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Biomedical subjects

E J Schaefer

Publications and source records attributed to E J Schaefer.

At least 127 records · Page 7Linked to original sources
PubMed1996

Lipoproteins, apolipoproteins, and low-density lipoprotein size among diabetics in the Framingham offspring study.

Diabetes mellitus has been shown to be associated with lipid abnormalities. Prior studies have indicated that women with diabetes have a risk of coronary heart disease similar to that of men. We compared lipid parameters in diabetic and nondiabetic participants in cycle 3 of the Framingham Offspring Study. Values for plasma total cholesterol (TC), triglyceride, lipoprotein, cholesterol, apolipoprotein (apo) A1, B, apo and lipoprotein(a) [Lp(a)] and low-density lipoprotein (LDL) particle size were analyzed in 174 diabetic and 3,757 nondiabetic subjects. Data from a total of 2,025 men and 2,042 women participating in the third examination (1983 to 1987) of the Framingham Offspring Study were subjected to statistical analysis. Male and female diabetics showed lower high-density lipoprotein (HDL) cholesterol, higher triglycerides, higher very-low-density lipoprotein (VLDL) cholesterol, lower apo A1, and higher LDL particle scores, indicating smaller size, than nondiabetics. Female diabetics also showed significantly higher TC and apo B values than nondiabetics. The results remained statistically significant after controlling for obesity and menopausal status. The presence of small dense LDL particles (pattern B) was highly associated with diabetes and hypertriglyceridemia in both sexes, and the relative odds for pattern B remained significant in women but not in men after adjustment for age and hypertriglyceridemia. No differences in apo E isoform distribution were found for diabetics and nondiabetics. Diabetes was not associated with elevated LDL cholesterol levels. In conclusion, diabetics have lower HDL cholesterol and higher triglyceride levels and are more likely to have small dense LDL particles. Diabetes is not a secondary cause of elevated LDL cholesterol. Lipid screening of diabetics should include full quantification of lipids for proper assessment of potential atherosclerotic risk.

Adult↗
PubMed1996

Effects of National Cholesterol Education Program Step 2 diets relatively high or relatively low in fish-derived fatty acids on plasma lipoproteins in middle-aged and elderly subjects.

The effects of two National Cholesterol Education Program (NCEP) Step 2 diets (< or = 30% of energy as total fat, < 7% of energy as saturated fat, and < 200 mg cholesterol/d), one relatively high and the other relatively low in fish-derived fatty acids, on plasma lipoprotein concentrations and blood pressure were compared in 22 men and women with a mean (+/- SD) age of 63 +/- 10 y. Subjects were placed on a baseline diet similar to the diet currently consumed in the United States (35% of energy as total fat, 14% of energy as saturated fat, 35 mg cholesterol/MJ) for 6 wk and then on either an NCEP Step 2 diet relatively high in fish (Step 2 high-fish, n = 11) or relatively low in fish (Step 2 low-fish, n = 11) for 24 wk. All food and drinks were provided. Compared with baseline values, consumption of both the Step 2 high-fish and the Step 2 low-fish diets under weight-stable conditions was associated with significant decreases in plasma concentrations of total cholesterol (-14% and -19%, respectively), low-density-lipoprotein (LDL) cholesterol (-15% and -20%, respectively), and high-density-lipoprotein (HDL) cholesterol (-11% and -17%, respectively). Postprandial, but not fasting, triacylglycerol concentrations were significantly reduced during consumption of the Step 2 high-fish diet. There were no significant changes in these indexes after consumption of the Step 2 low-fish diet compared with the baseline diet. LDL particle size decreased significantly (-12%) only in subjects on the Step 2 low-fish diet. Both Step 2 diets caused small but significant reductions in diastolic blood pressure. Our results indicate that NCEP Step 2 diets relatively high or relatively low in fish are both effective in significantly reducing total and LDL-cholesterol concentrations without changes in the ratio of total cholesterol to HDL cholesterol under controlled weight-stable conditions in middle-aged and elderly subjects. A beneficial effect on diastolic blood pressure was also observed.

Aged↗
PubMed1996

Relationship between plasma homocysteine, vitamin status and extracranial carotid-artery stenosis in the Framingham Study population.

Recent studies demonstrated associations between occlusive vascular disease and hyperhomocysteinemia of both genetic and nutritional origin. In the present study we analyzed plasma samples from the 20th biannual examination of the Framingham Heart Study cohort to determine distribution of plasma homocysteine concentrations with emphasis on relationships to B vitamins and prevalence of carotid artery stenosis. Results showed that homocysteine exhibited strong inverse association with plasma folate and weaker associations with plasma vitamin B-12 and pyridoxal-5'-phosphate (PLP). Homocysteine was also inversely associated with intakes of folate and vitamin B-6, but not vitamin B-12. Prevalence of high homocysteine (>14 micromol/l) was 29.3% in this cohort, and inadequate plasma concentrations of one or more B vitamins appear to contribute to 67% of the cases of high homocysteine. Prevalence of stenosis > or = 25% was 43% in men and 34% in women with an odds ratio of 2.0 for individuals in the highest homocysteine quartile (> or = 14.4 micromol/l) compared with those in the lowest quartile (< or = 9.1 micromol/l), after adjustment for sex, age, high density lipoprotein cholesterol, systolic blood pressure and cigarette smoking (Ptrend < 0.001). Plasma concentrations of folate and pyridoxal-5'-phosphate and folate intake were inversely associated with extracranial carotid stenosis after adjustment for age, sex and other risk factors.

Aged↗
PubMed1996

Apolipoprotein E alleles and risk of coronary disease. A meta-analysis.

A meta-analysis was undertaken to assess the impact of apolipoprotein E (apo E) alleles (epsilon 2, epsilon 3, and epsilon 4) on coronary disease in 14 published observational studies (9 clinical coronary disease and 5 coronary angiography). In comparison with epsilon 3, the epsilon 4 allele was associated with greater odds for coronary heart disease, and summary estimates of the odds ratios (ORs) and (95% confidence intervals) for both sexes combined were OR = 0.98 (0.85-1.14) for epsilon 2 and OR = 1.26 (1.13-1.41) for epsilon 4. Separate analyses for men and women showed similar associations. In angiographic studies the relative odds for significant coronary artery disease among both sexes combined was OR = 0.76 (0.55-1.05) for epsilon 2 and OR = 1.11 (0.88-1.40) for epsilon 4. The overall impression is that epsilon 4 is associated with clinical and coronary disease and that results are similar in men and women.

Adolescent↗
PubMed1996

Impact of body mass index on coronary heart disease risk factors in men and women. The Framingham Offspring Study.

Increased body weight has been associated with an increased risk of morbidity and mortality from coronary heart disease (CHD) in several populations. We studied the distribution of body mass index (BMI, kg/m2) in men (n = 1566; mean age, 49 +/- 10 years) and women (n = 1627; mean age, 49 +/- 10 years) participating in the third examination cycle of the Framingham Offspring Study and the association of BMI with known CHD risk factors. In men, BMI increased with age until age 50 years, when it reached a plateau. In women, there was a trend toward an increase in BMI with age up to the seventh decade of life. Seventy-two percent of men and 42% of women had a BMI > or = 25.00, the cutoff point for the definition of overweight. In age-adjusted analyses, BMI was significantly and linearly associated with systolic blood pressure, fasting glucose levels, plasma total cholesterol, VLDL cholesterol, and LDL cholesterol levels and was inversely and linearly associated with HDL cholesterol levels (P < .001) in nonsmoking men and women. The association between BMI and apolipoprotein B and A-I was similar to that of LDL and HDL cholesterol, respectively. LDL size was also linearly associated with BMI: subjects with higher BMI had smaller LDL particles. Lipoprotein(a) levels were not associated with BMI in this population. Of all these risk factors for CHD, reduced HDL cholesterol levels and hypertension were those more strongly associated with higher BMI in both men and women. Elevated triglyceride levels and small LDL particles, and diabetes in women, were also strongly associated with higher BMI values in this population. Our results indicate that a high prevalence of adult Americans are overweight and support the concept that increased BMI is associated with an adverse effect on all major CHD risk factors. These results emphasize the importance of excess body fat as a public health issue.

Adolescent↗
PubMed1996

Effects of diet and exercise on qualitative and quantitative measures of LDL and its susceptibility to oxidation.

The purpose of this study was to investigate the effects of an intensive diet and exercise program on the quantity and quality of LDL as well as its susceptibility to in vitro oxidation. The diet was low in fat (< 10% kcal) and cholesterol (< 100 mg/d), while high in complex, unrefined carbohydrates (> 70% kcal) and fiber (35 g/1000 kcal). The study was composed of 80 participants in a 3-week residential program where food was provided ad libitum and there was daily aerobic exercise, primarily walking. In each subject, preparticipation and postparticipation fasting blood samples were drawn and LDL was isolated via density gradient ultracentrifugation. LDL particle diameter was determined by gradient gel electrophoresis of serum (n = 23). Isolated LDL was either separated into 6 subfractions by saline gradient equilibrium ultracentrifugation (n = 26) or subjected to in vitro copper oxidation (n = 32). Significant reductions (P < .01) in serum levels of cholesterol (20%). LDL-cholesterol (20%), HDL-cholesterol (17%), triglycerides (26%), and glucose (16%) as well as in body weight (4%) were noted for the total population. The mean particle diameter of the LDL increased (24.2 +/- 0.2 to 25.1 +/- 0.14 nm, P < .01) and was correlated with the reduction in serum triglycerides (r = .58, P < .01). Six of 22 subjects changed in LDL phenotype from B (< or = 25.5 nm) to A (> 25.5 nm). The percentage of LDL-cholesterol carried in the more dense subfractions fell significantly, while that carried by the less dense fractions increased. Initial oxidation levels fell (21%), while the lag time before copper-induced oxidation increased (13%). Reductions were observed in both the rate of oxidation (16%) and peak oxidation (20%). All of these changes should result in a dramatic reduction in the risk for atherosclerosis and its clinical sequelae.

Centrifugation, Density Gradient↗
PubMed1996

Apolipoprotein E epsilon4 association with dementia in a population-based study: The Framingham study.

Apolipoprotein E type 4 allele (apoE epsilon4) is associated with Alzheimer's disease (AD) in the late-onset familial form and in sporadic cases, but the age-associated risk in a randomly sampled elderly population is not established. We examined the association of apoE epsilon4 with AD and other dementias (mainly multi-infarct or dementia following stroke) in 1,030 persons aged 71 to 100 years in the population-based Framingham Study cohort. Kaplan-Meier survival analysis revealed that 55% of the apoE epsilon4/epsilon4 homozygotes developed AD by age 80, whereas 27% of apoE epsilon3/epsilon4 heterozygotes developed AD by age 85, and 9% of those without a 4 allele developed AD by age 85 years. In comparison with persons without a 4 allele, the risk ration for AD was 3.7 (95% CI = 1.9 to 7.5) for apoE epsilon3/epsilon4 heterozygotes and 30.1 (95% CI = 10.7 to 84.4) for apoE epsilon4 homozygotes. ApoE epsilon2 (2/2, 2/3, or 2/4 genotypes) was associated with an absence of AD. One-half (n=21) of the 43 AD patients were either homozygous or heterozygous for apoE epsilon4. We found evidence for an association of apoE epsilon4 with other dementia, primarily multi-infarct dementia and stroke. The risk ratio was 2.3 (95% CI = 0.9 to 6.1) for non-AD dementias among persons with apoE epsilon3/epsilon4. Although the apoE epsilon4 allele is a potent risk factor for AD and may be associated with other forms of dementia, most apoE epsilon4 carriers do not develop dementia, and about one-half of AD is not apoE epsilon4 associated. The low positive predictive value of this marker (0.10) suggest that use of apoE genotyping as a screening test for AD is not supported.

Adult↗
PubMed1996

Reference intervals for plasma apolipoprotein A-1 determined with a standardized commercial immunoturbidimetric assay: results from the Framingham Offspring Study.

We have evaluated a commercially available, standardized immunoturbidimetric assay of apolipoprotein (apo) A-I, the major protein constituent of high-density lipoproteins (HDL). We determined the reference ranges of plasma apo A-I concentration for white men and women and related these values to the risk of coronary heart disease (CHD). The mean between-run CV for this assay was 2.9%. As determined with individuals participating cycle 4 of the Framingham Offspring Study, the mean (+/- SD) apo A-I concentration was 13% lower in 1879 men (1.34 +/- 0.23 g/L) than in 1939 women (1.54 +/- 0.28 g/L) (P<0.001). An apo A-I concentration of 1.20 g/L roughly corresponded to the 25th percentile value in men and the 5th percentile in women, and subjects with a concentration below this value were significantly more likely to have CHD than subjects wit a higher concentration (P<0.001).

Adult↗
PubMed1996

Reference intervals for plasma apolipoprotein B determined with a standardized commercial immunoturbidimetric assay: results from the Framingham Offspring Study.

We evaluated a commercially available, standardized immunoturbidimetric assay for apolipoprotein (apo) B, the protein constituent of low-density lipoprotein (LDL), to establish reference ranges for men and women, and to determine the concentrations associated with increased risk of coronary heart disease (CHD). The between-run CV for assay of a normal-concentration control for this assay was 6.60%. The mean (+/-SD) apo B concentration was 1.03 +/- 0.24 g/L in 1880 men, significantly higher than the mean for 1944 women (0.96 +/- 0.26 g/L) participating in cycle 4 of the Framingham Offspring Study (P<0.001). An apo B value of 1.20 g/L corresponded roughly to the 75th percentile in men, similar to an LDL cholesterol concentration of 1.60 g/L, and subjects with concentrations greater than this were significantly more likely to have CHD than subjects with apo B concentrations less than 1.00 g/L, the approximate 50th percentile (P<0.05 in men and P<0.001 in women).

Adult↗
PubMed1996

The impact of physical activity on lipids, lipoproteins, and blood pressure in preadolescent girls.

OBJECTIVE: Inconsistent findings reported for the effect of physical activity on lipids, lipoproteins, and blood pressure in children may be due to errors inherent in the methods used to measure physical activity, lack of control for other cardiovascular risk factors, or both. The purpose of this study was to evaluate the association between physical activity assessed using direct measures of energy expenditure and cardiovascular risk factors, controlling for dietary intake and percent body fat. METHODS: Nonresting energy expenditure was determined in 49 8- to 11-year-old girls from measurements of daily energy expenditure (using doubly-labeled water, 2H2(18)O) and resting metabolic rate (using indirect calorimetry). Self-reported recall of the hours of participation in physical activities of at least moderate intensity (energy expenditure at least four times the resting metabolic rate, METS > or = 4) during the previous year was also obtained. Percent body fat was estimated from the measurement of total body water with H2(18)O. Concentrations of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B), apo A-I, lipoprotein (a), insulin, and estradiol, as well as the waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, and dietary intake from 7-day food records were measured. Data were analyzed using Pearson product-moment correlation and stepwise multiple regression. RESULTS: Self-reported hours of participation in activities with METS (metabolic equivalents) of 4 or greater significantly predicted LDL-C and apo B concentrations, even after adjustment for percent body fat and percentage of dietary energy from saturated fat. Nonresting energy expenditure adjusted for weight, a measure of the energy spent on physical activity, did not predict LDL-C or high-density lipoprotein cholesterol concentrations. Body mass index and insulin concentration predicted systolic and diastolic blood pressure, respectively. CONCLUSIONS: These findings suggest that the intensity of physical activity may be a more important determinant of LDL-C in children than the energy spent on physical activity.

Anthropometry↗
PubMed1996

Effects of gender and menopausal status on plasma lipoprotein subspecies and particle sizes.

The risk of coronary heart disease (CHD) is lower in women than in men, but increases in women after menopause. Some of the gender, age, and menopausal-related differences in CHD risk may relate to differences in lipoprotein subspecies. We therefore examined these subspecies in three groups of healthy subjects: premenopausal women (W, n = 72, mean age 41.2 +/- 6.5), postmenopausal women (PMW, n = 74, 55.8 +/- 7.4), and men (M, n = 139, 48.8 +/- 10.7). We measured plasma levels of lipids, lipoprotein cholesterol, apolipoproteins A-I, A-IV, B, C-III, and E, and lipoprotein subspecies Lp A-I, Lp A-I:A-II, Lp B, Lp B:C-III, and Lp B:E, as well as LDL and HDL particle sizes. Our data indicate that women have significantly higher values of HDL-C, apoA-I, apoE, and Lp A-I; larger LDL and HDL particle sizes; and lower values of triglyceride, apoB, and Lp B:C-III particles than men, with no difference in Lp A-I:A-II. Postmenopausal status was associated with significantly higher values of total cholesterol, triglyceride, VLDL-C, and LDL-C; increased levels of apoB, C-III, and E; elevated values of Lp B, Lp B:C-III, and Lp B:E; and lower levels of HDL-C along with smaller HDL particle size. Moreover, we noted a strong correlation between LDL and HDL particle size. Our data are consistent with the concepts that male gender confers decreases in HDL subspecies due to lower Lp A-I levels; while postmenopausal status results in higher levels of all apoB-containing lipoproteins (Lp B, Lp B:C-III, and Lp B:E). The lipoprotein alterations associated with male gender and postmenopausal status would be expected to increase CHD risk.

Adult↗
PubMed1996

Differences in LDL subspecies involve alterations in lipid composition and conformational changes in apolipoprotein B.

In order to investigate causes of variability in low density lipoprotein (LDL) particle size, we have assessed LDL composition in plasma from 66 subjects, each with a single LDL band, by 2-16% gradient gel electrophoresis, with a total of eight discrete sizes (LDL-1 to LDL-8). Lipoprotein concentrations were analyzed by standard methods; specific proteins were assessed by immunoassay and electrophoresis. Results showed decreased anhydrous molecular weight with size (2.67 +/- 0.07 x 10(6) to 1.78 +/- 0.19 x 10(6)), along with decreased relative content for cholesteryl ester (41.5% to 24.3%), free cholesterol (10.1% to 4.6%), and phospholipid (23.7% to 18.9%), and increased triglyceride (4.1% to 21.0%) and protein (20.5% to 31.2%) content. As LDL size decreased, the ratio of surface cholesterol to phospholipid decreased from 0.53 to 0.29, and the fraction of surface area covered by lipid decreased from 0.74 to 0.47. Moreover, core volume decreased with size from 24.2 A3 x 10(5) to 15.9 A3 x 10(5), and the ratio of surface-to-core lipids fell from 0.59 to 0.46. Based on surface pressures of 30 mN/m, the area covered by surface lipid was calculated to range from 6.45 A2 x 10(4) in the largest LDL, to 3.10 A2 x 10(4) in the smallest. Computer modeling indicates that alterations in the tertiary structure of apoB-100 are required to account for surface changes. The estimated core surface area requiring coverage by apoB increased with decreasing particle size from 2.26 A2 x 10(4) to 3.46 A2 x 10(4). To accommodate coverage of increasing relative surface area associated with decreasing size, apoB thickness at the interface was calculated to decrease from approximately 25 A to 16 A. Such conformational changes in apoB may alter exposed epitopes, possibly causing changes in LDL receptor binding affinity and resistance to oxidation.

Adult↗
PubMed1996

Frequency of phenotype-genotype discrepancies at the apolipoprotein E locus in a large population study.

Apolipoprotein E (apoE) genotypes were determined in a random subset of 1041 subjects enrolled in the Framingham Offspring Study by using DNA amplification followed by restriction isotyping. The results were compared with the apoE phenotypes previously assessed by isoelectric focusing. Discrepancies in apoE allele assignment were found in 98 subjects (9.4%). Both genotype and phenotype were reassessed in these subjects. Genotype misclassification was observed in 20 subjects, whereas the initial phenotype assignment was modified in 46 subjects. No concordance between apoE phenotype and genotype remained in 32 subjects (3.07%). Both methods resulted in similar apoE allele frequencies. Furthermore, no differences were observed regarding the average allelic effect on total cholesterol, LDL cholesterol, or HDL cholesterol concentrations; however, a significant difference was noted on triglyceride concentrations. Our results indicate that most discrepancies between genotype and phenotype assessment of apoE polymorphism were due to sample mishandling, data entry, and technical difficulties rather than true discordances.

Adult↗
PubMed1995

Body weight and low-density lipoprotein cholesterol changes after consumption of a low-fat ad libitum diet.

OBJECTIVE: To assess the effects of a diet restricted in fat, saturated fat, and cholesterol, under weight-maintenance and ad libitum conditions on body weight and plasma lipid levels in hypercholesterolemic subjects. DESIGN: Dietary intervention study. SETTING AND PARTICIPANTS: Twenty-seven free-living, healthy middle-aged and elderly men (n = 13, age range, 41 to 81 years) and women (n = 14, age range, 52 to 79 years) with moderate hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] > or = 3.36 mmol/L [130 mg/dL]) participated in the study. INTERVENTION: Subjects underwent three dietary phases. First, subjects were provided with a diet similar to the average US diet (baseline diet; 35.4% total fat, 13.8% to 14.1% saturated fat, and 30 to 35 mg/1000 kJ [128 to 147 mg/1000 kcal] cholesterol). During the second dietary phase, subjects consumed a low-fat diet (15.1% total fat, 5.0% saturated fat, 17 mg/1000 kJ [73 mg/1000 kcal] cholesterol). During the baseline and low-fat diet phases, which lasted 5 to 6 weeks each, the energy intake was adjusted to keep body weight constant. During the third diet phase (low-fat ad libitum diet) subjects were given the same low-fat diet for 10 to 12 weeks, but could adjust their intake between 66% and 133% of the energy required to maintain body weight. MAIN OUTCOME MEASURES: Body weight and plasma lipid levels. RESULTS: Consumption of the low-fat diet under weight-maintenance conditions had significant lowering effects on plasma total cholesterol (TC), LDL-C, and high-density lipoprotein cholesterol (HDL-C) levels (mean change, -12.5%, -17.1%, and -22.8%, respectively). This diet significantly increased plasma triglyceride levels (+47.3%) and the TC/HDL-C ratio (+14.6%). In contrast, consumption of the low-fat ad libitum diet was accompanied by significant weight loss (3.63 kg), by a mean decrease in LDL-C (124.3%), and by mean triglyceride levels and TC/HDL-C ratio that were not significantly different from values obtained at baseline. CONCLUSIONS: Our results indicate that a low-fat ad libitum diet promotes weight loss and LDL-C lowering without adverse effects on triglycerides or the TC/HDL-C ratio in middle-aged and elderly men and women with moderate hypercholesterolemia.

Aged↗
PubMed1995

Identification and molecular analysis of two apoB gene mutations causing low plasma cholesterol levels.

BACKGROUND: Familial hypobetalipoproteinemia (FHB) is an autosomal codominant disorder characterized by abnormally low plasma levels of apoB and LDL cholesterol. Heterozygotes for FHB almost always have plasma LDL cholesterol levels < 70 mg/dL and are asymptomatic. Because the low cholesterol levels may protect FHB heterozygotes from coronary heart disease, the mechanisms for FHB are of considerable interest. METHODS AND RESULTS: The plasma lipoproteins of 29 subjects with LDL cholesterol levels < 70 mg/dL were examined by SDS-PAGE. One subject who had virtually undetectable levels of LDL cholesterol had a truncated apoB, apoB-44.4, in his lipoproteins; a second subject with an LDL cholesterol level of 44 mg/dL had apoB-55 in his lipoproteins. The apoB-44.4 (2014 amino acids in length) resulted from a frameshift caused by an 11-bp insertion in exon 26 of the apoB gene; the apoB-55 (2494 amino acids) was caused by a nonsense mutation in exon 26 of the apoB gene. The apoB-55 mutation occurred at a CpG dinucleotide pair, a mutational hot spot, and was identical to a mutation described previously in a subject with hypobetalipoproteinemia. Our subject with apoB-55, however, had a different haplotype than the subject described previously, suggesting that the two apoB-55 mutations may have arisen independently. Of note, the apoB-55 proband's father, who had very low cholesterol levels and who probably carried the apoB-55 mutation, had significant coronary and aortic atherosclerosis at autopsy. CONCLUSIONS: In a study of adults with low LDL cholesterol levels, we discovered two subjects with truncated apoB proteins and identified the responsible mutations. ApoB gene mutations causing truncated apoB are not particularly rare in subjects with low cholesterol levels. The role of these mutations in preventing atherosclerosis deserves further study.

Apolipoproteins B↗
PubMed1995

Lovastatin inhibits diet induced atherosclerosis in F1B golden Syrian hamsters.

3-Hydroxy-3-methylglutaryl-CoA (HMG CoA) reductase inhibitors are the drugs most commonly prescribed in the US to lower blood cholesterol. Previous studies have shown their efficacy in reducing plasma low density lipoprotein (LDL) cholesterol. However, little is known about their effects on preventing diet induced atherosclerosis. We have investigated the changes in lipoprotein profiles and extent of atherogenesis in hamsters (F1B strain) consuming an atherogenic diet with and without lovastatin. Thirty-six animals were randomized into 3 groups of 12 animals each, with similar plasma cholesterol levels. One group of animals received a basal chow diet, and the other two groups a basal diet plus 10% (w/w) coconut oil and 0.05% cholesterol. After 2.5 weeks, one of the groups received the latter diet supplemented with lovastatin (25 mg/kg/day). A second study was carried out in which animals received the same diets, but lovastatin was given during the 10 week period at a dose of 12.5 mg/kg/day. At the end of the experimental period, animals were sacrificed and lipoprotein cholesterol, liver enzymes, and aortic foam cell development were determined. Animals fed the high fat diet plus lovastatin had significantly lower levels of non-high density lipoprotein (HDL) cholesterol than those fed the unsupplemented high fat diet. No differences were observed in mean levels of this parameter between animals fed the low fat diet and those receiving lovastatin. The amount of aortic lipid staining was significantly less in the lovastatin and low fat groups when compared to the unsupplemented high fat groups. These results indicate that lovastatin can prevent diet induced aortic lipid deposition in this animal model.

Analysis of Variance↗
PubMed1995

Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis.

BACKGROUND: Epidemiologic studies have identified hyperhomocysteinemia as a possible risk factor for atherosclerosis. We determined the risk of carotid-artery atherosclerosis in relation to both plasma homocysteine concentrations and nutritional determinants of hyperhomocysteinemia. METHODS: We performed a cross-sectional study of 1041 elderly subjects (418 men and 623 women; age range, 67 to 96 years) from the Framingham Heart Study. We examined the relation between the maximal degree of stenosis of the extracranial carotid arteries (as assessed by ultrasonography) and plasma homocysteine concentrations, as well as plasma concentrations and intakes of vitamins involved in homocysteine metabolism, including folate, vitamin B12, and vitamin B6. The subjects were classified into two categories according to the findings in the more diseased of the two carotid vessels: stenosis of 0 to 24 percent and stenosis of 25 to 100 percent. RESULTS: The prevalence of carotid stenosis of > or = 25 percent was 43 percent in the men and 34 percent in the women. The odds ratio for stenosis of > or = 25 percent was 2.0 (95 percent confidence interval, 1.4 to 2.9) for subjects with the highest plasma homocysteine concentrations (> or = 14.4 mumol per liter) as compared with those with the lowest concentrations (< or = 9.1 mumol per liter), after adjustment for sex, age, plasma high-density lipoprotein cholesterol concentration, systolic blood pressure, and smoking status (P < 0.001 for trend). Plasma concentrations of folate and pyridoxal-5'-phosphate (the coenzyme form of vitamin B6) and the level of folate intake were inversely associated with carotid-artery stenosis after adjustment for age, sex, and other risk factors. CONCLUSIONS: High plasma homocysteine concentrations and low concentrations of folate and vitamin B6, through their role in homocysteine metabolism, are associated with an increased risk of extracranial carotid-artery stenosis in the elderly.

Aged↗