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This study was designed to determine whether a soluble dietary fiber supplement containing gum arabic and pectin in apple juice would lower serum lipids in 110 hypercholesterolemic men and women. Subjects were stabilized on an American Heart Association Phase I Diet for 8 wk. Those with elevated low density lipoprotein cholesterol levels, despite dietary modification, continued to follow the diet and were randomly assigned to receive 720 mL/d of apple juice containing 0 (control), 5, 9 or 15 g of gum arabic and pectin (4:1 ratio) for 12 wk, followed by a 6-wk apple juice-only washout phase. Serum lipid profiles, body weight and 3-day diet records were collected at 3-wk intervals. No significant differences among groups were observed in serum lipid responses during treatment or washout. During the treatment phase, mean serum total cholesterol and triglyceride concentrations increased by 3.5 and 28.5%, respectively (all groups combined, P < 0.0001). The high density lipoprotein cholesterol level did not change significantly from baseline in any group. During washout, mean total cholesterol concentration rose by an additional 2.4% (P < 0.05) compared with the value at the end of the treatment period, suggesting that the apple juice used to deliver the fiber supplement may have contributed to the adverse changes observed in the serum lipid profile. These findings do not support the hypothesized hypocholesterolemic effect of the gum arabic/pectin (4:1) mixture studied, but do underline the importance of selecting appropriate vehicles for delivery of dietary fiber mixtures.

This randomized, multicenter, double-blind parallel-group study was performed to evaluate the lipid-altering efficacy and safety of simvastatin 80 mg/day, a dose twice the current maximum recommended dose. At 20 centers in the United States, 521 male and female hypercholesterolemic patients were randomly assigned in a ratio of 2:3 to receive simvastatin 40 or 80 mg once daily, respectively, for 24 weeks in conjunction with a lipid-lowering diet. Patients met National Cholesterol Education Program (NCEP) low-density lipoprotein (LDL) cholesterol criteria for pharmacologic treatment. The mean percentage reductions (95% confidence intervals) from baseline in LDL cholesterol averaged at weeks 18 and 24 were 38% (-40 to -36) and 46% (-47 to -45) for the 40- and 80-mg groups, respectively (p <0.001 between groups). One third of patients on the 40- and 80-mg doses achieved an LDL cholesterol reduction of 46% and > or = 53%, respectively. Decreases in apolipoprotein B, total cholesterol, and triglycerides were also significantly greater among patients receiving 80 mg/day. Simvastatin was well tolerated in both groups. Two patients (0.6%) in the 80-mg group developed myopathy. Consecutive, clinically significant hepatic transaminase elevations occurred in 3 (1.0%) and 6 (1.9%) patients in the 40- and 80-mg groups, respectively (p= 0.486). In conclusion, simvastatin 80 mg/day provided substantial reductions in LDL cholesterol, allowing most patients to reach their NCEP target levels; it also had an excellent safety and tolerability profile.

Objective: Recognising the importance of treating hyperlipidaemia, the National Cholesterol Education Program (NCEP) has established widely accepted treatment goals for low density lipoprotein cholesterol (LDL-C). Medications used most commonly to achieve these LDL-C goals are HMG-CoA reductase inhibitors. The relative resource utilisation and cost associated with the use of reductase inhibitors of different LDL-C lowering efficacy are unknown, but are major health and economic concerns. The objective of this study was to determine the mean total cost of care to reach NCEP goals with various reductase inhibitors., Design: In a randomised, 54-week, 30-centre controlled trial we compared resources used and costs associated with treating patients to achieve NCEP goals using 4 reductase inhibitors: atorvastatin, simvastatin, lovastatin and fluvastatin., Patients and Participants: The trial studied 662 patients; 318 had known atherosclerotic disease., Interventions: Reductase inhibitor therapy was initiated at recommended starting doses and increased according to NCEP guidelines and package insert information. For patients who did not reach the goal at the highest recommended dose of each reductase inhibitor, the resin colestipol was added., Main Outcome Measures and Results: Patients treated with atorvastatin, compared-with other reductase inhibitors, were more likely to reach NCEP goals during treatment (p < 0.05), required fewer office visits (p < 0.001) and less adjuvant colestipol therapy (p = 0.001). Consequently, the mean total cost of care (1996 values) to reach NCEP goals was lower with atorvastatin [$US1064; 95% confidence interval (CI): $US953 to $US1176] compared with simvastatin ($US1471, 95% CI: $US1304 to $US1648), lovastatin ($US1972; 95% CI: $US1758 to $US2186) and fluvastatin ($US1542; 95% CI: $US1384 to $US1710). Results were similar for patients with or without known atherosclerotic disease., Conclusions: In patients requiring drug therapy for hypercholesterolaemia, NCEP LDL-C goals are achieved significantly more often using fewer resources with atorvastatin compared with simvastatin, lovastatin or fluvastatin.

The effects of consuming foods containing 0 (control), 3.4, 6.8, or 10.2 g psyllium seed husk (PSH)/d for 24 wk on the serum lipid profile were assessed in this randomized, double-blind controlled study. Men and women (n = 286) with LDL-cholesterol concentrations between 3.36 and 5.68 mmol/L (130 and 220 mg/dL) were randomly assigned to one of four treatment groups after following a low-fat diet for > or = 8 wk. At week 24, LDL cholesterol was 3% above baseline in the control group. In the group consuming 10.2 g PSH/d, LDL cholesterol remained below baseline during treatment, with a value 5.3% below that of the control group at week 24 (P < 0.05 compared with the control group). No significant differences were observed in HDL cholesterol or triacylglycerol. Although modest, the effect of 10.2 g PSH/d on LDL cholesterol (relative to the control) persisted throughout the 24-wk treatment period, indicating potential for long-term benefit.

Objective: The primary aim of this study was to evaluate the effects of age on the relationships between commonly used measures of adiposity [abdominal circumference (AC) and body mass index (BMI)] and serum lipids in men., Methods: AC, height, weight, and a fasting serum lipid profile were measured in 194 male volunteers, aged 18 to 81 years, who were free of diabetes mellitus and had participated in one of several studies on metabolic cardiovascular risk factors in the authors' laboratory. Least squares linear regression and two-way analysis of variance were used to assess relationships between measures of adiposity and fasting serum lipid values in two age groups: 18 to 49 (n = 53) and 50 to 81 years (n = 141)., Results: Increasing AC correlated with serum triglycerides [r = 0.32 (younger) and 0.43 (older)], and was inversely associated with high-density lipoprotein cholesterol (r = -0.26 and -0.26). Regression lines for these relationships did not differ between age groups. Low-density lipoprotein cholesterol (LDL-C) increased with greater AC among younger subjects (r = 0.44), but not among men over 50 years (r = -0.01). The relationships between BMI and serum lipids generally paralleled those for AC, but were weaker than for AC in the younger group., Conclusions: These findings suggest that an interaction exists between age and adiposity as determinants of LDL-C levels, and that AC is a simple, clinically useful tool for assessing risk for adiposity-related dyslipidemia in men.

Marine oil plus simvastatin is an effective therapy for improving serum triglycerides, non-high-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in patients with combined hyperlipidemia. Concurrent administration does not attenuate the individual effects of either marine oil or simvastatin on the serum lipid profile.

Atorvastatin is a highly efficacious hydroxymethylglutaryl-coenzyme A reductase inhibitor that has been shown to reduce low-density lipoprotein cholesterol by 40% to 60%. Monotherapy with atorvastatin (10 to 80 mg/day) is well-tolerated, convenient, and appears to be effective for achieving National Cholesterol Education Program treatment goals in most patients, regardless of risk status.

One hundred two normal healthy males and females were given 0, 8, 20 or 32 g/d olestra to which had been added graded amounts of vitamins A, D and E for 8 wk in a parallel, double-blind study. The primary purpose of the study was to determine the amounts of vitamins D and E needed to offset the effect of olestra on the availability of these vitamins. Serum concentrations of retinol, carotenoids, 25-hydroxyvitamin D metabolites, alpha-tocopherol, phylloquinone, lipids, ferritin and total iron, iron-binding capacity and hematology parameters, plasma concentrations of des-gamma-carboxyprothrombin and prothrombin, and urinary gamma-carboxyglutamic acid (Gla) excretion were measured biweekly. Clinical chemistry and urinalysis parameters, vitamin B12 absorption, and serum 1,25-dihydroxyvitamin D concentration were measured at wk 0 and 8. Serum concentrations of alpha-tocopherol and 25-hydroxyergocalciferol were restored to control concentration by adding 2.1 mg d-alpha-tocopheryl acetate and 0.06 microg ergocalciferol per gram of olestra, respectively, to the diet. Olestra reduced serum concentrations of 25-hydroxyergocalciferol, carotenoids and phylloquinone in a dose-responsive manner but did not affect Gla excretion, plasma des-gamma-carboxyprothrombin and prothrombin concentrations, overall vitamin D status, vitamin B12 absorption or iron status. Laboratory evaluations showed no olestra-related effects. Subjects in all groups reported mild to moderately severe transient gastrointestinal symptoms. These symptoms did not affect study compliance or the integrity of the data.

Objectives: To evaluate and compare the lipid-altering effects of conjugated estrogens and pravastatin, alone and in combination, in postmenopausal women with hypercholesterolemia., Methods: This was a double-blind, randomized, placebo-controlled clinical trial with 4 parallel groups. Participants (N = 76) were randomly assigned to receive conjugated estrogens, 0.625 mg/d; pravastatin sodium, 20 mg/d; conjugated estrogens plus pravastatin; or a placebo for 16 weeks., Results: Primary end points were changes in serum lipid parameters. Among participants treated with conjugated estrogens, levels of non-high density lipoprotein cholesterol (non-HDL-C) (13.0%) and calculated low density lipoprotein cholesterol (LDL-C) (13.5%) decreased, while levels of HDL-C (22.5%) and triglycerides (4.2%) increased. Participants in the pravastatin group achieved reductions of 23.7% and 25.4% in non-HDL-C and calculated LDL-C levels, respectively. Levels of HDL-C increased slightly (3.7%) and triglycerides decreased by 12.1%. Among participants treated with a combination of conjugated estrogens plus pravastatin, the non-HDL-C (-25.2%) and calculated LDL-C (-28.7%) responses were similar to those of the pravastatin group, and the HDL-C response (21.2%) was similar to that observed in the conjugated estrogens group. Triglyceride levels remained similar to baseline (-0.9%) in the combined treatment group., Conclusions: Administration of conjugated estrogens resulted in potentially antiatherogenic changes in levels of non-HDL-C, HDL-C, and calculated LDL-C. The HDL-C response to combined treatment was similar to that observed in women taking conjugated estrogens alone, while the non-HDL-C and LDL-C responses to combined treatment were similar to those produced by pravastatin therapy alone. These findings support the position of the National Cholesterol Education Program that estrogen replacement, with a progestin where indicated, should be given consideration as a therapeutic option for the management of hypercholesterolemia in postmenopausal women.

Objective: The objective of this study was to evaluate the effects of daily dietary supplementation with 1.25 g or 2.5 g of docosahexaenoic (DHA), in the absence of eicosapentaenoic acid (EPA), on serum lipids and lipoproteins in persons with combined hyperlipidemia (CHL) [serum low-density lipoprotein cholesterol (LDL-C) 130 to 220 mg/dL and triglycerides 150 to 400 mg/dL]., Methods: After a 6-week dietary stabilization period, subjects entered a 4-week single-blind placebo (vegetable oil) run-in phase. Those with adequate compliance during the the run-in were randomized into one of three parallel groups (placebo, 1.25, or 2.5 g/day DHA) for 6 weeks of treatment. Supplements were administered in a triglyceride form contained in gelatin capsules. Primary outcome measurements were plasma phospholipid DHA content, serum triglycerides, high-density lipoprotein cholesterol (HDL-C). LDL-C and non-HDL-C., Results: The DHA content of plasma phospholipids increased dramatically (2 to 3 fold) in a dose-dependent manner. Significant (p < 0.05) changes were observed in serum triglycerides (17 to 21% reduction) and HDL-C (6% increase) which were of similar magnitude in both DHA groups. Non-HDL-C [+1.6 (NS) and +5.7% (p < 0.04)] and LDL-C [+9.3% (NS) and +13.6% (p < 0.001)] increased in the DHA treatment groups. All lipid effects reached an apparent steady state within the first 3 weeks of treatment., Conclusion: Dietary DHA, in the absence of EPA, can affect lipoprotein cholesterol and triglyceride levels in patients with combined hyperlipidemia. The desirable triglyceride and HDL-C changes were present at a dose which did not significantly increased non-HDL-C or LDL-C. These preliminary findings suggest that dietary supplementation with 1.25 g DHA/day, provided in a triglyceride form, may be an effective tool to aid in the management of hypertriglyceridemia.

The hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin is the most effective of the currently approved hypolipidemic drugs and has been shown to reduce mortality and coronary morbidity in patients with coronary artery disease. For these patients the United States National Cholesterol Education Program advocates reducing low-density lipoprotein (LDL) cholesterol to <100 mg/dl. However, in some patients this cannot be achieved using monotherapy with simvastatin 40 mg/day, the current maximal recommended dose. To evaluate the effectiveness of extending the dosage range, 156 subjects with LDL cholesterol >160 mg/dl and triglycerides (TG) <350 mg/dl were randomized to simvastatin at doses of 40, 80, and 160 mg/day in a 26 week, double-blind, 3-period, complete block crossover study. Each active treatment period was 6 weeks in duration with intervening 2 week washout periods. Median reductions from baseline in LDL cholesterol were 41%, 47%, and 53% in the 40-, 80-, and 160-mg groups, respectively. The corresponding reductions in plasma TG were 21%, 23%, and 33%. High-density lipoprotein (HDL) cholesterol increased by 6% to 8% in each group. One patient (0.7%) taking 160 mg developed myopathy; 1 patient (0.7%) taking 80 mg, and 3 (2.1%) taking 160 mg had transaminase elevations > 3 times the upper limit of normal. No new or unexpected adverse effects were observed. We conclude that simvastatin at doses of 80 and 160 mg/day provides additional efficacy with a low short-term incidence of adverse effects; our results support the continued investigation of simvastatin at these doses.

BACKGROUND: Combination lipid-lowering therapy may be desirable in patients with elevated low-density lipoprotein cholesterol, high triglycerides, and low high-density lipoprotein cholesterol. This study was conducted to determine the lipid-lowering efficacy of the combination of low-dose simvastatin and niacin in patients with combined hyperlipidemia and low high-density lipoprotein cholesterol. METHODS AND RESULTS: In this multicenter, prospective, randomized trial, 180 patients with hypercholesterolemia and hypertriglyceridemia and/or low high-density lipoprotein cholesterol were randomized to combination simvastatin (10 mg/day) and niacin (0.75 g/day) or to either drug alone for 9 weeks. The dose of niacin was doubled (from 0.75 g/day to 1.5 g/day) in both the combination and niacin arms for the remaining 8 weeks. The combination of simvastatin, 10 mg/day, and niacin, 1.5 g/day, reduced total, low-density lipoprotein, and very low-density lipoprotein cholesterol and triglycerides by 24%, 29%, 45%, and 31%, respectively, while increasing high-density lipoprotein cholesterol by 31%. The addition of niacin to simvastatin did not enhance the low-density lipoprotein cholesterol by 31%. The addition of niacin to simvastatin did not enhance the low-density lipoprotein cholesterol-lowering effect of simvastatin; however, the combination was more effective than either monotherapy at raising high-density lipoprotein cholesterol and lowering very low-density lipoprotein cholesterol (P <.05). More patients discontinued treatment because of an adverse event in the niacin (P <.03) and combination groups (P =.06) than the simvastatin group. CONCLUSIONS: Treatment of patients with combined hyperlipidemia and/or low high-density lipoprotein with combination low-dose simvastatin and niacin resulted in large reductions in total, low-density lipoprotein, and very low-density lipoprotein cholesterol and increases in HDL cholesterol. Although the combination was well tolerated in the current trial, its safety needs to be evaluated in larger trials of longer duration.

Objective: To determine the effect of incorporating quick-service meals into a Step I diet on the achievement of the National Cholesterol Education Program (NCEP) guidelines and on the blood lipid response of hyperlipidemic subjects (as possibly, the achievement of, and adherence to, dietary goals may be assisted by the inclusion of familiar foods, instead of their exclusion)., Methods: This was a randomized, parallel design study in free-living subjects. Hypercholesterolemic men and women (low-density lipoprotein cholesterol [LDL-C] level, 3.36 to 5.69 mmol/L [130 to 220 mg/dL]) who were consuming a high-fat diet (> 33% of total calories from fat) were randomly assigned to either a traditional NCEP Step I diet (n = 44) or an NCEP Step I diet with the incorporation of frequent quick-service meals (NCEP-QS, n = 45)., Results: After 8 weeks of treatment, both groups similarly reduced their reported dietary intakes of energy (approximately 30%), total percent fat (approximately 8%), percent saturated fat (approximately 3%), and cholesterol (approximately 38% to 28%). Both groups also experienced a decrease in the levels of total serum cholesterol (NCEP Step I diet, 8%; NCEP-QS Step I diet, 3%) and LDL-C (NCEP Step I diet, 10%; NCEP-QS Step I diet, 4%). However, compared with the group receiving the NCEP-QS Step I diet, the subjects who were consuming the NCEP Step I diet showed a significantly greater reduction in their total serum cholesterol and LDL-C levels over time (P < .05). Weight loss was significantly correlated (P < .001) with the decrease in the total serum cholesterol and LDL-C levels for all subjects combined., Conclusions: Hyperlipidemic subjects who were consuming an NCEP Step I diet, with or without the incorporation of quick-service meals, experienced a significant decrease in their total serum cholesterol and LDL-C levels, body weight, and reported fat intake. The beneficial responses in lipid levels were modestly mitigated in the quick-service diet group.

Objective: To assess the lipid-lowering effect of atorvastatin (a new 3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitor) on levels of serum triglycerides and other lipoprotein fractions in patients with primary hypertriglyceridemia, determine if atorvastatin causes a redistribution of triglycerides in various lipoprotein fractions, and assess its safety by reporting adverse events and clinical laboratory measurements., Design: Randomized double-blind, placebo-controlled, parallel-group, multicenter trial., Setting: Community- and university-based research centers., Patients: A total of 56 patients (aged 26 to 74 years) with a mean baseline triglyceride level of 6.80 mmol/L (603.3 mg/dL) and a mean baseline low-density lipoprotein cholesterol (LDL-C) level of 3.07 mmol/L (118.7 mg/dL)., Interventions: Cholesterol-lowering diet (National Institutes of Health National Cholesterol Education Program Step I Diet) and either 5 mg, 20 mg, or 80 mg of atorvastatin, or placebo., Main Outcome Measures: Percent change from baseline in total triglycerides for three dose levels of atorvastatin compared with placebo., Results: Mean reductions in total triglycerides between 5 mg, 20 mg, and 80 mg of atorvastatin and placebo after 4 weeks of treatment were -26.5%, -32.4%, -45.8%, and -8.9%, respectively. Mean reductions in LDL-C were -16.7%, -33.2%, -41.4%, and -1.4%, respectively, and very low-density lipoprotein cholesterol (VLDL-C) were -34.3%, -45.9%, -57.7%, and -5.5%, respectively. Similar mean changes in total apolipoprotein B (apo B) (-16.9%, -32.8%, -41.7%, and +1.0%), apo B in LDL (-14.8%, -29.8%, -42.0%, and -3.1%), and apo B in VLDL (-23.8%, -35.8%, -34.4%, and +11.7%) were observed. In addition, comparable mean changes in LDL triglycerides (-22.5%, -30.7%, -39.9%, and +3.9%) and VLDL triglycerides (-28.1%, -34.0%, -47.3%, and -10.8%) were seen., Conclusions: In atorvastatin treatment groups, total serum triglyceride levels decreased in a dose-dependent manner, reductions in the 20-mg and 80-mg groups were statistically significant (P < .05) compared with placebo. Atorvastatin did not cause a redistribution of triglycerides but consistently lowered triglycerides in all lipoprotein fractions. Atorvastatin was well tolerated.

Psyllium, a water-soluble fiber, has been shown to lower total serum and low-density-lipoprotein (LDL)-cholesterol concentrations in adult hypercholesterolemic subjects and may be effective in the treatment of hypercholesterolemia in children. The effects of a psyllium-enriched cereal were compared with a matched control cereal in a double-blind, crossover fashion in 25 children, 6-18 y old, with hypercholesterolemia. After an 8-wk diet-stabilization period, the subjects were randomly assigned to receive the active or control cereals for 6 wk, followed by a 6-wk washout period and a 6-wk crossover treatment period. Whereas no changes were noted in total and LDL-cholesterol concentrations during consumption of the control cereal, significant changes were seen during the psyllium-cereal periods [0.31 mmol/L (12.1 mg/dL) and 0.28 mmol/L (10.9 mg/dL); P = 0.03 and 0.01, respectively]. The psyllium-enriched cereal was well tolerated throughout the trial. Consumption of the psyllium-enriched cereal resulted in a modest 7% reduction in LDL-cholesterol concentrations compared with the control cereal when used in this pediatric hypercholesterolemic sample. Psyllium offers a potential adjunct to a low-fat diet for the treatment of hypercholesterolemia in the pediatric population because of its ease of incorporation into various foods.

BACKGROUND: Inhibitors of hydroxymethylglutaryl co-enzyme A reductase are widely used for the treatment of hypercholesterolemia. Physicians and third-party payers need an accurate measure of their relative potency and hypolipidemic efficacy. We have therefore compared simvastatin against fluvastatin, the newest member of this class. METHODS AND RESULTS: One hundred fifty-eight hypercholesterolemic patients in seven United States lipid clinics participated in this balanced double-blind incomplete block study. After a placebo-diet run-in period, patients received treatment with active drug for three consecutive 5-week periods, with measurement of lipids in a NHLBI-CDC standardized central laboratory at the end of each period. Each patient was randomly assigned to three of the following five treatments: simvastatin 5 mg, 10 mg, and 20 mg and fluvastatin 20 mg and 40 mg. The mean percent reductions in low density lipoprotein cholesterol from baseline were 21, 27, 32, 16, and 23 respectively. The simvastatin/fluvastatin milligram potency ratio was 6.8 (95% CI, 5.3-9.3). At the same 20 mg dose, simvastatin produced an effect on LDL cholesterol approximately double that of fluvastatin and resulted in 46% of patients achieving their National Cholesterol Education Program low density lipoprotein cholesterol target levels, compared to 12% for fluvastatin. CONCLUSIONS: Fluvastatin at its maximal dose of 40 mg daily is approximately equivalent to simvastatin 5 mg daily. Higher doses of simvastatin are considerably more effective in the treatment of primary hypercholesterolemia.

This 6-week, double-blind clinical trial evaluated lipid parameter responses to different dosages of atorvastatin in patients with primary hypercholesterolemia. Atorvastatin is a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor under development. After completing an 8-week placebo-baseline dietary phase, 81 patients were randomly assigned to receive either placebo or 2.5, 5, 10, 20, 40, or 80 mg atorvastatin once daily for 6 weeks. Plasma LDL cholesterol reductions from baseline were dose related, with 25% to 61% reduction from the minimum dose to the maximum dose of 80 mg atorvastatin once a day. Plasma total cholesterol and apo B reductions were also dose related. Previously, reductions in LDL cholesterol of the magnitude observed in this study have been seen only with combination drug therapy. In this study, atorvastatin was well tolerated by hyperlipidemic patients, had an acceptable safety profile, and provided greater reduction in cholesterol than other previously reported HMG-CoA reductase inhibitors.

The purpose of this study was to investigate and compare the efficacy, safety, and patient acceptability of a new formulation of colestipol, colestipol tablets (T), with those of colestipol granules (G), in a randomized, double-blind, placebo-controlled, multicenter study. Three hundred and seventeen patients with primary hypercholesterolemia who were following a low-fat, low-cholesterol diet (NCEP Step I diet), and had low-density lipoprotein cholesterol (LDL-C) levels > or = 4.14 mmol/l (160 mg/dl) and < or = 6.46 mmol/l (250 mg/dl) were studied. Study medication was taken twice a day, with breakfast and supper, for 8 weeks. The six parallel treatment groups consisted of colestipol tablets 2 g b.i.d. and 8 g b.i.d., matching placebo tablets b.i.d., colestipol granules 2 g b.i.d. and 8 g b.i.d., and matching placebo granules b.i.d.. Study endpoints included absolute change and percentage change from baseline in selected lipid, lipoprotein, and apolipoprotein measurements; LDL-C lowering was the primary efficacy endpoint. Treatment with colestipol tablets and colestipol granules resulted in virtually identical, statistically significant (P < or = 0.05) reductions of LDL-C, total cholesterol (TC), TC/HDL-C, and apolipoprotein B (apo B). Compared with placebo, all active treatments (tablets 4 g/day, tablets 16 g/day, granules 4 g/day, granules 16 g/day) significantly reduced LDL-C (12%, 24%, 12%, 25%, respectively), TC (7%, 15%, 8%, 15%, respectively), TC/HDL-C (8%, 14%, 9%, 15%, respectively) and apo B (12%, 20%, 13%, 22%, respectively). All active treatments significantly increased lipoprotein particle AI (LpAI) (5%, 23%, 14%, 18%, respectively). VLDL-C and triglycerides increased significantly in the high-dose groups. The proportions of patients reporting adverse events, largely gastrointestinal-related, were not different among the active treatment groups. The treatments were well-tolerated, and no drug-related serious adverse events were reported. Patients experienced with granule medication prior to this study preferred tablets over granules. This study demonstrates that colestipol tablets are an effective treatment to reduce LDL-C in patients with primary hypercholesterolemia, are equivalent to colestipol granules, are well-tolerated, and are preferred over granules by patients.

A total of 96 patients with moderate elevations of low-density lipoprotein (LDL) cholesterol were randomly assigned to 4 different double-blind treatment regimens: placebo; colestipol 5 g and lovastatin 20 mg/day (C5 + L20); colestipol 10 g and lovastatin 20 mg/day (C10 + L20); and lovastatin 40 mg/day (L40). During 12 weeks of therapy, C10 + L20 achieved the greatest reduction in total cholesterol (-32%) and LDL cholesterol (-48%) levels from baseline. This combination also exhibited significantly greater reductions in LDL cholesterol levels than the C5 + L20 and L40 groups (p < 0.01). The differences in total and LDL cholesterol reduction between the C5 + L20 and L40 groups were not significant. Similar changes and differences between treatments were seen in apolipoprotein B levels. Whereas mean total apolipoprotein A-I levels increased with all treatments (p < 0.05), lipoprotein particles A-I were significantly increased in the C10 + L20 group (p < 0.01) only. Results demonstrate that the combination of low-dose lovastatin (20 mg/day) with low-dose colestipol (5 or 10 g/day) produces LDL cholesterol reductions equal to or greater than higher doses of lovastatin (40 mg/day). In addition, low-dose combinations are > 25% more cost-effective than high-dose monotherapy.

Fluvastatin is a totally synthetic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor that is effective in reducing cholesterol when given in a single evening dose. Absorption and rate of bioavailability may be affected when administered with food, but the effect of mealtime dosing on efficacy and safety has not been evaluated. This multicenter, double-blind, placebo-controlled crossover study was performed in 44 patients with primary hypercholesterolemia. Patients received 20 mg of fluvastatin with the evening meal and placebo at bedtime for 6 weeks, followed by 12 weeks of placebo at mealtime and fluvastatin at bedtime (group 1). Group 2 received the opposite treatment schedule, and group 3 received placebo at mealtime and at bedtime for 12 weeks before receiving 20 mg of fluvastatin at bedtime instead of placebo for the final 6 weeks. Fluvastatin with the evening meal resulted in a marginally lower peak serum concentration (p < 0.1) and a significantly delayed time to peak concentration compared with bedtime dosing, but there were no statistically significant differences in the extent of bioavailability. At the end of the first 6 weeks of treatment, similar reductions in low-density lipoprotein (LDL) cholesterol were obtained whether fluvastatin was given at mealtime (-21.8%; p < 0.001) or at bedtime (-23.9%; p < 0.001). After crossover of groups 1 and 2, the results remained constant. With fluvastatin, there were comparable reductions in total cholesterol (p < 0.001) and in LDL:high-density lipoprotein (HDL) ratio (p < 0.001) irrespective of the time of dosing. In conclusion, fluvastatin had a similar tolerability, safety, and efficacy, whether given with the evening meal or at bedtime. There were no serious adverse events nor changes in physical examination findings or laboratory values attributable to treatment.

The Fluvastatin Long-Term Extension Trial (FLUENT) evaluated the safety and efficacy of fluvastatin over a period of 48 weeks. All 918 enrolled patients had severe primary hypercholesterolemia (mean baseline low-density lipoprotein [LDL] cholesterol, 227 mg/dL) and had completed one of three previous short-term studies of fluvastatin. This open-label extension study used a starting dose of 20 mg of fluvastatin at bedtime. The dose was titrated to 40 mg to achieve LDL levels of < 3.36 mmol/L (130 mg/dL). If necessary, cholestyramine was added to the fluvastatin treatment to achieve this level. After 48 weeks of treatment, the mean percent change from baseline was statistically significant for LDL (-30.7%; p < 0.001), total (-21.9%; p < 0.001), and HDL (+3.5%; p < 0.001) cholesterol. Of the 836 patients who completed the study, only four (0.5%) withdrew because of drug-related adverse events, which were mainly gastrointestinal. There was one purported case of myopathy in a patient who had a recent history of strenuous physical activity. Newly occurring or worsening lens abnormalities were generally mild and did not require discontinuation of treatment. In conclusion, these results indicate that fluvastatin is safe, effective, and well tolerated in the long-term treatment of primary hypercholesterolemia.

Numerous angiographic trials have demonstrated that the atherosclerotic process can be modified through reductions in levels of low-density lipoprotein (LDL) cholesterol. Recent research has focused on other potential modalities by which atheroroma development might be inhibited. These newer strategies include reduction of the oxidative potential of LDL particles through modification of dietary fat intake; prevention of LDL oxidation through the use of antioxidants; and inhibition of monocyte and macrophage function by omega-3 fatty acids and leukotriene-1 antagonists. Inhibition of acyl-coenzyme A:cholesterol acyltransferase (ACAT) may block intestinal cholesterol absorption and reduce synthesis of very-low-density lipoprotein (VLDL), while simultaneously enriching high-density lipoprotein (HDL) cholesterol. Modification of cholesterol ester transfer protein may be associated with improved reverse cholesterol transport or enlarged HDL particles. In the future, a wide variety of therapeutic modalities may be available for use alone or in combination to reverse atherosclerosis or prevent its progression.

Competition between the (n - 3) and (n - 6) types of highly unsaturated fatty acids can diminish the abundance of (n - 6) eicosanoid precursors in a tissue, which in turn can diminish the intensity of tissue responses that are mediated by (n - 6) eicosanoids. The mixture of 20- and 22-carbon highly unsaturated fatty acids maintained in the phospholipids of human plasma is related to the dietary intake of 18:2 (n - 6) and 18:3 (n - 3) by empirical hyperbolic equations in a manner very similar to the relationship reported for laboratory rats (Lands, W.E.M., Morris, A. and Libelt, B. (1990) Lipids 25, 505-516). Analytical results from volunteers ingesting self-selected diets showed an inter-individual variance for the proportion of (n - 6) eicosanoid precursors in the fatty acids of plasma phospholipids of about 5%, but the variance among multiple samples taken from the same individual throughout the day was less (about 3%), closer to the experimental variance of the analytical procedure (about 1%). The reproducibility of the results makes it likely that analysis of fatty-acid composition of plasma lipids from individuals will prove useful in estimating the diet-related tendency for severe thrombotic, arthritic or other disorders that are mediated by (n - 6) eicosanoids. Additional constants and terms were included in the equations to account for the effects of 20- and 22-carbon highly unsaturated (n - 3) fatty acids in the diet. A lower constant for the 20- and 22-carbon (n - 3) fatty acids compared to that for the 18-carbon (n - 3) fatty acid in decreasing the ability of dietary 18:2 (n - 6) to maintain 20:4 (n - 6) in tissue lipids confirmed the greater competitive effectiveness of the more highly unsaturated n - 3 fatty acids in the elongation/desaturation process. Also, a lower constant for direct incorporation of 20-carbon fatty acids of the n - 6 vs. the n - 3 type indicated a greater competitive effectiveness of 20:4 (n - 6) relative to 20:5 (n - 3) in reesterification after release from tissue lipids. The equations may be used in reverse to estimate the dietary intakes of the (n - 3) and (n - 6) fatty acids by using the composition of the fatty acids that had been maintained in plasma lipids.

Because marine oil capsules may vary widely in their content of omega-3 fatty acids, saturated fat, and cholesterol composition and, therefore, their biologic potency, we compared the lipid-lowering effects of three representative preparations in patients with different forms of hyperlipidemia. The ester and triglyceride forms of marine oil both effectively lowered triglyceride, but the response of low-density lipoprotein cholesterol was variable; it declined modestly in patients with hypercholesterolemia and was either unchanged or increased in those with hypertriglyceridemia. The saturated fat and cholesterol content of the marine oil preparation appeared to influence the low-density lipoprotein cholesterol response. Therefore, marine oil capsules are useful for lowering levels of very-low-density lipoprotein cholesterol, but the large dose required to achieve and sustain this effect (4.5 g of omega-3 fatty acids, or nine to 18 capsules daily) may limit long-term compliance.

Oat cereals rich in the water-soluble fiber beta-glucan have been studied as a dietary therapy for hypercholesterolemia. To determine the hypocholesterolemic response of beta-glucan in the diet, 156 adults with low-density lipoprotein cholesterol (LDL-C) levels above 4.14 mmol/L (160 mg/dL) or between 3.37 and 4.14 mmol/L (130 and 160 mg/dL) with multiple risk factors were randomized to one of seven groups. Six groups received either oatmeal or oat bran at doses (dry weight) of 28 g (1 oz), 56 g (2 oz), and 84 g (3 oz). A seventh group received 28 g of farina (beta-glucan control). At week 6 of treatment, significant differences were found for both total cholesterol and LDL-C levels among the farina control and the treatment groups who were receiving 84 g of oatmeal, 56 g of oat bran, and 84 g of oat bran, with decreases in LDL-C levels of 10.1%, 15.9%, and 11.5%, respectively. Fifty-six grams of oat bran resulted in significantly greater reductions in LDL-C levels than 56 g of oatmeal. Nutrient analysis shows no difference in dietary fat content between these treatment groups; therefore, the higher beta-glucan content of oat bran most likely explains the significantly greater LDL-C reductions. A dose-dependent reduction in LDL-C levels with oat cereals supports the independent hypocholesterolemic effects of beta-glucan.

A pediatric nurse practitioner course has been described in which 30 nurse trainees spent six seeks in an intensive training program followed by six months of preceptorship with a pediatrician in their own agency. This short but intensive program had advantages of permitting the PNP student to retain her health care agency position during the intensive part of the program and of assuring her a position as a PNP once the course was completed. Evaluation of the students by written and practical examinations indicated that they had made significant gains in their knowledge and understanding of pediatrics and in their ability to evaluate and refer patients and to provide well-child care and maternal counseling.

MVP is a common condition with rare life-threatening implications. Recent follow-up studies over several years in children, and young and middle-aged adults failed to suggest increase in prolapse in most of the subjects. Older individuals with MVP appear to have increased complications, primarily due to mitral regurgitation. Echocardiography supports the diagnosis of MVP made by auscultation in over 90% of individuals, with excellent reproducibility. MVP is more common in young women than young men. The prevalence of prolapse decreases with age in women; it is relatively constant in men. Although complications are rare, MVP is the most common underlying disorder in rupture of the chordae tendineae. These spontaneous ruptures are usually unassociated with infective endocarditis. Familial studies indicate that isolated MVP is an autosomal dominant condition with variable expression. It is recommended that first-degree relatives of patients with isolated prolapse be examined. Infective endocarditis is uncommon, but it is recommended that antibiotic prophylaxis be implemented in patients with prolapse and evidence for mitral regurgitation. Prolapse is frequently associated with autonomic imbalance, primarily an increased catecholamine sensitivity. The use of beta blockers may reverse symptoms secondary to this abnormality. Sudden death is exceedingly rare despite marked arrhythmias in many patients. On the basis of retrospective studies, sudden death is associated with floppy valves, marked mitral regurgitation, and arrhythmias. There is no evidence that any class of antiarrhythmic agents can prevent the rare sudden deaths in these patients.

Although the triglyceride-lowering actions of n-3 fatty acids of marine lipids are now well-recognized, their effects on plasma lipoproteins have not been studied systematically in patients with hypercholesterolemia. To address this question, we supplemented the Phase 1 American Heart Association diets of 14 hypercholesterolemic ambulatory outpatients with a commercially available preparation of marine lipid concentrate (SuperEPA) containing 7.5 g n-3 fatty acids per day and studied their plasma lipids and lipoproteins before and after 30 days of treatment. Both plasma triglyceride and cholesterol levels fell uniformly in all patients while the mean VLDL- and LDL-cholesterol decreased by 58% (P less than 0.005) and 13% (P less than 0.025) respectively. The decrease in whole plasma cholesterol was significantly correlated with the fall in LDL-cholesterol (r = 0.85, P less than 0.01), and not VLDL-cholesterol (r = 0.39, NS). Among the other potentially beneficial actions observed was an increase in HDL2 in all patients (mean increment 41%, P less than 0.005), and an increase in the HDL2/HDL3 ratio (+46%, P less than 0.001) and decreases in the LDL/HDL ratio (-14%, P less than 0.005) and in the unesterified cholesterol/lecithin ratio (-17%; P less than 0.001) in plasma. The increase in the unesterified cholesterol/esterified cholesterol ratio in VLDL and HDL3 suggested that marine lipid therapy resulted in a reduction in the size of lipoprotein particles in these fractions. Since these changes may reduce cardiovascular risk, these findings suggest that marine lipids may prove useful in the treatment of certain patients with hypercholesterolemia.