- Email: [email protected]
Plasma Lipids-Lipoproteins in Coronary Artery Disease
with activity, or disease in the locomotor systenrie; quires individual assessment and tailored activity. Asymptomatic patients over 50 who are moderate or heavy smokers also fall into this category. ( 5) Patients with established defects in oxygen transport who wish to improve their effort tolerance (with or without supervision) require graded, progressive exercise testing, particularly if they wish to extend their activities to a level which may be potentially harmful. This type of test permits a precise exercise prescription, which justllles its costs. ( 6) Rehabilitation programs appear to be a desirable extension of our current management of many disease states. Those that care for patients with advanced disease should have advanced exercise testing capability. An increasing number of patients will be seeking advice in this area. Their approach to exercise (and ours) needs to be liberally spiced with common sense if they are to enjoy exercise and obtain whatever other benefits await them. Richard L. Hughes, M.D., F.C.C.P. Chicago Norman L. Jones, M.D. Hamilton, Ontario fu:FERENCES 1 Rechnitzer PA, Sangal S, Cunningham DA, et al: A controlled prospective study of the effect of endurance training on the recurrence rate of myocardial infarction. Am J Epidemiol 1975; 102:358-65 2 Oldridge NB: Med Sci Sports 1979; 11:313-15 3 Pickering TG: Jogging, marathon running and the heart. Am J Med 1979; 66:717-19 4 Darling RC: The significance of physical fitness. Arch Phys Med Rehabil 1946; 28:140-5 5 Opie LH: Sudden and sport. Lancet 1975; 1:263-6 6 RaskoJf WJ, Goldman S, Cohn K: The "athletic heart." JAMA 1976; 236:158-62 7 Wasserman K, Whipp BJ. Exercise physiology in health and disease. Am Rev Respir Dis 1975; 112:219-49 8 Bleigh HL, Boro ES: Fuel homeostasis in exercise. N Engl J Med 1975; 21:1078-84 9 Jones NL: Hydrogen ion balance in exercise. Clin Sci, in press 10 Auchincloss JH, Ashutosh K, Rana S, Peppi D, Johnson LW, Gilbert R: Effect of cardiac, pulmonary, and vascular disease on one-minute oxygen uptake. Chest 1976; 70:486-93 11 Young Ill, Woolcock AJ: Arterial blood gas tension changes at the start of exercise in chronic obstructive pulmonary disease. Am Rev Respir Dis 1979; 119:213-21
Plasma Lipids-Lipoproteins in Coronary Artery Disease Regulation and Control plasma lipids, especially cholesterol and triglycerides, have long been implicated in the pathoCHEST, 78: 5, NOVEMBER, 1980
genesis· of. c9ronary artery disease (CAD). 1-1 In oivo, the water-insoluble cholesterol and other lipids are complexed with proteins ( apoproteins) into lipoproteins for transportation and metabolism.8·' Five main types of lipoproteins have been classifled according to their size and density. These are the exogenous and endogenous triglyceride transporting chylomicrons and very low density lipoproteins (VLDL); the VLDL remnants-the intermediate density lipoproteins ( ILDL); the major cholesterol transporting low density lipoproteins ( LDL); and the postulated tissue-cholesterol-removing high density lipoproteins (HDL). Most of the epidemiologic, experimental, clinical, and genetic studies have emphasized the role of elevated levels of LDL or the cholesterol carried in this lipoprotein fraction ( LDL-C) in atherogenesis. In general, a relatively large amount of cholesterol in the LDL fraction is regarded as atherogenic, whereas that in the LDL of familial hypercholesterolemia or "familial" type 2 disease appears to be causally related to premature CAD. 11.s-10 Diagnostic criteria proposed by Fredrickson et al11 for type 2 disease include the following: (1) elevated LDL; ( 2) type 2 in a 6rst-degree relative; or ( 3) tendinous xanthomata. Furthermore, these patients do not exhibit a signiflcant lowering of their LDL-C values with a standardized low cholesterolsaturated fat diet. 12 More recently, dysfunction( s) of speciflc LDL cellular receptors has been reported by Brown and Goldstein18 in familial type 2 patients. In view of the accelerated atherosclerosis in such patients with well-deflned metabolic abnormality, most would agree that familial type 2 patients with CAD could be utilized to determine whether reduction in plasma LDL-C level by means of an effective therapeutic program could actually retard the progression or even induce regression of CAD to improve angina pectoris, prevent myocardial infarction, and reduce deaths from CAD. Recently, an ever-increasing interest has focused on HDL. Barr et al1' made the early observation that the plasma alpha-lipoproteins ( HDL) levels of postmyocardial infarction patients are lower than those of healthy persons. This early observation is supported by the following: ( 1) epidemiologic studies which indicate that high HDL concentration constitutes an independent negative risk factor for CAD; 1 ~ 1 7 (2) clinical correlation study shows that normolipemic CAD patients frequently manifest depressed HDL; 18 and (3) families with high HDL levels have increased longevity. 111 Some experimental data suggest that HDL may function to facilitate removal of cholesterol from the tissues perEDITORIALS 879
haps including that from the athermatous lesion of the vessel wall. 20•21 These observations made on LDL and HDL indicate that intracellular cholesterol can be regulated by devising an intervention program which is capable of accomplishing a substantial reduction in the atherogenic LDL and VLDL fractions. A program which would reduce LDL and VLDL towards normal and would concomitantly increase the antiatherosclerotic HDL fraction will be highly desirable. Amelioration of Atherosclerosis
A number of experimentally induced atherosclerotic lesions in nonhuman primates have been found to regress following the removal of the atherogenic stimulus ( hypercholesterolemia), with rather drastic lowering of serum cholesterol levels.21..u Assuming that these animal studies could be extrapolated to human beings whose atherosclerosis has developed over the lifetime of the individual, the questions to be raised are: ( 1) Is the extent and the composition of the chronic lesion amenable to regression? ( 2) Could a substantial reduction in plasma cholesterol ( LDL-C) concentration and increment in HDL level be achieved and maintained in man with current diet-drug therapy? Despite the aforementioned reservations, a number of investigators have designed studies to determine whether there is evidence for atherosclerosis regression in man. Buchwald and associates211 have reported that ileal bypass operation can achieve substantial lowering of plasma cholesterol in hyperlipidemic patients to either reduce the rate of progression or to induce regression of angiographically documented CAD in 77 percent of 22 patients. Brandt et al28 have employed a precise and reproducible angiographic technique to show a positive correlation between regression of early femoral lesion and significant reduction in plasma LDL and VLDL concentration. Kuo and associates27 report that progression of angiographically documented CAD can be arrested for several years in a series of type 2 patients when their plasma cholesterol or LDL-C and their serum triglyceride-VLDL levels could be substantially reduced and maintained at low levels by combined low cholesterol-low saturated fat-low simple carbohydrate diet and bile acid sequestrating resin-colestipol therapy. Nikkila and associates21 also found that progression of CAD in patients with type 2 disease is reduced more dramatically in those who show the greatest amount of serum cholesterol lowering. Thus, evidence is acCumulating to suggest that in most cases, human CAD is potentially regressible or
am
EDITORIALS
stabilizable, if plasma cholesterol and LDL-choles· terol concentrations are vigorously reduced to more "ideal" levels-<220 mg/dl and <150 mg/dl, respectively. Since plasma triglyceride or VLDL levels are also involved in lipoprotein metabolism and implicated in CAD,2 simultaneous suppression of hypertriglyceridemia has been shown to contribute toward regression of early femoral arterial lesion. 28 Other Effects of Lipid-Lipoproteins on Atherosclerosis and its Complications
The diet-colestipol treatment has no effect upon HDL-cholesterol ( HDL-C) concentration of type 2 patients. 27 Although there is no absolute increase in HDL, the HDL-C/LDL-C ratio is increased as the result of LDL-C reduction. Thus, the possibility that a relative HDL increase may also contribute to the observed beneficial clinical response cannot be ruled out. Several investigators and ourselves29•30 have used nicotinic acid to enhance the hypolipemic effect of diet-resin therapy. Besides its hypolipemic effect, nicotinic acid in pharmacologic doses of 3 to 6 g per day has been shown to increase HDL-C and to alter the major apoprotein composition of HDL. The drug raises Apo A-I while it lowers Apo A-II content of HDL. Shepherd and his associates31 postulated that such changes induced by nicotinic acid in lipoprotein metabolism has prophylactic value for prevention of CAD. The complex relationships of platelets and cholesterol to atherosclerosis have been investigated in patients with familial type 2 disease. These studies have demonstrated that platelets from type 2 persons show increased sensitivity to epinephrine, ADP, and collagen, accompanied by several fold increases in nucleotide release. 32 In composition, these hypersensitive platelets from type 2 patients are found to exhibit elevated free cholesterol content and a C/P ratio 8 percent greater than platelets from normolipemic subjects. 33•34 Further elucidation of lipidinduced abnormal platelet activity to enhance thrombotic complications and premature CAD in type 2 disease may provide an insight on the lipidsplatelet interaction in the progression of arterial disease and the development of acute vascular complications. Indeed, Bizios et al36 and Tremoli et al38 have reported that patients with familial type 2 hyperlipoproteinemia may manifest an increased production of platelet thromboxane &, a potent proaggregatory and vasoconstricting agent. Peter T. Kuo, M.D., F.C.C.P. Piscataway, NJ
CHEST, 78: 5, NOVEMBER, 1980
Division of Cardiovascu1ar Diseases, Department of Medicine, College of Medicine and Dentistry of New Jersey, Rutgers MeClical School ·. Supported in part by research grants from the Leola.~. wiler Research and Tea~ Fund, the American Heart Association, New Jersey AfBliate, and Somerset County Heart Association. Reprint requesta: Dr. Kuo, DBTJattment of Medicine, Rutgers MedictJl School, Piscataway, New Jersey 08854 REFEllENCF.S
1 Kannel WB, Castelli WP, Gordon T, McNamara PM. Serum cholesterol, lipoproteins and risk of coronary heart disease: the Framingham study. Ann Intern Med 1971; 74:1 2 Carlson LA, Bottiger LW. Ischemic heart-disease in relation to fasting values of plasma triglycerides and cholesterol Lancet 1972; 1:865 3 Albrink MJ, Meigs JW, Man EB. Serum lipids, hypertension and coronary artery disease. Am J Med 1961; 31 :4 4 Brown DF, Kingh SH, Doyle JT. Serum triglycerides in health and in ischemic heart disease. N Engl J Med 1965; 273:947 5 Goldstein JL, Hazzard WR, Schrott HG, et al. Hyperlipidemia in coronary heart disease: I. Lipid levels in 500 survivors of myocardial infarction; II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia; and m. Evaluation of lipoprotein phenotypes of 156 genetically deflned survivors of myocardial infarction. J Clin Invest 1973; 52:1533-1577 6 Gofman JW, Young W, Tandy R. Ischemic heart disease, atherosclerosis and longevity. Circulation 1966; 34:679 7 Fredrickson DS, LeVY RI, Lees RS. Fat transport in lipoproteins-an integrated approach to mechanisms and disorders. N Engl J Med 1967; 276:34, 94, 148, 215, 273 8 Slack J. Risks of ischemic heart-disease in familial hyperlipoproteinemic states. Lancet 1969; 2:1380 9 Jensen J, Blankenhorn D. The inheritance of familial hypercholesterolemia. Am J Med 1972; 52:499 10 Stone NJ, LeVY RI, Fredrickson DS, Verter J. Coronary artery disease in 116 kindred with familial type II hyperlipoproteinemia. Circulation 1974; 49:476 11 Fredrickson DS, Goldstein JL, Brown MS. The familial hyperlipoproteinemias. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, eds. The metabolic basis of inherited diseases. Ed 4. New York: McGraw Hill, 1978:604-655 12 American Heart Association. Planning fat-controlled meals for approximately 2000-2600 calories. New York, American Heart Association Inc, 1967 13 Brown MS, Goldstein JL. Familial hypercholesterolemia: a genetic defect in the low-density lipoprotein receptor. N Engl J Med 1976; 294:1386 14 Barr DP, Russ EM, Eder HA. Protein lipid relationships in human plasma: II. In atherosclerosis and related conditions. AmJ Med 1951; 11:480 15 RhoadS G, Gulbrandsen CL, Kagan A. Serum lipoproteins and coronary heart disease in a population study of Hawaii Japanese men. N Engl J Med 1976; 294:293 16 Castelli W, Doyle JT, Gordon T, et al. HDL cholesterol and other lipids in coronary heart disease, the cooperative lipoprotein phenotyping study. Circulation 1977; 55:767 17 Miller NE, Thelle DS, Forde OH, Mjos OD. The Troms0
CHEST, 78: 5, NOVEMBER, 1980
18 19 20
21 22 23 24
25
heart-study, high-density lipoprotein and coronary heart disease:a prospective case-control study. Lancet 1977; 1:965 Miller 'cJ, Miller NE. Plasma-higb-density-lipoprotein concentration and development of ischemic heart-disease. Lancet 1975; 1: 16 Glueck CJ, Fallat RW, Millett F, et al. Faniilial hyperalpha-lipoproteinemia: studies in 18 kindreds. Metabolism 1975; 24:1243 Carew TE, Hayes SB, Koschinsky T, Steinberg D. A mechanism by which high-density lipoproteins may slow the atherogenic process. Lancet 1976; 1: 1315 Glomset JA. The plasma lecithin: cholesterol acyltransferase reaction. J Lipid Res 1968; 9: 155 Armstrong ML, Warner ED, Connor WE. Regression of coronary atheromatosis in Rhesus monkeys. Circ Res 1970;27:59 Vesselinovitch D, Wissler RW, Hughes R, et al. Reversal of advanced atherosclerosis in Rhesus monkeys: 1. Lightmicroscopic studies. Atherosclerosis 1976; 23: 155 Wissler RW, Visselinovitch D, Borensztajn et aL Regression of severe atherosclerosis in cholestyramine-treated Rhesus monkeys, with or without a low-fat, low-cholesterol diet. Circulation 1975; 52:11-16 Buchwald H, Moore RB, Varco RL. The partial ileal bypass operation in treatment of the hyperlipidemias. In: Lipids, lipoproteins and drugs. Kritchevsky D, Paoletti R, Homes WL, eds. New York: Plenum Press, 1975; 221230
26 Brandt R Jr, Blankenhom DH, Crawford DW, Brooks SH. Regression and progression of early femoral atherosclerosis in treated hyperlipoproteinemic patients. Ann Intern Med 1977; 86:139 27 Kuo PT, Hayase K, Kostis JB, Moreyra AK. Use of combined diet and colestipol in longterm ( 7-71' years) treatment of patients with type II hyperlipoproteinemia. Circulation 1979; 59:199 28 Nikklli:i EA, Viikinkoski Valle M. Effect of lipid lowering treatment on progression of coronary atherosclerosis assessed by angiography. Circulation 1978; 57:11-188 29 Kane JP, Tun P, Mallory NJ, Havel RJ. Heterozygous familial hypercholesterolemia: treatment with combined drug regimens. Clin Res 1978; 26:529A 30 Kuo PT, Kostis JB, Moreyra AE, Hayes JA. Effective control of familial hypercholesterolemia with diet and bile acid sequestrant plus nicotinic acid. Clin Res 1979; 27: 552.A 31 Shepherd J, Packard CJ, Patsch JF, et al. Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism. J Clin Invest 1979; 63:858 32 Carvalho ACA, Colman RW, Lees RS. Platelet function in hyperlipoproteinemia. N Engl J Med 1974; 290:434 33 Shattil SJ, Anaya-Galindo R, Bennett JS, et al. Platelet hypersensitivity induced by cholesterol incorporation. J Clin Invest 1975; 55:636 34 Bennett JS, Shattil SJ, Cooper RA, et al. Platelet hypersensitivity in familial hyperbetalipoproteinemia: the role of platelet lipid composition. J Hematol 1974; 44:918 35 Bizios R, Wong LK, Vaillancourt R, et al. Platelet prostaglandin endoperoxide formation in hyperlipidemias. Thromb Haemost 1977; 38:228 36 Tremoli E, Folco G, Agradi E, Galli C. Platelet thromboxanes and serum-cholesterol. Lancet 1979; 1: 107
EDITORIALS 881
Plasma Lipids-Lipoproteins in Coronary Artery Disease Regulation and Control plasma lipids, especially cholesterol and triglycerides, have long been implicated in the pathoCHEST, 78: 5, NOVEMBER, 1980
genesis· of. c9ronary artery disease (CAD). 1-1 In oivo, the water-insoluble cholesterol and other lipids are complexed with proteins ( apoproteins) into lipoproteins for transportation and metabolism.8·' Five main types of lipoproteins have been classifled according to their size and density. These are the exogenous and endogenous triglyceride transporting chylomicrons and very low density lipoproteins (VLDL); the VLDL remnants-the intermediate density lipoproteins ( ILDL); the major cholesterol transporting low density lipoproteins ( LDL); and the postulated tissue-cholesterol-removing high density lipoproteins (HDL). Most of the epidemiologic, experimental, clinical, and genetic studies have emphasized the role of elevated levels of LDL or the cholesterol carried in this lipoprotein fraction ( LDL-C) in atherogenesis. In general, a relatively large amount of cholesterol in the LDL fraction is regarded as atherogenic, whereas that in the LDL of familial hypercholesterolemia or "familial" type 2 disease appears to be causally related to premature CAD. 11.s-10 Diagnostic criteria proposed by Fredrickson et al11 for type 2 disease include the following: (1) elevated LDL; ( 2) type 2 in a 6rst-degree relative; or ( 3) tendinous xanthomata. Furthermore, these patients do not exhibit a signiflcant lowering of their LDL-C values with a standardized low cholesterolsaturated fat diet. 12 More recently, dysfunction( s) of speciflc LDL cellular receptors has been reported by Brown and Goldstein18 in familial type 2 patients. In view of the accelerated atherosclerosis in such patients with well-deflned metabolic abnormality, most would agree that familial type 2 patients with CAD could be utilized to determine whether reduction in plasma LDL-C level by means of an effective therapeutic program could actually retard the progression or even induce regression of CAD to improve angina pectoris, prevent myocardial infarction, and reduce deaths from CAD. Recently, an ever-increasing interest has focused on HDL. Barr et al1' made the early observation that the plasma alpha-lipoproteins ( HDL) levels of postmyocardial infarction patients are lower than those of healthy persons. This early observation is supported by the following: ( 1) epidemiologic studies which indicate that high HDL concentration constitutes an independent negative risk factor for CAD; 1 ~ 1 7 (2) clinical correlation study shows that normolipemic CAD patients frequently manifest depressed HDL; 18 and (3) families with high HDL levels have increased longevity. 111 Some experimental data suggest that HDL may function to facilitate removal of cholesterol from the tissues perEDITORIALS 879
haps including that from the athermatous lesion of the vessel wall. 20•21 These observations made on LDL and HDL indicate that intracellular cholesterol can be regulated by devising an intervention program which is capable of accomplishing a substantial reduction in the atherogenic LDL and VLDL fractions. A program which would reduce LDL and VLDL towards normal and would concomitantly increase the antiatherosclerotic HDL fraction will be highly desirable. Amelioration of Atherosclerosis
A number of experimentally induced atherosclerotic lesions in nonhuman primates have been found to regress following the removal of the atherogenic stimulus ( hypercholesterolemia), with rather drastic lowering of serum cholesterol levels.21..u Assuming that these animal studies could be extrapolated to human beings whose atherosclerosis has developed over the lifetime of the individual, the questions to be raised are: ( 1) Is the extent and the composition of the chronic lesion amenable to regression? ( 2) Could a substantial reduction in plasma cholesterol ( LDL-C) concentration and increment in HDL level be achieved and maintained in man with current diet-drug therapy? Despite the aforementioned reservations, a number of investigators have designed studies to determine whether there is evidence for atherosclerosis regression in man. Buchwald and associates211 have reported that ileal bypass operation can achieve substantial lowering of plasma cholesterol in hyperlipidemic patients to either reduce the rate of progression or to induce regression of angiographically documented CAD in 77 percent of 22 patients. Brandt et al28 have employed a precise and reproducible angiographic technique to show a positive correlation between regression of early femoral lesion and significant reduction in plasma LDL and VLDL concentration. Kuo and associates27 report that progression of angiographically documented CAD can be arrested for several years in a series of type 2 patients when their plasma cholesterol or LDL-C and their serum triglyceride-VLDL levels could be substantially reduced and maintained at low levels by combined low cholesterol-low saturated fat-low simple carbohydrate diet and bile acid sequestrating resin-colestipol therapy. Nikkila and associates21 also found that progression of CAD in patients with type 2 disease is reduced more dramatically in those who show the greatest amount of serum cholesterol lowering. Thus, evidence is acCumulating to suggest that in most cases, human CAD is potentially regressible or
am
EDITORIALS
stabilizable, if plasma cholesterol and LDL-choles· terol concentrations are vigorously reduced to more "ideal" levels-<220 mg/dl and <150 mg/dl, respectively. Since plasma triglyceride or VLDL levels are also involved in lipoprotein metabolism and implicated in CAD,2 simultaneous suppression of hypertriglyceridemia has been shown to contribute toward regression of early femoral arterial lesion. 28 Other Effects of Lipid-Lipoproteins on Atherosclerosis and its Complications
The diet-colestipol treatment has no effect upon HDL-cholesterol ( HDL-C) concentration of type 2 patients. 27 Although there is no absolute increase in HDL, the HDL-C/LDL-C ratio is increased as the result of LDL-C reduction. Thus, the possibility that a relative HDL increase may also contribute to the observed beneficial clinical response cannot be ruled out. Several investigators and ourselves29•30 have used nicotinic acid to enhance the hypolipemic effect of diet-resin therapy. Besides its hypolipemic effect, nicotinic acid in pharmacologic doses of 3 to 6 g per day has been shown to increase HDL-C and to alter the major apoprotein composition of HDL. The drug raises Apo A-I while it lowers Apo A-II content of HDL. Shepherd and his associates31 postulated that such changes induced by nicotinic acid in lipoprotein metabolism has prophylactic value for prevention of CAD. The complex relationships of platelets and cholesterol to atherosclerosis have been investigated in patients with familial type 2 disease. These studies have demonstrated that platelets from type 2 persons show increased sensitivity to epinephrine, ADP, and collagen, accompanied by several fold increases in nucleotide release. 32 In composition, these hypersensitive platelets from type 2 patients are found to exhibit elevated free cholesterol content and a C/P ratio 8 percent greater than platelets from normolipemic subjects. 33•34 Further elucidation of lipidinduced abnormal platelet activity to enhance thrombotic complications and premature CAD in type 2 disease may provide an insight on the lipidsplatelet interaction in the progression of arterial disease and the development of acute vascular complications. Indeed, Bizios et al36 and Tremoli et al38 have reported that patients with familial type 2 hyperlipoproteinemia may manifest an increased production of platelet thromboxane &, a potent proaggregatory and vasoconstricting agent. Peter T. Kuo, M.D., F.C.C.P. Piscataway, NJ
CHEST, 78: 5, NOVEMBER, 1980
Division of Cardiovascu1ar Diseases, Department of Medicine, College of Medicine and Dentistry of New Jersey, Rutgers MeClical School ·. Supported in part by research grants from the Leola.~. wiler Research and Tea~ Fund, the American Heart Association, New Jersey AfBliate, and Somerset County Heart Association. Reprint requesta: Dr. Kuo, DBTJattment of Medicine, Rutgers MedictJl School, Piscataway, New Jersey 08854 REFEllENCF.S
1 Kannel WB, Castelli WP, Gordon T, McNamara PM. Serum cholesterol, lipoproteins and risk of coronary heart disease: the Framingham study. Ann Intern Med 1971; 74:1 2 Carlson LA, Bottiger LW. Ischemic heart-disease in relation to fasting values of plasma triglycerides and cholesterol Lancet 1972; 1:865 3 Albrink MJ, Meigs JW, Man EB. Serum lipids, hypertension and coronary artery disease. Am J Med 1961; 31 :4 4 Brown DF, Kingh SH, Doyle JT. Serum triglycerides in health and in ischemic heart disease. N Engl J Med 1965; 273:947 5 Goldstein JL, Hazzard WR, Schrott HG, et al. Hyperlipidemia in coronary heart disease: I. Lipid levels in 500 survivors of myocardial infarction; II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia; and m. Evaluation of lipoprotein phenotypes of 156 genetically deflned survivors of myocardial infarction. J Clin Invest 1973; 52:1533-1577 6 Gofman JW, Young W, Tandy R. Ischemic heart disease, atherosclerosis and longevity. Circulation 1966; 34:679 7 Fredrickson DS, LeVY RI, Lees RS. Fat transport in lipoproteins-an integrated approach to mechanisms and disorders. N Engl J Med 1967; 276:34, 94, 148, 215, 273 8 Slack J. Risks of ischemic heart-disease in familial hyperlipoproteinemic states. Lancet 1969; 2:1380 9 Jensen J, Blankenhorn D. The inheritance of familial hypercholesterolemia. Am J Med 1972; 52:499 10 Stone NJ, LeVY RI, Fredrickson DS, Verter J. Coronary artery disease in 116 kindred with familial type II hyperlipoproteinemia. Circulation 1974; 49:476 11 Fredrickson DS, Goldstein JL, Brown MS. The familial hyperlipoproteinemias. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, eds. The metabolic basis of inherited diseases. Ed 4. New York: McGraw Hill, 1978:604-655 12 American Heart Association. Planning fat-controlled meals for approximately 2000-2600 calories. New York, American Heart Association Inc, 1967 13 Brown MS, Goldstein JL. Familial hypercholesterolemia: a genetic defect in the low-density lipoprotein receptor. N Engl J Med 1976; 294:1386 14 Barr DP, Russ EM, Eder HA. Protein lipid relationships in human plasma: II. In atherosclerosis and related conditions. AmJ Med 1951; 11:480 15 RhoadS G, Gulbrandsen CL, Kagan A. Serum lipoproteins and coronary heart disease in a population study of Hawaii Japanese men. N Engl J Med 1976; 294:293 16 Castelli W, Doyle JT, Gordon T, et al. HDL cholesterol and other lipids in coronary heart disease, the cooperative lipoprotein phenotyping study. Circulation 1977; 55:767 17 Miller NE, Thelle DS, Forde OH, Mjos OD. The Troms0
CHEST, 78: 5, NOVEMBER, 1980
18 19 20
21 22 23 24
25
heart-study, high-density lipoprotein and coronary heart disease:a prospective case-control study. Lancet 1977; 1:965 Miller 'cJ, Miller NE. Plasma-higb-density-lipoprotein concentration and development of ischemic heart-disease. Lancet 1975; 1: 16 Glueck CJ, Fallat RW, Millett F, et al. Faniilial hyperalpha-lipoproteinemia: studies in 18 kindreds. Metabolism 1975; 24:1243 Carew TE, Hayes SB, Koschinsky T, Steinberg D. A mechanism by which high-density lipoproteins may slow the atherogenic process. Lancet 1976; 1: 1315 Glomset JA. The plasma lecithin: cholesterol acyltransferase reaction. J Lipid Res 1968; 9: 155 Armstrong ML, Warner ED, Connor WE. Regression of coronary atheromatosis in Rhesus monkeys. Circ Res 1970;27:59 Vesselinovitch D, Wissler RW, Hughes R, et al. Reversal of advanced atherosclerosis in Rhesus monkeys: 1. Lightmicroscopic studies. Atherosclerosis 1976; 23: 155 Wissler RW, Visselinovitch D, Borensztajn et aL Regression of severe atherosclerosis in cholestyramine-treated Rhesus monkeys, with or without a low-fat, low-cholesterol diet. Circulation 1975; 52:11-16 Buchwald H, Moore RB, Varco RL. The partial ileal bypass operation in treatment of the hyperlipidemias. In: Lipids, lipoproteins and drugs. Kritchevsky D, Paoletti R, Homes WL, eds. New York: Plenum Press, 1975; 221230
26 Brandt R Jr, Blankenhom DH, Crawford DW, Brooks SH. Regression and progression of early femoral atherosclerosis in treated hyperlipoproteinemic patients. Ann Intern Med 1977; 86:139 27 Kuo PT, Hayase K, Kostis JB, Moreyra AK. Use of combined diet and colestipol in longterm ( 7-71' years) treatment of patients with type II hyperlipoproteinemia. Circulation 1979; 59:199 28 Nikklli:i EA, Viikinkoski Valle M. Effect of lipid lowering treatment on progression of coronary atherosclerosis assessed by angiography. Circulation 1978; 57:11-188 29 Kane JP, Tun P, Mallory NJ, Havel RJ. Heterozygous familial hypercholesterolemia: treatment with combined drug regimens. Clin Res 1978; 26:529A 30 Kuo PT, Kostis JB, Moreyra AE, Hayes JA. Effective control of familial hypercholesterolemia with diet and bile acid sequestrant plus nicotinic acid. Clin Res 1979; 27: 552.A 31 Shepherd J, Packard CJ, Patsch JF, et al. Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism. J Clin Invest 1979; 63:858 32 Carvalho ACA, Colman RW, Lees RS. Platelet function in hyperlipoproteinemia. N Engl J Med 1974; 290:434 33 Shattil SJ, Anaya-Galindo R, Bennett JS, et al. Platelet hypersensitivity induced by cholesterol incorporation. J Clin Invest 1975; 55:636 34 Bennett JS, Shattil SJ, Cooper RA, et al. Platelet hypersensitivity in familial hyperbetalipoproteinemia: the role of platelet lipid composition. J Hematol 1974; 44:918 35 Bizios R, Wong LK, Vaillancourt R, et al. Platelet prostaglandin endoperoxide formation in hyperlipidemias. Thromb Haemost 1977; 38:228 36 Tremoli E, Folco G, Agradi E, Galli C. Platelet thromboxanes and serum-cholesterol. Lancet 1979; 1: 107
EDITORIALS 881