Effectiveness of low-dose crystalline nicotinic acid in men with low high-density lipoprotein cholesterol levels.

BACKGROUND Hypoalphalipoproteinemia (low serum concentration of high-density lipoprotein cholesterol [HDL-C]) is a common pattern of dyslipidemia associated with coronary heart disease. High doses of nicotinic acid effectively raise HDL-C levels in this condition, but they are commonly accompanied by side effects. The efficacy of low doses of nicotinic acid that may produce fewer side effects has not been adequately studied. OBJECTIVE To determine the effects of low-dose nicotinic acid on HDL-C levels in patients with hypoalphalipoproteinemia. METHODS Forty-four men with low HDL-C levels (< 1.03 mmol/L [< 40 mg/dL]) entered the study. Twenty-four patients otherwise had normal lipid levels, and 20 were moderately hypertriglyceridemic (range of plasma triglyceride levels, 2.82 to 5.64 mmol/L 250 to 500 mg/dL). The trial consisted of 3 phases; each phase lasted 8 weeks. The first phase was diet only (30% fat diet); in the second phase, crystalline nicotinic acid was added at 1.5 g/d; and in the third phase, the dose was increased to 3 g/d. RESULTS Of the 44 patients who entered the study, 37 completed the low-dose phase (1.5 g/d); the remaining patients were withdrawn because of side effects to nicotinic acid. Four other patients who completed the low-dose phase were excluded from the higher dose phase because of side effects that developed when they were receiving the low dose. Ten other patients withdrew during the high-dose phase because of side effects. In both groups, responses to nicotinic acid therapy tended to be dose-dependent. For both groups, the higher dose generally produced a greater reduction in apolipoprotein B-containing lipoproteins and a greater rise in HDL-C levels. However, for both groups, the low dose of nicotinic acid gave an average 20% increase in HDL-C levels. CONCLUSIONS A low dose (1.5 g/d) of crystalline nicotinic acid causes an average 20% increase in HDL-C levels and significantly lowers triglyceride levels in both normolipidemic and hyperlipidemic patients with low HDL-C levels. Although the changes induced by this dose are less than those that can be achieved by a higher dose, the lower dose is better tolerated. Nicotinic acid may be useful in combined drug therapy for secondary prevention of coronary heart disease, and if higher doses cannot be tolerated, use of a lower dose should still be useful for producing a moderate rise in HDL-C levels in patients with hypoalphalipoproteinemia.

[1]  S. Grundy,et al.  Relation between cholesterol ester transfer protein activities and lipoprotein cholesterol in patients with hypercholesterolemia and combined hyperlipidemia. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[2]  M. Hayden,et al.  Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia. , 1994, The American journal of cardiology.

[3]  S. Grundy,et al.  Lipoprotein responses to treatment with lovastatin, gemfibrozil, and nicotinic acid in normolipidemic patients with hypoalphalipoproteinemia. , 1994, Archives of internal medicine.

[4]  S. Grundy,et al.  Activities of lipoprotein lipase and hepatic triglyceride lipase in postheparin plasma of patients with low concentrations of HDL cholesterol. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[5]  J. Mckenney,et al.  Summary of the second 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) , 1993, JAMA.

[6]  C. Lavie,et al.  Marked benefit with sustained-release niacin therapy in patients with "isolated" very low levels of high-density lipoprotein cholesterol and coronary artery disease. , 1992, The American journal of cardiology.

[7]  S. Marcovina,et al.  International Federation of Clinical Chemistry study on the standardization of apolipoproteins A-I and B , 1991 .

[8]  G. Ginsburg,et al.  Frequency of low serum high-density lipoprotein cholesterol levels in hospitalized patients with "desirable" total cholesterol levels. , 1991, The American journal of cardiology.

[9]  P. Zimetbaum,et al.  Nicotinic Acid for the Treatment of Hyperlipoproteinemia , 1991, Journal of clinical pharmacology.

[10]  G. Schmitz,et al.  High-density lipoprotein metabolism, reverse cholesterol transport and membrane protection , 1991 .

[11]  D. Salem,et al.  Prevalence of risk factors in men with premature coronary artery disease. , 1991, The American journal of cardiology.

[12]  C. Lavie,et al.  National Cholesterol Education Program's recommendations, and implications of "missing" high-density lipoprotein cholesterol in cardiac rehabilitation programs. , 1991, The American journal of cardiology.

[13]  M J Malloy,et al.  Regression of coronary atherosclerosis during treatment of familial hypercholesterolemia with combined drug regimens. , 1990, JAMA.

[14]  I. Holme,et al.  An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence. , 1990, Circulation.

[15]  J J Albers,et al.  Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. , 1990, The New England journal of medicine.

[16]  B. Rifkind,et al.  The value of lowering cholesterol after myocardial infarction. , 1990, The New England journal of medicine.

[17]  A. Tall Plasma high density lipoproteins. Metabolism and relationship to atherogenesis. , 1990, The Journal of clinical investigation.

[18]  L. Fong,et al.  High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein. , 1990, Biochimica et biophysica acta.

[19]  D. Steinberg,et al.  Prevention of low density lipoprotein aggregation by high density lipoprotein or apolipoprotein A-I. , 1990, Journal of lipid research.

[20]  L. Mead,et al.  Dyslipidemias with desirable plasma total cholesterol levels and angiographically demonstrated coronary artery disease. , 1990, The American journal of cardiology.

[21]  S. Grundy,et al.  Comparison of lovastatin and gemfibrozil in normolipidemic patients with hypoalphalipoproteinemia. , 1989, JAMA.

[22]  F. Sacks,et al.  Effect of a modified, well-tolerated niacin regimen on serum total cholesterol, high density lipoprotein cholesterol and the cholesterol to high density lipoprotein ratio. , 1989, The American journal of cardiology.

[23]  M. H. Luria,et al.  Effect of low-dose niacin on high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol ratio. , 1988, Archives of internal medicine.

[24]  J. Huttunen,et al.  Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. , 1987, The New England journal of medicine.

[25]  D H Blankenhorn,et al.  Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. , 1987, JAMA.

[26]  P. Wilson,et al.  Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. , 1986, JAMA.

[27]  S. Grundy,et al.  Influence of mevinolin on metabolism of low density lipoproteins in primary moderate hypercholesterolemia. , 1985, Journal of lipid research.

[28]  J. Albers,et al.  Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin. , 1985, Metabolism: clinical and experimental.

[29]  S. Grundy,et al.  Comparison of apolipoprotein B to cholesterol in low density lipoproteins of patients with coronary heart disease. , 1984, Journal of lipid research.

[30]  G. Assmann,et al.  Quantification of high-density-lipoprotein cholesterol by precipitation with phosphotungstic acid/MgCl2. , 1983, Clinical chemistry.

[31]  B. Zak,et al.  A peroxidase-coupled method for the colorimetric determination of serum triglycerides. , 1983, Clinical chemistry.

[32]  J. Albers,et al.  Characterization of proteoliposomes containing apoprotein A-I: a new substrate for the measurement of lecithin: cholesterol acyltransferase activity. , 1982, Journal of lipid research.

[33]  J. Yovos,et al.  Effects of nicotinic acid therapy on plasma lipoproteins and very low density lipoprotein apoprotein C subspecies in hyperlipoproteinemia. , 1982, The Journal of clinical endocrinology and metabolism.

[34]  J. Albers,et al.  Comparison of current methods for high-density lipoprotein cholesterol quantitation. , 1979, Clinical chemistry.

[35]  M C Hjortland,et al.  High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. , 1977, The American journal of medicine.

[36]  J. Stamler Clofibrate and niacin in coronary heart disease. , 1975, JAMA.

[37]  E. Bernt,et al.  Enzymatic determination of total cholesterol in serum. , 1974, Zeitschrift fur klinische Chemie und klinische Biochemie.

[38]  L. Carlson,et al.  Effect of treatment with nicotinic acid for one month on serum lipids in patients with different types of hyperlipidemia. , 1973, Atherosclerosis.

[39]  L. Carlson,et al.  A case of massive hypertriglyceridemia corrected by nicotinic acid or nicotinamide therapy. , 1972, Atherosclerosis.

[40]  R. Charman,et al.  Nicotinic Acid in the Treatment of Hypercholesterolemia , 1972, Angiology.

[41]  Seymour Geisser,et al.  Statistical Principles in Experimental Design , 1963 .

[42]  W. Parsons Treatment of hypercholesteremia by nicotinic acid. Progress report with review of studies regarding mechanism of action. , 1961, Archives of internal medicine.