Circulation, Vol 85, 2025-2033, Copyright © 1992 by American Heart Association
JJ Genest Jr, SS Martin-Munley, JR McNamara, JM Ordovas, J Jenner, RH Myers, SR Silberman, PW Wilson, DN Salem and EJ Schaefer
BACKGROUND. Genetic lipoprotein disorders have been associated with
premature coronary artery disease (CAD). METHODS AND RESULTS. The
prevalence of such disorders was determined in 102 kindreds (n = 603
subjects) in whom the proband had significant CAD documented by angiography
before the age of 60 years. Fasting plasma cholesterol, triglyceride, low
density lipoprotein (LDL) cholesterol, apolipoprotein (apo) B, and
lipoprotein (a) [Lp(a)] values above the 90th percentile and high density
lipoprotein (HDL) cholesterol and apo A-I below the 10th percentile of age-
and sex-specific norms were defined as abnormal. An abnormality was noted
in 73.5% of probands compared with 38.2% in age-matched controls (p less
than 0.001), with a low HDL cholesterol level (hypoalphalipoproteinemia)
being the most common abnormality (39.2% of cases). In these kindreds, 54%
had a defined phenotypic familial lipoprotein or apolipoprotein disorder.
The following frequencies were observed: Lp(a) excess, 18.6% (includes
12.7% with no other dyslipidemias); hypertriglyceridemia with
hypoalphalipoproteinemia, 14.7%; combined hyperlipidemia, 13.7% (11.7% with
and 2.0% without hypoalphalipoproteinemia); hyperapobetalipoproteinemia
(elevated apo B only), 5%; hypoalphalipoproteinemia, 4%;
hypercholesterolemia (elevated LDL only), 3%; hypertriglyceridemia, 1%;
decreased apo A-I only, 1%. Overall, 54% of the probands had a familial
dyslipidemia; unclassifiable lipid disorders (spouse also affected) were
found in 3%. No identifiable familial dyslipidemia was noted in 43% of
kindreds of those; nearly half (45%) had a sporadic lipid disorder.
Parent-offspring and proband- spouse correlations for these biochemical
variables revealed that lipoprotein and apolipoprotein levels are in part
genetically determined, with Lp(a) showing the highest degree of
parent-offspring correlation. CONCLUSIONS. Our data indicate that more than
half of patients with premature CAD have a familial lipoprotein disorder,
with Lp(a) excess, hypertriglyceridemia with hypoalphalipoproteinemia, and
combined hyperlipidemia with hypoalphalipoproteinemia being the most common
abnormalities.
ARTICLES
Familial lipoprotein disorders in patients with premature coronary artery disease
Lipid Metabolism Laboratory, U.S.D.A. Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111.
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J. M. Hoeg Evaluating Coronary Heart Disease Risk: Tiles in the Mosaic JAMA, May 7, 1997; 277(17): 1387 - 1390. [Abstract] [PDF]
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I. O. Nuotio, O. T. Raitakari, K. V.K. Porkka, L. Rasanen, T. Moilanen, and J. S.A. Viikari Associations Between Diet and the Hyperapobetalipoproteinemia Phenotype Expression in Children and Young Adults: The Cardiovascular Risk in Young Finns Study Arterioscler Thromb Vasc Biol, May 1, 1997; 17(5): 820 - 825. [Abstract] [Full Text]
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P. Pajukanta, K. V.K. Porkka, M. Antikainen, M.-R. Taskinen, M. Perola, S. Murtomaki-Repo, S. Ehnholm, I. Nuotio, L. Suurinkeroinen, A.-T. Lahdenkari, et al. No Evidence of Linkage Between Familial Combined Hyperlipidemia and Genes Encoding Lipolytic Enzymes in Finnish Families Arterioscler Thromb Vasc Biol, May 1, 1997; 17(5): 841 - 850. [Abstract] [Full Text]
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M. Tilly-Kiesi, A. H. Lichtenstein, J. M. Ordovas, G. Dolnikowski, R. Malmstrom, M.-R. Taskinen, and E. J. Schaefer Subjects With ApoA-I(Lys107->0) Exhibit Enhanced Fractional Catabolic Rate of ApoA-I in Lp(AI) and ApoA-II in Lp(AI With AII) Arterioscler Thromb Vasc Biol, May 1, 1997; 17(5): 873 - 880. [Abstract] [Full Text]
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H. R. Superko Beyond LDL Cholesterol Reduction Circulation, November 15, 1996; 94(10): 2351 - 2354. [Full Text]
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A. G. Bostom, L. A. Cupples, J. L. Jenner, J. M. Ordovas, L. J. Seman, P. W. F. Wilson, E. J. Schaefer, and W. P. Castelli Elevated Plasma Lipoprotein(a) and Coronary Heart Disease in Men Aged 55 Years and Younger: A Prospective Study JAMA, August 21, 1996; 276(7): 544 - 548. [Abstract] [PDF]
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R. S. Rosenson Beyond Low-Density Lipoprotein Cholesterol: A Perspective on Low High-Density Lipoprotein Disorders and Lp(a) Lipoprotein Excess Arch Intern Med, June 24, 1996; 156(12): 1278 - 1284. [Abstract] [PDF]
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R. G. Bakker-Arkema, M. H. Davidson, R. J. Goldstein, J. Davignon, J. L. Isaacsohn, S. R. Weiss, L. M. Keilson, W. V. Brown, V. T. Miller, L. J. Shurzinske, et al. Efficacy and Safety of a New HMG-CoA Reductase Inhibitor, Atorvastatin, in Patients With Hypertriglyceridemia JAMA, January 10, 1996; 275(2): 128 - 133. [Abstract] [PDF]
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M. Marcil, B. Boucher, L. Krimbou, B. C. Solymoss, J. Davignon, J. Frohlich, and J. Genest Jr Severe Familial HDL Deficiency in French-Canadian Kindreds : Clinical, Biochemical, and Molecular Characterization Arterioscler Thromb Vasc Biol, August 1, 1995; 15(8): 1015 - 1024. [Abstract] [Full Text]
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J. Hasler-Rapacz, M. F. Prescott, J. Von Linden-Reed, J. M. Rapacz Jr, Z. Hu, and J. Rapacz Elevated Concentrations of Plasma Lipids and Apolipoproteins B, C-III, and E Are Associated With the Progression of Coronary Artery Disease in Familial Hypercholesterolemic Swine Arterioscler Thromb Vasc Biol, May 1, 1995; 15(5): 583 - 592. [Abstract] [Full Text]
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H. Miettinen, H. Gylling, I. Ulmanen, T. A. Miettinen, and K. Kontula Two Different Allelic Mutations in a Finnish Family With Lecithin:Cholesterol Acyltransferase Deficiency Arterioscler Thromb Vasc Biol, April 1, 1995; 15(4): 460 - 467. [Abstract] [Full Text]
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M. Dammerman and J. L. Breslow Genetic Basis of Lipoprotein Disorders Circulation, January 15, 1995; 91(2): 505 - 512. [Full Text]
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D. J. Rader, J. M. Hoeg, and H. B. Brewer Quantitation of Plasma Apolipoproteins in the Primary and Secondary Prevention of Coronary Artery Disease Ann Intern Med, June 15, 1994; 120(12): 1012 - 1025. [Abstract] [Full Text]
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E. J. Schaefer, S. Lamon-Fava, J. L. Jenner, J. R. McNamara, J. M. Ordovas, C. E. Davis, J. M. Abolafia, K. Lippel, and R. I. Levy Lipoprotein(a) Levels and Risk of Coronary Heart Disease in Men: The Lipid Research Clinics Coronary Primary Prevention Trial JAMA, April 6, 1994; 271(13): 999 - 1003. [Abstract] [PDF]
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V. Gurewich and M. Mittleman Lipoprotein(a) in Coronary Heart Disease: Is It a Risk Factor After All? JAMA, April 6, 1994; 271(13): 1025 - 1026. [Abstract] [PDF]
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R. S. Rosenson Low Levels of High-Density Lipoprotein Cholesterol (Hypoalphalipoproteinemia) An Approach to Management Arch Intern Med, July 12, 1993; 153(13): 1528 - 1538. [Abstract] [PDF]
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K. N. Fix and A. Oberman Barriers to Following National Cholesterol Educational Program Guidelines: An Appraisal of Poor Physician Compliance Arch Intern Med, December 1, 1992; 152(12): 2385 - 2387. [Abstract] [PDF]
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