Biomedical subjects

E J Schaefer

Publications and source records attributed to E J Schaefer.

At least 181 records · Page 10Linked to original sources

PubMed1994

Effect of apolipoprotein E phenotype on diet-induced lowering of plasma low density lipoprotein cholesterol.

The National Cholesterol Education Program (NCEP) has recommended that dietary total fat, saturated fat, and cholesterol intake be reduced to < or = 30% of calories, < 10% of calories, and < 300 mg/day, respectively (Step 1 diet) in the general population to reduce plasma low density lipoprotein (LDL) cholesterol levels and heart disease risk. We examined the LDL cholesterol-lowering response to such a diet (26% fat, 8% saturated fat, and 201 mg/day of cholesterol) as compared to an average American diet (39% fat, 15% saturated fat, and 435 mg/day of cholesterol) in 128 subjects using diet periods of 4-24 weeks for each diet phase. The mean LDL cholesterol reduction was 15% in males (n = 83) and 8% in post-menopausal females (n = 45). The effect of apolipoprotein (apo) E phenotype on responsiveness was examined. LDL cholesterol lowering in males was 14% for 60 apoE3/3 subjects, 23% for 10 apoE3/4 subjects, and 16% for 13 apoE3/2 subjects. Male apoE3/4 subjects had a significantly greater LDL cholesterol reduction (P = 0.006) and a greater decrease in the LDL/HDL ratio (P = 0.047) than apoE3/3 subjects. In females, 7% lowering in LDL cholesterol was observed in 34 apoE3/3 subjects and 11% lowering was observed in 7 apoE3/4 subjects (P = 0.12). A meta-analysis of data from published studies supports this conclusion. These data indicate that apoE phenotype modulates the LDL cholesterol-lowering response to a diet meeting NCEP Step 1 criteria, and that male subjects carrying the apoE4 allele are more responsive than other subjects.

Adult↗

PubMed1994

Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study.

Plasma low density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B, the major protein constituent of LDL, were measured in 1,533 men (mean age 49 +/- 10 years) and 1,597 women (mean age 49 +/- 10 years) participating in the 3rd examination cycle of the Framingham Offspring Study. Mean plasma levels of LDL cholesterol and apoB were higher in men than in women (136 versus 132 mg/dl, P < 0.0001; and 109 versus 95 mg/dl, P < 0.0001, respectively). Increased age was associated with higher plasma LDL cholesterol and apoB levels, especially in women. After adjustment for age and body mass index, LDL cholesterol and apoB levels were still significantly higher in postmenopausal than in premenopausal women, indicating a hormonal effect on LDL metabolism. The associations between coronary heart disease (CHD) and LDL cholesterol, non-HDL cholesterol, apoB, and other plasma lipid and lipoprotein parameters were examined by dividing participants in four groups, based on approximate quartiles for these parameters. Elevated LDL cholesterol levels were not significantly associated with CHD in men, but were in women. This result, at variance with that of several longitudinal studies, is likely due to the cross-sectional design of our analysis. Elevated non-HDL cholesterol and apoB levels were significantly associated with the presence of CHD, in both males and females. A plasma apoB value > or = 125 mg/dl may be associated with an increased risk for CHD. Low plasma levels of HDL cholesterol were also significantly associated with CHD. Plasma triglyceride levels, age and body mass index were strong determinants of LDL cholesterol, non-HDL cholesterol, and apoB levels in men and women. In women, postmenopausal status and elevated blood pressure were also significantly associated with elevated levels of these parameters.

Adult↗

PubMed1994

Factors associated with low and elevated plasma high density lipoprotein cholesterol and apolipoprotein A-I levels in the Framingham Offspring Study.

A decreased high density lipoprotein (HDL) cholesterol level (< 35 mg/dl) has been shown to be a significant independent risk factor for coronary heart disease (CHD). Moreover, increased HDL cholesterol levels (> or = 60 mg/dl) are associated with a decreased CHD risk. Levels of HDL cholesterol and apoA-I, the major protein constituent of HDL, were measured in plasma from fasting participants in the Framingham Offspring Study (1,584 men and 1,639 women, mean age 49 +/- 10 years). In this population, an HDL cholesterol value < 35 mg/dl was observed in 18.2% of men and 3.8% of women, and these subjects had mean apoA-I levels of 104 and 106 mg/dl, respectively, and triglyceride levels of 234 and 261 mg/dl, respectively. CHD was observed in 14.2% of men and 14.5% of women in this category. An HDL cholesterol level > or = 60 mg/dl was observed in 11.7% of men and 39.3% of women, and these subjects had mean apoA-I levels of 182 and 185 mg/dl, respectively, and mean triglyceride levels of 81 and 75 mg/dl, respectively. CHD was noted in 2.7% of men and 1.9% of women in this category. HDL cholesterol levels were much more strongly related to triglycerides (r = -0.54 in men and -0.47 in women) than was apoA-I (r = -0.26 in men and -0.13 in women). The relationship between plasma HDL cholesterol and triglyceride levels was not linear. In both men and women, triglycerides, body mass index (BMI), and alcohol intake contributed significantly to HDL cholesterol and apoA-I variability.

Adult↗

PubMed1994

Interaction of dietary fat saturation and cholesterol level on cholesterol synthesis measured using deuterium incorporation.

To examine interactive effects of dietary fat saturation and cholesterol level on serum lipids and de novo cholesterogenesis, moderately hypercholesterolemic subjects were fed solid-foods diets containing 30% fat (80 mg C.1000 Kcal-1) in which 2/3 fat was either corn oil or beef tallow, with and without 120 mg C.1000 Kcal-1, for 5 wk. At the end of each diet period, subjects were given deuterium (D) oxide orally and de novo cholesterol synthesis was measured over 24 h from D incorporation into cholesterol as fractional synthesis rates (FSR) and absolute synthetic rate (ASR) into the rapid exchangeable cholesterol pool. Plasma total and low density lipoprotein levels were elevated (P < 0.01) with both beef tallow and cholesterol feeding. High density lipoprotein (HDL) levels were not influenced by fat saturation or cholesterol level; however, HDL was higher with addition of cholesterol to corn oil versus beef tallow (P < 0.02). Plasma triglycerides were higher (P < 0.02) with beef tallow feeding but were not influenced by cholesterol level. FSR was increased (P < 0.02) by feeding corn oil, versus beef fat, but not by dietary cholesterol level. Calculated cholesterol pools sizes did not differ across groups; however, ASR was also elevated with corn oil versus beef tallow feeding (P < 0.02). Results indicate that corn oil feeding lowers circulating cholesterol by mechanisms other than reduced synthesis, and that cholesterol at the level of supplementation used is not associated with feedback inhibition of cholesterogenesis. However, with the exception of HDL levels, dietary fat saturation and cholesterol levels do not interactively influence circulating lipoprotein cholesterol levels and cholesterol synthesis.

Aged↗

PubMed1994

Quantification of lipoprotein(a) in plasma by assaying cholesterol in lectin-bound plasma fraction.

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL)-like particle in which apolipoprotein(a) [apo(a)] is disulfide-linked to apolipoprotein B (apoB). High concentrations of Lp(a) in plasma are associated with an increased risk of coronary heart disease (CHD). Lp(a) has traditionally been measured by immunoassay and expressed as total mass of Lp(a). Measuring Lp(a) by its cholesterol content will provide a way to directly compare Lp(a) with other lipoproteins that are measured by cholesterol. We have developed an assay to quantify Lp(a) by its cholesterol content [Lp(a)-C], using lectin affinity to isolate Lp(a) from other lipoproteins, and then measuring the cholesterol within the isolated fraction. We compared the Lp(a)-C assay with an ELISA for Lp(a) mass in 47 plasma samples from normotriglyceridemic, fasting individuals with high Lp(a) contents (mean +/- SD, 446 +/- 350 mg/L). The mean Lp(a)-C concentration was 110 +/- 89 mg/L and correlated very highly with Lp(a) mass (r = 0.9975). Lp(a)-C measurement is an alternative method to screen for this CHD risk factor.

Cholesterol↗

PubMed1993

Increased expression of apolipoprotein genes accompanies differentiation in the intestinal cell line Caco-2.

We have analyzed determinants of the synthesis and secretion of apolipoproteins including mRNA for apolipoproteins, in the human colon carcinoma cell line Caco-2 during differentiation in continuous culture. Significant increases in both cellular and secreted apolipoprotein A-I were observed early in the differentiation process. Increases in apolipoprotein B were limited to secreted protein and started later in the differentiation process. Levels of mRNA for apolipoproteins A-I, A-IV, B, C-III, and E increased significantly between the time cells reached confluence and 1 week postconfluence. The kinetics of mRNA accumulation were influenced by culture conditions. Nuclear extracts from postconfluent Caco-2 cells contained increased amounts of protein that bound to oligonucleotides containing the control regions of the apolipoprotein A-I and B genes. A competition experiment suggested that this protein recognized the control regions of both genes. We propose to name this protein DRIFT-1 (differentiation-related intestinal factor for transcription 1).

Adenocarcinoma↗

PubMed1993

Nucleotide sequences of the Macaca fascicularis apolipoprotein C-III and A-IV genes.

The cynomolgus monkey (Macaca fascicularis) apolipoprotein C-III and apolipoprotein A-IV genes have been isolated from a cynomolgus genomic DNA library and completely sequenced. These genes span 3.1 and 2.8 kilobases (kb), respectively. Apolipoprotein C-III gene is interrupted by three intervening sequences of 613, 135 and 1699 bp, respectively. The open reading frame encodes a protein of 99 amino acids which is 87% similar to the human. The cynomolgus mature protein is 79 residues long. Thr-74 is also present what might allow the formation of O-glycosidic linkage observed in the human protein. Apolipoprotein A-IV gene consist of two intervening sequences of 352 and 774 bp, respectively. The open reading frame encodes a protein of 429 amino acids which is 87% similar to the human. The cynomolgus mature protein is 409 residues long, 33 amino acids longer than the human, due to an insertion of 33 residues in its COOH-terminal region. This insertion is mainly composed of glutamine and glutamic acid, which confers cynomolgus apolipoprotein a higher hydrophilicity.

Amino Acid Sequence↗

PubMed1993

Molecular cloning and sequence of the cynomolgus monkey apolipoprotein A-II gene.

A clone containing the coding region for cynomolgus monkey (Macaca fascicularis) apolipoprotein A-II has been isolated from a cynomolgus genomic DNA library. The gene spans 1.4 kilobases (kb). The complete nucleic acid sequence of the apolipoprotein A-II gene has been determined, establishing that the gene is interrupted by three intervening sequences of 170, 273 and 394 bp, respectively. The open reading frame encodes a protein of 100 amino acids, and shows 94% sequence similarity with its human equivalent. Both apolipoproteins have identical signal peptide. A noticeable feature is the substitution of mature human Cys-6 for Ser. This change explains the existence of cynomolgus apolipoprotein A-II as a monomer and may have important consequences in the kinetics of this apolipoprotein.

Animals↗

PubMed1993

Rationale and design of the Department of Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (HIT) for secondary prevention of coronary artery disease in men with low high-density lipoprotein cholesterol and desirable low-density lipoprotein cholesterol.

Although a large body of epidemiologic evidence suggests that low levels of high-density lipoprotein (HDL) cholesterol are strongly associated with an increased risk of coronary artery disease (CAD), no large-scale clinical trials focusing on this association have been reported. This report describes the rationale and design of the Department of Veterans Affairs HDL Intervention Trial (HIT), a multicenter, randomized, controlled clinical trial designed to determine whether lipid therapy reduces the combined incidence of CAD death and nonfatal myocardial infarction in men with established CAD who have low levels of HDL cholesterol with "desirable" levels of low-density lipoprotein (LDL) cholesterol. Twenty-five hundred men with CAD and HDL cholesterol < or = 40 mg/dl, LDL cholesterol < or = 140 mg/dl, and triglycerides < or = 300 mg/dl are being recruited at 20 Department of Veterans Affairs medical centers, randomized to either gemfibrozil or placebo, and followed in a double-blind manner for an average of 6 years. In this population, gemfibrozil is expected to increase HDL cholesterol by 10 to 15%, have a negligible effect on LDL cholesterol, and lower triglycerides by 30 to 40%. Because an estimated 20 to 30% of patients with CAD have a low HDL cholesterol as their primary lipid abnormality, the results of this trial are expected to have far-reaching clinical implications.

Adult↗

PubMed1993

A diet enriched in monounsaturated fats decreases low density lipoprotein concentrations in cynomolgus monkeys by a different mechanism than does a diet enriched in polyunsaturated fats.

To determine the mechanisms whereby dietary fat saturation influences LDL cholesterol and apolipoprotein B concentrations, 10 cynomolgus monkeys were fed each of three experimental diets enriched in saturated, monounsaturated or polyunsaturated fatty acids in a crossover design consisting of three 13-wk periods. Each diet contained 30% of energy as fat with 0.05 mg cholesterol/kJ and differed solely by the isocaloric substitution of fatty acids as 60% of total fat energy. The replacement of dietary saturated fatty acids with either mono- or polyunsaturated fatty acids resulted in significant reductions of plasma total cholesterol (-17% and -30%, respectively), HDL cholesterol (-32% and -41%, respectively), apoA-1 (-37% and -44%, respectively), and apolipoprotein B (-28% and -36%, respectively) concentrations. Additionally, when dietary polyunsaturated fatty acids were substituted for saturated fatty acids, a 27% reduction in VLDL + LDL cholesterol was significant. Metabolic experiments suggested that the significantly reduced concentrations of apolipoprotein B observed during the monounsaturated and polyunsaturated fatty acid phases relative to the saturated fatty acid phase could not be entirely explained by changes in LDL apolipoprotein B clearance but rather were likely due to decreased LDL apolipoprotein B production rates. However, enhanced LDL apolipoprotein B catabolism accounted for the even greater reductions in VLDL + LDL cholesterol and apolipoprotein B concentrations observed during the polyunsaturated fatty acid phase vs. the monounsaturated fatty acid phase. Our data suggest that monounsaturated and polyunsaturated fatty acids lower apolipoprotein B concentrations by distinct mechanisms, with polyunsaturated fatty acids affecting LDL apolipoprotein B catabolism as well as production.

Analysis of Variance↗

PubMed1993

New recommendations for the diagnosis and treatment of plasma lipid abnormalities.

Elevated total blood cholesterol levels (at or above 240 mg/dL) due to increased low density lipoprotein (LDL) cholesterol values (at or above 160 mg/dL) have been associated with an increased risk of coronary heart disease (CHD). It has been shown in controlled prospective studies that when LDL cholesterol is lowered with diet or diet and drug treatment, subsequent risk of CHD morbidity and, in some cases, mortality can be reduced. New guidelines have recently been released by the Adult Treatment Panel (ATP II) of the National Cholesterol Education Program (NCEP). Risk factors for CHD in addition to elevated LDL cholesterol now include: 1) male 45 years or older; 2) female 55 or older, or with premature menopause and not on estrogen replacement; 3) high density lipoprotein (HDL) cholesterol less than 35 mg/dL; 4) hypertension; 5) cigarette smoking; 6) diabetes mellitus; and 7) a family history of premature CHD. After screening with total cholesterol and HDL cholesterol measurements, patients with total cholesterol values at or above 200 mg/dL, HDL cholesterol below 35 mg/dL, and/or CHD should have a fasting cholesterol, triglyceride, and HDL cholesterol measurement. Candidates for diet therapy are those with LDL cholesterol values at or above 1) 160 mg/dL; 2) 130 mg/dL in the presence of two or more CHD risk factors; or 3) 100 mg/dL in the presence of CHD. Candidates for drug therapy after diet treatment are those with LDL cholesterol values at or above 1) 190 mg/dL; 2) 160 mg/dL in the presence of two or more CHD risk factors; or 3) 130 mg/dL in the presence of CHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol, HDL↗

PubMed1993

Plasma lipoprotein and apolipoprotein levels in Taipei and Framingham.

We compared the plasma lipoprotein cholesterol, triglyceride, apolipoprotein (apo) A-I, apoB, and lipoprotein(a) [Lp(a)] concentrations in a low coronary heart disease (CHD) risk population (n = 440) in Taipei with a high CHD risk population (n = 428) in Framingham matched for age, sex, and menopausal status. Taipei men had significantly lower low-density lipoprotein cholesterol (LDL-C) (-20 mg/dL, -14%, P < .01) and apoB (-7 mg/dL, -6%, P < .05) levels and significantly higher high-density lipoprotein cholesterol (HDL-C) levels (6 mg/dL, 13%, P < .01) than Framingham men. Taipei women had significantly lower LDL-C (-18 mg/dL, -15%, P < .01) and higher HDL-C (4 mg/dL, 7%, P < .01) levels than Framingham women. Median concentrations and distributions of Lp(a) by sex were similar in Taipei and Framingham. After adjusting for body mass index and smoking status, only differences in total cholesterol and LDL-C levels remained significantly different for both sexes between the two populations (P < .01). Gender differences for lipids within populations were similar. After adjusting for age, body mass index, and smoking status, women in both Taipei and Framingham had significantly lower mean triglyceride, LDL-C, and apoB levels and significantly higher HDL-C and apoA-I levels than men. Postmenopausal women in Taipei had significantly higher mean total cholesterol, LDL-C, HDL-C, apoA-I, apoB, and Lp(a) levels than premenopausal women (P < .05), whereas in Framingham postmenopausal women had significantly higher total cholesterol, triglyceride, LDL-C, and apoB levels than premenopausal women (P < .05). Our data are consistent with the concept that plasma lipoprotein cholesterol levels (especially LDL-C) but not apolipoprotein values explain some of the twofold difference in age-adjusted CHD mortality between these two populations.

Apolipoproteins↗

PubMed1993

Effects of canola, corn, and olive oils on fasting and postprandial plasma lipoproteins in humans as part of a National Cholesterol Education Program Step 2 diet.

The most stringent dietary recommendations of the National Cholesterol Education Program (NCEP) are to limit fat intake to < 30% of calories, saturated fat intake to < 7% of calories, and cholesterol intake to < 200 mg/d (Step 2 diet). There is debate as to whether the remaining fat in the diet should be relatively high in monounsaturated or polyunsaturated fatty acids. We examined this issue by testing the effects of diets meeting the aforementioned guidelines that were enriched in three different vegetable oils on plasma lipids in the fasting and postprandial states in a clinically relevant population. Female and male subjects (n = 15, mean age, 61 years) with low-density lipoprotein cholesterol (LDL-C) concentrations > 130 mg/dL were studied under strictly controlled conditions. Subjects were first placed on a diet similar to that currently consumed in the United States to stabilize plasma lipids with respect to identical fat and cholesterol intakes. The subjects then received diets meeting NCEP Step 2 criteria in which two thirds of the fat calories were given either as canola, corn, or olive oil in a randomized, double-blinded fashion for 32 days each. Plasma cholesterol concentrations declined after consumption of diets enriched in all the test oils; however, the declines were significantly greater for the canola (12%) and corn (13%) than for the olive (7%) oil-enriched diet. Mean plasma LDL-C concentrations declined after consumption of diets enriched in all the test oils (16%, 17%, and 13% for canola, corn, and olive oil, respectively), and the magnitude of the declines was statistically indistinguishable among the test oils. Mean plasma high-density lipoprotein cholesterol (HDL-C) concentrations declined after consumption of the baseline diet, and these declines were significant for the canola (7%) and corn (9%) oil-enriched diets. Changes in LDL apolipoprotein (apo)B concentrations paralleled those of LDL-C. Switching from the baseline to the vegetable oil--enriched diets had no significant effect on plasma triglyceride, apoA-I, and lipoprotein(a) concentrations or the total cholesterol to HDL-C ratio. LDL apoB to apoA-I ratios were significantly reduced when the subjects consumed the vegetable oil--enriched diets. Differences similar to those observed in the fasting state were observed in the postprandial state.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1993

Familial hypoalphalipoproteinemia in premature coronary artery disease.

Hypoalphalipoproteinemia (HA) is a common finding in patients with premature coronary artery disease. To characterize the common familial forms of HA, we studied 102 families of probands with premature coronary artery disease; 40 probands (39.2%) had HA. Of these, 25 had at least one first-degree relative affected with HA; 11 had familial hypertriglyceridemia with HA (FTgHA); 10 had familial combined hyperlipidemia (FCH); and 4 had familial HA (FHA) with no other lipoprotein abnormalities. In the remaining 15 families, no lipoprotein abnormalities were observed in first-degree relatives. We measured apolipoprotein (apo) A-I, B, C-III, and E levels as well as lipoprotein particle (Lp) levels of LpA-I (containing apoA-I only), LpA-I:A-II (containing both apoA-I and A-II), LpB:E, and LpB:C-III. Compared with a reference group of healthy men (n = 103) and women (n = 106), probands with familial forms of HA had lower high-density lipoprotein cholesterol levels by selection criteria. Triglyceride levels were higher in FTgHA and FCH probands than in the reference group or FHA subjects. Despite selection of FTgHA and FCH by low-density lipoprotein (LDL) cholesterol, the latter was not significantly different between the three groups and the reference group. ApoA-I levels were decreased in FCH, FHA, and FTgHA probands, and LpA-I and LpA-I:A-II were lower in FHA and FTgHA probands. ApoB levels were significantly higher in all familial HA groups compared with the reference group, being highest in FCH individuals, but not significantly higher between FCH, FTgHA, or FHA probands. LpB:E levels were higher in the FCH and FTgHA groups than in the reference group. There were no significant differences between groups for apoE, apoC-III, and LpB:C-III. LDL particle size was smaller in all three forms of FHA, which, in combination with higher apoB levels, reflects an increased number of smaller, denser LDL particles. Affected children had, on average, higher apoB and LpB:E levels than nonaffected siblings. Our data suggest that common forms of FHA in subjects with coronary artery disease represent a spectrum of overlapping disorders characterized by an increase in apoB-containing lipoproteins, especially LpB:E particles, and smaller, denser LDL particles. When using appropriate age- and gender-adjusted cutpoints, approximately half the offspring (in young adulthood) appeared to be affected.

Adult↗

PubMed1993

Hydrogenation impairs the hypolipidemic effect of corn oil in humans. Hydrogenation, trans fatty acids, and plasma lipids.

The effects of plasma lipoproteins and apolipoproteins of replacing corn oil with corn-oil margarine in stick form as two thirds of the fat in the National Cholesterol Education Program (NCEP) Step 2 diet were assessed in 14 middle-aged and elderly women and men (age range, 44-78 years) with moderate hypercholesterolemia (low density lipoprotein cholesterol [LDL-C] range, 133-219 mg/dl [3.45-5.67 mmol/l] at screening). During each 32-day study phase, subjects received all their food and drink from a metabolic kitchen. Subjects were first studied while being fed a diet approximating the composition of the current US diet (baseline), which contained 35% of calories as fat (13% saturated fatty acids [SFAs], 12% monounsaturated fatty acids [MUFAs; 0.8% 18:1n-9 trans], and 8% polyunsaturated fatty acids [PUFAs]) and 128 mg cholesterol/1,000 kcal. This baseline phase was followed by a corn oil-enriched diet containing 30% fat (6% SFA, 11% MUFA [0.4% 18:1n-9 trans], and 10% PUFA) and 83 mg cholesterol/1,000 kcal, and then a corn-oil margarine-enriched diet containing 30% fat (8% SFA, 12% MUFA [4.2% 18:1n-9 trans], and 8% PUFA) and 77 mg cholesterol/1,000 kcal. All diets were isocaloric. Mean fasting LDL-C and apolipoprotein (apo) B levels were 153 mg/dl (3.96 mmol/l) and 101 mg/dl on the baseline diet, 17% and 20% lower (both p < 0.001) on the corn oil-enriched diet, and 10% and 10% lower (both p < 0.01) on the margarine-enriched diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Effects of age, sex, and menopausal status on plasma lipoprotein(a) levels. The Framingham Offspring Study.

BACKGROUND: Lipoprotein(a) [Lp(a)] is an atherogenic particle that structurally resembles a low density lipoprotein (LDL) particle but contains a molecule of apolipoprotein(a) attached to apolipoprotein B-100 by a disulfide bond. Because elevated plasma levels of Lp(a) have been shown to be an independent risk factor for coronary artery disease, it is important to define normal ranges for this lipoprotein. METHODS AND RESULTS: We have measured Lp(a) in 1,284 men (mean age, 48 +/- 10 years) and 1,394 women (mean age, 48 +/- 10 years) free of cardiovascular and cerebrovascular disease and not on medications known to affect lipids who were seen at the third examination cycle of the Framingham Offspring Study. Plasma Lp(a) levels were measured by an enzyme-linked immunosorbent assay, which uses a "capture" monoclonal anti-apo(a) antibody that does not cross-react with plasminogen, and a polyclonal anti-apo(a) antibody conjugated to horseradish peroxidase. The assay was calibrated to total Lp(a) mass. The Lp(a) frequency distribution was highly skewed to the right, with 56% of the values in the 0-10-mg/dL range. Mean plasma Lp(a) concentrations were 14 +/- 17 mg/dL in men and 15 +/- 17 mg/dL in women. Values of more than 38 mg/dL were above the 90th percentile and values of more than 22 mg/dL were above the 75th percentile in both men and women. CONCLUSIONS: We have determined mean Lp(a) levels for men and women participating in the Framingham Offspring Study. In this population, there was an inverse association between plasma levels of Lp(a) and triglycerides for both sexes (p < 0.006), but triglycerides accounted for only approximately 0.5% of the variation in Lp(a) levels. Associations of Lp(a) levels with total and LDL cholesterol levels were not significant after correction for the estimated contribution of Lp(a) cholesterol to total and LDL cholesterol. After controlling for age, Lp(a) values were 8% greater in postmenopausal women than in premenopausal women, but this difference was not statistically significant. Body mass index, alcohol consumption, cigarette smoking, use of beta-blockers or cholesterol-lowering medications, and use of drugs for the treatment of diabetes and hypertension were not correlated with Lp(a) levels.

Age Factors↗

PubMed1993

Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived N-3 fatty acid enrichment.

Reductions in dietary fat, saturated fat, and cholesterol have been recommended to reduce the risk of heart disease in our society. The effects of these modifications on human cytokine production and immune responses have not been well studied. 22 subjects > 40 yr of age were fed a diet approximating that of the current American (14.1% of calories as saturated fatty acids, [SFA], 14.5% monounsaturated fatty acids [MUFA], 6.1% [n-6] polyunsaturated fatty acids [PUFA], 0.8% [n-3] PUFA, and 147 mg cholesterol/1,000 calories) for 6 wk, after which time they consumed (11 in each group) one of the two low-fat, low-cholesterol, high-PUFA diets based on National Cholesterol Education Panel (NCEP) Step 2 recommendations (4.0-4.5% SFA, 10.8-11.6% MUFA, 10.3-10.5% PUFA, 45-61 mg cholesterol/1,000 calories) for 24 wk. One of the NCEP Step 2 diets was enriched in fish-derived (n-3) PUFA (low-fat, high-fish: 0.54% or 1.23 g/d eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] [121-188 g fish/d]) and the other low in fish-derived (n-3) PUFA (low-fat, low-fish [0.13% or 0.27 g/d EPA and DHA] [33 g fish/d]). Measurements of in vivo and in vitro indexes of immune responses were taken after each dietary period. Long-term feeding of low-fat, low-fish diet enriched in plant-derived PUFA increased blood mononuclear cell mitogenic response to the T cell mitogen Con A, IL-1 beta, and TNF production and had no effect on delayed-type hypersensitivity skin response, IL-6, GM-CSF, or PGE2 production. In contrast, the low-fat, high-fish diet significantly decreased the percentage of helper T cells whereas the percentage of suppressor T cells increased. Mitogenic responses to Con A and delayed-type hypersensitivity skin response as well as the production of cytokines IL-1 beta, TNF, and IL-6 by mononuclear cells were significantly reduced after the consumption of the low-fat, high-fish diet (24, 40, 45, 35, and 34%, respectively; P < 0.05 by two-tailed Student's t test except for IL-1 beta and TNF, which is by one-tailed t test). Our data are consistent with the concept that the NCEP Step 2 diet that is high in fish significantly decreases various parameters of the immune response in contrast to this diet when it is low in fish. Such alterations may be beneficial for the prevention and treatment of atherosclerotic and inflammatory diseases but may be detrimental with regard to host defense against invading pathogens.

Aged↗

PubMed1993

Contribution of apoB-48 and apoB-100 triglyceride-rich lipoproteins (TRL) to postprandial increases in the plasma concentration of TRL triglycerides and retinyl esters.

After the ingestion of a fat-rich meal, there is a postprandial increase in the plasma concentration of both apolipoprotein B-48- and apoB-100-containing triglyceride-rich lipoproteins (apoB-48 and apoB-100 TRL). In order to determine the contribution of these lipoproteins to postprandial lipemia, the concentration of triglycerides (TG) and retinyl esters (RE) was measured in apoB-48 and apoB-100 TRL after an oral fat load. Six normolipidemic male subjects were fed heavy cream (1 g fat per kg body weight) containing vitamin A (3000 retinol equivalents). TRL were isolated by ultracentrifugation from plasma samples obtained at regular intervals after the meal, and apoB-100 TRL were separated from apoB-48 TRL by affinity chromatography using monoclonal antibodies. Postprandial increase in plasma TG concentration was due to an increase in TG in the TRL fraction, which in turn was predominantly (82 +/- 4%) due to an increase in TG in apoB-48 TRL. Contribution of apoB-100 TRL to postprandial increase in TRL TG was 3-27% in individual subjects. ApoB-100 TRL remained a significant carrier of total plasma triglyceride in the fed state, as reflected by similar apoB-100 and apoB-48 TRL TG concentrations at 2, 4, and 6 h after the fat meal. Retinyl esters were regularly detected in apoB-100 TRL. Seventy-five (+/- 9) percent of the increase in TRL-RE was due to RE in apoB-48 TRL and 25 +/- 9% was due to RE in apoB-100. These data suggest that RE in plasma are not always associated with apoB-48-containing lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗