Biomedical subjects

D S Freedman

Publications and source records attributed to D S Freedman.

At least 55 records · Page 3Linked to original sources

PubMed1992

Cholesterol and coronary artery disease: age as an effect modifier.

An elevation of serum cholesterol has been one of the more frequently cited risk factors for coronary heart disease, found in both case-control and cohort studies. As a result, this country has undertaken massive screening of adults older than 20 years of age in an attempt to identify those persons with cholesterol levels greater than 200 mg/dl, and follow up with an active approach for intervention. The suggested cutpoints for borderline (200-240 mg/dl), and definite (> or = 240 mg/dl) hypercholesterolemia have been applied to all age groups despite suggestions of a diminution of risk conferred by cholesterol in the elderly. This study of 2544 white men undergoing coronary angiography shows that for all men, aged 25-84 years, plasma cholesterol levels were associated with an increase in coronary artery occlusion (rs = 0.15, p < 0.01). However, when stratified by age, this association held only for the younger men, the association diminishing to near zero in the oldest age group. The negative interaction between cholesterol levels and age in predicting coronary artery disease proved highly significant (p < 0.001) in multivariable linear regression analysis, suggesting that cholesterol levels are much less predictive of coronary artery disease in the elderly as compared to the young. These results point to the need for a more finely tuned set of criteria for the evaluation of hypercholesterolemia, one that takes into account the age of the screenee.

Adult↗

PubMed1992

Interpretation of linear regression models that include transformations or interaction terms.

In linear regression analyses, we must often transform the dependent variable to meet the statistical assumptions of normality, variance stability, or linearity. Transformations, however, can complicate the interpretation of results because they change the scale on which the dependent variable is measured. In this setting, the inclusion of product terms or the transformation of some independent (or predictor) variables may further complicate interpretation. In this article, we present some interpretations of linear models that include transformations or product terms. We illustrate these interpretations using regression analyses designed to study determinants of serum testosterone levels. These examples show how one can present results using simple measures, such as medians, and interpret regression parameters.

Epidemiologic Methods↗

PubMed1992

Education, race, and high-density lipoprotein cholesterol among US adults.

OBJECTIVES: Although educational achievement is positively related to levels of high-density lipoprotein cholesterol (HDL-C) among White adults, there is an inverse association among Blacks. We assessed whether this interaction could be attributed to differences in the relation of education to correlates of HDL-C. METHODS: Cross-sectional analyses were based on data from 8391 White and 995 Black adults who participated in the Second National Health and Nutrition Examination Survey. RESULTS: Associations between education and HDL-C levels varied from negative (Black men), to nearly nonexistent (White men and Black women), to positive (White women). Mean HDL-C levels were higher among Blacks than among Whites, but differences varied according to educational achievement. Among adults with less than 9 years of education, mean levels were 6 to 10 mg/dL higher among Blacks, but the radical difference was less than 1 mg/dL among adults with at least 16 years of education. About 20% to 40% of these differences could be accounted for by obesity, alcohol consumption, and other characteristics. CONCLUSIONS: Because of the implications for coronary heart disease risk, consideration should be given to behavioral characteristics associated with the interaction between race and educational achievement.

Adult↗

PubMed1992

Tracking of serum cholesterol levels in a multiracial sample of preschool children.

The relation of an initial measurement of serum total cholesterol to subsequent levels over a (mean) 13-month interval was examined in a multiracial (white, Hispanic, American Indian, and black) sample of 1680 one- to four-year-olds. Although the relation of the initial level to the final measurement (r = .54) did not vary by race, sex, relative weight, or changes in relative weight, the association increased with age at the time of the initial measurement (eg, r = .64 among 4-year-olds). Based on the initial and final total cholesterol determinations, the within-person standard deviation was 21 mg/dL and the coefficient of variation was 13%. Although the final total cholesterol level was within 5 mg/dL of the initial level for 18% of the children, the two determinations differed by greater than or equal to 25 mg/dL for about 35% of the children and by greater than or equal to 50 mg/dL for about 8%. Of the 149 children who had an initial cholesterol level greater than or equal to 200 mg/dL, 34% (about five times the expected number) had a follow-up level that was similarly elevated whereas 25% had a subsequent measurement below 170 mg/dL. The results indicate that although an initial cholesterol level in early life is moderately predictive of subsequent levels, it may be difficult to interpret a single total cholesterol determination because of substantial within-person variability.

Child, Preschool↗

PubMed1991

Relationships between the proton nuclear magnetic resonance properties of plasma lipoproteins and cancer.

We conducted a comprehensive investigation of the origin of nuclear magnetic resonance (NMR) lineshape variability of plasma lipids among healthy individuals and those with cancer. The methyl and methylene resonances of lipid in human plasma, whose linewidths have been reported to correlate with the presence of malignancy, are composed of the overlapping resonances of "mobile" protons from the major lipoproteins (very-low-, low-, and high-density lipoproteins). We tested two hypotheses for the origin of the narrower plasma linewidths observed for cancer patients: (a) malignancy-associated differences in the spectral properties (chemical shift, lineshape) of one or more of the lipoproteins, and (b) differences in the fraction of lipoprotein lipid giving rise to detectable NMR signal. Analysis of the concentrations of lipoprotein lipid and of 500 MHz NMR spectra of the lipoprotein constituents in greater than 100 plasma samples failed to provide support for either hypothesis. Although linewidths were found to be significantly narrower for the cancer group, the difference is entirely attributable to differences in the concentrations of the lipoproteins.

Adult↗

PubMed1990

Differences between black and white men in correlates of high density lipoprotein cholesterol.

Although socioeconomic status has been positively related to levels of high density lipoprotein (HDL) cholesterol in white Americans, limited evidence suggests that an inverse association may exist among blacks. These associations were further examined using data collected in 1985-1986 from 3,562 white and 500 black men who ranged in age from 31 to 45 years. Overall, mean levels of HDL cholesterol were 8 mg/dl higher among blacks than among whites and, in each group, levels were related positively to alcohol consumption and negatively to Quetelet index and cigarette smoking. A statistically significant interaction, however, was observed between race and educational achievement: no association was seen between educational achievement and levels of HDL cholesterol among white men, but there was an inverse association among blacks. For example, a 13 mg/dl (55 vs. 42 mg/dl) difference in levels of HDL cholesterol was observed between black and white men who did not complete high school, but only a 3 mg/dl black excess (47 vs. 44 mg/dl) was seen among college graduates. About 40 percent of this reduction could be attributed to the effects of cigarette smoking, alcohol consumption, and relative weight. These results indicate that the higher levels of HDL cholesterol frequently found among black men in the United States may not apply to all social strata. Other characteristics, such as physical activity and diet, may account for the differing race-specific associations with educational achievement.

Adult↗

PubMed1990

Body fat distribution and male/female differences in lipids and lipoproteins.

The role of body fat distribution, as assessed by the ratio of waist-to-hip circumferences (WHR), in statistically explaining differences in levels of lipoproteins between men and women was studied using data collected in 1985-1986 from employed adults (mean age, 40 years). As compared with the 415 women, the 709 men had higher mean levels of triglycerides (+38 mg/dl) and apolipoprotein B (+11 mg/dl) as well as lower mean levels of high density lipoprotein (HDL) cholesterol (-15 mg/dl) and apolipoprotein A-I (-19 mg/dl). Additionally, men were more overweight, consumed more alcohol, and exercised more frequently than women but were less likely to smoke cigarettes. Controlling for these characteristics, however, did not alter the differences in lipoprotein levels between men and women. In contrast, adjustment for WHR (which was greater among men) reduced the sex differences in levels of apolipoprotein B (by 98%), triglycerides (by 94%), HDL cholesterol (by 33%), and apolipoprotein A-I (by 21%). Similar results were obtained using analysis of covariance, stratification, or matching; at comparable levels of WHR, differences in lipid and lipoprotein levels between men and women were greatly reduced. Although these results are based on cross-sectional analyses of employed adults and need to be replicated in other populations, the findings emphasize the relative importance of body fat distribution. Whereas generalized obesity and body fat distribution are associated with lipid levels, fat distribution (or a characteristic influencing fat patterning) can be an important determinant of sex differences in levels of triglycerides, HDL cholesterol, and apolipoproteins B and A-I.

Adipose Tissue↗

PubMed1989

Polymorphism in the 5'-flanking region of the insulin gene and its potential relation to cardiovascular disease risk: observations in a biracial community. The Bogalusa Heart Study.

The gene frequencies of a polymorphism in the 5'-flanking region of the insulin gene and its relationship to cardiovascular disease risk were studied in a well defined population of children (mean age 5.5 years) from a biracial community. The BglII endonuclease was used for digestion of the DNA around this polymorphic region. The risk factors studied included parental and grandparental self-reported histories of myocardial infarction and diabetes mellitus, fasting glucose and insulin levels, lipoprotein, cholesterol, and triglyceride levels, and skinfold thicknesses and weight. Four alleles were observed at this locus, with the class 2 allele being significantly more common among blacks than whites. Among white children, the class 3 allele was associated with increased risk for grandparental diabetes mellitus. White children with 2 copies of the class 3 allele had significantly higher levels of glucose. Black children with a copy of the class 3 allele had significantly higher levels of insulin. This study indicates that the class 3 allele is potentially associated with risk for diabetes mellitus and coronary heart disease that can be observed in childhood.

Alleles↗

PubMed1989

Risk factors and the anatomic distribution of coronary artery disease.

Differences in the importance of risk factors according to the anatomic location of coronary artery disease (CAD) were assessed in 4722 men and 1069 women who underwent arteriography. Examined characteristics included total and high-density lipoprotein (HDL)-cholesterol, triglycerides, obesity, smoking, alcohol consumption, diabetes, and hypertension. Of these risk factors, the ratio of total to HDL-cholesterol showed the highest correlation with the overall severity of CAD (r = 0.24, men; r = 0.38, women); in contrast, its relation to left main (LM) disease was much lower (r = 0.10, men; r = 0.08 women) than were correlations with stenotic disease in the left anterior descending, circumflex, and right coronary arteries. Other risk factors also showed weaker associations with LM disease than with stenoses in other vessels, and none was related to increased LM disease after controlling for disease in other vessels. For example, as compared with men who had no significant CAD, those with 1-, 2-, and 3-vessel disease had mean increases in total cholesterol of 12, 18, and 19 mg/dl, respectively. In contrast, after adjusting for disease in other vessels, LM disease (present in 293 men) was associated with only a 4 mg/dl increase in mean cholesterol levels (P = 0.20). These results indicate that the relation of risk factors to CAD differs according to the location of the stenotic disease, and that LM disease is poorly predicted by the standard risk factors.

Adult↗

PubMed1989

Health risks of obesity.

Evidence implicating obesity as a risk-factor disease is critically reviewed. Possible reasons for the many conflicting findings are addressed. The classification of obesity, based upon the site of body fat distribution, and possible biologic mechanisms associating regional adiposity with morbidity, are discussed.

Adipose Tissue↗

PubMed1989

Relation of body fat patterning to lipid and lipoprotein concentrations in children and adolescents: the Bogalusa Heart Study.

Although a truncal distribution of adipose tissue in adults is associated with several metabolic complications, its importance in early life has received little attention. The relation of several anthropometric measures to serum concentrations of lipids, lipoproteins, and apolipoproteins was therefore examined in 361 children who were between ages 6 and 18 y. (Children had been selected previously because of extreme levels of very-low-density- and low-density-lipoprotein cholesterol.) Analyses revealed two groups of anthropometric variables: truncal measures (waist circumference and subscapular, subcostal, and suprailiac skinfold thicknesses) and thickness of peripheral skinfolds (femoral, triceps, calf, and biceps). After generalized obesity was adjusted for children with high concentrations of both cholesterol fractions had more truncal fat but less peripheral fat than did children with low lipoprotein cholesterol concentrations. A truncal fat pattern was also associated with decreased concentrations of high-density-lipoprotein cholesterol and apolipoprotein A-1. Knowledge of fat patterning may help identify persons prone to hyperlipidemia.

Adipose Tissue↗

PubMed1989

Risk factors in early life as predictors of adult heart disease: the Bogalusa Heart Study.

The adult heart diseases, coronary artery disease and essential hypertension, are now clearly recognized to begin in childhood. The evidence comes from autopsy studies of cardiovascular-renal changes in the first two decades of life. Cardiovascular risk factors can be identified in children just as in adults and these have a high correlation with the anatomic disease. This relationship underscores the importance of risk factor screening of children. Of interest is that clinical risk factors tend to persist within a rank (track) so that studies in childhood can be predictive of future levels. Behavior and lifestyle of eating, cigarette smoking, alcohol intake, and use of oral contraceptive pills influence risk factors in children. Familial aggregation of risk factors are also noted. Studies of apolipoproteins, B and A-I, have identified subsets of children that have a greater frequency of paternal myocardial infarction. The findings from the Bogalusa Heart Study and other epidemiological studies of children show the need to begin prevention of adult heart disease in early life. Approaches to prevention should include high risk families and children and a public health or population approach. Cardiovascular health education for elementary school children should be directed to children in the general population in an effort to encourage them to adopt healthy life styles.

Aging↗

PubMed1989

Cigarette smoking and non-fatal myocardial infarction in women: is the relation independent of coronary artery disease?

The relation of cigarette smoking to both coronary disease and non-fatal myocardial infarction was examined in a cross sectional study of 1053 women who underwent coronary arteriography. As compared with the 489 women who had never smoked cigarettes, ever-smokers (mean duration of smoking, 25 years) were 1.6 times as likely to have significant stenotic disease and were 1.9 times as likely to have suffered a myocardial infarction. These associations were strongest in women under 50 years of age, with odds ratios of 3.5 for coronary artery disease and 4.5 for myocardial infarction. Although the extent of stenotic disease and prior myocardial infarction were strongly associated, women who smoked cigarettes remained at increased risk of a myocardial infarction even after their increased coronary artery disease had been taken into account. For example, heavy smokers (greater than 30 pack-years) were 2.3 times as likely to have had a myocardial infarction as were non-smokers; controlling for the extent of stenotic disease (in addition to age and other risk factors) reduced the estimated relative risk to only 1.9. Stratified analyses showed that this increased risk for clinical disease among smokers was evident at all levels of occlusion, even among women with minimal stenotic disease. These results, collected at the time of arteriography, suggest that non-atherogenic mechanisms may be important in the aetiology of myocardial infarction among women who smoke cigarettes.

Coronary Artery Disease↗

PubMed1989

The relation of body fat distribution, as assessed by six girth measurements, to diabetes mellitus in women.

Independently of the amount of adipose tissue, certain patterns of fat distribution increase the risk of non-insulin-dependent diabetes. Although the ratio of waist to hip (WHR) circumferences has been consistently related to diabetes mellitus, it is possible that only two measures do not completely characterize fat topography. The current study, therefore, examines the cross-sectional relation of six girths (waist, hip, neck, bust, wrist, and ankle) to diabetes mellitus in 43,595 women. As compared with non-diabetics, Quetelet index (kg/m2) and all circumferences were elevated among diabetics. Stratified analyses showed that WHR, and waist, neck, and bust girths were consistently related to diabetes independently of the degree of overweight. As estimated from a logistic regression model that simultaneously controlled for age and all anthropometric variables, the prevalence of diabetes mellitus was positively related to Quetelet index, and to the waist, bust, and neck girths, with odds ratios (ORs) ranging from 1.4 to 2.6. However, diabetes was inversely related to hip (OR = 0.61) and ankle (OR = 0.73) girths; p less than 0.005 for each association. Although cross-sectional in nature, these results suggest that an adverse body fat distribution is not limited to the abdominal region, but that a relative preponderance of adipose tissue in various regions of the upper body is associated with diabetes mellitus in women.

Adipose Tissue↗

PubMed1988

Use of 86Rb and 22Na in assaying active and cotransport activities in human erythrocytes in a biracial population.

A defect in Na+-K+ transport across the red cell membrane has been shown to be associated with essential hypertension. A sensitive assay system to measure active, co- and countertransport systems in erythrocytes from normotensive adults was developed. Active, co- and countertransport systems in the erythrocytes were assayed by measuring the influx of radioactive 22Na+ and 86Rb+. In the biracial (black-white) population group studied, analysis of variance of the active transport showed a significant race effect (p = 0.003). Cotransport activity showed age by race interaction (p = 0.001) and age by sex (p = 0.02). Cotransport activity was significantly higher in whites than blacks (p = 0.0001). Countertransport activity did not vary either by sex or race. Of the Spearman correlation coefficients for transport activities and blood pressure, white males showed a strong positive correlation with countertransport, whereas in black males, blood pressures showed a strong interaction with active transport. Among the transport activities, active transport showed significant interaction with countertransport activity in black males, whereas cotransport activity in whites showed a strong interaction with countertransport. The results suggest a subtle difference in Na+-K+ transport systems between blacks and whites, and these variations may be related to differences for susceptibility to essential hypertension.

Adult↗

PubMed1988

Black/white differences in risk factors for arteriographically documented coronary artery disease in men.

Although the leading cause of death among black men in the United States is coronary artery disease (CAD), risk factors have not been well documented in black populations. Therefore, possible racial differences in the relation of several characteristics to the extent of CAD were assessed in 4,722 white and 169 black men who underwent arteriography. Associations between an occlusion score (ranging from 0 to 300), reflecting the severity of CAD, and levels of total and high-density lipoprotein (HDL) cholesterol, triglycerides, cigarette smoking, alcohol intake, relative weight, systemic hypertension and diabetes mellitus were examined. Most risk factors were significantly related to the extent of CAD in both races, but lipid levels showed stronger associations with CAD among blacks: correlations between CAD and total cholesterol were 0.16 (whites) vs 0.29 (blacks) and associations with HDL cholesterol were -0.22 (whites) vs -0.49 (blacks). In addition, at adverse levels of certain risk factors, blacks had more extensive CAD than did whites: mean occlusion scores were 148 (whites) and 238 (blacks) at HDL cholesterol levels less than 30 mg/dl. As assessed by multiple linear regression, however, only triglyceride levels were differentially related to CAD between whites (beta = 0) and blacks (beta = 0.47), p less than 0.01 for racial contrast. These results document the importance of risk factors in black men and indicate black/white differences in the relation of triglycerides to CAD.

Adult↗

PubMed1988

Diabetes mellitus and arteriographically-documented coronary artery disease.

Diabetics are at increased risk for coronary heart disease even after accounting for other risk factors, and the impact of diabetes mellitus may be particularly strong among females and at adverse levels of other risk factors. Therefore, the independent relation of diabetes to arteriographically-documented coronary artery disease (CAD) was examined in 5620 patients (18% female) referred to two Milwaukee hospitals from 1972 to 1986. As assessed by questionnaire, the prevalence of diabetes mellitus among these patients was 8% (n = 466). Diabetics had increased CAD (assessed by the number and severity of stenoses) even after accounting for levels of total and high-density lipoprotein cholesterol, triglycerides, hypertension, obesity, smoking, and alcohol consumption. In addition, regression analyses indicated that as compared with nondiabetics, female diabetics tended to have a greater increase in CAD than did male diabetics (p = 0.06 for sex x diabetes interaction). Although adverse levels of other risk factors did not increase the association between diabetes and CAD, female diabetics who were using oral hypoglycemics or insulin showed almost a two-fold increase in CAD severity (p less than 0.01). Results suggest that the higher relative risk of coronary heart disease among female (vs male) diabetics may be due to a proportionately greater increase in atherosclerosis.

Adult↗

PubMed1988

Relation of triglyceride levels to coronary artery disease: the Milwaukee Cardiovascular Data Registry.

Although levels of triglycerides have consistently shown a strong association with cardiovascular disease in both case-control and cohort studies, it remains controversial whether this relation exists independently of levels of cholesterol and other risk factors. The association of arteriographically documented coronary artery disease with plasma levels of triglycerides, total cholesterol, and high density lipoprotein (HDL) cholesterol was therefore examined in 5,216 white adults (81% were male) referred to two Milwaukee hospitals between 1972 and 1986. Elevated levels of triglycerides were related to the extent of coronary artery disease (estimated using the total number and severity of stenoses) in both sexes; this association existed independently of total cholesterol, age, obesity, hypertension, smoking, and alcohol consumption. In addition, the association between triglycerides and coronary artery occlusion was strongest at total cholesterol levels less than or equal to 250 mg/dl. However, both stratified and regression analyses indicated there was no residual association between triglyceride levels and occlusion after controlling for HDL cholesterol. (Levels of HDL cholesterol and triglycerides showed a moderate inverse association: r = -0.39 to -0.51.) These results indicate that the association between coronary artery occlusion and levels of triglycerides is indirect, and that the disparate findings of earlier studies may have resulted from not controlling for HDL cholesterol.

Aged↗