, only the Cook-Medley hostility score and a financial situation score were significantly and positively associated with WHR in all race and sex groups. In multivariate linear regression, these psychosocial factors were associated with WHR in some of the race and sex groups, accounting for less than 1% of the variation in WHR in any one group. These results suggest that fat distribution is weakly associated with these personality attributes and behaviours.
Adipose Tissue↗
Oat products and lipid lowering. A meta-analysis.
OBJECTIVES: To test the a priori hypothesis that consumption of oats will lower the blood total cholesterol level and to assess modifiers and confounders of this association. DATA SOURCES: A computerized literature (MEDLINE) search and the Quaker Oats Co identified published and unpublished trials as of March 1991. Raw data were requested for all trials. STUDY SELECTION: Trials were included in summary effect size estimates if they were randomized and controlled, if a formal assessment of diet and body weight changes occurred, and, if raw data were not received, if there was enough information in the published report to perform calculations. DATA SYNTHESIS: Twenty trials were identified. Using the methods of DerSimonian and Laird, a summary effect size for change in blood total cholesterol level of -0.13 mmol/L (-5.9 mg/dL) (95% confidence interval [CI], -0.19 to -0.017 mmol/L [-8.4 to -3.3 mg/dL]) was calculated for the 10 trials meeting the inclusion criteria. The summary effect size for trials using wheat control groups was -0.11 mmol/L (-4.4 mg/dL) (95% CI, -0.21 to -0.01 mmol/L [-8.3 to -0.38 mg/dL]). Calculation of Keys scores demonstrated that substituting carbohydrates for dietary fats and cholesterol did not account for the majority of blood cholesterol reduction. Larger reductions were seen in trials in which subjects had initially higher blood cholesterol levels (greater than or equal to 5.9 mmol/L [greater than or equal to 229 mg/dL]), particularly when a dose of 3 g or more of soluble fiber was employed. CONCLUSION: This analysis supports the hypothesis that incorporating oat products into the diet causes a modest reduction in blood cholesterol level.
Cholesterol↗
Uses of statistical editing of real-time ambulatory electrocardiographic recordings for quantitative ventricular ectopic beat counts.
Real-time ambulatory monitoring analyzes each heart beat, counts events, and stores ECG samples for later visual verification. Typically, a physician examines these to determine whether the computer algorithm accurately identified arrhythmias. Physician editing is performed using best clinical judgement. We developed a simple statistical editing procedure for adjusting false positive and false negative computer detections. In 20 subjects having 24-hr monitoring we compared statistically edited ventricular premature beat (VPB) counts and pair/run counts with the unedited monitor counts and with physician assessment using a visual counted gold standard. The agreement of the statistically edited count with the visual standard was 65% for total VPB, 85% for VPB pair/runs, and 90% for a risk score based on ventricular ectopy. Corresponding agreements for unedited monitor count were 15, 25, and 30%, respectively. Physician assessment was not sufficiently precise to allow quantitative count estimates. This study indicates a statistical editing procedure substantially increases the level of agreement between the visual standard and the monitor count of VPB frequency and complexity. Statistically edited data are suitable for quantitative counts of VPB and other arrhythmic events in research and in medical diagnosis and treatment. This editing procedure can be a useful adjunct to any ambulatory monitoring system.
Arrhythmias, Cardiac↗
Results from a statewide approach to adolescent tobacco use prevention.
BACKGROUND: The 1985 Minnesota Legislature established guidelines for school-based tobacco-use prevention programming and provided financial incentives to school districts to encourage them to adopt a broad range of preventive measures. The Minnesota-Wisconsin Adolescent Tobacco-Use Research Project was funded by the National Cancer Institute in 1986 to evaluate the Minnesota initiative through two parallel studies. METHODS: The Four Group Comparison Study was a prospective study of 48 school "units" which were randomly assigned to one of four conditions in 1987. Baseline observations were taken in the sixth grade in 1987, interventions were delivered in the seventh grade, and follow-up observations were taken in the seventh, eighth, and ninth grades. The Four Group Comparison Study was designed to evaluate the three middle-school interventions that were most widely adopted by Minnesota school districts as a result of the 1985 legislation. The Two State Comparison Study was a serial cross-sectional study of representative districts in Minnesota and Wisconsin. Annual surveys of ninth graders were conducted from 1986-1990. The Two State Comparison Study was designed to determine whether tobacco-use patterns changed in Minnesota relative to Wisconsin following the Minnesota legislation. RESULTS: The prospective study indicated that none of the interventions was more effective in reducing adolescent tobacco use compared with a randomized control group. The serial cross-sectional study revealed that there was a modest net decline in Minnesota relative to Wisconsin from 1986 to 1990, but that it was within the range of chance variation. CONCLUSIONS: Taken together, these results indicate that this legislative initiative was insufficient to reduce adolescent tobacco use statewide during the 5-year study period. Together with results from other recent studies, they suggest that even more intensive efforts may be required to effect widespread reductions in adolescent tobacco use.
Adolescent↗
Associations of body fat and its distribution with dietary intake, physical activity, alcohol, and smoking in blacks and whites.
Cross-sectional associations between body fat and its distribution and environmental factors influencing energy balance were examined in 5115 young adults. Protein was directly associated with body mass index (BMI) in all race and sex groups (P less than 0.01) after age, education, cigarette-smoking status, alcohol intake, and physical activity were adjusted for. Carbohydrate intake was inversely associated with BMI in males (P = 0.02). Total physical activity was inversely associated with BMI in white women and with skinfold-thickness measures (P less than 0.01) in all groups. Waist-to-hip-circumference ratio (WHCR) was positively associated with total kilojoules (kilocalories) in women, inversely associated with percent of kilojoules (kilocalories) from carbohydrates in whites, grams of crude fiber/4184 kJ (1000 kcal) (except in black men), and physical activity (except in white women). WHCR was directly associated with cigarette smoking except in black men, and with total alcohol intake in men. Beer was consistently associated with WHCR in all race and sex groups.
Adipose Tissue↗
Are race and sex differences in lung function explained by frame size? The CARDIA Study.
Using the CARDIA cohort of 20- to 32-yr-old black and white men and women, FVC and FEV1 were standardized for standing height, sitting height, leg height, elbow breadth, and biacromial diameter in such a way that the standardized lung function showed minimal statistical dependence on these measures of frame size. Race and sex differences in lung function have been reported even after adjustment for height; however, these differences might depend on aspects of frame size other than height. We found that within this age group height2 provided robust standardization for FVC and FEV1 for all race and sex strata of the population. Height explained approximately 40% of the variance of FVC and FEV1 in whites, 30% in black women, and 20% in black men. In black men only, standardization for the combination of sitting height, leg height, elbow breadth, and biacromial diameter improved explained variance to nearly 40% for FVC and nearly 30% for FEV1. After standardization for height, FVC and FEV1 were found to be 14 to 19% higher in whites than in blacks, and in men than in women. Standardization of FVC and FEV1 for sitting height, leg height, elbow breadth, and biacromial diameter combined reduced these differences to 13-16%. Thus, race and sex differences in lung function exist even after detailed adjustment for frame size.
Adult↗
The US decline in stroke mortality: what does ecological analysis tell us?
We review a study in this issue that concludes, from analyses of ecological associations, that the use of medication to lower high blood pressure has caused at most a small decline in US stroke mortality rates. Our analysis suggests that other possible sources of the decline may be population-wide falls in levels of blood pressure, cigarette smoking, and coronary heart disease mortality, as well as improved treatment of cardiac and respiratory sequelae of stroke. Although the ecological method is powerful for answering questions about medical interventions' population-wide effects on disease, it must be used with care. Of particular concern are variables with meanings that differ between the ecological and the individual levels, the number of ecological units available for analysis, the sample size within the ecological units, and the range of independent variables used in ecological regression.
Aged↗