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Biomedical subjects

R H Knopp

Publications and source records attributed to R H Knopp.

At least 37 records · Page 2Linked to original sources
PubMed2000

Differential effect of National Cholesterol Education Program (NCEP) Step II diet on HDL cholesterol, its subfractions, and apoprotein A-I levels in hypercholesterolemic women and men after 1 year: the beFIT Study.

We previously reported that high density lipoprotein cholesterol (HDL-C) decreases more in hypercholesterolemic (HC) women than in HC men ingesting an National Cholesterol Education Program (NCEP) Step II diet for 6 months. We examined these subjects to determine whether the differential HDL-C reduction persists after 12 months and whether it is associated with decreased HDL(2)-C and apoprotein A-I. Subjects were screened from an industrial workforce and were defined as HC if 2 low density lipoprotein cholesterol measurements were >/=75th percentile or defined as combined hyperlipidemic (CHL) if triglycerides were also >/=75th percentile. The subjects were then taught the NCEP Step II diet in 8 weekly classes and counseled quarterly. Seventy-three HC and 92 CHL women (mean ages 43 and 44 years, respectively) and 112 HC and 106 CHL men (ages 45 and 41 years, respectively) were studied. All groups reported similar total fat (24% to 26% kcal) and saturated fat (7.1% to 7.9% kcal) intakes at 1 year. HDL-C decreased 7.6% in HC women (P<0.01), exceeding the nonsignificant 1.3% decrease in HC men (P=0.000). HDL(2)-C decreased 16.7% in HC women (P<0.01) compared with the nonsignificant 0.5% increase in HC men (P=0.000). In CHL women and men, HDL-C decreased 3.5% and 3.9% (both P<0.01); HDL(2)-C decreased more in women (7.1%, P<0.01) than in men (4.3%, a nonsignificant difference). Apoprotein A-I decreased significantly (5.3%, P<0.01) in HC women only. Plasma triglycerides were unchanged. Low density lipoprotein cholesterol and weight changes were not different among the 4 groups. HDL-C, HDL(2)-C, and apoprotein A-I levels decreased more in HC women than in HC men after following the NCEP Step II diet for 1 year, continuing a trend observed with HDL-C at 6 months. The total HDL-C and HDL(2)-C reductions narrow the baseline differences between men and women by 50%. Whether this reduction impacts women's protection from cardiovascular disease deserves future study. Nonetheless, the results point to sex-based differences in intrahepatic glucose and fatty acid metabolism linked to alterations in HDL formation and removal.

Adult↗
PubMed1999

Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial.

CONTEXT: Heterozygous familial hypercholesterolemia (HeFH) is a common disorder associated with early coronary artery disease, especially in men. The age at which drug therapy should be started is still controversial, as is the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). OBJECTIVE: To assess the lipid-lowering efficacy, biochemical safety, and effect on growth and sexual development of lovastatin in adolescent boys with HeFH. DESIGN: One-year, double-blind, placebo-controlled, balanced, 2-period, 2-arm randomized trial. In the first period (24 weeks), lovastatin was increased at 8 and 16 weeks and the dosage remained stable during the second period (24 weeks). The study was conducted between 1990 and 1994. SETTING: Fourteen pediatric outpatient clinics in the United States and Finland. PATIENTS: Boys aged 10 to 17 years with HeFH. Of 132 randomized subjects (67 intervention, 65 placebo), 122 (63 intervention, 59 placebo) and 110 (61 intervention, 49 placebo) completed the first and second periods, respectively. INTERVENTION: Lovastatin, starting at 10 mg/d, with a forced titration at 8 and 16 weeks to 20 and 40 mg/d, respectively, or placebo. MAIN OUTCOME MEASURES: The primary efficacy outcome measure was low-density lipoprotein cholesterol (LDL-C). Primary safety measures were growth and sexual development. RESULTS: Compared with placebo, LDL-C levels of patients receiving lovastatin decreased significantly (P<.001) by 17%, 24%, and 27% receiving dosages of 10, 20, and 40 mg/d, respectively, and remained 25 % lower than baseline at 48 weeks. Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks (P = .85) and 48 weeks (P = .33); neither were serum hormone levels or biochemical parameters of nutrition. However, the study was underpowered to detect significant differences in safety parameters. Serum vitamin E levels were reduced with lovastatin treatment consistent with reductions in LDL-C, the major carrier of vitamin E in the circulation. CONCLUSIONS: This study in adolescent boys with HeFH confirmed the LDL-C-reducing effectiveness of lovastatin. Comprehensive clinical and biochemical data on growth, hormonal, and nutritional status indicated no significant differences between lovastatin and placebo over 48 weeks, although further study is required.

Adolescent↗
PubMed1999

Plasma lipid concentrations during episodic occupational stress.

The possibility that stress affects plasma lipid concentrations has been the subject of recent investigation, but the findings are equivocal in nonlaboratory settings. To determine whether psychological stress contributes to variability in plasma lipid concentrations and concomitant changes in health behaviors, the effect of increased work load on plasma lipids and apolipoproteins was examined in 173 lawyers. Plasma cholesterol, triglyceride, and apolipoprotein concentrations were studied during periods of high work load (corresponding to impending tax deadlines) and during periods of usual work load. Self-reports of stress, work load, and time pressure, and cortisol, blood pressure, and heart rate were measured to verify that impending deadlines were associated with increased stress levels. Health behaviors which may affect plasma lipoprotein concentrations, including dietary intake and exercise, were also examined. High work load was accompanied by increases in self-reported work load among lawyers most directly affected by the impending deadlines. Plasma apolipoprotein B and triglycerides increased during periods of high work load (M = 1.9 mg/dL, SD = 10.1 and M = 5.3, SD = 34.4, respectively). No changes in dietary intake and exercise were observed. Psychological stress (high work load) is associated with potentially atherogenic changes in plasma lipid concentrations. While the lipoprotein effect of this short-term work stress is small, the effects of longer-term stress on multiple rise factors including triglycerides and apolipoprotein B could have significance for the development of coronary artery disease.

Adult↗
PubMed1999

Comparison of the effects of triphasic oral contraceptives with desogestrel or levonorgestrel on apolipoprotein A-I-containing high-density lipoprotein particles.

Recent observations suggest that the risk of coronary artery disease (CAD) is associated with both the level and composition of the two major populations of apolipoprotein (apo)-defined high-density lipoprotein (HDL) particles: those containing both apo A-I and apo A-II [Lp(AI,AII)] and those containing apo A-I without apo A-II [Lp(AI)]. While sex hormones are known to affect HDL, their influence on these apo-defined HDL particles is not known. We have determined the effects of two triphasic oral contraceptive (OC) formulations on these HDL particles in healthy normolipidemic women aged 21 to 35 years. The formulations contain comparable quantities of ethinyl estradiol (EE) and either desogestrel (DG), a minimally androgenic progestin, or levonorgestrel (LN), a more androgenic progestin. Lipid and lipoprotein levels were measured during the third week of the normal menstrual cycle and the sixth month of OC use. The DG/EE formulation significantly increased total cholesterol (C) 15%, triglyceride (TG) 99%, phospholipid (PL) 17%, apo A-I 28%, apo A-II 34%, apo B 21%, very-low-density lipoprotein cholesterol (VLDL-C) 238%, HDL-C 20%, and HDL3-C 28% (P < .02 to .005, n = 11), but not low-density lipoprotein cholesterol (LDL-C). The LN/EE formulation also increased total C 15%, TG 33%, apo A-I 15%, HDL3-C 21% (P < .05, n = 10), apo B 30% (P < .005), and, additionally, LDL-C 19% (P < .05). Both formulations increased Lp(AI,AII) (DG/EE, 34%, P < .005; LN/EE, 24%, P < .01). These changes reflected comparable increases of small (7.0 to 8.2 nm) and medium (8.2 to 9.2 nm) particles in the LN/EE group and a predominant increase of medium-sized particles in the DG/EE group. Also, in the LN/EE group but not the DG/EE group, there were fewer large (9.2 to 11.2 nm) particles. Lp(AI) increased only in the DG/EE group (25%, P = .075) and was due to the presence of more large particles. The level of Lp(AI) did not change in the LN/EE group, but the lipid/A-I ratio of these particles was lower (P = .012) and there were more small particles. Thus, triphasic OC formulations with progestins of different androgenicity had different effects on VLDL, LDL, and the level and composition of HDL particles with and without apo A-II, possibly reflecting estrogen/progestin/androgen balance. Estrogen dominance increases both Lp(AI,AII) and Lp(AI) and favors large Lp(AI) particles, while progestin/androgen dominance increases only Lp(AI,AII) and favors small particles. Because of the importance of HDL in the arterial wall physiology, OC formulations with different estrogen and progestin content may affect arterial wall health to a different extent.

Adult↗
PubMed1999

Long-term blood cholesterol-lowering effects of a dietary fiber supplement.

BACKGROUND: The study evaluated the blood cholesterol-lowering effects of a dietary supplement of water-soluble fibers (guar gum, pectin) and mostly non-water-soluble fibers (soy fiber, pea fiber, corn bran) in subjects with mild to moderate hypercholesterolemia (LDL cholesterol, 3.37-4.92 mmol/L). METHODS: After stabilization for 9 weeks on a National Cholesterol Education Program Step 1 Diet, subjects were randomly assigned to receive 20 g/d of the fiber supplement (n = 87) or matching placebo (n = 82) for 15 weeks and then receive the fiber supplement for 36 weeks. The efficacy analyses included the 125 subjects (58 fiber; 67 placebo) who were treatment and diet compliant. One hundred two (52 fiber; 50 placebo) completed the 15-week comparative phase. Of these subjects 85 (45 fiber; 40 placebo) elected to continue in the 36-week noncomparative extension phase. RESULTS: The mean decreases during the 15-week period for LDL cholesterol (LDL-C), total cholesterol (TC), and LDL-C/HDL-C ratio were greater (P < 0.001) in the fiber group. The mean changes from pre-treatment values in LDL-C, TC, and LDL-C/HDL-C ratio for subjects in the fiber group were -0.51 mmol/L (-12.1%), -0.53 mmol/L (-8.5%), and -0.30 (-9.4%), respectively. The corresponding changes in the placebo group were -0.05 mmol/L (-1.3%), -0.05 mmol/L (-0.8%), and 0.05 (1.5%), respectively. The fiber supplement had no significant effects (P > 0.05) on HDL cholesterol (HDL-C), triglyceride, iron, ferritin, or vitamin A or E levels. Similar effects were seen over the subsequent 36-week noncomparative part of the study. CONCLUSIONS: The fiber supplement provided significant and sustained reductions in LDL-C without reducing HDL-C or increasing triglycerides over the 51-week treatment period.

Adolescent↗
PubMed1999

Opposing effects of estrogen and progestins on LDL oxidation and vascular wall cytotoxicity: implications for atherogenesis.

Estrogens are widely regarded as beneficial to arterial wall health. Among the mechanisms of this benefit are antioxidant effects on LDL and the arterial wall. Because progestins oppose the effect of estrogen in several systems, we asked if progestins oppose the antioxidant effect of estrogen. To study this question, LDL and various female sex hormones were incubated alone and combined in the absence or presence of bovine aortic endothelial cells, placental trophoblast, or macrophages, and LDL oxidation and cytotoxicity were quantitated. In the absence of cells, LDL incubated with copper in phosphate-buffered saline enhanced the oxidation of LDL. When 17beta-estradiol was added to this system, an antioxidant effect was observed. Progestins inhibited this protective estrogenic effect. In endothelial cell culture, progestins also opposed the antioxidant effect of estrogen, with the strongest antiestrogenic effect seen with the synthetic progestins, levonorgestrel and medroxyprogesterone acetate (MPA). Endothelial cell cytotoxicity was proportional to the enhanced lipid peroxide formation observed with progestins or estrogen. Similar opposing effects were seen when estrogen and progesterone were added to primary cultures of placental trophoblast or macrophages. Thus, three cell culture systems modeling circulating arterial blood contact with cell surfaces demonstrated opposing effects of estrogens and progestins on LDL oxidation and cell cytotoxicity. These studies are in keeping with published reports that female sex steroids influence LDL oxidation in vivo and consequent arterial wall injury.

Arteriosclerosis↗
PubMed1998

Clinical profiles of plain versus sustained-release niacin (Niaspan) and the physiologic rationale for nighttime dosing.

Niacin is the oldest and most versatile agent in use for the treatment of dyslipidemia. It has beneficial effects on low-density lipoprotein cholesterol; high-density lipoprotein cholesterol; the apolipoproteins B and A-I constituting these fractions; triglyceride; and lipoprotein(a). Together, these benefits lead to a diminished incidence of coronary artery disease among niacin users. The chief constraints against niacin use have been flushing, gastrointestinal discomfort, and metabolic effects including hepatotoxicity. Time-release niacin has been developed in part to limit flushing, and now a nighttime formulation (Niaspan) has been developed that assists in containing this untoward effect. In a pivotal metabolic study, bed-time administration of 1.5 g time-release niacin was shown to have the same beneficial effects as 1.5 g plain niacin in 3 divided doses and to be well tolerated. Previous studies suggest that bedtime niacin administration diminishes lipolysis and release of free fatty acids to the liver; this, in turn, leads to an abolition of the usual diurnal increase in plasma triglyceride, which may result in diminished formation and secretion of triglyceride in the very-low-density lipoprotein fraction.

Circadian Rhythm↗
PubMed1998

Iron and zinc status of women and men who followed cholesterol-lowering diets.

OBJECTIVE: To determine if men and women taught the National Cholesterol Education Program step 2 diet experienced diminished iron or zinc status after 2 years of consuming the diet. DESIGN: Subjects attended 8 weeks of diet classes and followup counseling. Four-day food records, zinc protoporphyrin/ heme (ZPP/H, a measure of iron stores), hematocrit, and plasma zinc values were collected at baseline, 1 year, and 2 years. SUBJECTS: Participants in a study of the efficacy of the step 2 diet (213 men and 151 women) who had low-density lipoprotein cholesterol levels above the 75th percentile, and who were not taking lipid-altering medication. STATISTICAL ANALYSES: Paired t tests to compare preintervention and postintervention test results. Two-sample t tests to compare gender, menopause status, and hormone-use groups. Analysis of variance was performed to compare plasma zinc levels among diet-adherence subgroups. Individual evaluation of outlying values and backward stepwise regression to determine the independent effects of variables were also completed. RESULTS: Mean dietary intake approached or exceeded step 2 guidelines. Density of iron intake increased. Density of zinc intake was unchanged, but mean intake was low. Mean ZPP/H and hematocrit did not change for premenopausal or postmenopausal women with or without supplemental hormones; men's values changed only slightly. Abnormal ZPP/H and hematocrit occurred sporadically. Mean plasma zinc levels did not differ from baseline for women, increased slightly for men, and did not differ by level of dietary adherence. No plasma zinc concentrations were below normal. APPLICATION: In this large-scale, 2-year prospective study of women and men, no adverse effects on intake or plasma indicators of iron and zinc were detected as a result of subjects being taught the NCEP step 2 diet.

Adult↗
PubMed1998

Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia.

This study compared the efficacy and safety of a once-a-night, time-release niacin formulation, Niaspan (Kos Pharmaceuticals, Miami Lakes, FL), with plain niacin and placebo for the treatment of primary hypercholesterolemia. The study was conducted in nine academic lipid research clinics in a randomized, double-blind design. Niaspan 1.5 g at bedtime was compared with plain niacin 1.5 g/d after 8 weeks and 3.0 g/d after 16 weeks in divided doses and with placebo. A total of 223 hypercholesterolemic adult men and women participated. Compared with placebo at 8 weeks, Niaspan versus plain niacin at 1.5 g/d showed comparable efficacy, comparably lowering total cholesterol (C) (8%/8%), triglycerides (16%/18%), low-density lipoprotein (LDL)-C (12%/12%), apolipoprotein (apo B) (12%/12%), apo E (9%/7%), and lipoprotein(a) [Lp(a)] (15%/11%), and raising high-density lipoprotein (HDL)-C (20%/17%), HDL2-C (37%/33%), HDL3-C (17%/16%), and apo A-I (8%/6%) (P < or = .05 in all instances). After 16 weeks, the Niaspan effect on LDL-C and triglyceride was unchanged while the plain niacin effect approximately doubled. At equal doses of 1.5 g/d of Niapan versus plain niacin, respectively, AST increased 5.0% versus 4.8% (difference not significant [NS]), fasting plasma glucose increased 4.8% versus 4.5% (NS), and uric acid concentrations increased less, 6% versus 16% (P=.0001). Flushing events were more frequent with plain niacin versus Niaspan (1,905 v 576, P < .001). Flushing severity was slightly greater with Niaspan, but still well tolerated. In conclusion, Niaspan 1.5 g hour of sleep (hs) has comparable efficacy, a lower incidence of flushing, a lesser uric acid rise, and an equivalent hepatic enzyme effect than 500 mg thrice-daily plain niacin in hyperlipidemic subjects. Niaspan may be an equivalent or better alternative to plain niacin at moderate doses in the management of hyperlipidemia.

Double-Blind Method↗
PubMed1998

Coronary heart disease moderates the relationship of chronic stress with the metabolic syndrome.

Metabolic syndrome levels (MSLs) were compared in caregivers (CGs) of spouses with Alzheimer's disease who had diagnoses of coronary heart disease (CHD; n = 27) with non CGs with CHD diagnoses (n = 18), and CGs (n = 44) to non CGs (n = 52) free of CHD. MSLs were greater for CGs than non CGs, but only in persons with CHD (CHD, B for CG status = -.41; non CHD, B = .12; p < .05) at study entry (Time 1 = T1) and CHD, B = -.32; non CHD, B = .14; p < .05) 15-18 months later (Time 2 = T2). In the CHD group, MSLs were associated with poorer health habits at T1 (r = .39, p < .01), uplifts (r = -.37, p < .01) at T2, and CG status (p < .05) at T1 and T2. Relationships of CG status and MSLs declined in the presence of poor health habits at T1 and uplifts at T2. Poorer health habits and fewer uplifts may be associated with elevated MSLs in CGs with CHD.

Aged↗
PubMed1998

Gestational diabetes and the risk of offspring obesity.

BACKGROUND: Intrauterine exposure to the metabolic alterations of maternal diabetes may increase the risk of later obesity. We determined whether offspring of mothers with diet-treated, gestational diabetes mellitus (GDM) have an increased risk of childhood obesity and examined the relationship between childhood obesity and metabolic markers of GDM. METHODS: At a health maintenance organization in Seattle, WA, we reviewed medical records to obtain the life-time height and weight measurements of 524, 8- to 10-year-old children whose mothers had been screened for GDM. Maternal plasma glucose and triglyceride levels were obtained in midgestation 1 hour after ingestion of 50 g of glucose. Those with glucose screening levels >/=7.77 mmol/L (140 mg/dL) underwent a 3-hour, 100-g, oral glucose tolerance test to determine GDM status. Cord serum insulin levels also were obtained at birth. Obesity was defined as an average body mass index between 5 and 10 years of age at or above the 85th percentile for age and sex. RESULTS: The prevalence of obesity was 19% in the 58 offspring of mothers with diet-treated GDM and 24% in the 257 offspring of mothers with negative glucose screen values. There also was no difference in mean body mass index (adjusted for age and sex) between these two groups of offspring. Among all 524 offspring, there was no significant increase in the rate of offspring obesity according to the quartile of maternal screening glucose, triglyceride, oral glucose tolerance test, or cord serum insulin level. CONCLUSION: Prenatal exposure to the metabolic effects of mild, diet-treated GDM does not increase the risk of childhood obesity.

Adult↗
PubMed1998

The Diabetes in Early Pregnancy Study: beta-hydroxybutyrate levels in type 1 diabetic pregnancy compared with normal pregnancy. NICHD-Diabetes in Early Pregnancy Study Group (DIEP). National Institute of Child Health and Development.

OBJECTIVE: The objective was to assess relationships between beta-hydroxybutyrate (beta-OHB) level and pregnancy outcome in human pregnancy in light of the fact that high levels of beta-OHB cause malformations and growth retardation in in vitro studies. RESEARCH DESIGN AND METHODS: We analyzed beta-OHB in prospectively collected specimens from the National Institute of Child Health and Human Development-Diabetes in Early Pregnancy Study, in gestational weeks 6-12 in diabetic (n = 204-239) and nondiabetic (n = 316-332) pregnant women. RESULTS: Levels of beta-OHB in diabetic women were 2.5-fold higher than in nondiabetic pregnant women at 6 weeks' gestation and declined to 1.6-fold above nondiabetic women by 12 weeks' gestation (P < 0.0001 at all times). beta-OHB was positively correlated with glucose levels (P < 0.0001) in diabetic mothers, probably reflecting degree of diabetic control. beta-OHB correlated inversely with glucose (P < 0.0003) (gestational week 6 only) in nondiabetic mothers, possibly reflecting caloric intake. beta-OHB tended to be lower (not higher) in diabetic and nondiabetic mothers with malformed infants or pregnancy losses, but the difference was not statistically significant. beta-OHB in diabetic mothers at 8, 10, and 12 weeks correlated inversely with birth weight (P = 0.004-0.02), even after adjusting for maternal glucose levels. beta-OHB levels were also generally lower in diabetic mothers of macrosomic infants, and week 12 ultrasound crown-rump measurements were inversely related to beta-OHB levels. CONCLUSIONS: The lst trimester beta-OHB is significantly higher in diabetic than nondiabetic pregnant women. In both groups, beta-OHB tended to be lower, not higher, in mothers who had a malformed infant or pregnancy loss. beta-OHB was inversely related to crown-rump length and birth weight. The modest beta-OHB elevation in the 1st trimester of reasonably well-controlled diabetic pregnancy is not associated with malformations, probably because beta-OHB levels causing malformations in embryo culture models are 20- to 40-fold higher. The mechanism of the beta-OHB association with impaired fetal growth is unknown.

3-Hydroxybutyric Acid↗
PubMed1998

LDL oxidation and human placental trophoblast and macrophage cytotoxicity.

We have previously shown that LDL is oxidized by placental cells in primary tissue culture and that this process causes cytotoxicity proportional to LDL oxidation in the presence of sex steroid hormones. Here we describe further experiments linking LDL oxidation to placental cell cytotoxicity. Trophoblast and macrophages were isolated from healthy elective caesarean section placentas by enzymatic digestion and separated by centrifugation on a 40% Percoll gradient and maintained in primary culture for up to 5 days. LDL was oxidized by exposure to 5 microM CuCl2, cells were incubated in the absence of albumen to favor oxidation, and cytotoxicity was measured by 51Cr release from prelabelled cells and cell protein content. Native LDL was oxidized by both cell types with a 10%-50% increase in lipid peroxides and an approximately 4-fold increase in TBARS formation. Increasing concentrations of native LDL and oxidized-LDL increased 51Cr release and diminished protein content in cells incubated in HAM's F-10 medium. Addition of 5 microM Cu2+ augmented cytotoxicity of LDL in macrophage and trophoblast culture, but more in macrophages than trophoblast. Cytotoxicity was diminished by adding 0.001-0.1 mM EDTA to the system, diminishing 51Cr release from 91 +/- 0.5 to 40.8 +/- 1.0% in macrophages and 54.2 +/- 1.2 to 33.1 +/- 1.3% in trophoblast (P < 0.001 in both instances). Similarly, the absence of transition metal ion in culture (MEM medium) blocked an increase in 51Cr release compared to its presence (HAM's F-10 medium). An antioxidant, butylated hydroxytoluene, diminished 51Cr release and LDL electrophoretic mobility in HAM's F-10 medium in placental macrophage culture. LDL oxidation injures placental macrophages and trophoblast, the former more than the latter. The process is LDL- and transition metal ion-dependent and is inhibited by antioxidant. This model of LDL oxidation and placental cell damage in vitro provides a basis for studying mechanisms of placental dysfunction and senescence in human pregnancy.

Antioxidants↗
PubMed1997

Long-term cholesterol-lowering effects of 4 fat-restricted diets in hypercholesterolemic and combined hyperlipidemic men. The Dietary Alternatives Study.

CONTEXT: The long-term effect of aggressively vs moderately fat-restricted diets has not been studied extensively in free-living subjects with different types of hyperlipidemia. OBJECTIVE: To compare the cholesterol-lowering effects of 4 levels of dietary fat intake restriction after 1 year. DESIGN: Randomized, parallel, comparison trial. SETTING: Male employees of a large industry. PARTICIPANTS: A total of 444 men had low-density lipoprotein cholesterol (LDL-C) levels above the 75th age-specific percentile. Subjects with triglyceride (TG) levels less than the 75th age-specific percentile were defined as hypercholesterolemic (HC) and those with TG levels at or above the 75th age-specific percentile were defined as combined hyperlipidemic (CHL). INTERVENTIONS: Hypercholesterolemic subjects were randomized to diets 1, 2, 3, and 4 taught to contain 30%, 26%, 22%, and 18% fat, and the CHL subjects were randomized to diets 1, 2, and 3. All 4 diets were taught to subjects and spouses or partners in 8 weekly 2-hour classes. MAIN OUTCOME MEASURES: Plasma lipoprotein levels after 1 year. RESULTS: Fat intake after 1 year declined from a mean of 34% to 36% of energy to 27%, 26%, 25%, and 22% in the 4 HC diet groups and 28%, 26%, and 25% in the 3 CHL diet groups. Mean+/-SD percent LDL-C reductions were 5.3%+/-16.2%, 13.4%+/-12.6%, 8.4%+/-11.2%, and 13.0%+/-15.7% in the HC diet groups and 7.0%+/-16.2%, 2.8%+/-15.8%, and 4.6%+/-13.5% in the CHL diet groups (P<.01 in all but 1 instance). Apoprotein B levels decreased 8.6%, 10.7%, 4.3%, and 5.3% in the HC groups and 14.6%, 11.4%, and 9.9% in the CHL groups (P<.05-.01 in each instance). Triglyceride levels increased significantly in subjects following HC diets 3 and 4, 21.7% and 38.7% (P<.05 and .01), but not in any CHL subjects. High-density lipoprotein cholesterol decreased 2.8% and 3.2% in subjects on HC diets 3 and 4, respectively (P<.05 in both cases). CONCLUSIONS: After 1 year, moderate restriction of dietary fat intake attains meaningful and sustained LDL-C reductions in HC subjects and apoprotein B reductions in both HC and CHL subjects. More extreme restriction of fat intake offers little further advantage in HC or CHL subjects and potentially undesirable effects in HC subjects.

Apolipoproteins↗
PubMed1997

Moderate dose, three-drug therapy with niacin, lovastatin, and colestipol to reduce low-density lipoprotein cholesterol <100 mg/dl in patients with hyperlipidemia and coronary artery disease.

The efficacy, safety, and tolerability of a moderate dose, 3-drug lipid-lowering regimen were evaluated among 29 male patients with hyperlipidemia and coronary artery disease. In an initial 12-month phase, regular niacin, 500 mg qid, lovastatin, 20 mg bid, and colestipol, 10 g/bid, were given with dose adjustment for lipid targets and side effects. This was followed by 2 random sequence crossover phases (8 months each) alternating regular niacin with a polygel controlled-release formulation of niacin for use in this regimen. Lipid, lipoprotein, apoprotein, and clinical chemistry determinations were obtained at baseline, during the initial phase, at the 2 crossover phases, and at 6 weeks after therapy. A final questionnaire queried specific side effects and overall preferences. Low-/high-density lipoprotein (LDL/HDL) changed from means of 215/46 mg/dl at baseline, to 94/59 mg/dl after run-in, to 85/52 mg/dl after 8 months of controlled-release niacin, and to 98/56 mg/dl after 8 months of regular niacin (regular niacin vs controlled-release niacin, p <0.005/<0.05). The target of LDL < or = 100 mg/dl was achieved at 8 months by 83% of these patients with controlled-release niacin and by 52% with regular niacin (p <0.01). Compliance was 95% with controlled-release niacin versus 85% with regular niacin (p <0.001). The controlled-release niacin and regular niacin regimens did not differ in terms of uric acid, glucose, insulin, or asparate aminotransferase levels. Overall, 21% of patients called the 3 drugs "very easy" and 72% "fairly easy" to take. The controlled-release niacin-containing regimen was preferred by 21 patients and the regular niacin by 4. In conclusion, these regimens achieve striking lipid changes among hyperlipidemic patients. Controlled release is the preferred niacin preparation in terms of LDL reduction, compliance, patient preference, and achieving the National Cholesterol Education Program guideline of LDL < or = 100 mg/dl. The 2 niacin preparations did not differ in evidence of toxicity.

Cholesterol, LDL↗