Familial Hypercholesterolaemia and Premature Coronary Heart Disease - The EARS Findings
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Mortality over two centuries in large pedigree with familial hypercholesterolaemia: family tree mortality studyCommentary: Role of other genes and environment should not be overlooked in monogenic disease
Familial Hypercholesterolaemia and Premature Coronary Heart Disease - The EARS Findings
EDITOR - The study by Sijbrands and colleagues is a valuable
contribution to our understanding of the natural history and clinical
significance of Familial Hypercholesterolaemia (FH).1
Studies on FH are susceptible biase as the families are almost
invariably identified when members present with coronary heart disease
(CHD). The findings of the First and Second European Atherosclerosis
Research Studies (EARS I and II) indicate that FH is not a significant
factor in premature CHD. The EARS studies were established to investigate
the importance and interaction of genetic and environmental factors in the
development of atherosclerosis.2
In the EARS studies, University students between the ages of 18 and
26 years, whose fathers had proven CHD before the age of 55 years, were
recruited from the local indigenous population attending 18 Universities
throughout Europe. Age and sex-matched controls were recruited from the
same populations for each case. Applying the Simon Broome Foundation
criteria for the diagnosis of possible FH, ie a cholesterol >7.5
mmol/l,3 only 2 of 1089 students with a proven family history of paternal
premature CHD and 4 of 1727 controls had FH. Thus, the prevalence of FH
in both groups was not significantly different at approximately 1 in 500,
which is the estimated prevalence of the condition in the general
population.
While it has been proven beyond reasonable doubt that hyperlipidaemia
is a major risk factor for atherosclerosis and that reducing plasma lipid
concentrations by lifestyle or drug treatment will delay or even reverse
the development of atherosclerosis, the evidence that heterozygote FH is,
of itself, a cause of atherosclerosis is unsatisfactory.
Denis St.J O'Reilly, EARS Project Leader
Department of Biochemistry, Royal Infirmary, Glasgow G4 0SF
EARS Database, INSERM U525, 91 Bd de l'Hôpital, 75634 Paris, France
ON BEHALF OF THE EARS GROUP
CONFLICT OF INTEREST - NONE.
1 Sijbrands EJG, Westendorp RGJ, Defesche JC, de Meier PHEM, Smelt
AHM, Kastelein JPJ. Mortality over two centuries in large pedigree with
familial hypercholesterolaemia: family tree mortality study. Br Med J
2001; 7293: 1019-22.
2 The EARS Group. The European Atherosclerosis Research Study
(EARS): Design and Objectives. Int J Epidemiol 1994; 23(3): 465-71.
3 Scientific Steering Committee of the Simon Broome Register Group.
Risk of fatal coronary heart disease in familial hypercholesterolaemia.
Br Med J 1991; 303: 873-6.
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Familial Hypercholesterolaemia and Premature Coronary Heart Disease - The EARS Findings
EDITOR - The study by Sijbrands and colleagues is a valuable
contribution to our understanding of the natural history and clinical
significance of Familial Hypercholesterolaemia (FH).1
Studies on FH are susceptible biase as the families are almost
invariably identified when members present with coronary heart disease
(CHD). The findings of the First and Second European Atherosclerosis
Research Studies (EARS I and II) indicate that FH is not a significant
factor in premature CHD. The EARS studies were established to investigate
the importance and interaction of genetic and environmental factors in the
development of atherosclerosis.2
In the EARS studies, University students between the ages of 18 and
26 years, whose fathers had proven CHD before the age of 55 years, were
recruited from the local indigenous population attending 18 Universities
throughout Europe. Age and sex-matched controls were recruited from the
same populations for each case. Applying the Simon Broome Foundation
criteria for the diagnosis of possible FH, ie a cholesterol >7.5
mmol/l,3 only 2 of 1089 students with a proven family history of paternal
premature CHD and 4 of 1727 controls had FH. Thus, the prevalence of FH
in both groups was not significantly different at approximately 1 in 500,
which is the estimated prevalence of the condition in the general
population.
While it has been proven beyond reasonable doubt that hyperlipidaemia
is a major risk factor for atherosclerosis and that reducing plasma lipid
concentrations by lifestyle or drug treatment will delay or even reverse
the development of atherosclerosis, the evidence that heterozygote FH is,
of itself, a cause of atherosclerosis is unsatisfactory.
Denis St.J O'Reilly,
EARS Project Leader
Department of Biochemistry, Royal Infirmary, Glasgow G4 0SF
doreilly@clinmed.gla.ac.uk
Laurence Tiret
EARS Database, INSERM U525, 91 Bd de l'Hôpital, 75634 Paris, France
ON BEHALF OF THE EARS GROUP
CONFLICT OF INTEREST - NONE.
1 Sijbrands EJG, Westendorp RGJ, Defesche JC, de Meier PHEM, Smelt
AHM, Kastelein JPJ. Mortality over two centuries in large pedigree with
familial hypercholesterolaemia: family tree mortality study. Br Med J
2001; 7293: 1019-22.
2 The EARS Group. The European Atherosclerosis Research Study
(EARS): Design and Objectives. Int J Epidemiol 1994; 23(3): 465-71.
3 Scientific Steering Committee of the Simon Broome Register Group.
Risk of fatal coronary heart disease in familial hypercholesterolaemia.
Br Med J 1991; 303: 873-6.
Competing interests: No competing interests