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Association between elevated plasma fibrinogen and the small, dense low-density lipoprotein phenotype among postmenopausal women
side effects or serious drug-drug interactions. Finally, although it may be true that phenytoin has a selective effect on raising HDL cholesterol, it is unclear whether, as Dr. Lane suggests, this agent should be used in the control arm in future, prospective, randomized, controlled trials. The use of 2 active treatments (phenytoin vs a different lipid-altering agent) would make it difficult to interpret the results of any such study without a true placebo group, unless phenytoin were administered to both groups and the test agent to 1 group alone. William E. Boden,
MD
Syracuse, New York Thomas A. Pearson,
MD, PhD, MPH
Rochester, New York 27 April 2000 1. Miller M, Burgan RG, Osterlund L, Segrest JP, Garber DW. A prospective, randomized trial of phenytoin in nonepileptic subjects with reduced HDL cholesterol. Arterioscler Thromb Vasc Biol 1995;15:2151–2156. 2. Pita-Calandre E, Rodriguez-Lopez CM, Cano MD, Pena-Bernal M. Serum lipids, lipoproteins, and apolipoproteins in adult epileptics treated with carbamazepine, valproic acid, or phenytoin. Rev Neurol 1998;27:785–789 (in Spanish). 3. McKenney JM, Petrizzi KS, Briggs GC, Wright JT Jr. The effect of low-dose phenytoin on highdensity lipoprotein cholesterol. Pharmacotherapy 1992;12:183–188. PII S0002-9149(00)01030-4
Association Between Elevated Plasma Fibrinogen and the Small, Dense Low-Density Lipoprotein Phenotype Among Postmenopausal Women
We read with interest the article by Maki et al,1 which describes an
association between hyperfibrinogenemia and low-density lipoprotein (LDL) subclass pattern B (a predominance of small, dense LDL lipoprotein particles) in postmenopausal women. Both characteristics are important risk factors for atherosclerotic disease.2– 4 Until fairly recent evidence from prospective trials, the use of hormone replacement therapy (HRT) in postmenopausal women had long been considered to have a beneficial effect on the lipid profile by increasing high-density lipoprotein (HDL) levels and decreasing LDL levels.5,6 Nevertheless, HRT has also been shown to increase the proportion of atherogenic small LDL particles.7 In a prospective longitudinal study of 17 women with surgically induced menopause, 6 weeks of treatment with HRT was associated with an increase in the proportion of the atherogenic small, dense LDL subfractions (p ⬍0.01) despite a decrease in total cholesterol and an increase in HDL cholesterol. Fibrates can actually lead to an increase in LDL particle size, which may be less atherogenic, and there is some evidence that these drugs can reduce cardiovascular events. Indeed, the observation of hyperfibrinogenemia and the predominance of small, dense LDL lipoprotein particles in postmenopausal women has potential implications for the management of cardiovascular risk in this population. In particular, caution should be exercised when starting HRT, because LDL subfractions
126 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 86
JULY 1, 2000
are not routinely measured in clinical practice. The reduction in total cholesterol:HDL ratio with HRT use may give physicians a false reassurance so that they think they may be “doing good” and reducing cardiovascular risk. PII S0002-9149(00)00997-8
Eiry Edmunds, Martin Landray, Gregory Y.H. Lip,
MD MD MD
Birmingham, England 20 April 2000 1. Maki KC, Davidson MH, Marx P, Cyrowski MS, Maki A. Association between elevated plasma fibrinogen and the small, dense low-density lipoprotein phenotype among postmenopausal women. Am J Cardiol 2000;85:451– 456. 2. Rajman I, Kendall MJ, Cramb R, Holder RL, Salih M, Gammage MD. Investigation of low density lipoprotein subfractions as a coronary risk factor in normotriglyceridaemic men. Atherosclerosis 1996;125:231–242. 3. Landray MJ, Sagar G, Muskin J, Murray S, Holder RL, Lip GY. Association of low-density lipoprotein subfractions with carotid atherosclerosis. QJM 1998;91:345–351. 4. Lip GYH. Fibrinogen and cardiovascular disorders. QJM 1995;88:155–165. 5. Lip GYH, Blann AD, Jones AF, Beevers DG. Effects of hormone-replacement therapy on heamostatic factors, lipid factors and endothelial function in women undergoing surgical menopause: implications for prevention of atherosclerosis. Am Heart J 1997;134:764 –771. 6. The Writing Group for the PEPI trial. Effect of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions trial. JAMA 1995;273:199 –208. 7. Rajman I, Lip GYH, Cramb R, Maxwell SR, Zarifis J, Beevers DG, Kendall MJ. Adverse change in low-density lipoprotein subfractions profile with estrogen-only hormone replacement therapy. QJM 1996;89:771–778. 8. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999;341:410 – 418.
MD
Syracuse, New York Thomas A. Pearson,
MD, PhD, MPH
Rochester, New York 27 April 2000 1. Miller M, Burgan RG, Osterlund L, Segrest JP, Garber DW. A prospective, randomized trial of phenytoin in nonepileptic subjects with reduced HDL cholesterol. Arterioscler Thromb Vasc Biol 1995;15:2151–2156. 2. Pita-Calandre E, Rodriguez-Lopez CM, Cano MD, Pena-Bernal M. Serum lipids, lipoproteins, and apolipoproteins in adult epileptics treated with carbamazepine, valproic acid, or phenytoin. Rev Neurol 1998;27:785–789 (in Spanish). 3. McKenney JM, Petrizzi KS, Briggs GC, Wright JT Jr. The effect of low-dose phenytoin on highdensity lipoprotein cholesterol. Pharmacotherapy 1992;12:183–188. PII S0002-9149(00)01030-4
Association Between Elevated Plasma Fibrinogen and the Small, Dense Low-Density Lipoprotein Phenotype Among Postmenopausal Women
We read with interest the article by Maki et al,1 which describes an
association between hyperfibrinogenemia and low-density lipoprotein (LDL) subclass pattern B (a predominance of small, dense LDL lipoprotein particles) in postmenopausal women. Both characteristics are important risk factors for atherosclerotic disease.2– 4 Until fairly recent evidence from prospective trials, the use of hormone replacement therapy (HRT) in postmenopausal women had long been considered to have a beneficial effect on the lipid profile by increasing high-density lipoprotein (HDL) levels and decreasing LDL levels.5,6 Nevertheless, HRT has also been shown to increase the proportion of atherogenic small LDL particles.7 In a prospective longitudinal study of 17 women with surgically induced menopause, 6 weeks of treatment with HRT was associated with an increase in the proportion of the atherogenic small, dense LDL subfractions (p ⬍0.01) despite a decrease in total cholesterol and an increase in HDL cholesterol. Fibrates can actually lead to an increase in LDL particle size, which may be less atherogenic, and there is some evidence that these drugs can reduce cardiovascular events. Indeed, the observation of hyperfibrinogenemia and the predominance of small, dense LDL lipoprotein particles in postmenopausal women has potential implications for the management of cardiovascular risk in this population. In particular, caution should be exercised when starting HRT, because LDL subfractions
126 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 86
JULY 1, 2000
are not routinely measured in clinical practice. The reduction in total cholesterol:HDL ratio with HRT use may give physicians a false reassurance so that they think they may be “doing good” and reducing cardiovascular risk. PII S0002-9149(00)00997-8
Eiry Edmunds, Martin Landray, Gregory Y.H. Lip,
MD MD MD
Birmingham, England 20 April 2000 1. Maki KC, Davidson MH, Marx P, Cyrowski MS, Maki A. Association between elevated plasma fibrinogen and the small, dense low-density lipoprotein phenotype among postmenopausal women. Am J Cardiol 2000;85:451– 456. 2. Rajman I, Kendall MJ, Cramb R, Holder RL, Salih M, Gammage MD. Investigation of low density lipoprotein subfractions as a coronary risk factor in normotriglyceridaemic men. Atherosclerosis 1996;125:231–242. 3. Landray MJ, Sagar G, Muskin J, Murray S, Holder RL, Lip GY. Association of low-density lipoprotein subfractions with carotid atherosclerosis. QJM 1998;91:345–351. 4. Lip GYH. Fibrinogen and cardiovascular disorders. QJM 1995;88:155–165. 5. Lip GYH, Blann AD, Jones AF, Beevers DG. Effects of hormone-replacement therapy on heamostatic factors, lipid factors and endothelial function in women undergoing surgical menopause: implications for prevention of atherosclerosis. Am Heart J 1997;134:764 –771. 6. The Writing Group for the PEPI trial. Effect of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions trial. JAMA 1995;273:199 –208. 7. Rajman I, Lip GYH, Cramb R, Maxwell SR, Zarifis J, Beevers DG, Kendall MJ. Adverse change in low-density lipoprotein subfractions profile with estrogen-only hormone replacement therapy. QJM 1996;89:771–778. 8. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999;341:410 – 418.