Oxygenated carotenoid lutein and progression of early atherosclerosis: the Los Angeles atherosclerosis study.

BACKGROUND: Carotenoids are hypothesized to explain some of the protective effects of fruit and vegetable intake on risk of cardiovascular disease. The present study assessed the protective effects of the oxygenated carotenoid lutein against early atherosclerosis. EPIDEMIOLOGY: Progression of intima-media thickness (IMT) of the common carotid arteries over 18 months was determined ultrasonographically and was related to plasma lutein among a randomly sampled cohort of utility employees age 40 to 60 years (n=480). Coculture: The impact of lutein on monocyte response to artery wall cell modification of LDL was assessed in vitro by quantification of monocyte migration in a coculture model of human intima. Mouse models: The impact of lutein supplementation on atherosclerotic lesion formation was assessed in vivo by assigning apoE-null mice to chow or chow plus lutein (0.2% by weight) and LDL receptor-null mice to Western diet or Western diet plus lutein. IMT progression declined with increasing quintile of plasma lutein (P for trend=0.007, age-adjusted; P=0.0007, multivariate). Covariate-adjusted IMT progression (mean+/-SEM) was 0.021+/-0.005 mm in the lowest quintile of plasma lutein, whereas progression was blocked in the highest quintile (0.004+/-0.005 mm; P=0.01). In the coculture, pretreatment of cells with lutein inhibited LDL-induced migration in a dose-dependent manner (P<0.05). Finally, in the mouse models, lutein supplementation reduced lesion size 44% in apoE-null mice (P=0.009) and 43% in LDL receptor-null mice (P=0.02). CONCLUSIONS: These epidemiological, in vitro, and mouse model findings support the hypothesis that increased dietary intake of lutein is protective against the development of early atherosclerosis.

North-American twins with IDDM. Genetic, etiological, and clinical significance of disease concordance according to age, zygosity, and the interval after diagnosis in first twin.

In 224 twin pairs (132 monozygotic, 86 dizygotic, and 6 of uncertain zygosity) in whom the index twin had developed IDDM before 30 yr of age, 51 of the co-twins (38 monozygotic, 10 dizygotic, and 3 of uncertain zygosity) subsequently became diabetic. On the basis of concordance ratios, which were significantly discrepant (P < 0.01) between monozygotic and dizygotic twins, the substantial genetic role in IDDM etiology is confirmed. For the monozygotic co-twin of an IDDM case, the relative risk is significantly related to an early age at proband diagnosis (P < 0.01 for 0-4 vs. 5-9 yr of age). However, among monozygotic co-twins at any age, IDDM risk decreases as time passes after the proband diagnosis (P < 0.01 for 0-23 vs. > or = 24 mo after a proband diagnosis at 5-9 yr of age). Moreover, a structural-equation analysis suggests a profound contribution to liability (as much as 79%) from the twins' shared environment. Risk to like-sex male dizygotic co-twins is as high as that to monozygotic co-twins, significantly higher than that to like-sex female dizygotic co-twins (P < 0.005), and even higher than that to male co-twins in unlike-sex dizygotic pairs (P < 0.05). Overall, the risk to the dizygotic co-twin of a case is significantly higher (P < 0.001) than that to a non-twin sibling, as reported in the literature. The observed male excess is consistent with reported patterns of IDDM in experimental animals, and in certain circumstances in humans. Taken together, these observations suggest an important early acquired determinant of IDDM, independent of genetic determinants. On the basis of Kaplan-Meier IDDM-free survival curves, if the proband is diagnosed before 15 yr of age, the long-term risk to the co-twin is estimated at 44% (monozygotic) and 19% (dizygotic); it reaches 65% for the co-twin of a monozygotic proband diagnosed before 5 yr of age. An IDDM discordant period of no more than 3 yr was observed in 60% of the pairs destined to become concordant, offering a very brief window for intervention following the recognition of high risk.

Serum cholesterol level and mortality due to suicide and trauma in the Honolulu Heart Program.

BACKGROUND: Recent results from cholesterol level-lowering trials and some, but not all, observational studies support an intriguing link between low or lowered serum cholesterol levels and violent death. The reasons behind this relationship are far from clear. METHODS: In this report, we further investigate this issue by assessing the relationship of baseline serum cholesterol levels with long-term risk of mortality due to trauma and suicide in a cohort of 7309 middle-aged Japanese-American men. RESULTS: After 23 years of follow-up, a total of 75 traumatic fatalities and 24 deaths by suicide were documented. Rather than an inverse relation, a positive association between serum cholesterol level and risk of suicide death was observed. After controlling for potential confounders, the relative risk of suicide associated with an increment of 0.98 mmol/L (38 mg/dL) in serum cholesterol level (1 SD) was 1.46 (95% confidence interval, 1.04 to 2.05; P = .02). Multivariate analysis of traumatic mortality failed to detect a relation with serum cholesterol level (relative risk = 0.89; 95% confidence interval, 0.70 to 1.13; P = .44). Heavy alcohol consumption (> 1200 mL of alcohol per month, top quintile) was an independent risk factor for trauma death relative to abstinence (relative risk = 1.86; 95% confidence interval, 1.07 to 3.22; P = .02). CONCLUSIONS: These findings contradict the hypothesis of an inverse relation between serum cholesterol level and suicide, but they support the hypothesis that heavy alcohol consumption is a risk factor for traumatic fatal events.

Longitudinal changes in body fat in African American and Caucasian children: influence of fasting insulin and insulin sensitivity.

Obesity is associated with hyperinsulinemia and reduced insulin sensitivity, both risk factors for type 2 diabetes. However, it is not clear whether these risk factors occur as a result of obesity or whether they contribute to the development of obesity. The aims of this study were to determine whether baseline (first visit) or changes in insulin measures over time were associated with longitudinal changes in body fat mass during growth in children. The study group consisted of 137 children (83 Caucasian and 54 African American) with a mean age of 8.1 yr at baseline. The children returned for 3-6 annual visits for measurement of fasting insulin, insulin sensitivity (Si), and acute insulin response (AIR) from the tolbutamide-modified frequent sampling iv glucose tolerance test and for determination of body composition by dual energy x-ray absorptiometry. Data were analyzed using SAS Proc mixed growth models. Total fat mass increased with time by 15.6%/yr (P = 0.013), but the rate of increase was not significantly influenced by race, sex, or Tanner stage. However, fasting insulin (positive effect), Si (negative effect), and AIR (positive effect) were significantly associated with the rate of increase in fat mass. In conclusion, in this cohort of children, growth-related increases in body fat were significantly associated with increases in fasting insulin and AIR and decreases in Si.

Dietary calcium, calcium supplementation, and blood pressure in African American adolescents.

BACKGROUND: Intake of calcium from the diet is inversely associated with blood pressure in observational studies and animal models but randomized trials in humans have found only small effects of calcium supplementation on blood pressure. A blood pressure-lowering effect of calcium supplementation may thus be restricted to persons with a low intake of calcium from the diet and specific genetic or other characteristics. OBJECTIVE: A randomized trial was conducted to assess the effect of calcium supplementation on blood pressure in African American adolescents. Rapid growth during adolescence may increase calcium requirements, and avoidance of milk and milk products by some African Americans can result in low intake of calcium. DESIGN: One hundred sixteen adolescents (65 girls, 51 boys; mean age: 15.8 y) were given calcium (1.5 g/d) or placebo for 8 wk in a randomized, double-blind, crossover design. Blood pressure was measured after 2, 4, and 8 wk. Dietary calcium was determined with a validated food-frequency questionnaire. RESULTS: The net effect (+/-SE) of calcium supplementation on diastolic blood pressure was a reduction of 1.9 +/- 1.1 mm Hg (P = 0.04, one-tailed t test). Blood pressure reduction was greater in adolescents with lower intake of calcium from the diet (P = 0.003, one-tailed t test for interaction): -4.9 +/- 1.6, -2.3 +/- 1.6, and 1.4 +/- 1.8 mm Hg for change in the lower (0.024-0.067 g Ca/MJ), middle (0.069-0.091 g Ca/MJ), and upper (0.093-0.217 g Ca/MJ) tertiles, respectively. No main effect on systolic blood pressure was detected. CONCLUSION: These findings suggest that calcium supplementation may lower diastolic blood pressure in African American adolescents with low dietary intakes of calcium.

Reproducibility of stress redistribution thallium-201 SPECT quantitative indexes of hypoperfused myocardium secondary to coronary artery disease.

To determine the reproducibility of quantitative indexes of hypoperfused myocardium by exercise thallium-201 single-photon emission computed tomography, duplicate studies were performed in 16 stable patients within 1 month. Twenty-three other patients, with intervals up to 13 months between studies, were retrospectively identified from medical records. Symptoms, weight, heart rate achieved and peak systolic blood pressure during the 2 studies were similar. Maximal counts circumferential profiles' polar maps were generated and divided into 3 vascular territories. The hypoperfused myocardium was defined as the percent stress profile points below the normal level. The observed values were compared between the 2 studies for each patient. Defect size ranged from 0 to 73%. The concordance correlation coefficient (a measure of the closeness of the data points to the line of identity) and mean absolute deviation were 0.94 and 4.5%, respectively, when all patients were considered together, 0.93 and 3.2%, respectively in the reproducibility group, and 0.94 and 5.1%, respectively, in the retrospective group. Inter- and intraobserver reproducibility were also very high. For individual vessels, the concordance correlation coefficients were all > or = 0.89 and the mean absolute deviations between 3.7 and 9%. Thus, in stable patients with repeat thallium studies within a year, the percent hypoperfused myocardium is highly reproducible.

Oral magnesium supplementation inhibits platelet-dependent thrombosis in patients with coronary artery disease.

The use of magnesium in the treatment of acute myocardial infarction remains controversial despite preliminary experimental evidence that magnesium plays a beneficial role as a regulator of thrombosis. This study examines whether oral magnesium treatment inhibits platelet-dependent thrombosis (PDT) in patients with coronary artery disease (CAD). In a randomized prospective, double-blind, crossover, and placebo-controlled study, 42 patients with CAD (37 men, 5 women, mean age 68 +/- 9 years) on aspirin received either magnesium oxide tablets (800 to 1,200 mg/day) or placebo for 3 months (phase 1) followed by a 4-week wash-out period, and the crossover treatment for 3 months (phase 2). PDT, platelet aggregation, platelet P-selectin flow cytometry, monocyte tissue factor procoagulant activity (TF-PCA), and adhesion molecule density were assessed before and after each phase. PDT was evaluated by an ex vivo perfusion model using the Badimon chamber. Median PDT was significantly reduced by 35% in patients who received magnesium versus placebo (delta change from baseline -24 vs 26 mm2/mm; p = 0.02, respectively). There was no significant effect of magnesium treatment on platelet aggregation, P-selectin expression, monocyte TF-PCA, or adhesion molecules. Oral magnesium treatment inhibited PDT in patients with stable CAD. This effect appears to be independent of platelet aggregation or P-selectin expression, and is evident despite aspirin therapy. These findings suggest a potential mechanism whereby magnesium may beneficially alter outcomes in patients with CAD.

Mediating mechanisms in a school-based drug prevention program: first-year effects of the Midwestern Prevention Project.

Describes (a) the effects of a social-influences-based drug prevention program (the Midwestern Prevention Project) on the mediating variables it was designed to change and (b) the process by which the effects on mediating variables changed use of drugs (tobacco, alcohol, and marijuana). Students in 42 middle schools and junior high schools in Kansas City, Missouri, and Kansas City, Kansas, were measured in the fall of 1984 (N = 5,065) and again 1 year later (N = 5,008) after 24 of the schools had been through the program. Compared to students in control schools, students in program schools became less likely to express belief in the positive consequences of drug use, less likely to indicate that they would use such drugs in the future, more likely to report that their friends were less tolerant of drug use, and more likely to believe that they were better able to communicate with their friends about drug or school problems. Change in perceptions of friends' tolerance of drug use was the most substantial mediator of program effects on drug use. There was evidence that intentions to use and beliefs about the positive consequences of use may also mediate program effects on drug use.

Relative effectiveness of comprehensive community programming for drug abuse prevention with high-risk and low-risk adolescents.

This article reviews major risk factors for cigarette smoking, alcohol, and other drug abuse and promising community-based approaches to primary prevention. In a longitudinal experimental study, 8 representative Kansas City communities were assigned randomly to program (school, parent, mass media, and community organization) and control (mass media and community organization only) conditions. Programs were delivered at either 6th or 7th grade, and panels were followed through Grade 9 or 10. The primary findings were (a) significant reductions at 3 years in tobacco and marijuana use and (b) equivalent reductions for youth at different levels of risk. This study provides evidence that a comprehensive community program-based approach can prevent the onset of substance abuse and that the benefits are experienced equally by youth at high and low risk.

Automated intima-media thickness: the Los Angeles Atherosclerosis Study.

Common carotid artery (CCA) intima-media thickness (IMT) from B-mode ultrasound is a widely used measure of early atherosclerosis. This study evaluated within- and between-sonographer reproducibility of automated edge-tracking IMT using a low-cost mobile scanner. B-mode images of the left and right CCA were acquired on two occasions (interval of 2-14 days) by two sonographers for 38 subjects, aged 31-75 y. Reproduciblity error was measured as the mean absolute difference (MAD+/-SEM) and the standard deviation of differences (SDdelta) between repeated measurements. Within-sonographer (MAD=0.027+/-0.006 mm; SDdelta=0.044 mm) and between-sonographer errors (MAD=0.041+/-0.008 mm; SDdelta=0.064) in IMT (mean=0.74, SD=0.14) of a single artery were small compared to those of other protocols. Combined averaging across both body positions and arteries reduced intersonographer MAD by 47% (MAD=0.022+/-0.003 mm; SDdelta=0.029 mm). These data demonstrate that the proposed IMT protocol reduces reproducibility error by more than 50% relative to several protocols used in other major studies.

From early to late adolescence: alcohol use and anger relationships.

PURPOSE: To evaluate the longitudinal relationship of alcohol use in early adolescence to anger in late adolescence. METHODS: Data were collected in Indianapolis, Indiana, from 1987 to 1993 as part of a large drug abuse prevention trial. Fifty percent of the 1201 students were female, 75%, white, and 69%, low socioeconomic status, who were surveyed in grades 6/7, 9/10, and 11/12. Subjects were asked four anger-related questions: "When I have a problem, I get mad at people," "When I have a problem, I do bad things or cause trouble," "When I have a problem, I say or do nasty things," and "I am a hotheaded person." Two additional items asked subjects to report the number of alcoholic drinks consumed and frequency of drunkenness in the past 30 days. Odds ratios (OR) were used to assess the predictive relationship of alcohol use in early adolescence to anger in late adolescence. RESULTS: Early use of alcohol increased the odds of later anger. Specifically, alcohol use in the past month in grade 6/7 increased the odds in grade 11/12 of saying or doing nasty things (OR = 8.23, p < .01), self-reported hotheadedness (OR = 9.72, p < .01), and high anger on a composite anger scale (OR = 4.84, p < .05). Drunkenness in the past month in grade 6/7 increased the odds of self-reported hotheadedness (OR = 6.17, p <.05) and high anger on the anger scale (OR = 3.20, p < .05) in grade 9/10 and doing something bad to cause trouble in grade 11/12 (OR = 24.97, p < .01). For subjects in grade 9/10, alcohol use in the past month increased the odds in grade 11/12 of doing something bad to cause trouble (OR = 2.79, p < .05), saying or doing nasty things (OR = 2.02, p < .05), and self-reported hotheadedness (OR = 2.51, p < .05). CONCLUSIONS: The present study showed that alcohol use in early adolescence was associated with increased anger, both in middle and late adolescence, controlling for gender, age, and socioeconomic status. The findings suggest that alcohol and drug prevention programs delivered in early adolescence may have the capacity to prevent risk for later anger and related violent behavior.

Alcohol outlet density and motor vehicle crashes in Los Angeles County cities.

The extent to which the availability of alcohol encourages alcohol consumption resulting in alcohol-related problems remains controversial. In order to address this issue we used 1990 data from 72 cities within Los Angeles County to estimate the relation between densities of four types of alcohol outlets (restaurants, bars, liquor stores, mini-markets) and rates of two types of alcohol-related motor vehicle crashes reported by police (injury, property damage). After logarithmic transformation of variables, crash rates were regressed on outlet densities and possible demographic confounders. The demographic covariates accounted for 25% of the variance in injury crashes; adding the combined outlet density to the model yielded a significant elasticity estimate (beta +/- SE) (beta = 0.55 +/- 0.13). Separate models for types of outlets yielded significant elasticities for restaurants (beta = 0.22 +/- 0.07), liquor stores (beta = 0.46 +/- 0.17) and mini-markets (beta = 0.34 +/- 0.13), but not for bars (beta = 0.08 +/- 0.07). Alcohol-related crashes resulting in property damage also showed positive associations with outlet densities, but these associations were smaller and reached statistical significance for restaurants (beta = 0.19 +/- 0.11) and bars (beta = 0.21 +/- 0.10). Direction of influence cannot be inferred from these cross-sectional findings, but they do indicate that increased alcohol availability is geographically associated with increased alcohol-related motor vehicle crashes and that this association is independent of measured confounders.

A measurement model of adolescent smoking.

Self report measures of smoking may contain substantial measurement error. If these errors are nonrandom, then they may be correlated with substantive variables in epidemiologic or intervention studies, thus confounding and biasing estimates of structural relations. In efforts to circumvent such bias, investigators have supplemented questionnaires with biological indicators of exposure to tobacco smoke. However, errors in biological indicators may also include systematic errors that produce biased estimates. The current study was designed to estimate the variance of systematic and random errors in self report and two biologic measures of smoking in adolescents. A linear model was fit to data from 342 males and 250 females with repeated measures separated by 1 year. Thiocyanate and self report were found to have substantial nonrandom error components that were correlated with psychosocial variables. In contrast, errors in carbon monoxide in expired air were not autocorrelated, and were uncorrelated with psychosocial variables.

Beneficial antithrombotic effects of the association of pharmacological oral magnesium therapy with aspirin in coronary heart disease patients.

The use of magnesium in the treatment of acute myocardial infarction remains controversial despite preliminary experimental evidence that magnesium plays a beneficial role as a regulator of thrombosis. The aim of our study was to determine whether oral magnesium treatment inhibits platelet-dependent thrombosis (PDT) in stable patients with coronary artery disease (CAD). In a randomized prospective, double-blind, cross-over and placebo controlled study, 42 patients with stable CAD (37 men, 5 women, mean age 68 +/- 9 years) on aspirin received either magnesium oxide tablets (800-1,200 mg/day) or placebo for 3 months (Phase 1) followed by a 4-week washout period, and the cross-over treatment for 3 months (Phase 2). PDT, platelet aggregation, platelet P-selectin flow-cytometry, monocyte tissue factor procoagulant activity (TF-PCA) and adhesion molecules density were assessed before and after each phase. PDT was evaluated by an ex-vivo perfusion model using the Badimon chamber. Median PDT was significantly reduced by 35 percent in patients who received magnesium versus placebo (D change from baseline: -24 vs. 26 microm2/mm; p = 0.02, respectively). There was no significant effect of magnesium treatment on platelet aggregation, P-selectin expression, monocyte TF-PCA or adhesion molecules. Oral magnesium treatment inhibits PDT in patients with stable CAD. This effect appears to be independent of platelet aggregation or P-selectin expression, and is evident despite aspirin therapy. These findings suggest a potential mechanism whereby magnesium may beneficially alter outcomes in patients with CAD.

The left: lateral eye movements and ideology.

The lateral eye movements of 24 college students were videotaped as they reflected on spatial and analytical questions. As predicted, participants with more initial movements to the left had significantly higher scores on the leftist (or humanistic) index of the Tomkin's Polarity Scale. The direction of this relationship was reversed for the rightist index (right movers scoring higher) but this difference was not significant. Results are interpreted as additions to evidence which suggests a connection between the left and right sides of the human body and more global dichotomies of ideology or personality.

Cultural differences in hemisphericity: a critique.

A series of four articles on the "other side" of the brain has been published in this journal by Dr. Joseph Bogen and his colleagues (1, 2, 3, 4). The first three of these are rapidly becoming minor classics for those of us interested in hemispheric specialization. However, the fourth article reports a combination of sociologic and neurologic observations which, in our opinion, are misinterpreted. This misinterpretation stems primarily from the use of inappropriate statistical procedures and the misleading characteristics of a variable which is comprised of a ratio of two other variables (i.e. the A/P ratio). In short, we argue that the sociologic data presented (4) are not consistent with the constant sum model of hemisphericity discussed in that paper. An alternative model is discussed.

Acculturation and low birthweight among Latinos in the Hispanic HANES.

Self reports from 1,645 Latino mothers of Mexican descent who participated in the Hispanic Health and Nutrition Examination Survey (HHANES) were used to relate the birthweight of their infants to the HHANES acculturation index. After controlling for parity, a one point increase on the acculturation scale was found to be associated with a 1.19 (95% CI = 1.05, 1.34) increase in risk of maternal low birthweight (LBW) (1.98 risk increase for four points). The estimated relative risk increased to 1.34 (1.12, 1.60) with controls for age at interview, wealth, city size, and years of education; controlling for current smoking status reduced the relative risk to 1.31. US-born respondents were also at increased risk relative to Mexican-born, but this relation was explained by acculturation. The effect of education was found to depend on level of acculturation. Years of education was unrelated to risk among the Mexican-oriented, while increased education was associated with reduced risk in the US-oriented. These results suggest that factors associated with a Mexican cultural orientation may be protective against the risk of LBW.

Abdominal obesity and carotid artery wall thickness. The Los Angeles Atherosclerosis Study.

OBJECTIVE: To determine whether or not abdominal obesity is associated with the intima-media thickness (IMT) of the carotid artery wall independently of total body obesity and major risk factors for atherosclerosis. DESIGN: : Longitudinal epidemiological study. SUBJECTS: A total of 573 middle-aged employees of a utility company. MEASUREMENTS: Sagittal and transverse abdominal diameters, their ratio and difference were used as measures of abdominal obesity. RESULTS: Abdominal diameters and body mass index (BMI) were significantly associated with blood pressure, serum lipoproteins and fasting insulin. In cross-sectional multiple regression models, the sagittal/transverse ratio and BMI were significantly associated with IMT in the presence of atherosclerosis risk, but the sagittal diameter was not. In longitudinal models, baseline BMI was an independent predictor of IMT progression but the sagittal and transverse diameters were not. CONCLUSION: These findings do not support the hypothesis that abdominal obesity is an independent predictor of carotid artery IMT. The consistent pattern of association of measures of general obesity with carotid artery IMT emphasizes the continuing need for prevention and control of this important risk factor.