The Efficacy of Intensive Dietary Therapy Alone or Combined with Lovastatin in Outpatients with Hypercholesterolemia
Donald B. Hunninghake, Evan A. Stein, Carlos A. Dujovne, William S. Harris, Elaine B. Feldman, Valery T. Miller, Jonathan A. Tobert, Peter M. Laskarzewski, Elaine Quiter, Jolene Held, Alice M. Taylor, Suzanne Hopper, Sandra B. Leonard, and Brenda K. Brewer
Background A diet low in saturated fat and cholesterol is thestandard initial treatment for hypercholesterolemia. However,little quantitative information is available about the efficacyof dietary therapy in clinical practice or about the combinedeffects of diet and drug therapy.
Methods One hundred eleven outpatients with moderate hypercholesterolemiawere treated at five lipid clinics with the National CholesterolEducation Program Step 2 diet (which is low in fat and cholesterol)and lovastatin (20 mg once daily), both alone and together.A diet high in fat and cholesterol and a placebo identical inappearance to the lovastatin were used as the respective controls.Each of the 97 patients completing the study (58 men and 39women) underwent four consecutive nine-week periods of treatmentaccording to a randomized, balanced design: a high-fat diet-placeboperiod, a low-fat diet-placebo period, a high-fat diet-lovastatinperiod, and a low-fat diet-lovastatin period.
Results The level of low-density lipoprotein (LDL) cholesterolwas a mean of 5 percent (95 percent confidence interval, 3 to7 percent) lower during the low-fat diet than during the high-fatdiet (P<0.001). With lovastatin therapy as compared withplacebo, the reduction was 27 percent. Together, the low-fatdiet and lovastatin led to a mean reduction of 32 percent inthe level of LDL cholesterol. The level of high-density lipoprotein(HDL) cholesterol fell by 6 percent (95 percent confidence interval,4 to 8 percent) during the low-fat diet (P<0.001) and roseby 4 percent during treatment with lovastatin (P<0.001).The ratio of LDL to HDL cholesterol and the level of total triglycerideswere reduced by lovastatin (P<0.001), but not by the low-fatdiet.
Conclusions The effects of the low-fat-low-cholesterol dietand lovastatin on lipoprotein levels were independent and additive.However, the reduction in LDL cholesterol produced by the dietwas small, and its benefit was possibly offset by the accompanyingreduction in the level of HDL cholesterol.
Source Information
From the Heart Disease Prevention Clinic, Minneapolis (D.B.H., E.Q.); the Christ Hospital Cardiovascular Research Center, Cincinnati (E.A.S., S.H.); the University of Kansas Medical Center, Kansas City (C.A.D., W.S.H.); the Medical College of Georgia, Augusta (E.B.F., S.B.L.); George Washington University, Washington, D.(V.T.M., B.K.B.); Merck Research Laboratories, Rahway, N.J. (J.A.T., A.M.T.); Medical Research Laboratories, Cincinnati (P.M.L.); and Professional Nutrition Systems, Kansas City, Kans. (J.H.). The following persons also participated in the study: Heart Disease Prevention Clinic, Minneapolis -- J. Peters and K. Gardner; Christ Hospital Cardiovascular Research Center, Cincinnati -- D.M. Black, G.E. Lamkin, and S. Ames; University of Kansas Medical Center, Kansas City -- P. Krehbiel and S. Horniman; Medical College of Georgia, Augusta -- T.T. Kuske and J.M. Greene; George Washington University, Washington, D. -- D.B. Stoy and G. Gasparis; and Medical Research Laboratories, Cincinnati -- P.M. Steiner.
Address reprint requests to Dr. Hunninghake at the Heart Disease Prevention Clinic, 151 Variety Club Heart & Research Center, 401 E. River Rd., Minneapolis, MN 55455.
Treatment of and Screening for Hyperlipidemia
Ornish D., Brown S. E., Kottke B. A., Shea S., Barth J. D., Bryan G. K., Hokanson J. E., Austin M. A., Ginsberg H. N., Tall A. R., Deckelbaum R. J., Hunninghake D. B., Criqui M. H., Heiss G., Sox H. C.
Extract |
Full Text
N Engl J Med 1993;
329:1124-1128, Oct 7, 1993.
Correspondence
This article has been cited by other articles:
Berglund, L., Lefevre, M., Ginsberg, H. N, Kris-Etherton, P. M, Elmer, P. J, Stewart, P. W, Ershow, A., Pearson, T. A, Dennis, B. H, Roheim, P. S, Ramakrishnan, R., Reed, R., Stewart, K., Phillips, K. M, for the DELTA Investigators,
(2007). Comparison of monounsaturated fat with carbohydrates as a replacement for saturated fat in subjects with a high metabolic risk profile: studies in the fasting and postprandial states. Am. J. Clin. Nutr.
86: 1611-1620
[Abstract][Full Text]
Kashani, A., Phillips, C. O., Foody, J. M., Wang, Y., Mangalmurti, S., Ko, D. T., Krumholz, H. M.
(2006). Risks Associated With Statin Therapy: A Systematic Overview of Randomized Clinical Trials. Circulation
114: 2788-2797
[Abstract][Full Text]
Aude, Y. W., Agatston, A. S., Lopez-Jimenez, F., Lieberman, E. H., Marie Almon, , Hansen, M., Rojas, G., Lamas, G. A., Hennekens, C. H.
(2004). The National Cholesterol Education Program Diet vs a Diet Lower in Carbohydrates and Higher in Protein and Monounsaturated Fat: A Randomized Trial. Arch Intern Med
164: 2141-2146
[Abstract][Full Text]
Henkin, Y., Shai, I.
(2003). Dietary Treatment of Hypercholestrolemia: Can We Predict Long-Term Success?. J. Am. Coll. Nutr.
22: 555-561
[Abstract][Full Text]
Fraser, G. E., Bennett, H. W., Jaceldo, K. B., Sabate, J.
(2002). Effect on Body Weight of a Free 76 Kilojoule (320 Calorie) Daily Supplement of Almonds for Six Months. J. Am. Coll. Nutr.
21: 275-283
[Abstract][Full Text]
Jula, A., Marniemi, J., Huupponen, R., Virtanen, A., Rastas, M., Ronnemaa, T.
(2002). Effects of Diet and Simvastatin on Serum Lipids, Insulin, and Antioxidants in Hypercholesterolemic Men: A Randomized Controlled Trial. JAMA
287: 598-605
[Abstract][Full Text]
Lichtenstein, A. H., Ausman, L. M., Jalbert, S. M., Vilella-Bach, M., Jauhiainen, M., McGladdery, S., Erkkila, A. T., Ehnholm, C., Frohlich, J., Schaefer, E. J.
(2002). Efficacy of a Therapeutic Lifestyle Change/Step 2 diet in moderately hypercholesterolemic middle-aged and elderly female and male subjects. J. Lipid Res.
43: 264-273
[Abstract][Full Text]
Sun, Z., Welty, F. K, Dolnikowski, G. G, Lichtenstein, A. H, Schaefer, E. J
(2001). Effects of a National Cholesterol Education Program Step II Diet on apolipoprotein A-IV metabolism within triacylglycerol-rich lipoproteins and plasma. Am. J. Clin. Nutr.
74: 308-314
[Abstract][Full Text]
Muldoon, M. F, Manuck, S. B, Mendelsohn, A. B, Kaplan, J. R, Belle, S. H
(2001). Cholesterol reduction and non-illness mortality: meta-analysis of randomised clinical trials. BMJ
322: 11-15
[Abstract][Full Text]
Knopp, R. H., Retzlaff, B., Walden, C., Fish, B., Buck, B., McCann, B.
(2000). One-Year Effects of Increasingly Fat-Restricted, Carbohydrate-Enriched Diets on Lipoprotein Levels in Free-Living Subjects. Exp. Biol. Med.
225: 191-199
[Abstract][Full Text]
Hulley, S. B, Grady, D., Browner, W. S
(2000). Statins: underused by those who would benefit. BMJ
321: 971-972
[Full Text]
Walden, C. E., Retzlaff, B. M., Buck, B. L., Wallick, S., McCann, B. S., Knopp, R. H.
(2000). Differential Effect of National Cholesterol Education Program (NCEP) Step II Diet on HDL Cholesterol, Its Subfractions, and Apoprotein A-I Levels in Hypercholesterolemic Women and Men After 1 Year : The beFIT Study. Arterioscler. Thromb. Vasc. Bio.
20: 1580-1587
[Abstract][Full Text]
Hunninghake, D. B., Maki, K. C., Kwiterovich, P. O. Jr, Davidson, M. H., Dicklin, M. R., Kafonek, S. D.
(2000). Incorporation of Lean Red Meat into a National Cholesterol Education Program Step I Diet: A Long-Term, Randomized Clinical Trial in Free-Living Persons with Hypercholesterolemia. J. Am. Coll. Nutr.
19: 351-360
[Abstract][Full Text]
Swan, H. J. C.
(2000). The Framingham offspring study: A commentary. J Am Coll Cardiol
35: 13B-17B
Barnard, N. D., Davidson, M. H., Maki, K. C.
(2000). The Lipid-Lowering Effect of Lean Meat Diets Falls Far Short of That of Vegetarian Diets. Arch Intern Med
160: 395-396
[Full Text]
Dhein, S., Salameh, A.
(1999). Amlodipine Releases Nitric Oxide From Canine Coronary Microvessels: An Unexpected Mechanism of Action of a Calcium Channel–Blocking Agent. Circulation
100: 1011-1015
[Full Text]
Barnard, R. J., Baschetti, R., Ornish, D., Lichtenstein, A. H., Van Horn, L.
(1999). Very-Low-Fat Diets • Response. Circulation
100
: 1011-1015
[Full Text]
Herbert, P. N., Miller, M., Lear, S. A., Ornish, D.
(1999). Effect of Lifestyle Changes on Coronary Heart Disease. JAMA
282: 130-132
[Full Text]
Waters, D.
(1999). Cholesterol Lowering : Should It Continue to Be the Last Thing We Do?. Circulation
99: 3215-3217
[Full Text]
Denke, M. A
(1999). Revisiting the effectiveness of the National Cholesterol Education Program's Step I and Step II diets: cholesterol-lowering diets in a pharmaceutically driven world. Am. J. Clin. Nutr.
69: 581-582
[Full Text]
Swan, H. J. C.
(1999). The Framingham Offspring Study: a commentary. J Am Coll Cardiol
33: 1136-1140
[Full Text]
Velez-Carrasco, W., Lichtenstein, A. H., Welty, F. K., Li, Z., Lamon-Fava, S., Dolnikowski, G. G., Schaefer, E. J.
(1999). Dietary Restriction of Saturated Fat and Cholesterol Decreases HDL ApoA-I Secretion. Arterioscler. Thromb. Vasc. Bio.
19: 918-924
[Abstract][Full Text]
Nilausen, K., Meinertz, H.
(1999). Lipoprotein(a) and dietary proteins: casein lowers lipoprotein(a) concentrations as compared with soy protein. Am. J. Clin. Nutr.
69: 419-425
[Abstract][Full Text]
Ornish, D., Scherwitz, L. W., Billings, J. H., Gould, K. L., Merritt, T. A., Sparler, S., Armstrong, W. T., Ports, T. A., Kirkeeide, R. L., Hogeboom, C., Brand, R. J.
(1998). Intensive Lifestyle Changes for Reversal of Coronary Heart Disease. JAMA
280: 2001-2007
[Abstract][Full Text]
Stefanick, M. L., Mackey, S., Sheehan, M., Ellsworth, N., Haskell, W. L., Wood, P. D.
(1998). Effects of Diet and Exercise in Men and Postmenopausal Women with Low Levels of HDL Cholesterol and High Levels of LDL Cholesterol. NEJM
339: 12-20
[Abstract][Full Text]
Tang, J L, Armitage, J M, Lancaster, T, Silagy, C A, Fowler, G H, Neil, H A W, Smith, G. D., Ebrahim, S.
(1998). Systematic review of dietary intervention trials to lower blood total cholesterol in free-living subjects • Commentary: Dietary change, cholesterol reduction, and the public health---what does meta-analysis add?. BMJ
316: 1213-1220
[Abstract][Full Text]
Lefevre, M., Ginsberg, H. N., Kris-Etherton, P. M., Elmer, P. J., Stewart, P. W., Ershow, A., Pearson, T. A., Roheim, P. S., Ramakrishnan, R., Derr, J., Gordon, D. J., Reed, R., for the DELTA Research Group,
(1997). ApoE Genotype Does Not Predict Lipid Response to Changes in Dietary Saturated Fatty Acids in a Heterogeneous Normolipidemic Population. Arterioscler. Thromb. Vasc. Bio.
17: 2914-2923
[Abstract][Full Text]
Neufeld, E. J., Mietus-Snyder, M., Beiser, A. S., Baker, A. L., Newburger, J. W.
(1997). Passive Cigarette Smoking and Reduced HDL Cholesterol Levels in Children With High-Risk Lipid Profiles. Circulation
96: 1403-1407
[Abstract][Full Text]
Walden, C. E., Retzlaff, B. M., Buck, B. L., McCann, B. S., Knopp, R. H.
(1997). Lipoprotein Lipid Response to the National Cholesterol Education Program Step II Diet by Hypercholesterolemic and Combined Hyperlipidemic Women and Men. Arterioscler. Thromb. Vasc. Bio.
17: 375-382
[Abstract][Full Text]
Schafer, S., Schardt, C., Burkhard-Meier, U., Klein, R. M., Heintzen, M. P., Strauer, B. E.
(1996). Angina Pectoris and Progressive Fatigue in a 61-Year-Old Man. Circulation
94: 3376-3381
[Full Text]
Danese, M. D., Powe, N. R., Sawin, C. T., Ladenson, P. W.
(1996). Screening for Mild Thyroid Failure at the Periodic Health Examination: A Decision and Cost-effectiveness Analysis. JAMA
276: 285-292
[Abstract]
Kannel, W. B.
(1996). Preventive Efficacy of Nutritional Counseling. Arch Intern Med
156: 1138-1139
[Abstract]
Caggiula, A. W., Watson, J. E., Kuller, L. H., Olson, M. B., Milas, N. C., Berry, M., Germanowski, J.
(1996). Cholesterol-Lowering Intervention Program: Effect of the Step I Diet in Community Office Practices. Arch Intern Med
156: 1205-1213
[Abstract]
Berger, M. L., Wilson, H. M., Liss, C. L.
(1996). A Comparison of the Tolerability and Efficacy of Lovastatin 20 mg and Fluvastatin 20 mg in the Treatment of Primary Hypercholesterolemia. J CARDIOVASC PHARMACOL THER
1: 101-106
[Abstract]
Davidson, M. H., Kong, J. C., Drennan, K. B., Story, K., Anderson, G. H.
(1996). Efficacy of the National Cholesterol Education Program Step I Diet: A Randomized Trial Incorporating Quick-Service Foods. Arch Intern Med
156: 305-312
[Abstract]
Jacobson, T. A., Chin, M. M., Curry, C. L., Miller, V., Papademetriou, V., Schlant, R. C., LaRosa, J. C.
(1995). Efficacy and Safety of Pravastatin in African Americans With Primary Hypercholesterolemia. Arch Intern Med
155: 1900-1906
[Abstract]
Schaefer, E. J., Lichtenstein, A. H., Lamon-Fava, S., Contois, J. H., Li, Z., Rasmussen, H., McNamara, J. R., Ordovas, J. M.
(1995). Efficacy of a National Cholesterol Education Program Step 2 Diet in Normolipidemic and Hypercholesterolemic Middle-Aged and Elderly Men and Women. Arterioscler. Thromb. Vasc. Bio.
15: 1079-1085
[Abstract][Full Text]
Newman, T. B., Garber, A. M., Holtzman, N. A., Hulley, S. B.
(1995). Problems With the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Arch Pediatr Adolesc Med
149: 241-247
[Abstract]
Denke, M. A., Grundy, S. M.
(1995). Efficacy of Low-Dose Cholesterol-Lowering Drug Therapy in Men With Moderate Hypercholesterolemia. Arch Intern Med
155: 393-399
[Abstract]
Barnard, N. D., Akhtar, A., Nicholson, A.
(1995). Factors That Facilitate Compliance to Lower Fat Intake. Arch Fam Med
4: 153-158
[Abstract]
Denke, M. A.
(1995). Cholesterol-Lowering Diets: A Review of the Evidence. Arch Intern Med
155: 17-26
[Abstract]
Hulley, S. B., Newman, T. B.
(1994). Cholesterol in the Elderly: Is It Important?. JAMA
272: 1372-1374
[Abstract]
Denke, M. A.
(1994). Individual Responsiveness to a Cholesterol-Lowering Diet in Postmenopausal Women With Moderate Hypercholesterolemia. Arch Intern Med
154: 1977-1982
[Abstract]
Probstfield, J. L., Hunninghake, D. B.
(1994). Nicotinic Acid as a Lipoprotein-Altering Agent: Therapy Directed by the Primary Physician. Arch Intern Med
154: 1557-1559
[Abstract]
Smith, G D, Egger, M
(1994). Commentary: Statistical problems. BMJ
308: 1025-1027
[Full Text]
Denke, M. A., Grundy, S. M.
(1994). Individual Responses to a Cholesterol-Lowering Diet in 50 Men With Moderate Hypercholesterolemia. Arch Intern Med
154: 317-325
[Abstract]
Arca, M., Vega, G. L., Grundy, S. M.
(1994). Hypercholesterolemia in Postmenopausal Women: Metabolic Defects and Response to Low-Dose Lovastatin. JAMA
271: 453-459
[Abstract]
Law, M R, Wald, N J, Thompson, S G
(1994). By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease?. BMJ
308: 367-372
[Abstract][Full Text]
Ornish, D., Brown, S. E., Kottke, B. A., Shea, S., Barth, J. D., Bryan, G. K., Hokanson, J. E., Austin, M. A., Ginsberg, H. N., Tall, A. R., Deckelbaum, R. J., Hunninghake, D. B., Criqui, M. H., Heiss, G., Sox, H. C.
(1993). Treatment of and Screening for Hyperlipidemia. NEJM
329: 1124-1128
[Full Text]
(1993). LOW-FAT DIETS RELATIVELY INEFFECTIVE FOR HYPERCHOLESTEROLEMIA. JWatch General
1993: 3-3
[Full Text]
Sox, H. C.
(1993). Screening for Lipid Disorders under Health System Reform. NEJM
328: 1269-1271
[Full Text]
(V.T.M., B.K.B.); Merck Research Laboratories, Rahway, N.J. (J.A.T., A.M.T.); Medical Research Laboratories, Cincinnati (P.M.L.); and Professional Nutrition Systems, Kansas City, Kans. (J.H.). The following persons also participated in the study: Heart Disease Prevention Clinic, Minneapolis -- J. Peters and K. Gardner; Christ Hospital Cardiovascular Research Center, Cincinnati -- D.M. Black, G.E. Lamkin, and S. Ames; University of Kansas Medical Center, Kansas City -- P. Krehbiel and S. Horniman; Medical College of Georgia, Augusta -- T.T. Kuske and J.M. Greene; George Washington University, Washington, D.
