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February 27, 1991, Vol 265, No. 8 >
ARTICLE | February 27, 1991

Lovastatin Efficacy in Reducing Low-Density Lipoprotein Cholesterol Levels on High- vs Low-Fat Diets FREE

Margaret M. Cobb, MD, PhD; Howard S. Teitelbaum, DO, PhD; Jan L. Breslow, MD
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Reprint requests to 1735 York Ave, New York, NY 10128 (Dr Cobb).


JAMA. 1991;265(8):997-1001. doi:10.1001/jama.1991.03460080067034
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References

The effectiveness of lovastatin was compared with both a high-fat vs low-fat diet. Hypercholesterolemic subjects were studied under metabolic ward conditions for diet periods of 3 weeks while receiving lovastatin (40 mg/d) or placebo. Multiple lipoprotein levels were measured during the final week of each diet period. Nineteen subjects completed the study on the high-fat (43% of kilojoules) diet and 16 on the low-fat (25% of kilojoules) diet. Lovastatin reduced total cholesterol by 23% and low-density lipoprotein cholesterol by 30%, compared with placebo on both diets, with no significant diet-drug interaction. High-density lipoprotein cholesterol was raised by 7% to 8% on the diet regimens. Addition of lovastatin to the low-fat diet permitted 80% of subjects on this diet, but less than 50% of those on the high-fat diet, to achieve current guidelines. Although lovastatin produces a comparable percentage reduction in lipoprotein profiles on either diet, the accompanying low-fat diet remains advisable for additional reduction of low-density lipoprotein cholesterol levels to specified goals.

(JAMA. 1991;265:997-1001)

REFERENCES

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 The Expert Panel. Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults . Arch Intern Med. 1988;;148:36-69.
2 +
Tobert JA, Shear CL, Chremos AN, Mantell GE.  Clinical experience with lovastatin . Am J Cardiol. 1990;;65:23F-26F.
3 +
Kovanen PT, Brown MS, Basu SK, et al.  Saturation and suppression of hepatic lipoprotein receptors: a mechanism for hypercholesterolemia of cholesterol-fed rabbits . Proc Natl Acad Sci U S A. 1981;;78:1396-1400.
4 +
Mahley RW, Hui DY, Innerarity TL, Weisgraber KH.  Two independent lipoprotein receptors on hepatic membranes of dog, swine, and man . J Clin Invest. 1981;;68:1197-1206.
5 +
Grundy SM, Bilheimer DW.  Inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase by mevinolin in familial hypercholesterolemia heterozygotes: effects on cholesterol balance . Proc Natl Acad Sci U S A. 1984;;81:2538-2542.
6 +
Morgan T, Anderson A.  Interaction of slow-channel calcium blocking drugs with sodium restriction, diuretics, and angiotensin converting enzyme inhibitors . J Hypertens. 1988;;6( (suppl 4) ): S652-S654.
7 +
Weinberger MH.  Additive effects of diuretics or sodium restriction with calcium channel blockers in the treatment of hypertension . J Cardiovasc Pharmacol. 1988;;12( (suppl 4) ):S72-S75.
8 +
Pence BC, Buddingh F.  Co-carcinogenic effect of carbon black ingestion with dietary fat on the development of colon tumors in rats . Toxicol Lett. 1987;;37:177-182.
9 +
Roane DS, Martin RJ.  Continuous sucrose feeding decreases pain threshold and increases morphine potency . Pharmacol Biochem Behav. 1990;; 35:225-229.
10 +
Rifkind BM, ed. The Lipid Research Clinics Populations Studies Data Book . Bethesda, Md: National Institutes of Health; 1980;;1:70, 73. NIH publication 80-1527.
11 +
Mabuchi H, Ho S, Haba T, et al.  Discrimination of familial hypercholesterolemia and secondary hypercholesterolemia by Achilles tendon thickness . Atherosclerosis. 1977;;28:61-68.
12 +
Harris JA, Benedict FG.  Biometric study of basal metabolism in man . Carnegie Inst Wash Bull. 1919;;279:227.
13 +
 Dietary intake source data: United States, 1976-80 . Vital Health Stat 11. 1981;;231:46-50, 68, 143,195.
14 +
Grundy SM.  AHA special report: recommendations for the treatment of hyperlipidemia in adults . Arteriosclerosis. 1984;;4:445A-468A.
15 +
Human Nutrition Information Service. Composition of Foods Washington, DC: US Dept of Agriculture; 1975;. Agriculture Handbook No. 8.
16 +
Tint GS, Guorong X, Batta AK, Shefer S, Niemann W, Salen G.  Ursodeoxycholic acid, chenodeoxycholic acid, and 7-ketolithocholic acid are primary bile acids of the guinea pig . J Lipid Res. 1990;;31:1301-1306.
17 +
Horwitz W, ed. Official Methods of Analysis of the Association of Official Analytical Chemists. 15th ed. Arlington, Va: Association of Official Analytical Chemists; 1987;.
18 +
Warnick GR, Henderson J, Albers JJ.  Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol . Clin Chem. 1982;;28:1379-1388.
19 +
Denke MA, Breslow JL.  Effects of a low-fat diet with and without intermittent saturated fat and cholesterol on plasma lipids, lipoprotein and apolipoprotein levels in normal volunteers . J Lipid Res. 1988;;29:963-969.
20 +
Herbert PN, Hymas JS, Bernier DN, et al.  Apolipoprotein B-100 deficiency: intestinal steatosis despite apolipoprotein B-48 synthesis . J Clin Invest. 1985;;76:403-412.
21 +
Netter J, Wasserman W, Kutner MH. Applied Linear Statistical Models: Regression, Analysis of Variance, and Experimental Design . Homewood, Ill: Richard D Irwin Inc; 1985;:Appendix Table A10.
22 +
Snedecor GW, Cochran WG, eds. Statistical Methods . Ames: Iowa State University Press; 1982;:255-273.
23 +
Schefler WC. Statistics for Health Professionals . Reading, Mass: Addison-Wesley Publishing Co; 1984;:222-223.
24 +
Witztum JL, Simmon D, Steinberg D, et al.  Intensive combination drug therapy of familial hypercholesterolemia with lovastatin, probucol, and colestipol hydrochloride . Circulation. 1989;;79:16-28.
25 +
Walker JF, Shapiro DR.  Hydroxymethyl coenzyme A reductase inhibitors as monotherapy in the treatment of hypercholesterolemia . Am J Cardiol. 1990;;65:19F-22F.
26 +
Tikkanen MJ, Helve KE, Jäättelä A, et al.  Comparison between lovastatin and gemfibrozil in the treatment of primary hypercholesterolemia: the Finnish Multicenter Study . Am J Cardiol. 1988;;62:35-43.
27 +
The Lovastatin Study Group II.  Therapeutic response to lovastatin (mevinolin) in nonfamilial hypercholesterolemia: a multicenter study . JAMA. 1986;;256:2829-2834.
28 +
Fisher EA, Blum CB, Zanni VI, Breslow JL.  Independent effects of dietary saturated fat and cholesterol on plasma lipids, lipoproteins, and apolipoprotein E . J Lipid Res. 1983;;24:1039-1048.
29 +
Keys A.  Serum cholesterol response to dietary cholesterol . Am J Clin Nutr. 1984;;40:351-359.
30 +
Ehnholm CJ, Huttunen JK, Pietinen P, et al.  Effect of a diet low in saturated fatty acids on plasma lipids, lipoproteins, and HDL subfractions . Arteriosclerosis. 1984;;4:265-269.
31 +
Kay RM, Jacobs M, Katan MB, Miller NE, Lewis B.  Relationship between changes in plasma lipoprotein concentrations and fecal steroid excretion in man during consumption of four experimental diets . Atherosclerosis. 1985;;55:15-23.
32 +
Schaefer EJ, Levy RI, Ernst ND, Van Sant FD, Brewer HB.  The effects of low cholesterol, high polyunsaturated fat, and low-fat diets on plasma lipid and lipoprotein cholesterol levels in normal and hypercholesterolemic subjects . Am J Clin Nutr. 1981;:34:1758-1763.
33 +
Grundy SM.  Comparison of monounsaturated fatty acids and carbohydrates for lowering plasma cholesterol . N Engl J Med. 1986;;314:745-748.
34 +
Castelli WP, Garrison RJ, Wilson PWF, Abbot RD, Kalousdian S, Kannell WB.  Incidence of coronary heart disease and lipoprotein levels: the Framingham Study . JAMA. 1986;;256:2835-2838.
35 +
Keys A, Menotti A, Karvonen MJ, Aravanic C.  The diet and 15-year death rate in the Seven Countries Study . Am J Epidemiol. 1986;;124:903-915.
36 +
Martens LL, Ruten FH, Erkelens DW, Ascoop CAP.  Clinical benefits and cost-effectiveness of lowering serum cholesterol levels: the case of simvastatin and cholestyramine in the Netherlands . Am J Cardiol. 1990;;65:27-32.
37 +
LaRosa J.  At what levels of total low- or high-density lipoprotein cholesterol should diet/ drug therapy be initiated? United States guidelines . Am J Cardiol. 1990;;65:7-10.

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1 +
 The Expert Panel. Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults . Arch Intern Med. 1988;;148:36-69.
2 +
Tobert JA, Shear CL, Chremos AN, Mantell GE.  Clinical experience with lovastatin . Am J Cardiol. 1990;;65:23F-26F.
3 +
Kovanen PT, Brown MS, Basu SK, et al.  Saturation and suppression of hepatic lipoprotein receptors: a mechanism for hypercholesterolemia of cholesterol-fed rabbits . Proc Natl Acad Sci U S A. 1981;;78:1396-1400.
4 +
Mahley RW, Hui DY, Innerarity TL, Weisgraber KH.  Two independent lipoprotein receptors on hepatic membranes of dog, swine, and man . J Clin Invest. 1981;;68:1197-1206.
5 +
Grundy SM, Bilheimer DW.  Inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase by mevinolin in familial hypercholesterolemia heterozygotes: effects on cholesterol balance . Proc Natl Acad Sci U S A. 1984;;81:2538-2542.
6 +
Morgan T, Anderson A.  Interaction of slow-channel calcium blocking drugs with sodium restriction, diuretics, and angiotensin converting enzyme inhibitors . J Hypertens. 1988;;6( (suppl 4) ): S652-S654.
7 +
Weinberger MH.  Additive effects of diuretics or sodium restriction with calcium channel blockers in the treatment of hypertension . J Cardiovasc Pharmacol. 1988;;12( (suppl 4) ):S72-S75.
8 +
Pence BC, Buddingh F.  Co-carcinogenic effect of carbon black ingestion with dietary fat on the development of colon tumors in rats . Toxicol Lett. 1987;;37:177-182.
9 +
Roane DS, Martin RJ.  Continuous sucrose feeding decreases pain threshold and increases morphine potency . Pharmacol Biochem Behav. 1990;; 35:225-229.
10 +
Rifkind BM, ed. The Lipid Research Clinics Populations Studies Data Book . Bethesda, Md: National Institutes of Health; 1980;;1:70, 73. NIH publication 80-1527.
11 +
Mabuchi H, Ho S, Haba T, et al.  Discrimination of familial hypercholesterolemia and secondary hypercholesterolemia by Achilles tendon thickness . Atherosclerosis. 1977;;28:61-68.
12 +
Harris JA, Benedict FG.  Biometric study of basal metabolism in man . Carnegie Inst Wash Bull. 1919;;279:227.
13 +
 Dietary intake source data: United States, 1976-80 . Vital Health Stat 11. 1981;;231:46-50, 68, 143,195.
14 +
Grundy SM.  AHA special report: recommendations for the treatment of hyperlipidemia in adults . Arteriosclerosis. 1984;;4:445A-468A.
15 +
Human Nutrition Information Service. Composition of Foods Washington, DC: US Dept of Agriculture; 1975;. Agriculture Handbook No. 8.
16 +
Tint GS, Guorong X, Batta AK, Shefer S, Niemann W, Salen G.  Ursodeoxycholic acid, chenodeoxycholic acid, and 7-ketolithocholic acid are primary bile acids of the guinea pig . J Lipid Res. 1990;;31:1301-1306.
17 +
Horwitz W, ed. Official Methods of Analysis of the Association of Official Analytical Chemists. 15th ed. Arlington, Va: Association of Official Analytical Chemists; 1987;.
18 +
Warnick GR, Henderson J, Albers JJ.  Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol . Clin Chem. 1982;;28:1379-1388.
19 +
Denke MA, Breslow JL.  Effects of a low-fat diet with and without intermittent saturated fat and cholesterol on plasma lipids, lipoprotein and apolipoprotein levels in normal volunteers . J Lipid Res. 1988;;29:963-969.
20 +
Herbert PN, Hymas JS, Bernier DN, et al.  Apolipoprotein B-100 deficiency: intestinal steatosis despite apolipoprotein B-48 synthesis . J Clin Invest. 1985;;76:403-412.
21 +
Netter J, Wasserman W, Kutner MH. Applied Linear Statistical Models: Regression, Analysis of Variance, and Experimental Design . Homewood, Ill: Richard D Irwin Inc; 1985;:Appendix Table A10.
22 +
Snedecor GW, Cochran WG, eds. Statistical Methods . Ames: Iowa State University Press; 1982;:255-273.
23 +
Schefler WC. Statistics for Health Professionals . Reading, Mass: Addison-Wesley Publishing Co; 1984;:222-223.
24 +
Witztum JL, Simmon D, Steinberg D, et al.  Intensive combination drug therapy of familial hypercholesterolemia with lovastatin, probucol, and colestipol hydrochloride . Circulation. 1989;;79:16-28.
25 +
Walker JF, Shapiro DR.  Hydroxymethyl coenzyme A reductase inhibitors as monotherapy in the treatment of hypercholesterolemia . Am J Cardiol. 1990;;65:19F-22F.
26 +
Tikkanen MJ, Helve KE, Jäättelä A, et al.  Comparison between lovastatin and gemfibrozil in the treatment of primary hypercholesterolemia: the Finnish Multicenter Study . Am J Cardiol. 1988;;62:35-43.
27 +
The Lovastatin Study Group II.  Therapeutic response to lovastatin (mevinolin) in nonfamilial hypercholesterolemia: a multicenter study . JAMA. 1986;;256:2829-2834.
28 +
Fisher EA, Blum CB, Zanni VI, Breslow JL.  Independent effects of dietary saturated fat and cholesterol on plasma lipids, lipoproteins, and apolipoprotein E . J Lipid Res. 1983;;24:1039-1048.
29 +
Keys A.  Serum cholesterol response to dietary cholesterol . Am J Clin Nutr. 1984;;40:351-359.
30 +
Ehnholm CJ, Huttunen JK, Pietinen P, et al.  Effect of a diet low in saturated fatty acids on plasma lipids, lipoproteins, and HDL subfractions . Arteriosclerosis. 1984;;4:265-269.
31 +
Kay RM, Jacobs M, Katan MB, Miller NE, Lewis B.  Relationship between changes in plasma lipoprotein concentrations and fecal steroid excretion in man during consumption of four experimental diets . Atherosclerosis. 1985;;55:15-23.
32 +
Schaefer EJ, Levy RI, Ernst ND, Van Sant FD, Brewer HB.  The effects of low cholesterol, high polyunsaturated fat, and low-fat diets on plasma lipid and lipoprotein cholesterol levels in normal and hypercholesterolemic subjects . Am J Clin Nutr. 1981;:34:1758-1763.
33 +
Grundy SM.  Comparison of monounsaturated fatty acids and carbohydrates for lowering plasma cholesterol . N Engl J Med. 1986;;314:745-748.
34 +
Castelli WP, Garrison RJ, Wilson PWF, Abbot RD, Kalousdian S, Kannell WB.  Incidence of coronary heart disease and lipoprotein levels: the Framingham Study . JAMA. 1986;;256:2835-2838.
35 +
Keys A, Menotti A, Karvonen MJ, Aravanic C.  The diet and 15-year death rate in the Seven Countries Study . Am J Epidemiol. 1986;;124:903-915.
36 +
Martens LL, Ruten FH, Erkelens DW, Ascoop CAP.  Clinical benefits and cost-effectiveness of lowering serum cholesterol levels: the case of simvastatin and cholestyramine in the Netherlands . Am J Cardiol. 1990;;65:27-32.
37 +
LaRosa J.  At what levels of total low- or high-density lipoprotein cholesterol should diet/ drug therapy be initiated? United States guidelines . Am J Cardiol. 1990;;65:7-10.

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