Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease.

BACKGROUND: Both lipid-modifying therapy and antioxidant vitamins are thought to have benefit in patients with coronary disease. We studied simvastatin-niacin and antioxidant-vitamin therapy, alone and together, for cardiovascular protection in patients with coronary disease and low plasma levels of HDL. METHODS: In a three-year, double-blind trial, 160 patients with coronary disease, low HDL cholesterol levels and normal LDL cholesterol levels were randomly assigned to receive one of four regimens: simvastatin plus niacin, vitamins, simvastatin-niacin plus antioxidants; or placebos. The end points were arteriographic evidence of a change in coronary stenosis and the occurrence of a first cardiovascular event (death, myocardial infarction, stroke, or revascularization). RESULTS: The mean levels of LDL and HDL cholesterol were unaltered in the antioxidant group and the placebo group; these levels changed substantially (by -42 percent and +26 percent, respectively) in the simvastatin-niacin group. The protective increase in HDL2 with simvastatin plus niacin was attenuated by concurrent therapy with antioxidants. The average stenosis progressed by 3.9 percent with placebos, 1.8 percent with antioxidants (P=0.16 for the comparison with the placebo group), and 0.7 percent with simvastatin-niacin plus antioxidants (P=0.004) and regressed by 0.4 percent with simvastatin-niacin alone (P<0.001). The frequency of the clinical end point was 24 percent with placebos; 3 percent with simvastatin-niacin alone; 21 percent in the antioxidant-therapy group; and 14 percent in the simvastatin-niacin-plus-antioxidants group. CONCLUSIONS: Simvastatin plus niacin provides marked clinical and angiographically measurable benefits in patients with coronary disease and low HDL levels. The use of antioxidant vitamins in this setting must be questioned.

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.

The Northwest Lipid Research Clinic Fat Intake Scale: validation and utility.

OBJECTIVES: This paper describes the Northwest Lipid Research Clinic Fat Intake Scale, a brief dietary questionnaire to screen and monitor dietary intake related to plasma cholesterol levels. METHODS: The 12-item instrument assesses intake of foods high in fat, saturated fat, and cholesterol. Test-retest reliability was assessed on 194 men and 116 women with high cholesterol prior to a dietary intervention study. To measure validity and responsiveness to dietary change, scores were compared with 4-day food records before and after diet education classes. RESULTS: Test-retest correlation coefficients were .88 for men and .90 for women (2 weeks between scores). Scores for men and women were correlated with nutrients shown by food records at baseline (.47 and .54, total fat; .50 and .51, saturated fat) and 18 months postintervention (.52 and .58, total fat; .56 and .64, saturated fat; all Ps < .001). Mean scores decreased from about 30 to 23 (P < .001, paired t test). CONCLUSIONS: The Fat Intake Scale, a qualitative instrument, has acceptable reliability and validity for estimating the level of cholesterol-related diet components and reflects dietary modification. The format of the instrument also lends itself to patient education and goal setting.

A double-blind, randomized, controlled trial of the effects of two eggs per day in moderately hypercholesterolemic and combined hyperlipidemic subjects taught the NCEP step I diet.

OBJECTIVE: We investigated the effect of egg feeding in 161 hypercholesterolemic (HC) or combined hyperlipidemic (CHL) free-living subjects taught the NCEP Step I Diet. METHODS: Subjects had LDL-C between 3.36 and 4.91 mmol/L (130 and 190 mg/dL). HC subjects had triglyceride concentrations < 75th %-ile, CHL > or = 75th %-ile. Six weeks after instituting the Step I Diet, subjects were randomized to two eggs or egg substitute daily for 12 weeks. RESULTS: Mean dietary intake (9-day food records) was within NCEP guidelines and 131 subjects finished with stable weight and adherence > 80%. Placebo group lipoprotein lipids were unchanged at study end for both HC (n = 35) and CHL (n = 21) subjects. Egg-fed HC subjects (n = 44) increased LDL-C nonsignificantly, 0.07 mmol/L (3 mg/dL) (p = 0.49). Egg-fed CHL subjects (n = 31) increased LDL-C 0.31 mmol/L (12 mg/dL) (p < 0.001). HDL-C increased significantly in both HC and CHL groups, 0.10 and 0.08 mmol/L (4 and 3 mg/dL, p = 0.003 and 0.02), respectively. HC and CHL subjects did not differ by apo E phenotype distribution. Postprandial triglyceride-rich lipoproteins and LDL subclass phenotype were unaffected by egg feeding in subsets of subjects. CONCLUSIONS: CHL subjects ingesting a Step I Diet in a free-living setting are sensitive to egg feeding and should benefit from dietary cholesterol restriction. The limited LDL-C rise in HC subjects resembles that seen in egg-fed normocholesterolemic subjects ingesting a Step I Diet, but requires confirmation.

Zinc intake and plasma zinc level are maintained in men consuming cholesterol-lowering diets.

OBJECTIVE: Reduced zinc intake has been reported when cholesterol-lowering diets are adopted. This study examined whether such diets compromise the zinc status of men with hypercholesterolemia. DESIGN: Zinc intake on baseline 4-day food records and baseline plasma zinc levels were compared with intake and levels 12 and 24 months after subjects adopted a low-fat, increased-fiber diet. Dietary fiber intake, supplement use, alcohol intake, and exercise were evaluated as possible confounding variables. SUBJECTS: Subjects were free-living men (n = 365) with baseline cholesterol level above the 75th percentile who were participants in a randomized trial comparing cholesterol-lowering diets with goals of 30%, 26%, 22%, and 18% of energy from fat and 300, 200, 100, and 100 mg cholesterol, respectively. STATISTICAL ANALYSES: Data were analyzed using two sample t tests, multiple linear regression, and analysis of variance. RESULTS: For all subjects combined, mean fat and cholesterol intakes approached or met the guidelines of the National Cholesterol Education Program step 2 diet, with approximately 30 g fiber per day. Density (mg/1,000 kcal) of zinc intake was unchanged from the baseline value. We found a slightly positive relationship between fiber and zinc intakes; no relationship between fiber intake and plasma zinc level; no effect of supplement use (category included all types of supplements), alcohol use, or level of exercise on plasma zinc levels; and no difference by dietary assignment in zinc intake or plasma zinc levels. APPLICATION: Zinc status does not appear to be at risk in adult men who adopt cholesterol-lowering diets. These results may not be generalized to higher-risk population groups or situations in which dietary counseling is less comprehensive.

Changes in plasma triacylglycerol concentrations among free-living hyperlipidemic men adopting different carbohydrate intakes over 2 y: the Dietary Alternatives Study.

We reported previously that low-fat, high-carbohydrate diets containing < 26% of energy as fat and > 57% of energy as carbohydrate induce hypertriacylglycerolemia (hypertriglyceridemia) in hypercholesterolemic but not in combined hyperlipidemic (CHL) subjects. Because subjects may not consistently adhere to an assigned diet long term, we examined the extent to which plasma triacylglycerols (triglycerides) increase at four consistently reported carbohydrate intakes at intervals of up to 2 y. Three hundred seventy-two subjects reported consistent carbohydrate intakes of < 45%, 45-51.9%, 52-59.9%, or > or = 60% of energy on food records for 3, 12, and 24 mo. Among hypercholesterolemic subjects reporting a carbohydrate intake > or = 60% of energy, triacylglycerols increased by 0.25, 0.18, and 0.27 mmol/L (22, 16, and 24 mg/dL) over baseline at 3, 12, and 24 mo, respectively (P < 0.01 in each instance), and 0.32 mmol/L (28 mg/dL) above the group with a carbohydrate intake 52-59.9% of energy (P < 0.05) after 3 mo. No statistically significant effects were observed among CHL subjects, but compared with baseline, triacylglycerols decreased during the first 3 mo (-0.29 to -0.04 mmol/L, or -26 to -4 mg/dL), were unchanged over 12 mo, and were increased after 24 mo in three of four carbohydrate intake strata (0.27-0.36 mmol/L, or 24-32 mg/dL). These data confirm our previous observation that a moderately but not extremely low-fat, high-carbohydrate diet can be used long-term without deleterious effects on plasma triacylglycerols in the management of hypercholesterolemia, whereas CHL is unaffected by the amount of carbohydrate ingested.

The successful recruitment of elderly black subjects in a clinical trial: the CRISP experience. Cholesterol Reduction in Seniors Program.

This article describes the recruitment of elderly black subjects into the Cholesterol Reduction in Seniors Program (CRISP), a federal, multi-center, randomized, double-masked feasibility study of cholesterol intervention in the elderly. The study tested the feasibility of recruiting significant numbers of hypercholesterolemic black men, black women, and white women over the age of 65, groups previously underrepresented in federal trials. The study involved dietary modification and drug intervention with either 20 mg or 40 mg of lovastatin or placebo. Maximum follow-up was 18 months. Over the 12-month screening and recruitment period, 431 subjects (108% of the recruitment goal) were randomized. A total of 311 (72% of the study cohort) was female; 105 subjects (24% of the total cohort) were minorities. Media sources were most effective in recruiting white subjects. Church screening was an effective strategy in the black community, although such an approach required considerable resources s and time. The CRISP feasibility study demonstrated that a large cohort of elderly black subjects could be recruited in a cholesterol intervention trial, although the use of community-based approaches required substantial resources and staff time.

Spouse support and long-term adherence to lipid-lowering diets.

Social support is inversely associated with heart disease risk. Support may influence heart disease by encouraging health behavior change in high-risk individuals. This study examined the association between spouse support and maintenance of low-fat diets in men with hypercholesterolemia. Participants were 254 men enrolled in a 24-month randomized trial of lipid-lowering diets initiated in 1985 in Seattle, Washington. The Evaluation of Spouse Support, which assesses the extent to which spouses supported maintenance of lipid-lowering diets, was administered after the last of eight dietary classes and at 3, 12, and 24 months postinstruction. Attainment of dietary goals was determined from food records completed at the end of the class and at 3, 12, and 24 months. Compared with those in the lowest quartile, those in the highest quartile of support were more likely to attain dietary goals at 3 months (odds ratio (OR) = 4.5, 95% confidence interval (CI) 1.9-10.4), 12 months (OR = 5.5, 95% CI 2.4-12.5), and 24 months (OR = 3.9, 95% CI 1.7-9.3). Support was not associated with end-of-class dietary goal achievement. Social support may be an important factor in the maintenance of low-fat diets.

Changes in vitamin and mineral intakes and serum concentrations among free-living men on cholesterol-lowering diets: the Dietary Alternatives Study.

Nutritional adequacy of diets with 18-30% of calories from fat was investigated in men with elevated serum cholesterol (n = 396) at the end of diet classes and 1 and 2 y later. On 4-d food records, intakes of vitamin A, beta-carotene, folate, vitamin C, magnesium, vitamin B-6, iron, thiamin, and riboflavin increased from baseline whereas niacin, selenium, vitamin E, and zinc decreased. Median zinc intake, 80% of the recommended dietary allowance (RDA) at baseline, decreased to approximately 75% of the RDA, most markedly when intakes of meat, fish, and poultry were limited to 85 g/d. Nutrient densities generally increased. Of the serum nutrients measured, median beta-carotene and vitamin C increased, whereas vitamin B-6, iron, and zinc were unchanged. Below-normal values were fewer for vitamin C and magnesium. Diets similar to the National Cholesterol Education Program Step-Two Diet [less than 7% saturated fatty acids, less than 200 mg cholesterol/d] appeared to provide increased levels of most micronutrients both short and long term to men receiving comprehensive dietary counseling.

Promoting adherence to low-fat, low-cholesterol diets: review and recommendations.

Evidence that lowering blood cholesterol levels reduces risk of coronary heart disease has prompted widespread recommendations that hyperlipidemic individuals undergo dietary therapy. However, the extent to which people can adopt and maintain diets to lower lipids is unclear. In our article, we review what is currently known regarding adherence to low-fat diets and present an approach to dietary counseling for lowering cholesterol that incorporates elements of behavioral self-management and social learning theory. We discuss specific recommendations for counseling hyperlipidemic patients based on the Dietary Alternatives Study. Recommendations include providing patients with an adequate knowledge base to make dietary changes, using goal setting and self-monitoring to help patients initiate dietary changes, enlisting support from the patient's family, and enhancing self-efficacy to promote long-term dietary maintenance.