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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