Showing papers by "Scott M. Grundy published in 1988"
TL;DR: New guidelines for the treatment of high blood cholesterol in adults 20 years of age and over are provided and which patients should go on to have lipoprotein analysis, and which should receive cholesterol-lowering treatment on the basis of their low density lipop protein levels and status with respect to other coronary heart disease risk factors are detailed.
Abstract: • This report of an expert panel of the National Cholesterol Education Program provides new guidelines for the treatment of high blood cholesterol in adults 20 years of age and over. Total cholesterol levels are classified as follows: ( Arch Intern Med 1988;148:36-69)
2,055 citations
TL;DR: It is concluded that stearic acid appears to be as effective as oleic acid in lowering plasma cholesterol levels when either replaces palmitic Acid in the diet.
Abstract: We studied the metabolic effects of stearic acid (18:0) on plasma lipoprotein levels in 11 subjects during three dietary periods of three weeks each. The three liquid-formula diets, which were used in random order, were high in palmitic acid (16:0), stearic acid, and oleic acid (18:1), respectively. Caloric intakes were the same during the three periods. As compared with the values observed when the subjects were on the high-palmitic-acid diet, plasma total cholesterol decreased by an average of 14 percent during consumption of the high-stearic-acid diet (P less than 0.005) and by 10 percent during consumption of the high-oleic-acid diet (P less than 0.02). Low-density lipoprotein cholesterol levels fell by 21 percent in subjects on the high-stearic-acid diet (P less than 0.005) and by 15 percent in subjects on the high-oleic-acid diet (P less than 0.005). No significant differences were observed in the plasma levels of triglycerides or high-density lipoprotein cholesterol among the three diets. Measurements of the intestinal absorption of palmitic, stearic, and oleic acids revealed essentially complete absorption of each during the three dietary periods. The oleic acid content of plasma triglycerides and cholesteryl esters increased significantly during the high-stearic-acid period, suggesting that stearic acid is rapidly converted to oleic acid. We conclude that stearic acid appears to be as effective as oleic acid in lowering plasma cholesterol levels when either replaces palmitic acid in the diet.
906 citations
TL;DR: If reductase inhibitors prove to be free of long-term adverse effects, they will undoubtedly be used widely for treating hypercholesterolemia and this review will examine lovastatin.
Abstract: THE recent introduction of a unique class of cholesterol-lowering drugs offers new promise for the treatment of hypercholesterolemia. These drugs are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the synthesis of cholesterol. Relatively low doses of these agents will reduce plasma cholesterol levels markedly, and in short-term studies, they have not been found to produce serious side effects. Thus, in 1987 the Food and Drug Administration approved one HMG-CoA reductase inhibitor — lovastatin. If reductase inhibitors prove to be free of long-term adverse effects, they will undoubtedly be used widely for treating hypercholesterolemia. This review will examine . . .
755 citations
TL;DR: Preliminary results suggest that partial replacement of complex carbohydrates with monounsaturated fatty acids in the diets of patients with NIDDM does not increase the level of LDL cholesterol and may improve glycemic control and the levels of plasma triglycerides and HDL cholesterol.
Abstract: We compared a high-carbohydrate diet with a high-fat diet (specifically, a diet high in monounsaturated fatty acids) for effects on glycemic control and plasma lipoproteins in 10 patients with non-insulin-dependent diabetes mellitus (NIDDM) receiving insulin therapy. The patients were randomly assigned to receive first one diet and then the other, each for 28 days, in a metabolic ward. In the high-carbohydrate diet, 25 percent of the energy was in the form of fat and 60 percent in the form of carbohydrates (47 percent of the total energy was in the form of complex carbohydrates); the high-monounsaturated-fat diet was 50 percent fat (33 percent of the total energy in the form of monounsaturated fatty acids) and 35 percent carbohydrates. The two diets had the same amounts of simple carbohydrates and fiber. As compared with the high-carbohydrate diet, the high-monounsaturated-fat diet resulted in lower mean plasma glucose levels and reduced insulin requirements, lower levels of plasma triglycerides and very-low-density lipoprotein cholesterol (lower by 25 and 35 percent, respectively; P less than 0.01), and higher levels of high-density lipoprotein (HDL) cholesterol (higher by 13 percent; P less than 0.005). Levels of total cholesterol and low-density lipoprotein (LDL) cholesterol did not differ significantly in patients on the two diets. These preliminary results suggest that partial replacement of complex carbohydrates with monounsaturated fatty acids in the diets of patients with NIDDM does not increase the level of LDL cholesterol and may improve glycemic control and the levels of plasma triglycerides and HDL cholesterol.
412 citations
283 citations
TL;DR: A solid-food diet rich in monounsaturated fatty acids is equivalent to a low-fat, high-carbohydrate diet for cholesterol lowering but does not reduce the HDL-cholesterol level.
181 citations
TL;DR: The beneficial effects of lovastatin on plasma lipid levels in patients with NIDDM could decrease the risk of the development of coronary heart disease.
Abstract: Coronary heart disease is an important cause of death in patients with non-insulin-dependent diabetes mellitus (NIDDM) and is particularly common in diabetic populations that have relatively high levels of plasma cholesterol. To determine whether plasma cholesterol levels in patients with NIDDM could be reduced by drug therapy, we assessed the effect of lovastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, in a randomized double-blind placebo-controlled manner in 16 white patients with NIDDM and mild to moderate elevations of plasma cholesterol. Lovastatin (20 mg twice daily) or a placebo was given for four weeks, during which blood glucose concentrations remained controlled. As compared with the placebo, lovastatin reduced total cholesterol by 26 percent, low-density lipoprotein (LDL) cholesterol by 28 percent, and LDL apolipoprotein B by 26 percent. Lovastatin therapy also reduced plasma triglycerides and very-low-density lipoprotein cholesterol by 31 percent and 42 percent, respectively. Although there was no change in the plasma level of high-density lipoprotein (HDL) cholesterol, the ratio of total cholesterol to HDL cholesterol fell by 29 percent. No side effects or abnormalities in serum values were noted during short-term lovastatin therapy. The beneficial effects of lovastatin on plasma lipid levels in patients with NIDDM could decrease the risk of the development of coronary heart disease.
174 citations
TL;DR: Data from three dietary studies carried out in the laboratory were pooled and used to evaluate how individuals vary in their responses in plasma concentrations of total cholesterol and low-density-lipoprotein cholesterol to the substitution of saturated fatty acids for unsaturated fatty acids.
162 citations
TL;DR: Although gemfibrozil with either colestipol or lovastatin favorably altered lipoprotein levels in patients with hypertriglyceridemia and familial combined hyperlipidemia, the combination of gemf fibroZil and lovastasin appeared superior overall.
Abstract: Study Objective:To compare the efficacy of gemfibrozil and colestipol with gemfibrozil and lovastatin in patients with familial combined hyperlipidemia. Design:A prospective, randomized tr...
140 citations
TL;DR: Overall, lovastatin appears to be an effective drug for the treatment of hyperlipidemia in the nephrotic syndrome.
131 citations
TL;DR: It is concluded that lovastatin is not effective in treatment of receptor-negative homozygous familial hypercholesterolemia, and the most likely mechanism of action for this drug is to increase LDL receptor activity.
TL;DR: In this paper, Lovastatin therapy generally lowered plasma concentrations of apolipoprotein E2 (apo E2) and cholesterol in VLDL and LDL, due mainly to a decrease in transport (production) rates for these fractions.
TL;DR: The binding of five apoB-100-specific monoclonal antibodies to abnormal LDL was assessed in a solid-phase RIA, and the convenience of this assay will facilitate screening of large populations to determine the frequency of this disorder.
Abstract: Familial defective apolipoprotein (apo) B-100 is a recently described genetic disorder that appears to result from a mutation in the apoB-100 gene. This disorder is characterized by hypercholesterolemia resulting from elevated plasma concentrations of low density lipoprotein LDL. The disorder was first detected in three members of one family. The LDL from affected subjects binds defectively (approximately 30% of normal) to LDL receptors, retarding the clearance of LDL from plasma. In the present study, two other members of the affected family were found to possess abnormal LDL. In addition, abnormal LDL with a similar binding defect were found in a second, unrelated family. In both families, the defect is transmitted over three generations as an autosomal codominant trait and all affected members are heterozygotes. Since there is only one apoB-100 molecule per LDL particle, the abnormal LDL in heterozygous subjects is made up of two populations of particles: one that has normal binding activity to receptors and one that binds defectively. To localize the mutation in apoB-100, the binding of five apoB-100-specific monoclonal antibodies to abnormal LDL was assessed in a solid-phase RIA. Only antibody MB47, whose epitope is between residues 3350 and 3506, distinguished abnormal LDL from normal LDL isolated from control subjects with normal lipid levels; MB47 bound with a higher affinity (by approximately 60%) to abnormal LDL. In every individual with abnormal LDL, the MB47 antibody bound with a higher affinity. The convenience of this assay will facilitate screening of large populations to determine the frequency of this disorder.
TL;DR: A workshop entitled The Impact of Dietary Cholesterol on Plasma Lipoproteins and Atherogenesis was held in Bethesda, Maryland on July 1-3, 1986 as discussed by the authors, with the purpose being to review existing data relating dietary cholesterol to coronary heart disease and to define needs for future research on this issue.
Abstract: Aworkshop entitled The Impact of Dietary Cholesterol on Plasma Lipoproteins and Atherogenesis was held in Bethesda, Maryland on July 1-3, 1986. This workshop was cosponsored by the National Heart, Lung, and Blood Institute and the Agricultural Research Service, United States Department of Agriculture (USDA). Its purpose was to review existing data relating dietary cholesterol to coronary heart disease (CHD) and to define needs for future research on this issue. The topics discussed ranged from basic science to epidemiology and included investigations using both humans and laboratory animals. A possible relation between dietary cholesterol and atherosclerosis was first brought to light in laboratory animals. The feeding of cholesterol can induce marked hypercholesterolemia and atherosclerosis in many species. This observation and the susceptibility of nonhuman primates to the plasma cholesterol-raising effects of dietary cholesterol has influenced thinking about the role of dietary cholesterol in the genesis of CHD in humans. For many years, however, skeptics have questioned whether findings in laboratory animals can be extended to humans. Clinical investigations have revealed that high intakes of cholesterol in humans do not induce a marked hypercholesterolemia. Thus, some workers have suggested that humans are basically resistant to dietary cholesterol, and they contend that CHD risk is not reduced by restricting dietary cholesterol. This workshop examined the bases for these opposing views by considering the known or potential effects of dietary cholesterol.
TL;DR: The World Health Organization Multinational Study of vascular disease in diabetics observed increased prevalence of CAD in diabetic populations with relatively high levels of plasma cholesterol and supports the concept that lowering cholesterol levels may significantly reduce coronary risk in NIDDM.
Abstract: Coronary artery disease (CAD) is the leading cause of death among whites with non-insulin-dependent diabetes mellitus (NIDDM). Several risk factors—dyslipidemia induced by NIDDM, obesity, hypertension and hyperglycemia—likely contribute to accelerated atherosclerosis. The dyslipidemia in NIDDM is characterized by abnormalities in composition and metabolism of very low density lipoproteins, low-density lipoproteins (LDL) and high-density lipoproteins (HDL). However, because of the lack of long-term prospective epidemiologic studies, the relative importance of lipoprotein risk factors in the causation of CAD in diabetic patients is not clear. The World Health Organization Multinational Study of vascular disease in diabetics observed increased prevalence of CAD in diabetic populations with relatively high levels of plasma cholesterol and supports the concept that lowering cholesterol levels may significantly reduce coronary risk in NIDDM. To determine the effectiveness of lovastatin, an inhibitor of HMG CoA reductase, for lowering cholesterol levels, 16 patients with NIDDM and mild to moderate increases in plasma cholesterol were given lovastatin (20 mg twice daily) in a randomized, double-blind, placebo-controlled manner for 4 weeks. Compared with the placebo, lovastatin reduced concentrations of total cholesterol (233 ± 10 vs 172 ± 7 mg/dl [standard error of the mean], p
TL;DR: Treatment with bile acid binding resins in hypercholesterolemic patients is contraindicated in the presence of hypertriglyceridemia, and the data presented show that fewer than 5 percent of patients whose total plasma triglyceride concentration exceeded 500 mg/dl had elevated low‐density lipoprotein cholesterol concentrations.
TL;DR: Dr Grundy summarizes the results of a five-year trial of the fibric acid gemfibrozil (Lopid) and discusses the effects on lipid transport and the differences in action of fibric acids as well as the indications for their use.
Abstract: PreviewAbnormal lipid and lipoprotein patterns pose a serious threat to cardiovascular health. Often, normalization cannot be achieved without pharmacologic intervention. One class of drugs that shows promise in altering lipid levels is the fibric acids. In this article, Dr Grundy summarizes the results of a five-year trial of the fibric acid gemfibrozil (Lopid). He also discusses the effects on lipid transport and the differences in action of fibric acids as well as the indications for their use.
TL;DR: This paper will examine the complexity of the hypertriglyceridemic state, and it will consider the following questions: what are the basic pathways of triglyceride metabolism in humans?
Abstract: The role of hypertriglyceridemia in the causation of coronary heart disease (CHD) is a subject of continuing controversy. Sonne investigatory hold that hypertriglyceridemia constitutes a major risk factor for CHD, but others claim the opposite, namely, that elevated triglyceride levels are of little significance for CHD risk* The very fact that so many experienced investigators hold such divergent views attests to the complexity of the issue. The crux of the problem appears to be that a high proportion of patients with CHD have hypertriglyceridemia, and yet high triglycerides per se are not a major causative factor; instead, elevated plasma triglycerides frequently appear to be associated with other atherogenic factors that have not been fully defined. This paper will examine the complexity of the hypertriglyceridemic state, and it will consider the following questions: (a) what are the basic pathways of triglyceride metabolism in humans? (b) what are the causes of hypertriglyceridemia? (c) what is the relation of hypertriglyceridemia to CHD?, and (d) what constitutes a rational approach to the treatment of hypertriglyceridemia?
TL;DR: The results show that guanabenz, although providing effective blood pressure control that is comparable to that of HCTZ, has more favorable effects on lipoproteins.
Abstract: The effects of hydrochlorothiazide (HCTZ) and guanabenz monotherapy on blood pressure and serum lipoprotein levels were compared in a 14-week, randomized, parallel, double-blind multicenter study of 218 outpatients with mild hypertension. Mean supine blood pressure decreased 13/9 mm Hg in the guanabenz group and 17/11 mm Hg in the HCTZ group, changes that were significantly (p < 0.01) different from baseline but not significantly different between the two treatment groups. Significant (p < 0.01) mean decreases in total cholesterol and low-density lipoprotein (LDL) cholesterol levels (of 9 mg/dl and 4 mg/dl from baseline values) occurred during guanabenz treatment; HDL cholesterol levels fell by an average of 4 mg/dl. In the HCTZ group, triglyceride levels were significantly (p < 0.01) increased by 13 mg/dl, and HDL cholesterol levels fell by 2 mg/dl. The change in LDL cholesterol levels, but not HDL cholesterol levels, was significantly different between guanabenz and HCTZ periods. The results show that guanabenz, although providing effective blood pressure control that is comparable to that of HCTZ, has more favorable effects on lipoproteins.
Clinical Pharmacology and Therapeutics (1988) 44, 297–302; doi:10.1038/clpt.1988.153
01 Jan 1988
TL;DR: A solid-food diet rich in monounsaturated fatty acids is equivalent to a low-fat, high-carbohydrate diet for cholesterol lowering but does not reduce the HDL-cholesterol level.
Abstract: To compare monounsaturated fauy acids and carbohydrates for actions on lipid and lipoprotein levels from solid-food diets, 10 men were studied on three diets. One diet was high in saturated fatty acids and very high in cholesterol (High Sat+Chol), a second was high in monounsaturates but low in cholesterol (High Mono), and a third was low in fat, high in carbohydrates, and low in cholesterol (Low Fat). All diets were consumed for 6 wk. Compared with the High Sat+Chol diet, the High Mono and Low Fat diets significantly and similarly reduced plasma cholesterol and LDL cholesterol. In contrast, the Low Fat diet significantly lowered HDL cholesterol whereas the High Mono diet did not. Therefore, a solid-food diet rich in monounsaturated fatty acids is equivalent to a low-fat, high-carbohydrate diet for cholesterol lowering but does not reduce the HDL-cholesterol level. Am J Clin Nuir
TL;DR: Findings support that deficiency of the C27-steroid 26-hydroxylase is the primary enzymatic defect in CTX.
Abstract: C27-steroid 26-hydroxylase activity in fibroblasts from two heterozygotes for CTX was determined, using an optimized enzyme assay. With 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol, 5 beta-cholestane-3 alpha,7 alpha-diol, 7 alpha-hydroxy-4-cholestane-3-one or 7 alpha-hydroxycholesterol as substrates, the activities were about 50% of those of control cells. The Km for the substrates was not increased in the CTX heterozygotes. These findings support that deficiency of the C27-steroid 26-hydroxylase is the primary enzymatic defect in CTX.
Journal Article•
TL;DR: The Adult Treatment Panel Report is the first major document emerging from the National Cholesterol Education Program, and it represents the program's contribution to the high risk strategy for treatment of high blood cholesterol.
Journal Article•