Phytosterols and cholesterol in malignant and benign breast tumors.

Tissue phytosterol and cholesterol levels in 10 benign and 8 malignant breast tumors were quantitated to reexamine the hypothesis that malignant tumors had distinctive phytosterol content. Phytosterols were present in 9 of 10 benign and 7 of 8 malignant breast tumors. Mean (+/- S.E.) cholesterol, campesterol, stigmasterol, and beta-sitosterol in malignant and benign tumors (microgram/g wet weight) did not significantly differ (p greater than 0.1): (formula: see text) In the malignant tumors, tissue cholesterol correlated with campesterol (r = 0.97) and beta-sitosterol (r = 0.97) (p less than 0.01), but not stigmasterol (r = -0.06). In benign tumors, tissue cholesterol correlated with campesterol (r = 0.43), stigmasterol (r = 0.64), and beta-sitosterol (r = 0.94), with p less than 0.01 for the latter two. Phytosterols were present in four samples of normal breast tissue with mean (+/- S.E.) campesterol, stigmasterol, and beta-sitosterol (2 +/- 0.8, 15 +/- 9, 7 +/- 5 microgram/g wet weight) slightly but not significantly lower than in benign and malignant breast tumors, p greater than 0.1. The comparability of tissue phytosterols in benign and malignant breast tumors and in normal breast tissue appears to render unlikely and putative etiological relationship between phytosterols and breast carcinoma.

The substitution of sucrose polyester for dietary fat in obese, hypercholesterolemic outpatients.

Our aim was to determine the effects of the substitution of sucrose polyester (SPE) for dietary fat in a 16-week outpatient study in 36 obese subjects with primary hypercholesterolemia. The subjects were randomized into three groups who followed a 16-week treatment period where all subjects received hypocaloric diets which provided approximately 7 kcal/lb body weight, a polyunsaturated/saturated (P/S) fat ratio of 0.9, and 180 mg cholesterol/day. The percentages of calories as fat in the 3 groups were as follows: a low fat diet group (n = 12) received 27% of dietary calories as fat, a low fat plus SPE group (n = 13) received 25% of calories as fat plus 27 g SPE/day as a bread spread and salad dressing, and a third group (placebo, n = 11) received 37% of calories as fat with a 27 g/day conventional fat placebo (bread spread and salad dressing). Mean weight loss from baseline in the 16 week treatment period was 2.6, 3.9, and 3.4% respectively in the placebo, diet, and SPE groups, p less than .05 for each group, without significant differences between the groups. There was a mean reduction of low density lipoprotein cholesterol (LDL-C) of 16% in the SPE group (p less than .05), more than twice the reductions in the placebo and diet groups, 5% and 6%, respectively. There was a mean 20% reduction in the SPE group in triglyceride and very low density lipoprotein cholesterol (p less than .05), compared to 7 and 10% reductions in the placebo and diet groups respectively. The degree of weight loss was correlated with the degree of reduction in LDL-C in the low fat diet group, and in the low fat diet group plus SPE (r = 0.59 for both groups). Without confounding by different levels of dietary cholesterol or P/S, SPE induced significant reductions in LDL-C in hypercholesterolemic obese subjects beyond the effects of weight loss alone. The effects of SPE were significantly greater than those achieved by the use of a diet which severely limited conventional dietary fat intake (to 40 g/day). SPE in the form of a bread spread and a salad dressing is a practical formulation for outpatient hypocholesterolemic low fat diets and provides the lubricity and organoleptic benefits of authentic foods without the dense caloric content of digestible fats.

A double-blind, placebo-controlled study of sucrose polyester in hypercholesterolemic outpatients.

Sucrose polyester (SPE) was studied in a double-blind, placebo-controlled trial in 91 outpatients with primary hypercholesterolemia. All patients maintained an isocaloric diet with cholesterol intake of 400 mg/day and a polyunsaturated to saturated fat ratio of 0.8 to 1.2 for the duration of the study. The study sequence consisted of a diet lead-in period, a first 8-wk treatment period, a 4-wk washout period, and a second 8-wk treatment period. Subjects were randomly assigned to six groups that differed by SPE dose (8, 16, and 32 g/day) and by the treatment period in which either SPE or an olive oil placebo was given in a bread spread formulation. Compared to placebo, the 8, 16, and 32 g/day doses of SPE decreased low-density lipoprotein cholesterol by 2%, 4% (p less than 0.05), and 5% (p less than 0.05) respectively, without changing high-density lipoprotein cholesterol. On SPE, 14/91 (15%) of the subjects experienced a decrease in low-density lipoprotein cholesterol greater than or equal to 10%, while only 2/91 (2%) showed this decrease with placebo.

Pravastatin experience in elderly and non-elderly patients.

Epidemiologic evidence linking elevated cholesterol concentrations and coronary heart disease (CHD) through the eighth decade of life provides a rationale for lowering cholesterol concentrations to reduce morbidity and mortality from CHD. Pravastatin, a well tolerated HMG CoA reductase inhibitor with a convenient once-daily dosing regimen, has been shown to effectively lower total and low density lipoprotein (LDL) cholesterol. Individual data from more than 1800 hypercholesterolemic patients enrolled in six double-blind, randomized, multicenter studies were pooled and then analyzed to compare the safety and efficacy of pravastatin in the elderly (i.e., patients at least 65 years old) and the non-elderly. In short-term studies (8-16 weeks), response was dose-related and similar in elderly and non-elderly subjects. Pravastatin 20 or 40 mg daily lowered total cholesterol 19-25%, LDL-cholesterol 25-33%, and triglycerides 14-23%; high density lipoprotein (HDL) cholesterol increased 5-10%. During long-term studies, improvements were sustained for more than 24 months in both the non-elderly and elderly. The incidences of adverse drug events and laboratory abnormalities were similar in the elderly and non-elderly patients in all groups (active treatment control with resin, pravastatin alone, or combination therapy). In short-term studies, treatment was discontinued because of adverse events in < 1% of all patients treated with pravastatin (all doses) or placebo. The frequency and profile of adverse events were similar among patients treated with pravastatin or placebo. In long-term studies, treatment was discontinued in 0.4% of patients in the pravastatin group and in 0.3% of the patients in the bile-acid-binding resin group. If drug therapy is warranted, pravastatin appears to be safe and effective for long-term use in elderly patients with hypercholesterolemia.

Effects of fenofibrate on lipids, lipoproteins, and apolipoproteins in 33 subjects with primary hypercholesterolemia.

The effects of fenofibrate on lipids, lipoproteins, and apolipoproteins in 33 subjects with primary hypercholesterolemia were assessed in a 6-month parallel group study, placebo (n = 15) versus fenofibrate 300 mg/day (n = 18), followed by an open label 6-month treatment period. After stabilization on an isocaloric low fat (less than 35% total calories) diet with less than 250 mg cholesterol/day and a P/S ratio of 1, and maintenance of LDL-cholesterol (LDL-C) levels greater than or equal to 175 mg/dl, subjects received placebo for 6 weeks and were then randomized into placebo or fenofibrate groups for 6 months, followed by open label treatment for 6 months. During the 6-month double-blind period, compared to the placebo group, the treatment group had significant reductions in total cholesterol, LDL-C, total apo B, and triglyceride, and increments in HDL-cholesterol, apolipoprotein A-I and apolipoprotein A-II (P less than 0.01 for all comparisons). Compared to placebo baseline, therapy with fenofibrate resulted in a reduction of LDL-C, apo B, and the LDL-C/HDL-C ratio of 15%, 13%, and 18% respectively; HDL-C, apo A-I, and apo A-II increased respectively 12%, 13% and 30% (P less than 0.01 for all comparisons). Mean adherence during the double blind phase of the trial was 95% in the drug group and 96% in the placebo group. An additional 6 months of open label fenofibrate therapy maintained the reduced total and LDL-C as well as the elevated HDL-C, apo A-I and apo A-II in the drug-drug group.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. II. Once-daily versus twice-daily dosing.

This 8-week multicenter, placebo-controlled trial compared the efficacy and safety of the HMG-CoA reductase inhibitor, pravastatin, when administered either as single doses of 40 mg in the morning (AM) or evening (PM) or 20 mg twice daily (bid) in 196 diet-stabilized outpatients with primary type II hypercholesterolemia. Mean reductions in total and low-density lipoprotein (LDL) cholesterol concentrations were observed in all pravastatin groups after 1 week and were sustained throughout the study (P less than or equal to 0.001 versus baseline and placebo). At week 8, mean reductions from baseline in the pravastatin treatment groups were 23-27% for total cholesterol and 30-34% for LDL cholesterol. LDL cholesterol was reduced greater than or equal to 15% by pravastatin in all patients in the group treated with 40 mg PM and in 88 and 96% in those receiving 20 mg bid and 40 mg AM, respectively. High density lipoprotein cholesterol was elevated (up to 8%) and triglycerides were reduced (up to 25%) by all pravastatin regimens (P less than or equal to 0.05). Pravastatin was well tolerated and was associated with a low incidence of adverse events. No patient withdrew from the study due to a pravastatin-related adverse event. Once-daily pravastatin is a safe and effective treatment for patients with primary hypercholesterolemia and has a favorable safety profile.

Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. I. A dose-response study.

This multicenter, double-blind, placebo-controlled, dose-response study was conducted in patients with primary hypercholesterolemia to examine the effects of pravastatin, a selective inhibitor of HMG-CoA reductase, on plasma lipids and lipoproteins. A total of 306 patients on cholesterol-lowering diets received twice daily doses of 5 mg, 10 mg, 20 mg pravastatin, or placebo for 12 weeks. Marked reductions in low density lipoprotein (LDL) cholesterol and total cholesterol were observed after 1 week of treatment; maximum lipid-lowering effects occurred at 4 weeks and were sustained for the duration of the trial. At week 12, pravastatin treatment resulted in dose-dependent mean reductions from baseline in LDL cholesterol of 17.5%, 22.9%, and 30.8% for the 3 doses tested (P less than or equal to 0001 compared with baseline and placebo). The reduction in LDL cholesterol was log-linear with respect to dose; each doubling of dose reduced LDL cholesterol an additional 6.5%. Dose-dependent reductions in total cholesterol from 12.9% to 23.3% also occurred (P less than or equal to 0.001). Triglycerides decreased by as 15.4% (P less than or equal to 0.001) and high-density lipoprotein (HDL) cholesterol increased approximately 7% (P less than or equal to 0.01), but these effects were not dose-dependent. No patient receiving pravastatin was discontinued during the 12-week trial. Transient episodes of rash and headache occurred. Slight increases in mean serum levels of ASAT and ALAT occurred, and 2% of both placebo- and pravastatin-treated patients reported myalgia although there was no clinically significant elevation of creatine kinase. These data indicate that pravastatin favorably affects all lipid parameters and is well tolerated.

Effects of fenofibrate on plasma lipoproteins in hypercholesterolemia and combined hyperlipidemia.

To investigate the lipoprotein effect of fenofibrate in hypercholesterolemia or combined hyperlipidemia (types II A and II B hyperlipidemias, respectively), 240 patients were recruited and 227 randomized to a double-blind randomized trial lasting 24 weeks and 192 patients continued to participate in an open-label phase for another 24 weeks. A 100-mg dose of fenofibrate or a matching placebo was given three times daily. Fenofibrate side effects in excess of placebo affected 6 percent of fenofibrate users and were confined almost entirely to skin rashes. In 180 hypercholesterolemic patients randomly assigned to receive fenofibrate versus placebo, triglyceride and very low-density lipoprotein cholesterol levels decreased 38 percent, total cholesterol levels decreased 17.5 percent, and low-density lipoprotein cholesterol levels decreased 20.3 percent with fenofibrate treatment. High-density lipoprotein cholesterol levels increased 11.1 percent with a decrease in the low-density lipoprotein cholesterol: high-density lipoprotein cholesterol ratio of 27 percent. All differences were statistically significant (p less than 0.01). In combined hyperlipidemic (type II B) patients, triglyceride levels decreased by 45 percent, very low-density lipoprotein cholesterol levels decreased 52.7 percent, total cholesterol levels decreased 16 percent, low-density lipoprotein cholesterol levels decreased 6 percent, and high-density lipoprotein levels increased 15.3 percent for a low-density lipoprotein cholesterol: high-density lipoprotein cholesterol ratio decrease of 13 percent. All differences were again statistically significant (p less than 0.01). In both groups of patients, the onset of the drug effect was generally rapid, with maximal total and low-density lipoprotein cholesterol level lowering achieved within four weeks in hypercholesterolemic patients and maximal triglyceride and cholesterol level lowering in hypertriglyceridemic patients achieved in two weeks. Maximum high-density lipoprotein increases occurred after four weeks in type II A patients and 12 to 16 weeks in type II B patients. Fenofibrate is a well-tolerated drug in the fibric acid series and has putatively beneficial effects on triglyceride, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein cholesterol concentrations in both type II A and type II B hyperlipidemic patients. If the lipid hypothesis of atherosclerosis applies to the lipoprotein changes induced by fenofibrate, reductions in cardiovascular disease risk in both type II A and II B hyperlipidemic patients should result from fenofibrate treatment.

Pediatric familial type II hyperlipoproteinemia: therapy with diet and colestipol resin.

Effects of a low-cholesterol, polyunsaturate-rich diet and a synthetic organic bile sequestrant polymer (U26,597A, colestipol) were studied in 21 children, heterozygous for familial hypercholesterolemia. Total cholesterol, beta-lipoprotein cholesterol, and triglyceride were measured twice on habitual diet, monthly for six months on a low-cholesterol diet, and monthly for six months on low-cholesterol diet plus 10 gm of colestipol per day. Total cholesterol (mean +/- 1 SD) was 295 +/- 37 on habitual diet, 278 +/- 29 on low-cholesterol diet, and fell significantly to 242 +/- 29 mg/100 ml on diet plus colestipol. Low-density lipoprotein (LDL) cholesterol was 234 +/- 37 on habitual diet, 220 +/- 28 on low-cholesterol diet, and fell significantly to 179 +/- 26 mg/100 ml on diet plus drug. Plasma triglyceride levels on habitual diet were 79 +/- 31, remained unchanged on low-cholesterol diet, 86 +/- 22, and were unaffected by low-cholesterol diet plus drug, 85 +/- 17 mg/100 ml. On diet alone, plasma LDL was not normalized (less than 170 mg/100 ml) in any of the 21 children, and cholesterol fell to within normal limits (less than 230 mg/100 ml) in only one child. The combination of diet plus colestipol resin normalized total and LDL cholesterol in 52% of the children. Cholesterol was lowered to a "moderately elevated" range of 230 to 250 mg/100 ml in an additional 14% of the children and LDL was lowered to a range of 170 to 190 mg/100 ml in an additional 29%. In 33% of the children, cholesterol remained greater than 250 mg/100 ml despite diet plus colestipol, while LDL was greater than 190 mg/100 ml in 19%. Colestipol is an effective and well-tolerated cholesterol lowering compound which, in conjunction with diet, may prove to be very useful in the treatment of children heterozygous for familial hypercholesterolemia.

Therapy of familial hypercholesterolemia in childhood: diet and cholestyramine resin for 24 to 36 months.

In 16 children heterozygous for familial hypercholesterolemia, two- to three-year therapy with diet and cholestyramine resin (16 gm/day) was assessed in terms of effectiveness, practicality, and safety. All 16 children had previously taken a low-cholesterol (less than 300 mg/day), polyunsaturate-rich (P/S ratio, 1.5:1) diet and choeltyramine resin (12 gm/day) for 12 months. In this study, the cholestyramine resin dose was increased to 16 gm/day, and follow-up was maintained through months 13 through 18, 19 through 24, 25 through 30, and 31 through 36. Eleven children had good drug adherence (four packs of cholestyramine per day) and five children had fair adherence (two to three packs per day). Plasma total cholesterol and low-density lipoprotein (LDL) cholesterol levels were not significantly lowered on the drug-plus-diet regimen as compared to diet alone in five children with fair drug adherence. For children with good drug adherence, mean plasma cholesterol level was lowered below levels achieved on diet alone by 13% (months 13 through 18), 12% (months 19 through 24), 12% (months 25 through 30), and 11% (months 31 through 36) (P less than .05). Reduction in plasma cholesterol level was no greater with 16 than with 12 gm of cholestyramine per day. There were no group changes in mean plasma triglyceride levels. Cholestyramine resin, when added to diet and maintained for two to three years effects a significant reduction in total and LDL cholesterol levels in about 60% of children heterozygous for familial hypercholesterolemia. Continued reinforcement of both diet and drug adherence is necessary in the face of gradual increments in plasma cholesterol level with time.

Plasma and dietary phytosterols in children.

Plasma phytosterol (plant sterol) levels were studied in 26 infants on various commercial formulas, in 36 infants on breast or cow's milk formulas, in 101 normal and 22 hypercholesterolemic children on a free diet, and in 32 hypercholesterolemic children on a low-cholesterol diet. Commercial formulas, poor in animal fats and enriched with vegetable oils, and low-cholesterol, phytosterol-rich diets generally elevated total plasma phytosterol levels in infants and hypercholesterolemic children from normal mean levels of 2 mg/100 ml to about 9 mg/100 ml. The implications of long-term three- to five-fold elevations of the plasma phytosterols (campesterol, stigmasterol, beta-sitosterol) in infancy and childhood are unknown. Watchful prospective analysis of plasma phytosterol levels may be useful, particularly in regards to otherwise unanticipated long-term effects of cholesterol-poor, phytosterol rich diets.

Hypercholesterolemia and hyper-alpha-lipoproteinemia in schoolchildren.

Elevated levels of high-density lipoprotein cholesterol (C-HDL) can explain apparent hypercholesterolemia in some children, and high C-HDL levels may aggregate in families. In this study, 17 kindreds were identified by virture of hypercholesterolemic proband children whose hypercholesterolemia was accounted for the elevated C-HDL levels Family lipod and lipoprotein sampling revealed three-generation vertical appearance of elevated C-HDL level in two kindreds, and two-generation vertical appearance in eight additional kindreds. Since CHDL level is inversely associated with coronary heart disease in adults, it is important to quantitate C-HDL and low-density lipoprotein cholesterol (C-LDL) in hypercholesterolemic children and to identify those with putatively reduced risk (elevated C-HDL level) or increased risk (elevated C-LDL level).

Safety and efficacy of long-term diet and diet plus bile acid-binding resin cholesterol-lowering therapy in 73 children heterozygous for familial hypercholesterolemia.

Our specific aim was to examine the efficacy and safety of long-term cholesterol-lowering diet and bile acid-binding resin therapy in 73 children heterozygous for familial hypercholesterolemia (FH). We prospectively followed accretion of height and weight in 40 FH children for 5.8 years on diet alone and in 33 FH children for 4.3 years on diet and bile acid-binding resins (8 to 20 g/d). In 67 of these 73 children, sequential data on plasma cholesterol lowering was obtained, including 32 children on diet plus bile acid-binding resins and 35 on diet alone. For all 73 children, median age, sex, and race-specific percentiles for height and weight at entry were 50 and 50, respectively, and 5.7 years later, were unchanged at 50 and 50. Initial and final percentiles for height (r = .76, P less than .001) and weight (r = .70, P less than .001) were closely correlated. Percentile distributions for height and weight at entry into the study did not differ from those at the end of follow-up (P greater than .1), in both the 40 FH children on diet alone and the 33 on diet plus bile acid-binding resins. Tracking of height and weight did not differ in the 40 children on diet alone v the 33 on diet plus bile acid-binding resins (P greater than .1). During 6 years of follow-up there were no significant differences in the percentage of serial, postbaseline measurements for height which were either less than or greater than or equal to baseline percentiles, comparing 40 FH children on diet alone, 33 FH children on diet plus resin, and 39 normal children (on ad libitum diet). FH children on diet or plus resin had a smaller percentage of weight measurements equal to or more than baseline percentiles than normals on follow-up (P less than .01), probably reflecting restriction of total fat intake to less than 35% of calories. On diet alone, 32 FH children had total plasma cholesterol of 307 +/- 8 mg/dL (mean +/- SE); bile acid-binding resins were added to diet in these children at an average age of 11.5 years, with this regimen maintained for 4.6 +/- 0.4 years, leading to a mean reduction in total plasma cholesterol of 12.5% +/- 2% beyond the effects of diet alone (P less than .01).(ABSTRACT TRUNCATED AT 400 WORDS)

Interrelationships between nutrient intake and plasma lipids and lipoproteins in schoolchildren aged 6 to 19: the Princeton School District Study.

Relationships between nutrient intakes and plasma lipids and lipoproteins were studied in 1,669 schoolchildren, aged 6 to 19 years; 948 were selected by random recall and 721 because of elevated plasma cholesterol or triglyceride (hyperlipidemic recall). Nutrient intake data was collected by using a 24-hour dietary recall. Median dietary cholesterol intakes for 6 to 9-year-old boys and girls in the random recall group were 222 and 230 mg/day, with polyunsaturated/saturated fat ratios of 0.34 and 0.33. For boys and girls, aged 10 to 12 years, median dietary cholesterol intakes were 296 and 235 mg/day, for 13 to 15 year olds, 343 and 237, and for 16 to 19 year olds, 418 and 221 mg/day. The dietary polyunsaturated/saturated fat ratios did not change appreciably with age. Partial correlation coefficients describing relationships between lipids, lipoproteins, and nutrients after adjustment for age, sex, race, and Quetelet index (W/H2) were calculated for all children (random and hyperlipidemic recall) after excluding children having plasma cholesterol, triglycerides, and calories less than or equal to the first or greater than or equal to the 99th percentiles for the random recall children. Plasma cholesterol was inversely and triglyceride positively correlated with dietary sucrose. Plasma low density lipoprotein cholesterol was inversely and triglyceride positively correlated with the dietary polyunsaturated/saturated fat ratio, total carbohydrate, and sugar. Potential relationships between nutrients and lipids-lipoproteins were also examined in children having low (first to tenth percentile), intermediate (45th to 55th percentile), and high (90th to 99th percentile) nutrient intake, after covariance adjustment for age, race, sex, and Quetelet index. Total plasma cholesterol fell as sucrose intake increased. Triglyceride rose along with caloric intake, total carbohydrate intake, and sucrose intake, while high density lipoprotein cholesterol levels fell with increasing caloric and sucrose intake. As dietary polyunsaturate ingestion rose from low to intermediate to high, plasma low density lipoprotein cholesterol increased. Nutrient intake may play a small but significant role relative to lipids and lipoproteins in children and, as such, may have importance relative to pediatric precursors of atherosclerosis.

Lipids in schoolchildren 6 to 17 years of age: upper normal limits.

As part of a multiclinic U.S. National Heart, Lung, and Blood Institute study of lipid levels of Americans, the University of Cincinnati studied a total school district's population. Out of a total of 8,906 eligible students from all grades, 6 to 17 years of age, 7,337 participated (82%). After fasting for 12 hours or more, plasma cholesterol and triglyceride levels were ascertained in 6,775 children. For white and black boys and girls, normal lipid values are given by age in both fasting and casual (nonfasting) states. This study group closely resembled a normal pediatric practice population, so that the values established may be used as baseline data for the practicing pediatrician. Since sex, race, and age are dominant sources for variations, care must be taken in the interpretation of minor changes that occur over time in a child.

Clinical chemistry determinations for a biracial cohort of 1,605 normal and hyperlipidemic schoolchildren aged 6 to 17.

Distributions of nine clinical chemistry determinations (serum bilirubin, globulin, creatinine, thyroxine, alkaline phosphatase, hematocrit, aspartate aminotransferase, uric acid, and plasma glucose) were assessed for 1,605 schoolchildren aged 6 to 17 years, in the Cincinati Lipid Research Clinic's Princeton School District study. Nine hundred and sixteen children were randomly recalled, and 689 were recalled by virtue of elevated (top decile) plasma cholesterol or triglyceride or both. For each clinical chemistry measurement, the following factors were considered: random and hyperlipidemic recall groups, age, sex, and race. The data were arrayed to provide the fifth percentile, the median, and the ninety-fifth percentile levels, as well as the 90% confidence interval of about the fifth and ninety-fifth percentile estimates. These data allow black-white age and sex, and normal-hyperlipidemic comparisons of commonly measured clinical chemistry determinations among a large population of children. This study also provides, for the methods used, accurate estimations of age-, sex-, race-, and recall group-specific percentile distributions for selected clinical chemistry determinations for children.

Cholesterol-free diet and the physiologic hyperlipidemia of pregnancy in familial hypercholesterolemia.

Longitudinal studies of the effects of a cholesterol-free diet and a less rigid 300 mg/day low cholesterol diet, both with a polyunsaturated to saturated fatty acid ratio of 1.8/1, were carried out preconception, during gestation, and postpartum in a women heterozygous for familial hypercholesterolemia. On the cholesterol-free diet, during weeks 8-14 of gestation, plasma cholesterol was lowered 25% (from 310 to 230mg/dl), and plasma low density lipoprotein cholesterol (C-LDL) (from 240 to 160 mg/dl), 33%. The 25% reduction in plasma cholesterol was slightly more than previously reported decrements of 19% in 14 normal women during pregnancy, also receiving a cholesterol-free diet. The 300 mg cholesterol diet was not as hypocholesterolemic as the cholesterol-free diet. Its maintenance throughout gestation limited the within-pregnancy increments of total plasma cholesterol and C-LDL to 21% (352-426 mg/dl) and 14% (286-326 mg/dl) respectively. Both the cholesterol-free and the 300 mg cholesterol diet were well tolerated, and should be nutritionally adequate for pregnant women, since they contain more than the recommended amounts of high quality protein, vitamins, minerals, and calories for pregnant women. Cholesterol restricted diets during pregnancy in familial hypercholesterolemics should reduce the physiologic hypercholesterolemia of pregnancy, and potentially reduce the increased risk of coronary heart disease relative to the degree and duration of elevations of total and LDL cholesterol.

Tracking of high- and low-density-lipoprotein cholesterol from childhood to young adulthood in a single large kindred with familial hypercholesterolemia.

Tracking of high- and low-density-lipoprotein cholesterol (HDLC, LDLC) from childhood to young adulthood was assessed in 77 children and in 53 adults from a single large pedigree with familial hypercholesterolemia who were respectively less than or equal to 19 and greater than or equal to 20 years old when first studied in 1973, with reassessment in 1984. No children and only five of the adults had received LDLC lowering therapy from 1973 to 1984. The rank correlations between the 1973 and 1984 measurements for LDLC were 0.73, 0.74, and 0.87; and for HDLC were 0.55, 0.73, and 0.65 (P less than 0.0001 for all correlations), respectively for relatives who were less than or equal to 12, 13 to 19, and greater than or equal to 20 years old in 1973. The 1973:1984 LDLC and HDLC correlations, categorized by relationships to the proband, were as follows: (1) unrelated, LDLC = 0.16, HDLC = 0.56;* (2) first-degree relatives, LDLC = 0.90, HDLC = 0.30; (3) second-degree relatives, LDLC = 0.79, HDLC = 0.39; and (4) other relatives, LDLC = 0.62, HDLC = 0.64. All nine of the probands' first-degree relatives who were above the age-sex specific LDLC 95th percentile in 1973 were also greater than the 95th percentile for LDLC in 1984. Similarly, seven of eight second-degree relatives with LDLC greater than the 95th percentile in 1973 were greater than the 95th percentile in 1984, as were ten of 15 other relatives. LDLC levels in childhood in this extended kindred were highly predictive of adult values.(ABSTRACT TRUNCATED AT 250 WORDS)

Black-white similarities in cord blood lipids and lipoproteins.

Cord blood lipoproteins were quantitated in 117 neonates (58 white, 50 black) to assess for potential early expression of racial lipid distinctions. In comparison of black and white neonates there were no differences in total cholesterol (TC), high-density lipoprotein cholesterol (C-HDL), low-density lipoprotein cholesterol (C-LDL), C-HDL/C-LDL, or C-HDL/TC. Cord blood triglycerides were slightly higher in black neonates (p = 0.02). Unlike certain adult black-white comparisons and within the limits of "genicity" as expressed by cord blood lipoproteins, there were no racial differences in C-HDL, C-LDL, and total cholesterol.

Neonatal familial hyperalphalipoproteinemia.

A kindred with four-generation vertical transmission of familial hyperalphalipoproteinemia was ascertained by measurement of elevated levels of cord blood high-density lipoprotein cholesterol (C-HDL) in a neonatal propositus. Quantitation of cord blood C-HDL coupled with family studies and longitudinal follow-up allows the diagnosis of familial hyperalphalipoproteinemia in infancy.