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Lipoprotein Responses to Treatment With Lovastatin, Gemfibrozil, and Nicotinic Acid in Normolipidemic Patients With Hypoalphalipoproteinemia

Lipoprotein Responses to Treatment With Lovastatin, Gemfibrozil, and Nicotinic Acid in... Abstract Background: The lipoprotein responses to conventional lipid-modifying drugs have not been adequately evaluated in normolipidemic patients with hypoalphalipoproteinemia (low levels of high-density lipoproteins). The purpose of this study was to compare responses to lovastatin, gemfibrozil, and nicotinic acid in such patients. Methods: The first phase of the study compared lipoprotein responses to lovastatin and gemfibrozil in 61 middle-aged men with low levels of high-density lipoproteins. In the second phase, 37 patients agreed to take nicotinic acid; 27 patients finished this phase at a dose of 4.5 g/d. Nicotinic acid results were compared with those with lovastatin and gemfibrozil in the same patients. Results: In the first phase, both drugs effectively lowered triglyceride levels. Gemfibrozil therapy increased high-density lipoprotein cholesterol levels by 10% and lovastatin by 6%, but lovastatin was much more effective for reducing low-density lipoprotein levels. Nicotinic acid did not significantly lower low-density lipoprotein levels in the second phase, but it raised high-density lipoprotein levels by 30%. Conclusions: Gemfibrozil therapy produced the least favorable response of the three drugs. Lovastatin markedly lowered low-density lipoprotein levels but only modestly raised levels of high-density lipoprotein, whereas nicotinic acid had the opposite effect. Consequently, the latter two drugs similarly reduced low-density lipoprotein— high-density lipoprotein ratios, although these effects were obtained in different ways. Between these two drugs, lovastatin therapy was more likely to reduce low-density lipoprotein cholesterol levels to below 2.6 mmol/L (100 mg/dL), and in view of recent recommendations, it may be preferable to nicotinic acid for many normolipidemic patients with established coronary heart disease.(Arch Intern Med. 1994;154:73-82) References 1. Miller NE, Thelle DS, Forde OH, Mjos OD. The Tromso Heart-Study: high-density lipoprotein and coronary heart disease: a prospective case-control study . Lancet . 1977;1:965-968.Crossref 2. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease: the Framingham Study . Am J Med . 1977;62:707-714.Crossref 3. Keys A, Karvonen MJ, Punsar S, Menotti A, Fidanza F, Farchi G. HDL serum cholesterol and 24-year mortality in USSR and US middle-aged men: collaborative US-USSR mortality of men in Finland . Int J Epidemiol. 1984;13:428-435.Crossref 4. Garrison RJ, Kannel WB, Feinleib M, Castelli WP, McNamara PM, Padgett SJ. Cigarette smoking and HDL cholesterol: the Framingham study . Atherosclerosis . 1978;30:17-85.Crossref 5. Willett WC, Hennekens CH, Castelli WP, et al. Effects of cigarette smoking on fasting triglyceride, total cholesterol, and HDL-cholesterol in women . Am Heart J . 1983;105:417-421.Crossref 6. Wood PD, Stefanick ML, Dreon DM, et al. Changes in plasma lipids and lipoproteins in overweight men during weight loss through dieting as compared with exercise . N Engl J Med . 1988;319:1173-1179.Crossref 7. Garrison RJ, Wilson PW, Castelli WP, Feinleib M, Kannel WB, McNamara PM. Obesity and lipoprotein cholesterol in the Framingham offspring study . Metabolism . 1980;29:1053-1060.Crossref 8. Wolf R, Grundy SM. Influence of weight reduction on plasma lipoproteins in obese patients . Arteriosclerosis . 1983;3:160-169.Crossref 9. Schaefer EJ, Levy RI, Anderson DW, Dannu RN, Brewer HB. Plasma triglycerides in regulation of HDL-cholesterol . Lancet . 1978;2:391-393.Crossref 10. Patsch JR, Karlin JB, Scott LW, Smith LC, Gotto AM Jr. Inverse relationship between blood levels of high density lipoprotein subfraction 2 and magnitude of postprandial lipemia . Proc Natl Acad Sci U S A . 1983;80:1449-1453.Crossref 11. Castelli WP, Abbott RD, McNamara PM. Summary estimates of cholesterol used to predict coronary heart disease . Circulation . 1983;67:730-734.Crossref 12. Vega GL, Grundy SM. Comparison of lovastatin and gemfibrozil in normolipidemic patients with hypoalphalipoproteinemia . JAMA . 1989;262:3148-3153.Crossref 13. Castelli WP, Garrison RJ, Wilson PWF, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham Study . JAMA . 1986;256:2835-2838.Crossref 14. Expert Panel. Report of the National Cholesterol Education Program Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults, National Heart, Lung, and Blood Institute . Arch Intern Med . 1988;148:36-69.Crossref 15. National Cholesterol Education Program. Report of the Expert Panel on Population Strategies for Blood Cholesterol Reduction . Bethesda, Md: National Heart, Lung, and Blood Institute; (November) 1990. National Institutes of Health publication 90-3046. 16. Roeschlau P, Bernt E, Gruber W. Enzymatische bestimmung des gesamtcholesterins im serum . Z Klin Chem Klin Biochem. 1974;12:226-227. 17. McGowan MW, Artis JD. Strandbergh DR, Zak B. A peroxidase-coupled method for the colorimetric determination of serum triglycerides . Clin Chem . 1983;29: 538-542. 18. Lindgren FT, Jensen LC, Hatch FT. The isolation and quantitative analysis of serum lipoproteins in blood lipids and lipoproteins . In Nelson GS, ed. Quantitation, Composition and Metabolism . New York, NY: Wiley Interscience; 1972: 181-274. 19. Winer BJ. Statistical Principles in Experimental Design . 2nd ed. New York, NY: McGraw-Hill International Book Co; 1971:114. 20. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the Secondary Report of the National Cholesterol Education Program (NCEP): Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II) . JAMA . 1993;269:3015-3023.Crossref 21. Frick MH, Elo MO, Haapa K, et al. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia . N Engl J Med . 1987; 317:1237-1245.Crossref 22. Manninen V, Huttunen JK, Heinonen OP, Tenkanen L, Frick MH. Relation between baseline lipid and lipoprotein values and the incidence of coronary heart disease in the Helsinki Heart Study . Am J Cardiol . 1989;63:42H-47H.Crossref 23. Rossouw JE, Leufs B, Rifkind BM. The value of lowering cholesterol after myocardial infarction . N Engl J Med . 1990;323:1112-1119.Crossref 24. Rossouw JE, Rifkind BM. Contribution of high serum cholesterol to progression of coronary atherosclerosis and subsequent clinical events in patients with coronary heart disease . Coronary Artery Dis . 1991;2:870-874. 25. Hunninghake DB. Clinical management of dyslipidemia in patients with established coronary artery disease . Coronary Artery Dis . 1991;2:880-887. 26. National Institutes of Health Consensus Development Conference Statement on Triglycerides, High Density Lipoprotein, and Coronary Heart Disease . Bethesda, Md: National Institutes of Health; (Feb 26) -28, 1992;10(2). 27. Manninen V, Tenkanen L, Koskinen P, et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentration on coronary heart disease risk in the Helsinki Heart Study . Circulation . 1992:85:37-45. 28. Kesaniemi YA, Grundy SM. Influence of gemfibrozil and clofibrate on metabolism of cholesterol and plasma triglycerides in man . JAMA . 1984;251:2241-2246.Crossref 29. Vega GL, Grundy SM. Influence of lovastatin therapy on the metabolism of low density lipoproteins in mixed hyperlipidemia . J Intern Med . 1991;230:341-349.Crossref 30. Carlson LA, Oro L. Effect of treatment with nicotinic acid for one month on serum lipids in patients with different types of hyperlipidemia . Atherosclerosis . 1973;18:1-9.Crossref 31. Carlson LA, Froberg S, Oro L. A case of massive hypertriglyceridemia corrected by nicotinic acid or nicotinamide therapy . Atherosclerosis . 1972;16:359-368.Crossref 32. Grundy SM, Mok HYI, Zech L. Berman M. Influence of nicotinic acid on metabolism of cholesterol and triglycerides in man . J Lipid Res . 1981;22:24-26. 33. Parsons WB Jr. Studies of nicotinic acid use in hypercholesterolemia . Arch Intern Med . 1961;107:653-667.Crossref 34. Parsons WB Jr. Treatment of hypercholesterolemia by nicotinic acid . Arch Intern Med . 1961;107:639-652.Crossref 35. Knopp RH, Ginsberg J, Albers JJ, et al. Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin . Metabolism . 1985;34:642-650.Crossref 36. Carlson LA, Olsson AG, Ballantyne D. On the rise in low density and high density lipoproteins in response to the treatment of hypertriglyceridaemia in type IV and type V hyperlipoproteinaemias . Atherosclerosis . 1977;26: 603-609.Crossref 37. Lauria MH. The effect of low-dose niacin on high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein ratio . Arch Intern Med . 1988; 148:2493-2495.Crossref 38. Alderman JD, Pasternak RC, Sacks FM, Smith HS, Nonrad S, Grossman W. Effect of a modified, well tolerated niacin regimen on serum total cholesterol, high density lipoprotein cholesterol and the cholesterol to high density lipoprotein ratio . Am J Cardiol . 1989;64:725-729.Crossref 39. Blankenhorn DH, Nessim SA, Johnson RL, San Marco ME, Azen SP, Cashin-Hemphill L. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts . JAMA . 1987;257: 3233-3240.Crossref 40. Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B . N Engl J Med . 1990;323:1289-1298.Crossref 41. Lavie CJ. Mailander L, Milani RV. Marked benefit with sustained-release niacin therapy in patients with 'isolated' very low levels of high-density lipoprotein cholesterol and coronary artery disease . Am J Cardiol . 1992;69:1083-1085.Crossref 42. Garg A, Grundy SM. Nicotinic acid as therapy for dyslipidemia in noninsulin-dependent diabetes mellitus . JAMA . 1990;264:723-726.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Lipoprotein Responses to Treatment With Lovastatin, Gemfibrozil, and Nicotinic Acid in Normolipidemic Patients With Hypoalphalipoproteinemia

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Publisher
American Medical Association
Copyright
Copyright © 1994 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1994.00420010101012
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Abstract

Abstract Background: The lipoprotein responses to conventional lipid-modifying drugs have not been adequately evaluated in normolipidemic patients with hypoalphalipoproteinemia (low levels of high-density lipoproteins). The purpose of this study was to compare responses to lovastatin, gemfibrozil, and nicotinic acid in such patients. Methods: The first phase of the study compared lipoprotein responses to lovastatin and gemfibrozil in 61 middle-aged men with low levels of high-density lipoproteins. In the second phase, 37 patients agreed to take nicotinic acid; 27 patients finished this phase at a dose of 4.5 g/d. Nicotinic acid results were compared with those with lovastatin and gemfibrozil in the same patients. Results: In the first phase, both drugs effectively lowered triglyceride levels. Gemfibrozil therapy increased high-density lipoprotein cholesterol levels by 10% and lovastatin by 6%, but lovastatin was much more effective for reducing low-density lipoprotein levels. Nicotinic acid did not significantly lower low-density lipoprotein levels in the second phase, but it raised high-density lipoprotein levels by 30%. Conclusions: Gemfibrozil therapy produced the least favorable response of the three drugs. Lovastatin markedly lowered low-density lipoprotein levels but only modestly raised levels of high-density lipoprotein, whereas nicotinic acid had the opposite effect. Consequently, the latter two drugs similarly reduced low-density lipoprotein— high-density lipoprotein ratios, although these effects were obtained in different ways. Between these two drugs, lovastatin therapy was more likely to reduce low-density lipoprotein cholesterol levels to below 2.6 mmol/L (100 mg/dL), and in view of recent recommendations, it may be preferable to nicotinic acid for many normolipidemic patients with established coronary heart disease.(Arch Intern Med. 1994;154:73-82) References 1. Miller NE, Thelle DS, Forde OH, Mjos OD. The Tromso Heart-Study: high-density lipoprotein and coronary heart disease: a prospective case-control study . Lancet . 1977;1:965-968.Crossref 2. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease: the Framingham Study . Am J Med . 1977;62:707-714.Crossref 3. Keys A, Karvonen MJ, Punsar S, Menotti A, Fidanza F, Farchi G. HDL serum cholesterol and 24-year mortality in USSR and US middle-aged men: collaborative US-USSR mortality of men in Finland . Int J Epidemiol. 1984;13:428-435.Crossref 4. Garrison RJ, Kannel WB, Feinleib M, Castelli WP, McNamara PM, Padgett SJ. Cigarette smoking and HDL cholesterol: the Framingham study . Atherosclerosis . 1978;30:17-85.Crossref 5. Willett WC, Hennekens CH, Castelli WP, et al. Effects of cigarette smoking on fasting triglyceride, total cholesterol, and HDL-cholesterol in women . Am Heart J . 1983;105:417-421.Crossref 6. Wood PD, Stefanick ML, Dreon DM, et al. Changes in plasma lipids and lipoproteins in overweight men during weight loss through dieting as compared with exercise . N Engl J Med . 1988;319:1173-1179.Crossref 7. Garrison RJ, Wilson PW, Castelli WP, Feinleib M, Kannel WB, McNamara PM. Obesity and lipoprotein cholesterol in the Framingham offspring study . Metabolism . 1980;29:1053-1060.Crossref 8. Wolf R, Grundy SM. Influence of weight reduction on plasma lipoproteins in obese patients . Arteriosclerosis . 1983;3:160-169.Crossref 9. Schaefer EJ, Levy RI, Anderson DW, Dannu RN, Brewer HB. Plasma triglycerides in regulation of HDL-cholesterol . Lancet . 1978;2:391-393.Crossref 10. Patsch JR, Karlin JB, Scott LW, Smith LC, Gotto AM Jr. Inverse relationship between blood levels of high density lipoprotein subfraction 2 and magnitude of postprandial lipemia . Proc Natl Acad Sci U S A . 1983;80:1449-1453.Crossref 11. Castelli WP, Abbott RD, McNamara PM. Summary estimates of cholesterol used to predict coronary heart disease . Circulation . 1983;67:730-734.Crossref 12. Vega GL, Grundy SM. Comparison of lovastatin and gemfibrozil in normolipidemic patients with hypoalphalipoproteinemia . JAMA . 1989;262:3148-3153.Crossref 13. Castelli WP, Garrison RJ, Wilson PWF, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham Study . JAMA . 1986;256:2835-2838.Crossref 14. Expert Panel. Report of the National Cholesterol Education Program Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults, National Heart, Lung, and Blood Institute . Arch Intern Med . 1988;148:36-69.Crossref 15. National Cholesterol Education Program. Report of the Expert Panel on Population Strategies for Blood Cholesterol Reduction . Bethesda, Md: National Heart, Lung, and Blood Institute; (November) 1990. National Institutes of Health publication 90-3046. 16. Roeschlau P, Bernt E, Gruber W. Enzymatische bestimmung des gesamtcholesterins im serum . Z Klin Chem Klin Biochem. 1974;12:226-227. 17. McGowan MW, Artis JD. Strandbergh DR, Zak B. A peroxidase-coupled method for the colorimetric determination of serum triglycerides . Clin Chem . 1983;29: 538-542. 18. Lindgren FT, Jensen LC, Hatch FT. The isolation and quantitative analysis of serum lipoproteins in blood lipids and lipoproteins . In Nelson GS, ed. Quantitation, Composition and Metabolism . New York, NY: Wiley Interscience; 1972: 181-274. 19. Winer BJ. Statistical Principles in Experimental Design . 2nd ed. New York, NY: McGraw-Hill International Book Co; 1971:114. 20. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the Secondary Report of the National Cholesterol Education Program (NCEP): Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II) . JAMA . 1993;269:3015-3023.Crossref 21. Frick MH, Elo MO, Haapa K, et al. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia . N Engl J Med . 1987; 317:1237-1245.Crossref 22. Manninen V, Huttunen JK, Heinonen OP, Tenkanen L, Frick MH. Relation between baseline lipid and lipoprotein values and the incidence of coronary heart disease in the Helsinki Heart Study . Am J Cardiol . 1989;63:42H-47H.Crossref 23. Rossouw JE, Leufs B, Rifkind BM. The value of lowering cholesterol after myocardial infarction . N Engl J Med . 1990;323:1112-1119.Crossref 24. Rossouw JE, Rifkind BM. Contribution of high serum cholesterol to progression of coronary atherosclerosis and subsequent clinical events in patients with coronary heart disease . Coronary Artery Dis . 1991;2:870-874. 25. Hunninghake DB. Clinical management of dyslipidemia in patients with established coronary artery disease . Coronary Artery Dis . 1991;2:880-887. 26. National Institutes of Health Consensus Development Conference Statement on Triglycerides, High Density Lipoprotein, and Coronary Heart Disease . Bethesda, Md: National Institutes of Health; (Feb 26) -28, 1992;10(2). 27. Manninen V, Tenkanen L, Koskinen P, et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentration on coronary heart disease risk in the Helsinki Heart Study . Circulation . 1992:85:37-45. 28. Kesaniemi YA, Grundy SM. Influence of gemfibrozil and clofibrate on metabolism of cholesterol and plasma triglycerides in man . JAMA . 1984;251:2241-2246.Crossref 29. Vega GL, Grundy SM. Influence of lovastatin therapy on the metabolism of low density lipoproteins in mixed hyperlipidemia . J Intern Med . 1991;230:341-349.Crossref 30. Carlson LA, Oro L. Effect of treatment with nicotinic acid for one month on serum lipids in patients with different types of hyperlipidemia . Atherosclerosis . 1973;18:1-9.Crossref 31. Carlson LA, Froberg S, Oro L. A case of massive hypertriglyceridemia corrected by nicotinic acid or nicotinamide therapy . Atherosclerosis . 1972;16:359-368.Crossref 32. Grundy SM, Mok HYI, Zech L. Berman M. Influence of nicotinic acid on metabolism of cholesterol and triglycerides in man . J Lipid Res . 1981;22:24-26. 33. Parsons WB Jr. Studies of nicotinic acid use in hypercholesterolemia . Arch Intern Med . 1961;107:653-667.Crossref 34. Parsons WB Jr. Treatment of hypercholesterolemia by nicotinic acid . Arch Intern Med . 1961;107:639-652.Crossref 35. Knopp RH, Ginsberg J, Albers JJ, et al. Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin . Metabolism . 1985;34:642-650.Crossref 36. Carlson LA, Olsson AG, Ballantyne D. On the rise in low density and high density lipoproteins in response to the treatment of hypertriglyceridaemia in type IV and type V hyperlipoproteinaemias . Atherosclerosis . 1977;26: 603-609.Crossref 37. Lauria MH. The effect of low-dose niacin on high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein ratio . Arch Intern Med . 1988; 148:2493-2495.Crossref 38. Alderman JD, Pasternak RC, Sacks FM, Smith HS, Nonrad S, Grossman W. Effect of a modified, well tolerated niacin regimen on serum total cholesterol, high density lipoprotein cholesterol and the cholesterol to high density lipoprotein ratio . Am J Cardiol . 1989;64:725-729.Crossref 39. Blankenhorn DH, Nessim SA, Johnson RL, San Marco ME, Azen SP, Cashin-Hemphill L. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts . JAMA . 1987;257: 3233-3240.Crossref 40. Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B . N Engl J Med . 1990;323:1289-1298.Crossref 41. Lavie CJ. Mailander L, Milani RV. Marked benefit with sustained-release niacin therapy in patients with 'isolated' very low levels of high-density lipoprotein cholesterol and coronary artery disease . Am J Cardiol . 1992;69:1083-1085.Crossref 42. Garg A, Grundy SM. Nicotinic acid as therapy for dyslipidemia in noninsulin-dependent diabetes mellitus . JAMA . 1990;264:723-726.Crossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Jan 10, 1994

References