Who uses needle exchange? A study of injection drug users in treatment in San Francisco, 1989-1990.

We examined use of the San Francisco needle exchange program (NEP) by 1093 injection drug users (IDUs) recruited in methadone maintenance and out-patient detoxification programs in the first 2 years after the opening of the NEP in 1988. Thirty-one percent of IDUs had ever used the NEP. IDUs who were frequent injectors, homeless, and aware of their serostatus were more likely to use the NEP. To assess self-selection of IDUs at risk for seroconversion for using needle exchange, we calculated pre-needle exchange seroconversion rates. Among 385 IDUs seen twice, the HIV seroconversion rate was 0.38% per person year among subjects who never used needle exchange, but it was 9.34% per person year among those who later used needle exchange (p = 0.003). NEP attracted a subset of IDUs at very high risk for HIV infection. Among injectors who were interviewed before and after the opening of the needle exchanges in San Francisco, the number of sharing partners did not change among IDUs who attended or among IDUs who never attended the NEP. The NEP attracted a very-high-risk subgroup of IDUs, as measured by risk behavior and pre-needle exchange HIV-seroconversion rate. NEPs should be considered prime sites for behavior-change interventions.

The associations of high-density lipoprotein subclasses with insulin and glucose levels, physical activity, resting heart rate, and regional adiposity in men with coronary artery disease: the Stanford Coronary Risk Intervention Project baseline survey.

We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the associations of high-density lipoprotein (HDL) subclasses with adiposity, physical activity, resting heart rate (an indicator of sympathetic drive), and plasma insulin and glucose levels in 97 men with angiographically documented coronary artery disease. These men neither smoked nor used medications known to affect lipoproteins. The absorbency of protein stain was used as an index of mass concentrations at intervals of 0.01 nm within five HDL subclasses: HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12 nm). HDL peak diameter was determined from the predominant peak of the HDL particle distribution when plotted against particle diameter. Four men who were non-insulin-dependent diabetics as defined by a fasting glucose exceeding 140 mg/dL had significantly higher plasma HDL3b levels and significantly smaller HDL peak diameters than nondiabetic men, and were therefore excluded from further analyses. In the remaining 93 nondiabetic men, plasma HDL3b levels correlated positively with indices of truncal obesity (waist to hip ratio and subscapular skinfold), whereas plasma HDL2b levels correlated negatively with indices of total adiposity (body mass index [BMI]) and truncal obesity (subscapular and abdominal skinfold). Fasting plasma insulin levels correlated negatively with HDL3a, HDL2a, and HDL2b. Obesity significantly affected the relationships of resting heart rate with insulin and HDL subclasses.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of weight loss by exercise or by dieting on plasma high-density lipoprotein (HDL) levels in men with low, intermediate, and normal-to-high HDL at baseline.

To assess whether baseline plasma high-density lipoprotein (HDL) cholesterol levels affected the HDL response to weight loss, we examined lipoprotein changes in overweight men aged 30 to 59 years who were randomized to lose weight by exercise training (primarily running, n = 46) or by caloric restriction (ie, dieting, n = 42) or to remain sedentary, nondieting controls (n = 42) in a 1-year study. In exercisers, absolute increases in HDL (mg/dL) were greatest in men with normal-to-high baseline HDL and least in men with low baseline HDL. Specifically, when divided into groups of low (< or = 37 mg/dL), intermediate (38 to 47 mg/dL), and normal-to-high HDL cholesterol (> or = 48 mg/dL) at baseline, the exercisers increased HDL cholesterol by 2.3 +/- 1.9, 4.9 +/- 1.1, and 7.0 +/- 1.3 mg/dL, respectively; HDL2 cholesterol by 0.8 +/- 1.6, 2.3 +/- 1.2, and 5.1 +/- 1.3 mg/dL; and HDL2 mass by 2.8 +/- 5.1, 9.5 +/- 8.9, and 31.7 +/- 11.0 mg/dL. Relative increases in HDL cholesterol were more similar in the low (7.1% +/- 6.1%), intermediate (12.4% +/- 3.9%), and normal-to-high men (13.2% +/- 4.0%). Regression analyses were performed to assess whether baseline HDL cholesterol was related to the amount of absolute HDL change per unit of weight loss. In exercisers, the increase in HDL3 cholesterol concentrations was significantly greater in men with low HDL than in those with normal-to-high HDL at entry (2.0 +/- 0.8 v 0.2 +/- 0.8 mg/dL per kg/m2 lost).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of low-fat diet, calorie restriction, and running on lipoprotein subfraction concentrations in moderately overweight men.

We studied the effects of exercise (primarily running), calorie restriction (dieting), and a low-fat, high-carbohydrate diet on changes in lipoprotein subfractions in moderately overweight men in a randomized controlled clinical trial. After 1 year, complete data were obtained for 39 men assigned to lose weight through dieting without exercise, 37 men assigned to lose weight through dieting with exercise (primarily running), and 40 nondieting sedentary controls. We instructed both diet groups to consume no more than 30% total fat, 10% saturated fat, and 300 mg/d of cholesterol, and at least 55% carbohydrates, and the controls were instructed to maintain their usual food choices. Analytic ultracentrifugation was used to measure changes in plasma lipoprotein mass concentrations. In addition, the absorbance of protein-stained polyacrylamide gradient gels was used as an index of concentrations for five high-density lipoprotein (HDL) subclasses that have been identified by their particle sizes, ie, HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12 nm). Relative to controls, weight decreased significantly in men who dieted with exercise (net difference +/- SE, -3.3 +/- 0.4 kg/m2) and in men who dieted without exercise (-2.0 +/- 0.4 kg/m2). Dieting with exercise significantly decreased very-low-density lipoprotein (VLDL)-mass concentrations and significantly increased plasma HDL2-mass, HDL3a, HDL2a, and HDL2b relative to both control and dieting without exercise. There were no significant changes in lipoprotein mass and HDL protein for dieters who did not run.(ABSTRACT TRUNCATED AT 250 WORDS)

Associations of age, adiposity, alcohol intake, menstrual status, and estrogen therapy with high-density lipoprotein subclasses.

We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the associations of age, adiposity, alcohol intake, and exogenous estrogen with high-density lipoprotein (HDL) subclasses in 427 members of 51 principally Mormon kindreds. The absorbency of protein stain was used as an index of mass concentrations at intervals of 0.01 nm within five HDL subclasses: HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12 mm). Age and alcohol intake were obtained from questionnaires, and body mass index was computed from clinic measurements as weight (kg)/height (m)2. The results suggest that HDL3b concentrations were higher after menopause than before. Adult men (> or = 18 years old) had significantly higher HDL3c and HDL3b and significantly lower HDL2b and HDL2a levels than younger boys. Compared with the women, adult men had higher levels of HDL3c and HDL3b and lower levels of HDL2b, HDL2a, and larger-diameter HDL3a particles. There were no significant differences between the HDL profiles of women and younger boys, suggesting that divergence in HDL occurs during puberty. Eighty-eight percent of the increase in HDL associated with estrogen replacement in postmenopausal women occurred within HDL3a and HDL2a. Reported alcohol intake in adult men correlated with two HDL regions: one within the HDL2b region and a second within the HDL3a/2a region, whereas in women the positive correlation between alcohol and HDL levels was within the HDL2b region only. In both men and premenopausal adult women, increasing levels of body mass index were associated with higher levels of HDL3b and lower levels of HDL2b.(ABSTRACT TRUNCATED AT 250 WORDS)

Familial correlations of HDL subclasses based on gradient gel electrophoresis.

We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the familial correlations of high density lipoprotein (HDL) subclasses for 150 offspring in 47 nuclear families. The absorbance of protein stain was used as an index of mass concentrations at intervals of 0.01 nm within five HDL subclasses: HDL3c (7.2-7.8 nm), HDL3b (7.8-8.2 nm), HDL3a (8.2-8.8 nm), HDL2a (8.8-9.7 nm), and HDL2b (9.7-12 nm). Parent-offspring correlations were computed for two different characterizations of the parents: 1) by sex (i.e., mother versus father) and 2) by their relative values (highest versus lowest HDL). Sibling resemblance was assessed by using the intraclass correlations coefficient. Family members were significantly related for the following subclasses: HDL3c (sibling and father-offspring), HDL3b (sibling), HDL3a (sibling and mother-offspring), HDL2a (mother-offspring), and HDL2b (sibling, father-offspring, and mother-offspring). The offsprings' HDL3c and HDL2b values were more strongly related to their fathers' than to their mothers' values, whereas their HDL2a levels were more strongly related to their mothers' than their fathers' values. In addition, fathers' HDL2b levels were inversely correlated with the offsprings' HDL3b. The parents' HDL subclass levels were more strongly related to subclass levels of their younger (< or = 20 years) than their older offspring. Among all subclasses, HDL2b showed the strongest parent-offspring relation, with the parents' HDL values accounting for over 30% of the variance in offsprings' HDL2b.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in laboratory values in HIV infection by sex, race, and risk group.

OBJECTIVES: To determine differences in CD4+ and CD8+ lymphocyte values, beta 2-microglobulin (beta 2M), and HIV p24 antigenemia by sex and race among HIV-seropositive and HIV-seronegative injecting drug users (IDU), and to compare these values with those in homosexual men of equivalent status. DESIGN: Baseline values from a cohort of 206 HIV-seropositive and 173 HIV-seronegative IDU were compared with values from a cohort of 288 HIV-seropositive homosexual men and 176 HIV-seronegative controls, who were prospectively followed at 6-month intervals, to examine differences in laboratory values in HIV-infected individuals by sex, race, and risk group. METHODS: Among HIV-seropositives, we compared white and black IDU only (n = 167), and white male IDU (n = 38) with white homosexual men (n = 256). Laboratory values from the cohort of homosexual men at 24, 36 and 48 months of follow-up were compared with IDU values. RESULTS: HIV-infected female IDU had significantly higher CD4+ lymphocyte counts (P < 0.03) and percentages of CD4+ lymphocytes (P < 0.004) than male IDU, resulting in higher CD4:CD8 ratios (P < 0.002). White IDU had significantly higher serum beta 2M levels than black IDU (P < 0.02). Black female IDU were much less likely to be HIV p24-antigenemic (1%) than all other groups (P < 0.005). Compared with homosexual men, male IDU had significantly elevated beta 2M levels (0.58 mg/l higher). When controlled for CD4+ lymphocyte values as a surrogate for length of time HIV-infected, beta 2M and HIV p24 antigenemia differences persisted. CONCLUSIONS: These differences should be considered when HIV p24 antigen, CD4+ lymphocyte counts and beta 2M levels are used as surrogate markers in clinical trials and management of HIV disease.

Correlations of plasma lipoproteins with LDL subfractions by particle size in men and women.

Nondenaturing gradient gel electrophoresis of plasma low density lipoprotein (LDL) has been used to identify major LDL subclasses that are influenced by genetic and other factors. In the present paper, this technique has been extended by measuring absorbance of lipid- or protein-stained gels as an index of concentration at intervals of 0.05 nm across the entire LDL particle size range (21.8-30 nm) in moderately overweight men (n = 115) and women (n = 78). When LDL absorbance levels were correlated with other lipoprotein variables, we found that the strengths of the correlations with each of triglycerides, apolipoprotein (apo) B, high density lipoprotein (HDL)2, and apoA-I achieve relative maximum values for two regions within the small LDL range (21-26 nm), one within LDL-IVB (22-23.2 nm) and a second within LDL-III (24.2-25.5 nm). We also found that the increase in LDL accompanying higher triglyceride levels occurs below 25.5 nm in men and between 24.5 and 26.5 nm in women, suggesting either that triglycerides are related to different LDL subclasses in men and women, or that particle sizes of metabolically homologous LDL subclasses may differ in men and women. As compared to analytic ultracentrifuge measurements, gradient gel measurements of LDL absorbance by the procedure described here provide greater resolution of LDL subclasses but less precision in estimating LDL levels.

Effects of weight-loss by exercise and by diet on apolipoproteins A-I and A-II and the particle-size distribution of high-density lipoproteins in men.

We studied separately the effects of weight-loss by dieting or by running on apolipoprotein (apo) A-I, apo A-II, and high-density lipoprotein (HDL) subfractions in sedentary, moderately overweight men assigned at random into three groups: exercise without calorie restriction, calorie restriction without exercise, and control. The absorbance of protein-stained polyacrylamide gradient gels was used as an index of mass concentrations for five HDL subclasses that have been identified by their particle sizes: HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12.9 nm). During the 1-year trial, the exercisers ran (mean +/- SD) 15.6 +/- 9.1 km/wk, and the dieters reported eating 340 +/- 71 fewer calories per day than at baseline. Total body weight and fat weight were both reduced significantly more in dieters (-7.2 +/- 4.1 and -6.2 +/- 4.1 kg, respectively) and in exercisers (-4.0 +/- 3.9 and -4.6 +/- 3.5 kg) than in controls (0.6 +/- 3.7 and -0.7 +/- 2.7 kg). As compared with mean changes in controls, exercisers and dieters each decreased HDL3b and increased HDL2b. Exercisers also significantly increased plasma apo A-I concentrations. Analysis of covariance was used to statistically adjust the mean lipoprotein changes for the effects of weight-loss. The adjustment eliminated the significant reductions in HDL3b and the significant increases in HDL2b in exercisers and dieters, and it eliminated the significant increase in apo A-I in exercisers. When adjusted, the dieters' mean changes in HDL2b had significantly decreased relative to those of both exercisers and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Associations of lipoproteins and apolipoproteins with gradient gel electrophoresis estimates of high density lipoprotein subfractions in men and women.

We examined the relations of gender and lipoproteins to subclasses of high density lipoproteins (HDLs) in a cross-sectional sample of moderately overweight men (n = 116) and women (n = 78). The absorbance of protein-stained polyacrylamide gradient gels was used as an index of mass concentrations of HDL at intervals of 0.01 nm across the entire HDL particle size range (7.2-12 nm). At least five HDL subclasses have been identified by their particle sizes: HDL3c (7.2-7.8 nm), HDL3b (7.8-8.2 nm), HDL3a (8.2-8.8 nm), HDL2a (8.8-9.7 nm), and HDL2b (9.7-12 nm). Men had significantly higher HDL3b and significantly lower HDL2a and HDL2b than did women. Correlations of HDL subclasses with concentrations of other lipoprotein variables were generally as strong for gradient gel electrophoresis as for analytical ultracentrifugation measurements of HDL particle distributions. In both sexes, high levels of HDL3b were associated with coronary heart disease risk factors, including high concentrations of triglycerides, apolipoprotein B, small low density lipoproteins, intermediate density lipoproteins, and very low density lipoproteins and low concentrations of HDL2 cholesterol and HDL2 mass. Plasma concentrations of HDL3 cholesterol were unrelated to protein-stained HDL3b levels. HDL3 cholesterol concentrations also did not exhibit the sex difference or the relations with lipoprotein concentrations that characterized HDL3b. Thus, low HDL3b levels may contribute in part to the low heart disease risk in men and women who have high HDL cholesterol. Measurements of HDL3 cholesterol may not identify clinically important relations involving HDL3b.

Crack use and human immunodeficiency virus infection among San Francisco intravenous drug users.

The relationship between crack use, human immunodeficiency virus (HIV) infection, and risk behavior among 1281 intravenous drug users in treatment is analyzed. Of these patients, 23% reported crack use, and blacks and women were more likely to use crack. Of crack users 19% were HIV positive, in comparison to 8% of non-users (OR = 2.9, P = 0.0001). In multivariate analysis, the association was no longer significant (OR = 1.4, P = 0.14). Independent behavioral predictors of HIV seropositivity were number of sexual partners, and intravenous cocaine use among blacks. Crack use was a marker for high-risk sexual and drug use behavior in the study population.

Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk.

In a community-based study of 301 subjects from 61 nuclear families, two distinct phenotypes (denoted A and B) were identified by nondenaturing gradient gel electrophoretic analysis of low density lipoprotein (LDL) subclasses. Phenotype A was characterized by predominance of large, buoyant LDL particles, and phenotype B consisted of a major peak of small, dense LDL particles. Previous analysis of the family data by complex segregation analysis demonstrated that these phenotypes appear to be inherited as a single-gene trait. In the present study, the phenotypes were found to be closely associated with variations in plasma levels of other lipid, lipoprotein, and apolipoprotein measurements. Specifically, phenotype B was associated with increases in plasma levels of triglyceride and apolipoprotein B, with mass of very low and intermediate density lipoproteins, and with decreases in high density lipoprotein (HDL) cholesterol, HDL2 mass, and plasma levels of apolipoprotein A-I. Thus, the proposed genetic locus responsible for LDL subclass phenotypes also results in an atherogenic lipoprotein phenotype.

Identifying the predominant peak diameter of high-density and low-density lipoproteins by electrophoresis.

Particle size distributions of high-density (HDL) and low-density (LDL) lipoproteins, obtained by polyacrylamide gradient gel electrophoresis, exhibit apparent predominant and minor peaks within characteristic subpopulation migration intervals. In the present report, we show that identification of such peaks as predominant or minor depends on whether the particle size distribution is analyzed according to migration distance or particle size. The predominant HDL peak on the migration distance scale is frequently not the predominant HDL peak when the distribution is transformed to the particle size scale. The potential physiologic importance of correct identification of the predominant HDL peak within a gradient gel electrophoresis profile is suggested by our cross-sectional study of 97 men, in which diameters associated with the predominant peak, determined using migration distance and particle size scales, were correlated with plasma lipoprotein and lipid parameters. Plasma concentrations of HDL-cholesterol, triglycerides, and apolipoproteins A-I and B correlated more strongly with the predominant peak obtained using the particle size scale than the migration distance scale. The mathematical transformation from migration distance to particle diameter scale had less effect on the LDL distribution. The additional computational effort required to transform the HDL-distribution into the particle size scale appears warranted given the substantial changes it produces in the gradient gel electrophoresis profile and the strengthening of correlations with parameters relevant to lipoprotein metabolism.

The effects of polyunsaturated fat vs monounsaturated fat on plasma lipoproteins.

The effect on plasma lipoproteins of exchanging fat type within currently recommended reduced-fat diets was studied in a free-living group of 19 men and 20 women who consumed both a polyunsaturated fat-enriched diet and a monounsaturated fat-enriched diet, each for a 12-week period, with saturated fat and cholesterol held constant. Mean plasma concentrations of low-density lipoprotein cholesterol and low-density lipoprotein total mass (analytic ultracentrifuge), and high-density lipoprotein (HDL) cholesterol and HDL total mass, did not change significantly on exchanging fat type. However, HDL2 cholesterol concentration was 50% higher and HDL3 cholesterol concentration was 7% lower for polyunsaturated compared with monounsaturated fat. Mean total mass of HDL2 was also 23.5% higher and concentration of apolipoprotein B was 5.4% lower on transfer to the polyunsaturated fat diet. Contrary to frequent assertions, we find no advantage with respect to plasma HDL concentrations in using predominantly monounsaturated rather than polyunsaturated fats in subjects who consumed reduced-fat, solid-food diets.

The effect of weight loss by dieting or exercise on resting metabolic rate in overweight men.

While resting metabolic rate (RMR) is known to decline during periods of energy restriction, the effect of exercise training during weight loss on RMR is less clear. We studied separately the effect of energy restriction and exercise training on weight loss and RMR in a one-year randomized, controlled trial. One hundred twenty-one overweight, sedentary men (age 30-59) who were randomly assigned to a control (C), energy restriction only (D), or exercise only (E) group were examined at baseline and after one year for changes in RMR as measured by standard indirect calorimetry. Relative to controls, E increased fitness and jogged an average of 9.97 +/- 5.6 miles/week and did not change energy intake while D significantly reduced energy consumption. Both groups achieved significant weight loss and fat mass loss when compared to the controls at the end of one year. After one year, the D group showed a small yet significant decline in RMR (kcal/h and kcal/FFM/h) when compared to controls and exercisers, while the E group showed no significant changes. Therefore, in moderately overweight men, a one-year program of weight loss by energy restriction produced a significant decline in RMR while weight loss by exercise did not change RMR.

Changes in lipoprotein subfractions during diet-induced and exercise-induced weight loss in moderately overweight men.

We studied separately the effects of weight loss by calorie restriction (dieting) and by calorie expenditure (primarily, running) on lipoprotein subfraction concentrations in sedentary, moderately overweight men assigned at random into three groups as follows: exercise without calorie restriction (n = 46), calorie restriction without exercise (n = 42), and control (n = 42). Plasma lipoprotein mass concentrations were measured by analytic ultracentrifugation for flotation rates (F0(1.20), S0f) within high density lipoprotein (HDL) (F0(1.20) 0-9), low density lipoprotein (LDL) (S0f 0-12), intermediate density lipoprotein (IDL) (S0f 12-20), and very low density lipoprotein (VLDL) (S0f 20-400) particle distributions. Particle diameter and flotation rate of the most abundant LDL species were determined by nondenaturing polyacrylamide gradient gel electrophoresis and analytic ultracentrifugation, respectively. During the 1-year trial, the exercisers ran (mean +/- SD) 15.6 +/- 9.1 km/wk, and the dieters ate 340 +/- 71 fewer kilocalories per day than at baseline. Total body weight was reduced significantly more in dieters (-7.2 +/- 4.1 kg) and exercisers (-4.0 +/- 3.9 kg) than controls (0.6 +/- 3.7 kg). As compared with mean changes in controls, the exercisers and dieters significantly increased HDL2 mass (48.6% and 47.1%, respectively), decreased VLDL mass (-23.9% and -25.5%), and increased LDL peak particle diameter (2.4 and 3.2 A). When adjusted to an equivalent change in body mass index by analysis of covariance, 1) exercise-induced and diet-induced weight loss produced comparable mean changes in the mass of small LDL and VLDL, and in LDL peak particle diameter; 2) the exercisers versus control group difference in HDL2 was attributed to the exercisers' reduced body mass index; and 3) HDL2 increased significantly less in dieters than in exercisers. In dieters, low calorie intake might mitigate the effects of weight loss on HDL2.

Effects of exercise-induced weight loss on low density lipoprotein subfractions in healthy men.

One-year changes in low density lipoprotein (LDL) peak flotation (Sf) rate and serum mass concentrations of LDL of Sf 0 to 7 (small LDL), LDL of Sf 7 to 12 (large LDL), intermediate density lipoprotein (IDL) of Sf 12 to 20, and very low density lipoprotein (VLDL) of Sf 20 to 400 were compared between men assigned at random to a 1-year exercise program (N = 48) or to a sedentary control condition (N = 31). Distance run among exercisers varied substantially (mean +/- SD: 12.7 +/- 8.9 km/week). Mean changes were not significantly different between the exercise and control groups for any of the low to very low density lipoprotein measurements. However, within the exercise group: 1) distance run correlated negatively with changes in the mass concentrations of small LDL; and 2) weight loss and reduced upper body obesity correlated positively with changes in small LDL, IDL, and VLDL mass and negatively with change in LDL peak flotation rate. Analyses with partial correlations suggest that weight loss may primarily affect LDL mass distributions through metabolic processes associated with high density lipoprotein2 or small VLDL (Sf 20 to 60). The decrease in small LDL concentrations and the increase in LDL peak flotation rate suggest that exercise-induced weight loss may be effective in reducing coronary heart disease risk in persons genetically predisposed to a high-risk lipoprotein profile.

Inheritance of low-density lipoprotein subclass patterns: results of complex segregation analysis.

Heterogeneity in the size of low-density lipoprotein (LDL) particles was used to identify two distinct patterns based on gradient gel electrophoresis analysis. These two phenotypes, LDL subclass pattern A and pattern B, were characterized by a predominance of large, buoyant LDL particles and small, dense LDL particles, respectively. The inheritance of these LDL subclass patterns was investigated in a sample of 61 healthy families including 301 individuals. LDL subclass pattern B was present in 31% of the subjects, with the prevalence varying by gender, age, and (in women) menopausal status. Complex segregation analysis suggested a major locus controlling LDL subclass patterns. The model providing the best fit to the data included a dominant mode of inheritance with a frequency of .25 for the allele determining LDL subclass pattern B and reduced penetrance for men under age 20 and for premenopausal women. Thus, the allele for the LDL subclass pattern characterized by a predominance of small, dense LDL particles appears to be very common in the population, although not usually expressed until adulthood in men and until after menopause in women. The presence of a major gene controlling LDL subclass could explain much of the familial aggregation of lipid and apolipoprotein levels and may be involved in increased risk of coronary heart disease.

Changes in plasma lipids and lipoproteins in overweight men during weight loss through dieting as compared with exercise.

We studied separately the influence of two methods for losing fat weight on the levels of plasma lipids and lipoproteins in overweight sedentary men--decreasing energy intake without increasing exercise (diet), and increasing energy expenditure without altering energy intake (exercise, primarily running)--in a one-year randomized controlled trial. As compared with controls (n = 42), dieters (n = 42) had significant loss of total body weight (-7.8 +/- 0.9 kg [mean +/- SE]), fat weight (-5.6 +/- 0.8 kg), and lean (non-fat) weight (-2.1 +/- 0.5 kg) (P less than 0.001 for each variable), and exercisers (n = 47) had significant loss of total body weight (-4.6 +/- 0.8 kg) and fat weight (-3.8 +/- 0.7 kg) (P less than 0.001 for both variables) but not lean weight (-0.7 +/- 0.4 kg). Fat-weight loss did not differ significantly between dieters and exercisers. All subjects were discouraged from altering their diet composition; however, dieters and exercisers had slight reductions in the percentage of kilojoules derived from fat. As compared with the control group, both weight-loss groups had significant increases (P less than 0.01) in plasma concentrations of high-density lipoprotein (HDL) cholesterol (diet vs. exercise, 0.13 +/- 0.03 vs. 0.12 +/- 0.03 mmol per liter), HDL2 cholesterol (0.07 +/- 0.02 vs. 0.07 +/- 0.02 mmol per liter), and HDL3 cholesterol (0.07 +/- 0.02 vs. 0.06 +/- 0.02 mmol per liter) and significant decreases (P less than 0.05) in triglyceride levels (diet vs. exercise, -0.35 +/- 0.14 vs. -0.24 +/- 0.12 mmol per liter). Levels of total and low-density lipoprotein cholesterol were not significantly changed, relative to values in controls. None of these changes were significantly different between dieters and exercisers. Thus, we conclude that fat loss through dieting or exercising produces comparable and favorable changes in plasma lipoprotein concentrations.

Blood cholesterol treatment attitudes of community physicians: a major problem.

Blood cholesterol treatment attitudes of community physicians are an important component of the NIH recommendation to reduce blood cholesterol. To determine current blood cholesterol treatment attitudes, a survey of 2413 multispecialty Northern California physicians was conducted. A total of 793 physicians responded. Results show that treatment habits among medical specialties are similar with a tendency for lower initial treatment levels in the subspecialties of endocrinology and cardiology. No specialty or subspecialty group indicated an aggressive plasma lipid treatment attitude. The findings include the following: Mean values at which physicians reported treating hypercholesterolemia with medication (312 +/- 44 mg/dl) exceed the NIH definition of "high risk." Younger physicians treated hypercholesterolemia with diet at significantly lower blood cholesterol levels than did older colleagues (p = 0.04). Physicians exposed to the CPPT-LRC investigation did not show a difference in treatment attitudes with regard to blood cholesterol levels when compared to physicians without such an experience. The type of lipid-lowering medication used differs significantly among medical specialties and subspecialties. Physicians lack confidence in the precision of laboratory measurement of plasma lipids. Physician treatment attitudes require substantial change if the NIH cholesterol consensus conference goals are to be achieved.