Abstract
The role of hypertriglyceridemia in the causation of coronary heart disease (CHD) is a subject of continuing controversy. Sonne investigatory hold that hypertriglyceridemia constitutes a major risk factor for CHD, but others claim the opposite, namely, that elevated triglyceride levels are of little significance for CHD risk* The very fact that so many experienced investigators hold such divergent views attests to the complexity of the issue. The crux of the problem appears to be that a high proportion of patients with CHD have hypertriglyceridemia, and yet high triglycerides per se are not a major causative factor; instead, elevated plasma triglycerides frequently appear to be associated with other atherogenic factors that have not been fully defined. This paper will examine the complexity of the hypertriglyceridemic state, and it will consider the following questions: (a) what are the basic pathways of triglyceride metabolism in humans? (b) what are the causes of hypertriglyceridemia? (c) what is the relation of hypertriglyceridemia to CHD?, and (d) what constitutes a rational approach to the treatment of hypertriglyceridemia?
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
M.J. Albrink and E.B. Man, Serum lipids, hypertension and coronary artery disease, Am J Med 31:4 (1961).
A.M. Gotto, G.A. Gorry, J.R. Thompson, J.S. Cole, R. Trost, D. Yeshurun and M.E. DeBakey, Relationship between plasma lipid concentrations and coronary artery disease in 496 patients, Circulation 56:875 (1977).
L.A. Carlson, L.E. Bottinger and P-E. Ahfeldt, Risk factors for myocardial infarction in the Stockholm prospective study: A 14-year followup focusing on the role of plasma triglyceride and cholesterol, Acta Med Scand 206:351 (1979).
L.A. Carlson and L.E. Bottinger, Ischemic heart disease in relation to fasting values of plasma triglycerides and cholesterol, Lancet 1:865 (1972).
S, B. Hulley, R.H. Rosenman, R.D. Bawol and R.J. Brand, Epidemiology as a guide to clinical decisions: The association between triglyceride and coronary heart disease, N Eng J Med 302:1383 (1980).
M.S. Brown and J.L. Goldstein, A receptor-mediated pathway for cholesterol homeostasis, Science 232:34 (1986).
R.W. Mahley and T.L. Innerarity, Lipoprotein receptors and cholesterol homeostasis, Biochim Biophys Acta 737:197 (1983).
G.L. Vega, C. East and S.M. Grundy, Lovastatin therapy in familial dysbetalipoproteinemia: Effects on kinetics of apolipoprotein B, Atherosclerosis (in press).
C.J. Packard, A. Munro, A.R. Lorimer, A.M. Gotto Jr. and J. Shepherd, Metabolism of apolipoprotein B in large triglyceriderich VLDL of normal and lipoprotein lipase-deficient humans, J Clin Invest 74:2178 (1984).
A.F.H. Stalenhoef, J.J. Malloy, J.P. Kane and R.J. Havel, Metabolism of apolipoprotein B-48 and B-100 of triglyceride-rich lipoproteins in normal and lipoprotein lipase-deficient humans, Proc Natl Acad Sci USA 81:1839 (1984).
W.F. Beltz, Y.A. Kesaniemi, B.V. Howard and S.M. Grundy, Development of an integrated model for analysis of the kinetics of apolipoprotein B in plasma lipoproteins VLDL, IDL, and LDL, J Clin Invest 76:575 (1985).
Y.A. Kesaniemi, W.F. Beltz and S.M. Grundy, Comparisons of metabolism of apolipoprotein B in normal subjects, obese patients, and patients with coronary heart disease, J Clin Invest 76:586 (1985).
G. Egusa, W.F. Beltz, S.M. Grundy and B.V. Howard, The influence of obesity on the metabolism of apolipoprotein B in man, J Clin Invest 76:596 (1985).
G.L. Vega and S.M. Grundy, Lovastatin therapy in nephrotic hyperlipidemia: Effects on lipoprotein metabolism, Kidney International (in press).
C.L. Malmendier and M. Berman, Endogenously labeled low density lipoprotein triglyceride and apoprotein B kinetics, J Lipid Res 19:978 (1978).
M. Berman, W.F. Beltz, R. Riemke, A. Sedaghat, and S.M. Grundy, HDL triglyceride kinetics and exchanges with VLDL in vivo. in “Lipoprotein Kinetics and Modeling”, M. Berman, S.M. Grundy, and B.V. Howard, eds. Academic Press, New York pp. 299–305 (1982).
S.M. Grundy (chairman), E. Barrett-Connor, E.L. Biemaan, T.B. Clarkson, W.R. Harlan, W.R. Hazzard, D.B. Hunninghake, D.T. Mason, G. O’Keefe, H. Rifkin, A.A. Spector, M. Winston and P.D. Wood, The Consensus Development Conference on the Treatment of Hypertriglyceridemia, National Institutes of Health. Published J Amer Med Assn 215:1196 (1984)
S.M. Grundy (chairman), E. Barrett-Connor, E.L. Biemaan, T.B. Clarkson, W.R. Harlan, W.R. Hazzard, D.B. Hunninghake, D.T. Mason, G. O’Keefe, H. Rifkin, A.A. Spector, M. Winston and P.D. Wood, The Consensus Development Conference on the Treatment of Hypertriglyceridemia, National Institutes of Health. Arteriosclerosis 4:296 (1984).
A. Chait, J.J. Albers and J.D. Brunzell, Very low density lipoprotein overproduction in genetic forms of hypertriglyceridemia, Eur J Clin Invest 10:161 (1980).
J.W. Farquhar, R.D. Gross, R.M. Watner and G.M. Raven, Validation of liver and plasma triglyceride in man, J Lipid Res 6:119 (1965).
G.M. Reaven, D.B. Hill, R.C. Gross and J.W. Farquhar, Kinetics of triglyceride turnover of very low density lipoprotein of human plasma, J Clin Invest 44:1826 (1965).
S.M. Grundy and G.L. Vega, Are plasma triglyceride concentrations explained by saturation kinetics?, in “Lipoprotein Kinetics and Modeling,” M. Berman, S.M. Grundy and B.V. Howard, eds., Academic Press, New York pp. 272–286 (1982).
S.M. Grundy, A. Chait and J.D. Brunzell, Familial combined hyperlipidemia workshop, Arteriosclerosis 7:203 (1987).
E.E. Nikkila and M. Kekki, Polymorphism of plasma triglyceride kinetics in normal human adult subjects, Acta Med Scand 190:49 (1971).
U. Beil, S.B. Grundy, J.R. Crouse and L. Zech, Triglyceride and cholesterol metabolism in primary hypertriglycerides, Arteriosclerosis 2:44 (1982).
Y.A. Kesaniemi and S. M, Grundy, Dual defect in metabolism of very low density lipoprotein triglycerides In patients with type 5 hyperlipoproteinemia, J Amer Med Assn 251:2542 (1984).
F.L. Dunn, P. Raskin, D.W. Bilheimer and S.M. Grundy, The effect of diabetic control on very low-density lipoprotein - T glvceride metabolism in patients with type II diabetes and marked hypertriglyceridemia, Metabolism 33:117 (1984).
J. Melish, N.A. Le, H. Ginsberg, D. Steinberg and W.V. Brown, Dissociation of apoprotein B and triglyceride production in very-low-density lipoproteins, Am J Physiol 239:E354 (1980).
J.R. Crouse and S.M. Grundy, Effects of alcohol on plasma lipoproteins and triglyceride metabolism in man, J Lipid Res 25: 486 (1984).
J.J. Abrams, H. Ginsberg and S.M. Grundy, Metabolism of cholesterol and plasma triglycerides in nonketotic diabetes mellitus, Diabetes 31:903 (1982).
M.R. Taskinen, W.F. Beltz, I. Harper, R.M. Fields, G. Schonfeld, S.M. Grundy and B.V. Howard, Effects of NIDDM on very-lowdensity lipoprotein triglyceride and apolipoprotein B metabolism: Studies before and after sulfurylurea therapy, Diabetes 35:1268 (1986).
M. Sanfelippo, S.M. Grundy and L. Henderson, Transport of very low density lipoprotein triglyceride (VLDL-TG): Comparison of hemodialysis and hemofiltration, Kidney International 16:868 (1979).
S.M. Grundy and H.Y.I. Mok, Chylomicron clearance in normal and hyperlipidemic man, Metabolism 25:1227 (1976).
S. Gianturco, A.M. Gotto Jr., R.L. Jackson, J.R. Patsch, H.D. Sybers, 0. D. Taunton, D.L. Yeshurun and L.C. Smith, Control of 3-hydroxy-3-methylglutaryl-CoA reductase activity in cultured human fibroblasts by very low density lipoproteins of subjects with hypertriglyceridemia, J Clin Invest 61:320 (1978).
S.H. Gianturco, S.G. Eskin, L.T. Navarro, C.J. Lahart, L.C. Smith and A.M. Gotto Jr., Abnormal effects of hypertriglyceridemic very-low-density lipoproteins on 3-hydroxy-3-methy1glutaryl-CoA reductase activity and viability of cultured bovine aortic endothelial cells, Biochim Biophys Acta 618:143 (1980).
J. Shepherd, M.J. Caslake, A.R. Lorimar, B.D. Vallance and C.J. Packard, Fenofibrate reduces low density lipoprotein catabolism in hypertriglyceridemic subjects, Arteriosclerosis 5:162 (1985).
G.L. Vega and S.M. Grundy, Gemfibrozil therapy in primary hypertriglyceridemia associated with coronary heart disease, J Amer Med Assn 253:2398 (1985).
G.L. Vega and S.M. Grundy, Kinetic heterogeneity of low density lipoproteins in primary hypertriglyceridemia, Arteriosclerosis 6:395 (1986).
S. Eisenberg, D. Gavish, Y. Oschry, M. Fainaru and R.J. Deckelbaum, Abnormalities in very low, low, and high density lipoproteins in hypertriglyceridemia: Reversal toward normal with bezafibrate treatment, J Clin Invest 74:470 (1984).
E.D. Janus, A.M. Nicole, P.R. Turner, P. Magill and B. Lewis, Kinetic basis of the primary hyperlipidemias: Studies of apolipoprotein B turnover in genetically defined subjects, Euro J Clin Invest 10:161 (1980).
A.H. Kissebah, S. Alfarzi and P.W. Adamo, Integrated regulation for very low density lipoprotein triglyceride and apolipoprotein-B kinetics in man: Normolipidemic subjects, familial hypertriglyceridemia, and familial combined hyperlipidemia, Metabolism 30:856 (1981).
J.L. Goldstein, W.R. Hazzard, H.G. Schrott, E.L. Bierman and A.G. Motulsky, Hyperlipidemia in coronary heart disease. I. Lipid levels in 500 survivors of myocardial infarction, J Clin Invest 52:1533 (1973).
J.L. Goldstein, H.G. Schrott, W.R. Hazzard, E.L. Bierman and A.G. Motulsky, Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia, J Clin Invest 52:1544 (1973).
G.L. Vega and S.M. Grundy, Kinetic heterogeneity of low density lipoproteins in primary hypertriglyceridemia, Arteriosclerosis 6: 395 (1986).
S.M. Grundy, Pathogenesis of hyperlipoproteinemia, J Lipid Res 25: 1611 (1984).
S.M. Grundy, H.Y.I. Mok, L.A. Zech, D. Steinberg and M. Berman, Transport of very low density lipoprotein-triglycerides in varying degrees of obesity and hypertriglyceridemia, J Clin Invest 63:1274 (1979).
E. Shafrir and T. Brenner, Lipoprotein lipid and protein synthesis in experimental nephrosis and plasmapheresis. I. Studies in the rat in vivo, Lipids 14:695 (1979).
R.J. Havel, Familial dysbetalipoproteinemia. New aspects of pathogenesis and diagnosis, Med Clin N Am 69:441 (1982).
J.P. Kane, G. Chen, R.L. Hamilton, D.H. Hardman, M.J. Mallory and R.J. Havel, Remnants of lipoproteins of intestinal and hepatic origin in familial dysbetalipoproteinemia, Arteriosclerosis 3:47 (1983).
S.M. Grundy (ed), A.M. Gotto Jr., E.L. Bierman et al., The Nutrition Committee, and Council on Arteriosclerosis of the American Heart Association. Recommendations for Treatment of Hyperlipidemia in Adults, Circulation 69:1067A (1984) and Arteriosclerosis 4:445A (1984).
Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, Arch Intern Med 148:36 (1988).
S.M. Grundy, Comparison of monounsaturated fatty acids and carbohydrates for plasma cholesterol lowering, N Engl J Med 314: 745 (1986).
S.M. Grundy, H.Y.I. Mok, L. Zech and M. Berman, Influence of nicotinic acid on metabolism of cholesterol and triglycerides in man, J Lipid Res 22:24 (1981).
T. Langer and R.I. Levy, The effect of nicotinic acid on turnover of low density lipoproteins in Type II hyperlipoproteinemia, in “Metabolic Effects of Nicotinic Acid and Its Derivatives”, K.F. Gey and L.A. Carlson, eds., Huber, Bern, New York (1971).
M.E. Maragandakis and H. Hankin, On the mode of action of lipid lowering agents. V. Kinetics of the inhibition in vitro of rat acetyl CoA carboxylase, J Biochem 246:348 (1971).
J. Boberg, M. Boberg, R. Gross, S.M. Grundy, J. Augustin and V. Brown, The effect of treatment with clofibrate on hepatic triglyceride and lipoprotein lipase activities of post heparin plasma in male patients with hyperlipoproteinemia, Atherosclerosis 27:499 (1977).
C. East, D.W. Bilheimer and S.M. Grundy, Combination drug therapy for treatment of familial combined hyperlipidemia, types IIB and IV, Ann Intern Med (in press).
C.A. East, S.M. Grundy and D.W. Bilheimer, Preliminary Report: Treatment of type 3 hyperlipoproteinemia with mevinolin, Metabolism 35:97 (1986).
A. Garg and S.M. Grundy, Lovastatin for lowering cholesterol levels in non-insulin-dependent diabetes mellitus, N Engl J Med 318:81 (1988).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 Plenum Press, New York
About this chapter
Cite this chapter
Vega, G.L., Grundy, S.M. (1988). Pathogenesis of Hypertriglyceridemia: Implications for Coronary Heart Disease and Therapy. In: Malmendier, C.L., Alaupovic, P. (eds) Eicosanoids, Apolipoproteins, Lipoprotein Particles, and Atherosclerosis. Advances in Experimental Medicine and Biology, vol 243. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0733-4_39
Download citation
DOI: https://doi.org/10.1007/978-1-4613-0733-4_39
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-8055-2
Online ISBN: 978-1-4613-0733-4
eBook Packages: Springer Book Archive