Biomedical subjects

E J Schaefer

Publications and source records attributed to E J Schaefer.

At least 109 records · Page 6Linked to original sources

PubMed1997

Effects of dietary fatty acids on lipoproteins and cardiovascular disease risk: summary.

Cardiovascular disease is the leading cause of death and disability in the United States and other countries. To reduce the risk of cardiovascular disease, dietary saturated fat and cholesterol should be reduced. This section of the workshop included a discussion of pragmatic issues associated with translating complex scientific information on the fat and fatty acid content of foods for the public; an overview of and a theoretical framework for cholesterol and lipoprotein metabolism; information on the role of cholesterol in the control of low-density-lipoprotein cholesterol (from animal studies); epidemiologic studies on the association between dietary fat and fatty acids and lipids and lipoproteins; the appropriate experimental design for fatty acid studies; and clinical studies evaluating the effects of individual fatty acids on plasma lipids and lipoproteins. The evidence to date indicates that the individual fatty acids elicit distinctly different physiologic effects. There is still much to be learned about the effects of individual fatty acids on lipids and lipoproteins, their metabolic fate, and the responsible biological mechanisms.

Animals↗

PubMed1997

Plasma retinol and plasma and lipoprotein tocopherol and carotenoid concentrations in healthy elderly participants of the Framingham Heart Study.

Data on plasma concentrations of tocopherols and the major carotenoids in adults aged > or = 65 y, particularly in those > 80 y, are sparse. In the current study retinol, tocopherol (alpha- and gamma-tocopherols), and carotenoid (lutein/zeaxanthin, cryptoxanthins, lycopene, and alpha- and beta-carotene) concentrations were determined in 638 subjects, 230 men (aged 75 +/- 5 y) and 408 women (76 +/- 6 y), of the Framingham Heart Study. All subjects were free of clinical evidence of cardiovascular disease and cancer. Percentile ranges were comparable with those established in younger cohorts. Moreover, women had significantly higher plasma alpha-tocopherol and plasma and lipoprotein concentrations of beta-cryptoxanthin and alpha- and beta-carotene than did men. Lycopene concentrations were inversely correlated with age and lowest among subjects > or = 80 y. Total intakes (diet+supplements) of vitamin C and vitamin E, but not dietary intakes alone, were positively associated with plasma alpha-tocopherol and inversely associated with gamma-tocopherol concentrations. In multivariate analyses, plasma cholesterol and triacylglycerol concentrations and total intake of vitamins E and C predicted 64% and 55% of the plasma alpha-tocopherol concentrations in men and women, respectively. Important predictors for the majority of carotenoids included plasma cholesterol concentration, body mass index (negative effect), and smoking status (negative effect); for lycopene concentration they included cholesterol concentration and age (negative effect). In summary, percentile ranges and lipoprotein distributions were comparable with those established in younger cohorts, suggesting that overall antioxidant status is not altered in people between the ages of 67 and 96 y.

Aged↗

PubMed1997

Lovastatin decreases de novo cholesterol synthesis and LDL Apo B-100 production rates in combined-hyperlipidemic males.

The effect of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, on the kinetics of de novo cholesterol synthesis and apolipoprotein (apo) B in very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) was investigated in five male patients with combined hyperlipidemia. Subjects were counseled to follow a Step 2 diet and were treated with lovastatin and placebo in randomly assigned order for 6-week periods. At the end of each experimental period, subjects were given deuterium oxide orally and de novo cholesterol synthesis was assessed from deuterium incorporation into cholesterol and expressed as fractional synthesis rate (C-FSR) and production rate (C-PR). Simultaneously, the kinetics of VLDL, IDL, and LDL apo B-100 were studied in the fed state using a primed-constant infusion of deuterated leucine to measure fractional catabolic rates (FCR) and production rates (PR). Drug treatment resulted in significant decreases in total cholesterol (-29%), VLDL cholesterol (-40%), LDL cholesterol (-27%), and apo B (-16%) levels and increases in HDL cholesterol (+13%) and apolipoprotein (apo) A-I (+11%) levels. Associated with these plasma lipoprotein responses was a significant reduction in both de novo C-FSR (-40%; P = .04) and C-PR (-42%; P = .03). Treatment with lovastain in these patients had no significant effect on the FCR of apoB-100 in VLDL, IDL, or LDL, but resulted in a significant decrease in the PR of apoB-100 in IDL and LDL. Comparing the kinetic data of these patients with those of 10 normolipidemic control subjects indicates that lovastatin treatment normalized apoB-100 IDL and LDL PR. The results of these studies suggest that the declines in plasma lipid levels observed after treatment of combined hyperlipidemic patients with lovastatin are attributable to reductions in the C-FSR and C-PR of de novo cholesterol synthesis and the PR of apoB-100 containing lipoproteins. The decline in de novo cholesterol synthesis, rather than an increase in direct uptake of VLDL and IDL, may have contributed to the decline in the PR observed.

Adult↗

PubMed1997

Ethnic variation and in vivo effects of the -93t-->g promoter variant in the lipoprotein lipase gene.

Recently, a (t-->g) transition at nucleotide -93 in the lipoprotein lipase (LPL) gene promoter has been observed in Caucasians. Here, we have compared the frequency of the -93g carriers in three distinct populations (Caucasians, South African Blacks, and Chinese). The carrier frequency in the Caucasian population was 1.7% (4/232), which was in contrast to the South African Black population, which had a frequency for this allele of 76.4% (123/161) of the individuals tested. This transition was not observed in the Chinese population under study. Near complete linkage disequilibrium between the -93g and the previously described D9N mutation was observed in the Caucasian population but not in South African Blacks. To further assess the ancestral origins of these DNA changes, DNA haplotyping using a CA repeat 5' to these substitutions was performed. The -93t allele was associated with only a few specific dinucleotide repeat sizes. In contrast, the -93g allele occurred on chromosomes with many different repeat lengths. The broad distribution of repeats on -93g carrying chromosomes, their high frequency in the South African Black population, and the conservation of the -93g allele among different species may suggest that the -93g allele is the ancestral allele on which a transition to t and the D9N mutations arose. The very high frequency of the -93g allele distinct from the N9 allele in a cohort of Black South Africans allowed us to specifically assess the phenotypic effects of the -93g allele on lipids. Individuals homozygous for the g allele at -93 showed mildly decreased triglycerides compared with individuals homozygous for the t allele (1.14 +/- 0.66 mmol/L versus 0.82 +/- 0.3; P = .04). Thus, the -93g allele in this cohort is associated with low plasma triglyceride levels.

Adult↗

PubMed1997

Impact of gender on the metabolism of apolipoprotein A-I in HDL subclasses LpAI and LpAI:AII in older subjects.

The behavior of apolipoprotein (apo) A-I in lipoprotein (Lp) AI and LpAI:AII was studied in 11 postmenopausal females and 11 males matched for plasma triglyceride and total cholesterol levels. Subjects consumed a baseline diet [35% fat (14% saturated, 15% monounsaturated, and 7% polyunsaturated), 15% protein, 49% carbohydrate, and 147 mg cholesterol/1000 kcal] for 6 weeks before the start of the kinetic study. At the end of the diet period, using a primed-constant infusion of [5,5,5-2H3]leucine, residence times (RT) and secretion rates (SR) of apoA-I were determined in 2 subpopulations of high-density lipoprotein (HDL) particles, LpAI and LpAI:AII. Plasma total cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations were similar in males and females. The mean plasma HDL cholesterol concentration in males (1.14 +/- 0.23 mmol/L; mean +/- SD) was lower than in females (1.42 +/- 0.18 mmol/L; P =. 0034). Similarly, the mean plasma concentration of apoA-I in males (130 +/- 21 mg/dL) was lower than that in females (150 +/- 19 mg/dL; P = .0421). The RT of apoA-I in either LpAI or LpAI:AII was similar between men and women. Despite the higher plasma apo A-I levels in female compared with male subjects, total apoA-I and apoA-I in LpAI and LpAI:AII pool sizes were similar between the two groups, attributable to the lower body weight of the female subjects. The mean SR of total apoA-I in males (8.5 +/- 2.7 mg.kg-1.d-1) was 22% lower than in females (10.9 +/- 2.3 mg.kg-1.d-1; P = .0389). The SR of both apoA-I in LpAI and LpAI:AII was lower in males than females, although the differences did not reach statistical significance. These data suggest that the difference observed in HDL cholesterol concentration between males and females is attributable to SR of apoA-I and not the catabolic rate.

Aged↗

PubMed1997

Subjects with ApoA-I(Lys107-->0) exhibit enhanced fractional catabolic rate of ApoA-I in Lp(AI) and ApoA-II in Lp(AI with AII).

Our purpose was to examine HDL metabolism in a Finnish kindred with a 3-bp deletion in the apolipoprotein (apo) A-I gene, resulting in a deletion of Lys107 in the mature apoA-I. Patients with this mutation [apoA-I(Lys107-->0)] have reduced plasma HDL cholesterol and lipoprotein (AI with AII) [Lp(AI w AII)] concentrations, but not Lp(AI) levels, compared with unaffected family members. Using primed constant infusions of [5,5,5-2H3]leucine, we determined the residence time (RT) and absolute production rate (APR) of apoA-I and apoA-II entering plasma in two subpopulations of HDL particles: [Lp(AI) and Lp(AI w AII)] in three patients heterozygous for apoA-I(Lys107-->0) and in seven healthy control subjects. In patients, the mean RT of apoA-I in Lp(AI) (3.75+/-1.68 days) was less than half that observed in control subjects (8.01+/-2.51 days, P<.05). The mean RT of apoA-I in Lp(AI w AII) was also lower in patients than in control subjects, but differences were not statistically significant (4.72+/-2.42 versus 6.50+/-2.19 days). The mean RT of apoA-II in Lp(AI w AII) was significantly lower in patients (5.24+/-1.65 days) than in control subjects (9.64+/-3.57 days, P<.05). The APR of apoA-I into Lp(AI) was twofold higher in patients (5.9+/-2.1 mg x kg(-1) x d(-1)) than in control subjects (2.5+/-0.9, P<.05). The APRs of apoA-I and apoA-II into Lp(AI w AII) were similar in patients and control subjects. Our results are consistent with the concept that patients heterozygous for the apoA-I(Lys107-->0) mutation have enhanced fractional catabolism of apoA-I and apoA-II in both HDL subspecies, especially in Lp(AI), and an increase in apoA-I production only into Lp(AI), which may be compensatory. Therefore, only their Lp(AI w AII) levels are decreased.

Adult↗

PubMed1997

Decreased production and increased catabolism of apolipoprotein B-100 in apolipoprotein B-67/B-100 heterozygotes.

Apolipoprotein (apo) B-67 is a truncated form of apoB-100 due to deletion of an adenine at cDNA 9327. Heterozygotes have one allele making apoB-100; therefore, plasma apoB levels would be predicted to be at least 50% of normal. However, apoB-67 heterozygotes have total plasma apoB levels that are 24% of normal. To determine the mechanisms responsible for the lower-than-expected levels of apoB, in vivo kinetics of apoB-100 were performed in three apoB-67/apoB-100 heterozygotes and compared with those of six control subjects by using a primed-constant infusion of [5,5,5-2H3]leucine in the fed state. Kinetic parameters were calculated by multicompartmental modeling of the data. The mean total apoB plasma concentration of the apoB-67 subjects was 21.8+/-6.1 mg/dL, or 24% of that of control subjects (89.6+/-24.1 mg/dL, P=.002). ApoB-67 subjects had lower mean VLDL apoB-100 production rates (3.6+/-1.2 versus 13.9+/-3.5 mg x kg(-1) x d(-1), P=.002) and lower mean transport rates of apoB-100 into LDL (3.5+/-1.4 versus 12.6+/-4.1 mg x kg(-1) x d(-1), P=.008) compared with control subjects. The transport rate into IDL was not significantly different (1.2+/-0.5 versus 6.2+/-4.0 mg x kg(-1) x d(-1), P=.07). The fractional catabolic rate of VLDL apoB-100 was significantly higher in apoB-67 subjects than in control subjects (18.1+/-8.6 versus 7.6+/-1.6 mg x kg(-1) x d(-1), P=.017). ApoB-100 IDL and LDL fractional catabolic rates were not significantly different. VLDL apoB-100 pool size in apoB-67 subjects was 11% of that of control subjects (15.8+/-7.7 versus 141.6+/-33.7 mg, P=.0004) due to a 74% lower production rate (26% of control values) and a 2.4-fold higher fractional catabolic rate. LDL apoB-100 pool size in apoB-67 subjects was 22% of that of control subjects (665.3+/-192.4 versus 2968.3+/-765.2 mg, P=.002) due primarily to a lower production rate (27% of control values). Thus, both decreased production of VLDL and LDL apoB-100 and increased catabolism of VLDL apoB-100 are responsible for the low levels of apoB-100 in apoB-67 subjects.

Adult↗

PubMed1997

Urbanization elicits a more atherogenic lipoprotein profile in carriers of the apolipoprotein A-IV-2 allele than in A-IV-1 homozygotes.

Coronary heart disease (CHD) is increasing in developing countries, particularly in urban areas. The impact of urbanization and apolipoprotein (apo) A-IV genetic polymorphism on plasma lipoproteins was studied in 222 men and 236 women from rural and urban Costa Rica. The apoA-IV allele frequencies were 0.937 for apoA-IV-1 and 0.062 for apoA-IV-2, Significant interactions between the apoA-IV polymorphism and area of residence (rural versus urban) were detected for HDL cholesterol (P = .003), apoA-I (P = .05), LDL particle size (P = .01), and LDL/HDL cholesterol ratio (P = .005). Urban compared with rural carriers of the apoA-IV-2 allele had significantly lower plasma HDL cholesterol (0.95 versus 1.17 mmol/L) and apoA-I (980 versus 1140 mg/L), a significantly higher LDL/HDL cholesterol ratio (3.35 versus 2.39), and significantly smaller LDL particles (258 versus 263 A). In contrast, no significant rural-urban differences for these parameters were found in apoA-IV-1 homozygotes. Regardless of their apoA-IV phenotype, urban residents consumed more saturated fat (P = .02) and smoked more cigarettes per day (P = .03) than rural residents. A significant interaction between saturated fat intake and apoA-IV phenotype was found for HDL cholesterol (P < .0003) and LDL/HDL cholesterol ratio (P < .003). Increased saturated fat intake (13.6% versus 8.6% of calories) was significantly associated with 6% higher HDL cholesterol and no change (0.7%) in LDL/HDL cholesterol ratio in apoA-IV-1 homozygotes and with 19% lower HDL cholesterol and 37% higher LDL/HDL cholesterol ratio among carriers of the apoA-IV-2 allele. Smokers (> or = 1 cigarette per day) had significantly lower HDL cholesterol (P < .005) and apoA-I (P < .01) concentrations than nonsmokers (< 1 cigarette per day), particularly among carriers of the apoA-IV-2 allele (-19% and -13%) compared with apoA-IV-1 (-4% for both). After taking these lifestyle characteristics into account, the areas of residence by phenotype interactions for plasma lipoprotein concentrations were no longer statistically significant. Lifestyles associated with an urban environment, such as increased smoking and saturated fat intake, elicit a more adverse plasma lipoprotein profile among Costa Rican carriers of the apoA-IV-2 allele than in apoA-IV-1 homozygotes. Therefore, under the conditions studied, persons with the apoA-IV-2 allele may be more susceptible to CHD.

Adult↗

PubMed1997

Plasma lipoprotein (a) levels in men and women consuming diets enriched in saturated, cis-, or trans-monounsaturated fatty acids.

Studies that have shown adverse effects of trans-unsaturated fatty acids on plasma lipoprotein (a) [Lp(a)] levels have used levels of trans-fatty acid that are higher than those in the average U.S. diet. This study was conducted to clarify the effects on Lp(a) of trans-fatty acids levels commonly found in U.S. diets. Lp(a) levels were measured in a double-blind study of 29 men and 29 women who ate 4 controlled diets in random order for 6 weeks each. Fatty acids represented 39% to 40% of energy. The diets were: (1) Oleic (16.7% of energy as oleic acid); (2) Moderate trans (3.8% of energy as trans-monoenes, approximately the trans content of the U.S. diet); (3) High trans (6.6% of energy as trans-monoenes); (4) Saturated (16.2% of energy as lauric plus myristic plus palmitic acids). The Saturated diet lowered Lp(a) levels significantly (by 8% to 11%). Compared to the Oleic diet, the trans diets had no adverse effect on Lp(a) levels when all subjects were considered collectively. A subset with initially high levels of Lp(a) (> or = 30 mg/dL), however, responded to the High trans diet with a slight (5%) increase in Lp(a) levels relative to the Oleic and Moderate trans diets. Thus, in amounts commonly found in the typical U.S. diet, saturated fatty acids consistently decrease Lp(a) concentrations. The adverse effects of replacing cis- with trans-fatty acids are only suggestive and are restricted to high trans intakes in subjects with high Lp(a) levels.

Adult↗

PubMed1997

The BsmI vitamin D receptor restriction fragment length polymorphism (bb) influences the effect of calcium intake on bone mineral density.

Previous studies of the vitamin D receptor (VDR) polymorphisms and bone mineral density (BMD) have suggested that there may be differences in calcium absorption among groups of women with different VDR genotypes, and that the association may be stronger in younger women. To investigate the association between the VDR polymorphisms and BMD, this study was undertaken in the Framingham Study Cohort and a group of younger volunteers. Subjects from the Framingham Study (ages 69-90 years) included those who underwent BMD testing and who had genotyping for the VDR alleles (n = 328) using polymerase chain reaction methods and restriction fragment length polymorphisms with BsmI (B absence, b presence of cut site). A group of younger volunteer subjects (ages 18-68) also underwent BMD testing and VDR genotyping (n = 94). In Framingham Cohort subjects with the bb genotype, but not the Bb or BB genotypes, there were significant associations between calcium intake and BMD at five of six skeletal sites, such that BMD was 7-12% higher in those with dietary calcium intakes greater than 800 mg/day compared with those with intakes < 500 mg/day. The data also suggested that BMD was higher in persons with the bb genotype only in the group with calcium intakes above 800 mg/day. No significant differences were found in the Framingham Cohort for age-, sex-, and weight-adjusted BMD at any skeletal site between those with the BB genotype and those with the bb genotype regardless of 25-hydroxyvitamin D levels or country of origin. In the younger volunteers, BMD of the femoral neck was 5.4% higher (p < 0.05) in the bb genotype group compared with the BB group and 11% higher (p < 0.05) in males with the bb genotype compared with the BB group. There were no significant differences at the lumbar spine. In this study, the association between calcium intake and BMD appeared to be dependent upon VDR genotype. The findings of an association between dietary calcium intake and BMD only in the bb genotype group suggests that the VDR genotype may play a role in the absorption of dietary calcium. Studies that do not consider calcium intake may not detect associations between VDR genotype and BMD. In addition, the association between VDR alleles and BMD may become less evident in older subjects.

Adult↗

PubMed1997

Production of apolipoprotein B-67 in apolipoprotein B-67/B-100 heterozygotes: technical problems associated with leucine contamination in stable isotope studies.

In vivo kinetics of apoB were performed in three apoB-67/apoB-100 heterozygotes using a primed-constant infusion of (5,5,5-(2)H3)-leucine. Mean plasma VLDL and LDL apoB-67 concentrations were 0.05 +/- 0.01 mg/dl and 0.62 +/- 0.17 mg/dl, respectively, which were 0.2% and 2.8% of total plasma apoB concentrations. When cation exchange chromatography was used to separate plasma amino acids from fragments of polyacrylamide gels, the tracer/tracee ratio at plateau for VLDL apoB-67 was less than 50% of that observed when centrifugation was used. Mean fractional catabolic rate for LDL apoB-67 was 2-fold higher when the lower plateau was used in multicompartmental analysis compared to the higher plateau (0.70 +/- 0.21 versus 0.37 +/- 0.06 pools per day, P = 0.06). The lower plateau resulted from introduction of unlabeled leucine during cation exchange chromatography; therefore, all samples were processed with centrifugation. Mean fractional catabolic rates for VLDL and LDL apoB-67 were not significantly different from VLDL and LDL apoB-100 (VLDL: 9.7 +/- 3.4 versus 18.1 +/- 8.6 pools per day, respectively, P = 0.19; LDL: 0.37 +/- 0.06 versus 0.34 +/- 0.11 pools per day, respectively, P = 0.66). Mean secretion rate of VLDL apoB-67 was 5.6% of VLDL apoB-100 (0.20 +/- 0.04 versus 3.6 +/- 1.3 mg/kg/day, P = 0.01). Fifty-three % of apoB-67 was directly removed from VLDL compared to only 3.5% of apoB-100 (P = 0.003), thus accounting for the lower proportion of apoB-67 in LDL (3.3 +/- 1.8%) as compared to VLDL (11.2 +/- 2.5%). Mean LDL production rate for apoB-67 was 2.6% of LDL apoB-100 (0.09 +/- 0.02 versus 3.50 +/- 1.39 mg/kg/day, P = 0.05). Thus, decreased secretion of apoB-67 is responsible for low levels of apoB-67.

Adult↗

PubMed1996

Effects of regular and extended-release gemfibrozil on plasma lipoproteins and apolipoproteins in hypercholesterolemic patients with decreased HDL cholesterol levels.

We have studied, in a prospective blinded fashion, the effects of regular and extended-release gemfibrozil on plasma lipoprotein and apolipoprotein (apo) levels in hypercholesterolemic subjects with decreased high density lipoprotein (HDL) cholesterol (C) levels. Study participants were men and women 19 to 80 years of age with baseline plasma low density lipoprotein (LDL) C levels > or = 4.5 mmol/l (175 mg/dl), HDL-C levels < or = 1.2 mmol/l (45 mg/dl), and triglyceride levels < or = 3.4 mmol/L (300 mg/dl). All subjects were stabilized on a diet for eight weeks prior to entry into two different protocols. In the first protocol 229 subjects were randomized to placebo or extended-release gemfibrozil (1200 mg/day) for 3 months (placebo trial). In the second protocol 655 subjects were randomized to regular or extended-release gemfibrozil (1200 mg/day) for 6 months (equivalency trial). Changes in lipids and apos were stratified by baseline HDL-C levels (< 0.9 mmol/l, and 0.9-12.2 mmol/l). In both studies, treatment with gemfibrozil, either regular or extended-release, was associated with significant (P < 0.05) decreases in plasma very low density lipoprotein (VLDL) C and triglyceride levels of 42-45% and 33-37%, respectively, in subjects with HDL-C level < 0.9 mmol/l, and of 38-47% and 32-39%, respectively, in patients with HDL-C levels of 0.9-1.2 mmol/l. Modest reductions from baseline in directly measured LDL-C levels were observed in both groups (3-6% and 8-9%, respectively). These reductions were less than those observed for calculated LDL-C (7-10% and 11%, respectively). For apo B, reductions were 11-14% and 16-17% in the two groups. HDL-C, apo A-I, and apo A-II levels increased by 15-16%, 5-6%, and 21-25%, respectively, in patients with HDL-C < 0.9 mmol/l, and by 6-7%, 2-3%, and 19-22%, respectively, in patients with HDL-C of 0.9-1.2 mmol/l. These differences in HDL-C levels reached statistical significance in the equivalency trial (P < 0.0001) and were independent of baseline triglyceride levels. Our data indicate that gemfibrozil, either regular or extended-release, is highly effective in lowering plasma triglyceride levels and increases HDL-C levels by approximately 15% in hypercholesterolemic patients with low HDL-C levels (< 0.9 mmol/l). Moreover, this agent lowers VLDL-C somewhat more than triglyceride, resulting in an underestimation of calculated VLDL-C reductions and in an overestimation of calculated LDL-C reductions. This agent also raises apo A-II levels much more than apo A-I levels.

Administration, Oral↗

PubMed1996

Plasma lipoprotein(a) distribution in the Framingham Offspring Study as determined with a commercially available immunoturbidimetric assay.

The purpose of our research was to evaluate a commercially available, automated, immunoturbidimetric assay for lipoprotein(a) (Lp(a)), to determine the distribution of Lp(a) in the Framingham Offspring Study population, and to determine Lp(a) levels that may be useful for assessing coronary heart disease risk. The mean between-run coefficient of variation for this assay was 5.65%. Lp(a) concentration was slightly, but significantly, higher in 1949 white women (mean +/- S.D. 214 +/- 195 mg/l, median 150 mg/l) than in 1884 white men (mean +/- S.D. 200 +/- 193 mg/l, median 130 mg/l) participating in Cycle 4 of the Framingham Offspring Study (P = 0.0015). Lp(a) values of 300 mg/l and 500 mg/l corresponded to approximately the 75th and 90th percentiles, respectively, for both men and women, and subjects with concentrations greater than or equal to 500 mg/l were more likely to have coronary heart disease than subjects with an Lp(a) concentration less than 300 mg/l (P < 0.05 for men).

Adult↗

PubMed1996

Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study.

OBJECTIVE: To establish whether elevated lipoprotein(a) [Lp(a)], detected as a sinking pre-beta-lipoprotein band on electrophoresis of fresh plasma, is an independent risk factor for the development of premature coronary heart disease (CHD) in men. DESIGN AND SETTING: Prospective study of the Framingham offspring cohort. PARTICIPANTS: A total of 2191 men aged 20 to 54 years old who were free of cardiovascular disease when they were examined between 1971 and 1975. MAIN OUTCOME MEASURES: Incident CHD (myocardial infarction, coronary insufficiency, angina pectoris, or sudden cardiac death) occurring by age 55 years. RESULTS: After a median follow-up of 15.4 years, there were 129 CHD events. The relative risk (RR) estimates (with 95% confidence intervals [CIs]) for premature CHD derived from a proportional hazards model that included age, body mass index, and the dichotomized risk factor covariables elevated plasma Lp(a) level, total cholesterol level of 6.2 mmol/L (240 mg/dL) or more, high-density lipoprotein (HDL) level less than 0.9 mmol/L (35 mg/dL), smoking, glucose intolerance, and hypertension were as follows: elevated Lp(a) level, RR, 1.9 (95% CI, 1.2-2.9), prevalence, 11.3%; total cholesterol level of 6.2 mmol/L or more, RR, 1.8 (95% CI, 1.2-2.7), prevalence, 14.3%; HDL level of less than 0.9 mmol/L, RR, 1.8 (95% CI, 1.2-2.6), prevalence 19.2%; smoking, RR 3.6 (95% CI, 2.2-5.5), prevalence, 46.7%; glucose intolerance, RR, 2.7 (95% CI, 1.4-5.3), prevalence, 2.6%; hypertension, RR, 1.2 (95% CI, 0.8-1.8), prevalence, 26.3%. CONCLUSIONS: Elevated plasma Lp(a) is an independent risk factor for the development of premature CHD in men, comparable in magnitude and prevalence (ie, attributable risk) to a total cholesterol level of 6.2 mmol/L (240 mg/dL) or more, or an HDL level less than 0.9 mmol/L (35 mg/dL).

Adult↗

PubMed1996

Absence of association or genetic linkage between the angiotensin-converting-enzyme gene and left ventricular mass.

BACKGROUND: Homozygous carries of the D allele of the angiotensin-converting-enzyme (ACE) gene have been reported to be at increased risk for various cardiovascular disorders, including left ventricular hypertrophy. We investigated the potential role of the ACE gene in influencing left ventricular mass. METHODS: Quantitative echocardiographic data and DNA samples were available for 2439 subjects from the Framingham Heart Study. ACE genotypes were determined by an assay based on the polymerase chain reaction. (The D allele of the ACE gene contains a deletion, whereas the I [insertion] allele does not.) Left ventricular mass and the prevalence of left ventricular hypertrophy, adjusted for clinical covariates, were analyzed according to genotype. Genetic linkage between the ACE locus and left ventricular mass was evaluated by quantitative analysis of pairs of siblings. RESULTS: The ACE genotype was associated neither with left ventricular mass nor with the prevalence of left ventricular hypertrophy. Mean (+/-SE) left ventricular mass (adjusted for sex) among subjects carrying the DD, DI, and II genotypes was 165+/-1.6, 165+/-1.3, and 166+/-2.0 g, respectively (P=0.90). The prevalence of left ventricular hypertrophy among the three genotype groups was 15.6 percent, 13.6 percent, and 15.6 percent, respectively (P=0.36), and the adjusted relative risk of left ventricular hypertrophy associated with the DD genotype was 1.10 (95 percent confidence interval, 0.86 to 1.19). Linkage analysis in 759 pairs of siblings using both the ACE D/I marker and a microsatellite polymorphism at the neighboring locus for the human growth hormone gene failed to support any role of ACE in influencing left ventricular mass. CONCLUSIONS: The ACE genotype showed no association with echocardiographically determined left ventricular mass, nor did it confer an increased risk of left ventricular hypertrophy. We found no appreciable role of the ACE gene in influencing left ventricular mass.

Adult↗

PubMed1996

Diet and plasma lipids in women. I. Macronutrients and plasma total and low-density lipoprotein cholesterol in women: the Framingham nutrition studies.

This study examined relationships between diet and plasma total and LDL cholesterol levels in a population-based sample of 695 premenopausal and 727 postmenopausal women participating in the Framingham Offspring/Spouse Study. Regression analyses controlled for age, caloric intake, apolipoprotein E isoform type, estrogen use, and important CVD risk factors indicated that plasma total and LDL-cholesterol levels were directly associated with consumption of saturated fat and inversely associated with total calorie intake. In contrast, dietary cholesterol was not a predictor of plasma total or LDL cholesterol levels. Total cholesterol levels were also directly associated with total fat, oleic acid, and animal fat, and inversely associated with carbohydrate intake. Stepwise regressions with key nutrients indicated that saturated fat was consistently associated with total and LDL cholesterol levels in Framingham women. These analyses suggest that diet explains 2% of the variability in these lipid levels in a cross-sectional sample of women; the full model explains 22-27%.

Adult↗

PubMed1996

Diet and plasma lipids in women. II. Macronutrients and plasma triglycerides, high-density lipoprotein, and the ratio of total to high-density lipoprotein cholesterol in women: the Framingham nutrition studies.

This study examined relationships between macronutrients and plasma triglycerides, HDL, and the total-to-HDL cholesterol ratio (T/H ratio) in a population-based sample of 695 premenopausal and 727 postmenopausal women participating in the Framingham Offspring/Spouse Study. Multivariate regression analyses revealed that plasma triglycerides were inversely related to protein, fiber, and polyunsaturated fat and directly related to saturated fat and oleic acid. Alcohol intake was directly related to HDL cholesterol and inversely related to the T/H ratio in all subgroups of women, except for postmenopausal women with the 3/2 or 2/2 apolipoprotein E phenotype. Similarly, a direct relationship between dietary fat and HDL cholesterol was limited to this single subgroup of postmenopausal women. Since dietary fat and alcohol do not appear to have consistent effects on plasma lipids in all groups of women, it is important to consider the genetic contribution to diet/lipid relationships in epidemiological studies and when evaluating lipid-lowering interventions.

Adult↗

PubMed1996

Impact of hydrogenated fat consumption on endogenous cholesterol synthesis and susceptibility of low-density lipoprotein to oxidation in moderately hypercholesterolemic individuals.

The effects of replacing corn oil with corn oil margarine in stick form on endogenous cholesterol synthesis and susceptibility of low-density lipoprotein (LDL) to oxidation were assessed in 14 middle-aged and elderly men and women aged 63 +/- 12 years (mean +/- SD) with moderate hypercholesterolemia (mean LDL-cholesterol [LDL-C], 4.24 +/- 0.59 mmol/L at the time of recruitment). Subjects consumed each of two diets for 32-day periods, one enriched in corn oil, which contained 30% of energy as fat (7% saturated fatty acid [SFA], 9% monounsaturated fatty acid [MUFA] [0.4% 18:1n9 trans], and 11% polyunsaturated fatty acid [PUFA]) and 85 mg cholesterol/4.2 MJ, and one enriched in stick corn oil margarine, which contained 30% fat (8% SFA, 12% MUFA [4.2% 18:1n9trans], and 8% PUFA) and 77 mg cholesterol/4.2 MJ. Both diets were isocaloric and supplied by a metabolic research kitchen. Mean total cholesterol levels were lowest (P = .039) when subjects consumed the corn oil-enriched diet (5.01 +/- 0.51 mmol/L) as compared with the margarine-enriched diet (5.30 +/- 0.58 mmol/L). LDL-C levels were 3.24 +/- 0.51 and 3.50 +/- 0.54 mmol/L when subjects consumed corn oil-and margarine-enriched diets, respectively (P = .058). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) or triglyceride concentrations between the two experimental periods. Consumption of the margarine-enriched diet versus the corn oil-enriched diet tended to result in lower cholesterol fractional synthetic rates ([C-FSRs] 0.0466 +/- 0.0175 and 0.0668 +/- 0.0298, respectively, P = .080) and cholesterol absolute synthetic rates ([C-ASRs] 1.1761 +/- 0.5375 and 1.6954 +/- 0.8685, respectively, P = .092); however, differences did not reach statistical significance. Consumption of the margarine-enriched diet versus the corn oil-enriched diet resulted in a significantly higher concentration of alpha-tocopherol in both plasma and LDL(P = .004 and P = .011, respectively). LDL particle size tended to be smaller after subjects consumed the margarine-enriched diet versus the corn oil-enriched diet (P = .103). Susceptibility of LDL to oxidation was similar after consumption of the corn oil- and margarine-enriched diets. These data suggest that an increased rate of endogenous cholesterol synthesis did not contribute to the higher plasma cholesterol concentrations during the period when subjects consumed the margarine-enriched diet. Therefore, the increase in cholesterol concentration resulting from margarine consumption was likely attributable, at least in part, to a decreased catabolic rate of cholesterol. Additionally, susceptibility of LDL to in vitro oxidation was not altered by consumption of hydrogenated fat.

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