© 1995 American Heart Association, Inc.
Articles |
Atherosclerotic Disease in Marked Hyperalphalipoproteinemia
Combined Reduction of Cholesteryl Ester Transfer Protein and Hepatic Triglyceride Lipase
From the Second Department of Internal Medicine, Osaka University Medical School, Suita, and the First Department of Internal Medicine, Hiroshima University School of Medicine, Minami-ku (Y.K., K. Hayashi), Japan.
Correspondence to Ken-ichi Hirano, MD, PhD, Section of Gastroenterology, Department of Medicine, University of Chicago, 5841 S Maryland Ave, Chicago, IL 60637.
Abstract Hyperalphalipoproteinemia (HALP) has been regarded
as a beneficial state accompanied by a longevity syndrome. However, we
reported the cases of markedly hyperalphalipoproteinemic subjects with
juvenile corneal opacification. These patients had reduced
postheparin hepatic triglyceride lipase (HTGL)
activities, and one of them has recently been identified to be
homozygous for a missense mutation in exon 15 (D442: G) in the
cholesteryl ester transfer protein (CETP) gene. In the current study,
to elucidate the clinical significance of and atherogenicity in marked
HALP, we determined the incidence of atherosclerotic
cardiovascular disease (ACD) in patients with marked
HALP and characterized the lipoprotein abnormalities in those who had
ACD, focusing especially on CETP and HTGL. The subjects were 201
patients (111 males and 90 females) with marked HALP (
2.58 mmol/L
[100 mg/dL]), 67% of whom were demonstrated to have the CETP gene
mutations in the intron 14 splice donor site or in exon 15. Their mean
age was 54±15 years. Plasma levels of total cholesterol,
HDL cholesterol, and triglyceride in all
subjects were 6.28±1.78, 3.15±0.90, and 1.08±0.53 mmol/L,
respectively. Ten of the male patients (9.0%) and two of the female
patients (2.2%) had apparent ACD such as myocardial infarction, angina
pectoris, and peripheral vascular diseases. Ten patients
with HALP who had ACD were identified to be heterozygotes for CETP
deficiency. To further clarify the characteristics of marked HALP in
patients with ACD, we compared the plasma lipids, lipoproteins, CETP,
and HTGL activities between heterozygotes for CETP deficiency who were
with and without ACD. There was no significant difference in plasma
lipids, lipoproteins, and CETP between the two groups, whereas HTGL
activities were significantly lower in the heterozygotes for CETP
deficiency with ACD than in the heterozygotes without ACD and in
control subjects. These results suggest that marked HALP may not always
be a beneficial state and that people who are heterozygotes for CETP
deficiency and who have low HTGL may be susceptible to ACD.
Key Words: atherosclerosis • cholesteryl ester transfer protein • hepatic triglyceride lipase • reverse cholesterol transport • hyperalphalipoproteinemia
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