Effect of a very-high-fiber vegetable, fruit, and nut diet on serum lipids and colonic function.

We tested the effects of feeding a diet very high in fiber from fruit and vegetables. The levels fed were those, which had originally inspired the dietary fiber hypothesis related to colon cancer and heart disease prevention and also may have been eaten early in human evolution. Ten healthy volunteers each took 3 metabolic diets of 2 weeks duration. The diets were: high-vegetable, fruit, and nut (very-high-fiber, 55 g/1,000 kcal); starch-based containing cereals and legumes (early agricultural diet); or low-fat (contemporary therapeutic diet). All diets were intended to be weight-maintaining (mean intake, 2,577 kcal/d). Compared with the starch-based and low-fat diets, the high-fiber vegetable diet resulted in the largest reduction in low-density lipoprotein (LDL) cholesterol (33% +/- 4%, P <.001) and the greatest fecal bile acid output (1.13 +/- 0.30 g/d, P =.002), fecal bulk (906 +/- 130 g/d, P <.001), and fecal short-chain fatty acid outputs (78 +/- 13 mmol/d, P <.001). Nevertheless, due to the increase in fecal bulk, the actual concentrations of fecal bile acids were lowest on the vegetable diet (1.2 mg/g wet weight, P =.002). Maximum lipid reductions occurred within 1 week. Urinary mevalonic acid excretion increased (P =.036) on the high-vegetable diet reflecting large fecal steroid losses. We conclude that very high-vegetable fiber intakes reduce risk factors for cardiovascular disease and possibly colon cancer. Vegetable and fruit fibers therefore warrant further detailed investigation.

Inhibition of cholesterol synthesis by atorvastatin in homozygous familial hypercholesterolaemia.

Patients with homozygous familial hypercholesterolaemia (HoFH) have markedly elevated low density lipoprotein (LDL) cholesterol levels that are refractory to standard doses of lipid-lowering drug therapy. In the present study we evaluated the effect of atorvastatin on steady state concentrations of plasma lipids and mevalonic acid (MVA), as well as on 24-h urinary excretion of MVA in patients with well characterized HoFH. Thirty-five HoFH patients (18 males; 17 females) received 40 mg and then 80 mg atorvastatin/day. The dose of atorvastatin was increased further to 120 mg/day in 20 subjects and to 160 mg/day in 13 subjects who had not achieved LDL cholesterol goal, or in whom the dose of atorvastatin had not exceeded 2.5 mg/kg body wt per day. LDL cholesterol levels were reduced by 17% at the 40 mg/day and by 28% at the 80 mg/day dosage (P<0.01). Reduction in LDL cholesterol in the five receptor negative patients was similar to that achieved in the 30 patients with residual LDL receptor activity. Plasma MVA and 24-h urinary excretion of MVA, as markers of in vivo cholesterol synthesis, were elevated at baseline and decreased markedly with treatment. Urinary MVA excretion decreased by 57% at the 40 mg/day dose and by 63% at the 80 mg/day dosage (P<0. 01). There was a correlation between reduction in LDL cholesterol and reduction in urinary MVA excretion; those patients with the highest basal levels of MVA excretion and thus the highest rates of cholesterol synthesis having the greatest reduction in LDL cholesterol (r=0.38; P=0.02). Increasing the dose of atorvastatin to 120 and 160 mg/day did not result in any further reduction in LDL cholesterol or urinary MVA excretion suggesting a plateau effect with no further inhibition of cholesterol synthesis at doses of atorvastatin greater than 80 mg/day.

Management of hypercholesterolemia.

Benefit from the treatment of hyperlipidemia has now been conclusively documented, and this article has focused on the clinical trial data supporting diet and drug therapy in adult patients with different lipoprotein disorders and discussed therapeutic approaches with a focus on reducing plasma concentrations of LDL cholesterol. National guidelines for the use of hypolipidemic drugs are strongly supported by the clinical trials and have appropriately set lower target concentrations of LDL cholesterol for patients with established atherosclerosis or diabetic patients as compared with patients with more than two cardiovascular risk factors or, the lowest risk group, patients without evidence of atherosclerosis and fewer than two known cardiovascular risk factors. The goals of therapy in patients with established atherosclerosis are to prevent further progression and potentially induce regression, whereas in high-risk patients (e.g., those with heterozygous familial hypercholesterolemia) without evidence of atherosclerosis, the aims of therapy are to reduce LDL cholesterol to a concentration at which subclinical atherosclerosis and xanthomas regress and the patient does not develop premature cardiovascular disease. Evidence-based medicine strongly supports clinical benefit from the treatment of hypercholesterolemia in men and women with and without known coronary artery disease, and the main goal should be ensure that patients who could benefit from lipid-lowering therapy are effectively treated and followed to ensure long-term compliance, efficacy, and safety.

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.

Angiotensin-converting enzyme DD genotype and cardiovascular disease in heterozygous familial hypercholesterolemia.

BACKGROUND: Controversy exists as to whether the deletion/deletion genotype (DD) of the ACE gene polymorphism increases the risk of myocardial infarction (MI). Studies have suggested that the ACE DD genotype is associated with increased plaque instability. We hypothesized that the ACE DD genotype may increase the risk of myocardial infarction and coronary heart disease (CHD) in patients with heterozygous familial hypercholesterolemia (FH) or familial defective apolipoprotein B-100 (FDB) who, as a group, are at high risk of having lipid-rich plaques in their coronary arteries. METHODS AND RESULTS: We determined the ACE genotypes and incidence of MI or surgical intervention for CHD in 213 adult patients with heterozygous FH or FDB. The incidence of MI in 35 male patients who carried the ACE DD genotype was 2.5 times that observed in male patients with the II or DI genotypes, and the incidence of CHD in male patients with the DD genotype was 2.2 times higher than in those who had ACE DI+II. The potential effects of ACE genotype on CHD could not be directly compared in female patients because of a disparity in the smoking history of the genotypic groups. From logistic regression analysis, the estimated odds ratio associated with the ACE DD genotype was 2.57 for MI and 2.21 for CHD adjusted for age, sex, and smoking history. CONCLUSIONS: The ACE DD genotype is associated with an increased risk of MI and CHD in patients with heterozygous FH or FDB. Determination of the ACE genotype in asymptomatic FH and FDB patients provides an additional means to identify those patients at greatest risk for the premature development of CHD.

Long-term effects of low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. Liposorber Study Group.

The short-term effectiveness of low-density lipoprotein (LDL) apheresis using a dextran sulfate cellulose adsorption column technique was previously examined in a 9-center, 22-week controlled trial in 64 patients with familial hypercholesterolemia (FH) who did not adequately respond to diet and drug therapy. Forty-nine patients (40 treatment, 9 controls) subsequently received LDL apheresis procedures as part of an optional follow-up phase. This study reports on the long-term safety, lipid lowering, and clinical efficacy of LDL apheresis for the 5-year period that includes both the initial controlled study and follow-up phase. During this time, patients received a total of 3,902 treatments of which 3,314 treatments were given during the follow-up phase. Adverse events were infrequent, occurring in 142 procedures (3.6%). Immediate reduction in LDL cholesterol was 76% both in homozygotes and in heterozygotes. Patients with homozygous FH had a progressive decrease in pretreatment LDL cholesterol level along with an increase in high-density lipoprotein (HDL) cholesterol level. There was no appreciable change in pretreatment lipoprotein level over time in heterozygotes. The rate of cardiovascular events during therapy with LDL apheresis and lipid-lowering drugs was 3.5 events per 1,000 patient-months of treatment compared with 6.3 events per 1,000 patient-months for the 5 years before LDL apheresis therapy. These findings support the long-term safety and clinical efficacy of LDL apheresis in patients with heterozygous and homozygous FH who are inadequately controlled with drug therapy.

Expanded-dose simvastatin is effective in homozygous familial hypercholesterolaemia.

Patients with homozygous familial hypercholesterolaemia (HFH) have abnormalities in both low-density lipoprotein (LDL) receptor alleles, resulting in severe hypercholesterolaemia and premature coronary heart disease. Limited treatment options are available and the response to drug therapy has been poor. In the present paper, we have evaluated the efficacy and safety of simvastatin at doses beyond the current maximal dose of 40 mg/day in patients with HFH. After a 4 week placebo diet run-in period, 12 patients with well-characterized HFH were randomized to simvastatin 80 mg/day administered in three divided doses (n = 8; group 1) or 40 mg once daily (n = 4; group 2). After 9 weeks, the dose in group 1 was increased to 160 mg/day while the dose in group 2 was kept at 40 mg/day, but with the drug given in three divided doses and treatment continued for an additional 9 weeks. All 12 patients completed the study and there were no serious or unexpected adverse effects. LDL-cholesterol concentrations fell by 14% at the 40 mg/day dose, but were reduced further at the higher doses (25% at the 80 mg/day and by 31% at the 160 mg/day dosage, P < 0.0001). Excretion of urinary mevalonic acid, as an index of in vivo cholesterol biosynthesis, was reduced but did not correlate with reduction in LDL-cholesterol in the individual patients. The magnitude of response to therapy was not predicted by the LDL-receptor gene defect as patients with the same LDL-receptor mutations responded differently to the same dose of simvastatin therapy. The ability of expanded doses of simvastatin (80 or 160 mg/day) to reduce LDL-cholesterol levels in patients with HFH, even if receptor negative, suggests that at these doses, the drug reduces LDL production. Simvastatin therapy, at doses of 80 or 160 mg/day, should therefore be considered in all patients with HFH, either as an adjunct to apheresis, or as monotherapy for those patients who do not have access to apheresis or other such treatment modalities.

Adverse ocular effects associated with niacin therapy.

In a retrospective survey of patients taking medication for hyperlipidaemia, those taking niacin (nicotinic acid) were more likely (p < 0.05) to report sicca syndromes, blurred vision, eyelid oedema, and macular oedema compared with those who never took niacin. Additionally, 7% of those taking niacin discontinued the drug owing to adverse ocular side effects, while none of the other lipid lowering agents were found to cause these side effects (p = 0.016). Data from spontaneous reporting systems support a possible association of decreased vision, cystoid macular oedema, sicca-like symptoms, discoloration of the eyelids with or without periorbital or eyelid oedema, proptosis, loss of eyebrow or eyelashes, and superficial punctate keratitis with the use of niacin in high doses. Decreased vision may be marked, and if the drug is not discontinued, may progress to cystoid macular oedema. All ocular side effects listed above are reversible if the association with niacin is recognised and the drug is discontinued; both the incidence and severity of the ocular side effects seem to be dose dependent.

Occurrence of a mutation associated with Wolman disease in a family with cholesteryl ester storage disease.

Cholesteryl ester storage disease (CESD) and Wolman disease (McKusick 278000) are two distinct autosomal recessive disorders, both attributable to a severe reduction in acid cholesteryl ester hydrolase/lysosomal acid lipase activity (EC 3.1.1.13). We have identified compound heterozygous mutations in a family with two siblings affected with CESD. Molecular genetic analysis revealed two mutations one of which has previously been seen only in Wolman disease. Analysis of these mutations acting in concert provides new insight into the correlation of genotype with phenotype in these allelic disorders.

How effective is drug therapy in heterozygous familial hypercholesterolemia?

The goals of drug therapy in adult patients with heterozygous familial hypercholesterolemia (FH) are directed at reducing plasma concentrations of low density lipoproteins (LDL), with a secondary goal in selected patients to concurrently decrease elevated plasma concentrations of lipoprotein(a), triglycerides, and potentially exert favorable effects on the concentrations of high density lipoproteins (HDL). Desirable goals of therapy are to reduce concentrations of LDL cholesterol to < 130-160 mg/dL in patients without evidence of coronary artery disease, and, in my opinion, to < 100 mg/dL in patients with evidence of coronary artery disease. The bile acid sequestrants, cholestyramine and colestipol, reduce LDL concentrations by 23-36%, when given in doses of 4-6 scoops/day, but reduce LDL concentrations to desirable levels in only 10-15% of patients. Similarly, nicotinic acid, in doses of 3-6 g/day, is capable of reducing LDL concentrations by up to 30%, but the majority of patients still remain hypercholesterolemic. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, which include lovastatin, simvastatin, and pravastatin, are the most effective of the currently available drugs and show dose-dependent effects on the concentrations of LDL cholesterol, which decrease by 20-45% in response to these drugs when used over the full dosage range. However, even with these agents, concentrations of LDL cholesterol remain > 200 mg/dL in one-third of male and female patients with heterozygous FH and remain > 160 mg/dL in 75-80% of treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypolipidemic effects of nicotinic acid in patients with familial defective apolipoprotein B-100.

Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder associated with hypercholesterolemia, in which an amino acid substitution in apolipoprotein B-100 results in low-density lipoprotein (LDL) particles that bind poorly to the LDL receptor and accumulate in plasma. Patients with FDB described to date have been heterozygous for this disorder, and their plasma contains both normal and defective-binding LDL particles. We have evaluated the hypocholesterolemic effects of nicotinic acid (3 g/d) in four patients with FDB, and compared the response to that of nine patients with heterozygous familial hypercholesterolemia (FH). Concentrations of LDL decreased by 24% in patients with FDB and by 14% in patients with FH. These results support the view that drugs which reduce LDL synthesis may be particularly effective in the treatment of patients with FDB.

Hypocholesterolemic effects of cholestyramine and colestipol in patients with familial defective apolipoprotein B-100.

Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder associated with hypercholesterolemia, in which substitution of the amino acid glutamine for arginine at position 3500 in the apoprotein B molecule results in LDL particles which bind poorly to the LDL receptor. To date, patients with FDB have been heterozygous for this disorder and their plasma contains both normal and defective-binding LDL particles, with a predominance of the latter. In the present report, we have compared the hypocholesterolemic effects of bile acid sequestrant therapy (cholestyramine or colestipol) in eight patients with FDB, to the response seen in sixteen patients with heterozygous familial hypercholesterolemia (FH), treated with the same drugs. Concentrations of LDL cholesterol fell by 32.0% in the patients with FDB and by 21.6% in the patients with FH. The results indicate that the hypercholesterolemia of both FDB and FH responds to treatment with bile acid sequestrants.

The potential role of antioxidants in the prevention of atherosclerosis.

Hypercholesterolemia attributable to increased plasma concentrations of low density lipoproteins is a well recognized risk factor for the premature development of coronary atherosclerosis in both experimental animals and humans. Recent studies have indicated that modifications to low density lipoprotein result in enhanced uptake of the modified lipoproteins by macrophages and lead to accelerated rates of lipid deposition and the creation of foam cells. Oxidation of low density lipoprotein has been shown to be one of the modifications which leads to uptake of this lipoprotein by scavenger receptors present on macrophages and results in intracellular lipid accumulation. Treatment of hypercholesterolemic animals with antioxidant drugs, including probucol, has been shown to reduce the development of atherosclerosis and xanthoma regression has been observed in patients with severe hypercholesterolemia treated with this drug. Epidemiologic studies support the view that low plasma concentrations of antioxidant vitamins, including vitamin E are associated with higher rates of coronary atherosclerosis in humans and that supplementation with vitamin E is associated with a decreased incidence of coronary artery disease. Prospective clinical trials to assess the potential benefit of antioxidant supplementation in high risk patients are currently in progress and these trials, when completed, should provide definitive information concerning the potential benefits to be derived from supplementation with antioxidant vitamins as an adjunctive therapy to prevent the premature development of atherosclerosis.

Treatment of refractory familial hypercholesterolemia by low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. The Liposorber Study Group.

A subgroup of patients with familial hypercholesterolemia (FH) respond inadequately to standard diet and drug therapy, and are therefore at high risk for the premature development or progression of coronary artery disease. This study evaluated low-density lipoprotein (LDL) cholesterol and lipoprotein (a) removal in a multicenter, controlled trial with a new LDL apheresis procedure (Liposorber LA-15 System). The study comprised patients with FH who had not responded adequately to diet and maximal drug therapy. There were 54 patients with heterozygous FH (45 randomized to treatment and 9 control subjects) and 10 with homozygous FH (all of whom received LDL apheresis). The study included three 6-week treatment phases and a 4-week rebound phase. Treatments were administered at 7- to 14-day intervals. Mean acute reductions in LDL cholesterol were 76% in heterozygous FH patients and 81% in homozygous ones. Time-averaged levels of LDL cholesterol were reduced 41% (243 to 143 mg/dl) in heterozygous FH patients and 53% (447 to 210 mg/dl) in homozygous ones. The substantial acute reduction of lipoprotein (a) (means: 65%, heterozygous FH; 68%, homozygous FH) has not been reported with other therapies. The Liposorber LA-15 System represents an important therapeutic option in FH patients who respond inadequately to diet and drug therapy.

Comparative hypolipidemic effects of lovastatin and simvastatin in patients with heterozygous familial hypercholesterolemia.

We have compared the effects of lovastatin and simvastatin on plasma lipoproteins, fibrinogen and urinary mevalonic acid excretion in twenty-three patients with heterozygous familial hypercholesterolemia. After a baseline period patients were randomly assigned to receive lovastatin or simvastatin at doses of 10, 20 and 40 mg twice daily, for a period of 2 months each, and then, after a 4-week wash-out period, all patients received the alternate drug for a similar period of therapy. Both drugs were well-tolerated and no patients were withdrawn due to side effects. Lipid values returned to baseline after discontinuation of therapy and no carry-over effect was observed. Treatment with lovastatin resulted in decreases in LDL cholesterol concentrations from 274 mg/dl at baseline to 211, 192 and 178 mg/dl, respectively, on doses of 20, 40 and 80 mg/day. Treatment with simvastatin reduced concentrations of LDL cholesterol to 194, 168 and 156 mg/dl, respectively, on doses of 20, 40 and 80 mg/day. Concentrations of HDL cholesterol increased on both drugs, but no dose response relationship was apparent. Both drugs reduced the 24-h urinary excretion of mevalonic acid, an intermediate in cholesterol biosynthesis, but the magnitude of decrease was similar with lovastatin and simvastatin. Small, but statistically non-significant decreases in fibrinogen occurred with both drugs. Patients who showed the greatest hypolipidemic effect during treatment with lovastatin also showed an excellent therapeutic response to simvastatin and vice versa. We conclude that, on a milligram per milligram basis, simvastatin is twice as potent as lovastatin in the treatment of familial hypercholesterolemia and that with both drugs, reductions in LDL cholesterol concentrations are accompanied by decreases in the urinary excretion of mevalonic acid.

Hypocholesterolaemic effects of lovastatin in familial defective apolipoprotein B-100.

Familial defective apolipoprotein B-100 (FDB) is an autosomal dominant disorder associated with hypercholesterolaemia in which an aminoacid substitution in apoprotein B-100 leads to low-density lipoprotein (LDL) particles which have defective binding to the LDL receptor. All known patients are heterozygous, and their plasma contains normal and poorly binding LDL particles. 12 hypercholesterolaemic patients from 10 unrelated families with FDB were treated with lovastatin. In 6 patients treated with 20 mg lovastatin daily, LDL cholesterol decreased by 21.5% from 6.23 to 4.89 mmol/l (95% confidence interval 0.74, 1.96 mmol/l), whereas it fell by 32.1%, from 6.99 to 4.81 mmol/l (95% CI 1.55, 2.70 mmol/l), in 9 patients who received 40 mg daily. These results indicate that the hypercholesterolaemia of FDB may respond to treatment with statins.

The influence of simvastatin on adrenal corticosteroid production and urinary mevalonate during adrenocorticotropin stimulation in patients with heterozygous familial hypercholesterolemia.

The adrenal gland requires a continuous supply of cholesterol for the biosynthesis of adrenal corticosteroids, which can be supplied by low density lipoprotein receptor-mediated uptake or local synthesis. The present study examined whether hypolipidemic therapy with a potent HMG CoA reductase inhibitor, simvastatin, compromises the adrenal response to ACTH stimulation in adult patients with heterozygous familial hypercholesterolemia. The adrenal response to a 36-h continuous ACTH infusion was determined at baseline and after 2 months of simvastatin treatment (40 mg, twice daily) in eight patients. Simvastatin reduced total and low density lipoprotein cholesterol levels by 36% and 45%, respectively. The time course of the increase in serum cortisol concentrations with continuous ACTH infusion was the same before and during simvastatin therapy, as were the rates of urinary excretion of free cortisol, 17-hydroxycorticosteroids, and 17-ketosteroids. Urinary excretion of mevalonate, which correlates with rates of whole body cholesterol synthesis, decreased from 3.8 +/- 0.42 (+/- SEM) mu,ol/24 h at baseline to 2.75 +/- 0.56 on simvastatin; no significant changes were seen in the urinary mevalonate levels before and after simvastatin therapy during ACTH stimulation. We conclude that the hypolipidemic effects of simvastatin in patients with heterozygous familial hypercholesterolemia are paralleled by a decrease in urinary mevalonate, but that the drug does not adversely affect ACTH-stimulated adrenal corticosteroid production.

Effects of fish oil on VLDL triglyceride kinetics in humans.

Dietary n-3 fatty acids (FAs) found in fish oils markedly lower plasma triglyceride (TG) and very low density lipoprotein (VLDL) levels in both normal and hypertriglyceridemic subjects. The present study examined the mechanism of this effect. Ten subjects with widely different plasma triglyceride levels (82 to 1002 mg/dl) were fed metabolically controlled diets containing 20% fat. The control diet contained a blend of cocoa butter and peanut oil (P/S = 0.8). The test diet contained fish oil (P/S = 1.1) and provided 10-17 g of n-3 FAs per day (depending on calorie intake). After 3 to 5 weeks of each diet, the kinetics of VLDL-TG were determined over a 48-h period after the injection of [3H]glycerol. The fish oil diet reduced the VLDL-TG synthetic rate from 23 +/- 14.3 (mean +/- SD) to 12.6 +/- 7.5 mg/h per kg ideal weight (P less than 0.005) and increased the fractional catabolic rate (FCR) for VLDL-TG from 0.23 +/- 0.12 to 0.38 +/- 0.16 h -1 (P less than 0.005). At the same time, there was a 66% reduction of plasma triglyceride levels, resulting largely from a 78% decrease in VLDL-TG levels (398 +/- 317 to 87 +/- 77 mg/dl; P less than 0.005). There was a strong correlation (r = 0.83; P less than 0.01) between the change in synthetic rates and pool sizes, but there was no correlation (r = 0.24; NS) between changes in FCRs and pool sizes. The VLDL cholesterol: triglyceride ratio increased during the n-3 diet suggesting that smaller VLDL particles were present. These particles would be expected to leave the VLDL fraction more rapidly than larger particles producing a higher FCR. We conclude that the hypotriglyceridemic effect of fish oil appears to be caused primarily by an inhibition of very low density lipoprotein-triglyceride synthesis, but an additional, independent effect upon VLDL catabolism cannot be ruled out.

Community cholesterol screening: medical follow-up in subjects identified with high plasma cholesterol levels.

Population screening or plasma cholesterol is an effective method of detecting hypercholesterolemia; however, follow-up and treatment are essential components of such a program. After a city-wide screening in 1987 of more than 19,872 persons, using a mailed survey with a response rate of 48%, we evaluated subsequent actions of 3,078 individuals with high plasma cholesterol levels. Slightly more than half the population was aware of high blood cholesterol levels prior to the time of screening and apparently used the program for follow-up. Overall, after the screening, 65% consulted a physician within 5 months of screening and blood cholesterol levels were remeasured in 80% of the sample. Procrastination and expense were cited as the primary reasons for failing to consult a physician. If screening is to be effectively utilized as a means of reducing the prevalence of high plasma cholesterol levels, diligent follow-up must be made of all individuals identified to be at increased risk on the basis of their initial values.