© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Stanol Ester Margarine Alone and With Simvastatin Lowers Serum Cholesterol in Families With Familial Hypercholesterolemia Caused by the FH–North Karelia Mutation
Presented in part at the 71st Scientific Sessions of the American Heart Association, Dallas, Tex, November 8–11, 1998, and published in abstract form (Circulation 199898[suppl I]:I-533–I-534).
From the Department of Medicine, University of Helsinki (A.F.V., H.G., K.K., T.A.M.), Helsinki, and the Central Hospital of North Karelia (H.T., P.K.), Joensuu, Finland.
Correspondence to Alpo Vuorio, MD, PhD, Department of Medicine, University of Helsinki, PO Box 340, FIN-00029 HYKS, Finland. E-mail alpo.vuorio{at}huch.fi
Abstract—In heterozygous familial
hypercholesterolemia (FH), serum low density
lipoprotein (LDL) cholesterol levels are already elevated
at birth. Premature coronary heart disease occurs in 
30% of
heterozygous untreated adult patients. Accordingly, to retard
development of atherosclerosis, preventive measures for
lowering cholesterol should be started even in childhood.
To this end, 19 FH families consumed dietary stanol ester for 3 months.
Stanol ester margarine lowers the serum cholesterol level
by inhibiting cholesterol absorption. Each individual in
the study replaced part of his or her daily dietary fat with 25 g
of 80% rapeseed oil margarine containing stanol esters (2.24 g/d
stanols, mainly sitostanol). The families who consumed this margarine
for 12 weeks included 24 children, aged 3 to 13 years, with the North
Karelia variant of FH (FH-NK), 4 FH-NK parents, and 16 healthy family
members, and a separate group of 12 FH-NK adults who consumed the
margarine for 6 weeks and who were on simvastatin therapy
(20 or 40 mg/d). Fat-soluble vitamins were measured by high-pressure
liquid chromatography, and cholesterol
precursor sterols (indexes of cholesterol synthesis) and
cholestanol and plant sterols (indexes of cholesterol
absorption efficiency) were assayed by gas-liquid
chromatography. No side effects occurred. Serum LDL
cholesterol levels were reduced by 18%
(P<0.001), 11%, 12% (P<0.001), and
20% (P<0.001) in the 4 groups, respectively. The serum
campesterol-to-cholesterol ratios fell by 31%
(P<0.001), 29%, 23% (P<0.001), and
36% (P<0.001), respectively, suggesting that
cholesterol absorption efficiency was inhibited. Serum
lathosterol ratios were elevated by 38% (P<0.001),
11%, 15% (P<0.001), and 19%
(P<0.001), respectively, suggesting that
cholesterol synthesis was compensatorily upregulated. The
FH-NK children increased their serum lathosterol ratio more than did
the FH-NK adults treated with stanol ester margarine and
simvastatin (P<0.01). In the FH-NK
children, serum retinol concentration and
-tocopherol–to-cholesterol ratios were
unchanged by stanol ester margarine, but - and ß-carotene
concentrations and ratios were decreased. As assayed in a genetically
defined population of FH patients, a dietary regimen with stanol
ester margarine proved to be a safe and effective hypolipidemic
treatment for children and adults. In FH-NK adults on
simvastatin therapy, serum LDL cholesterol
levels could be reduced even further by including a stanol ester
margarine in the regimen.
Key Words: stanol ester margarine • familial hypercholesterolemia • atherosclerosis • prevention • cholesterol
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