Familial Hypercholesterolaemia (FH) is the commonest autosomal co-dominantly inherited
condition affecting man. It is caused by mutation in one of three genes, encoding
the low-density lipoprotein (LDL) receptor, or the gene for apolipoprotein B (which
is the major protein component of the LDL particle), or in the gene coding for PCSK9
(which is involved in the degradation of the LDL-receptor during its cellular recycling).
These mutations result in impaired LDL metabolism, leading to life-long elevations
in LDL-cholesterol (LDL-C) and development of premature atherosclerotic cardiovascular
disease (ASCVD) [
1
,
2
,
3
]. If left untreated, the relative risk of premature coronary artery disease is significantly
higher in heterozygous patients than unaffected individuals, with most untreated homozygotes
developing ASCVD before the age of 20 and generally not surviving past 30 years [
- Wiegman A.
- Gidding S.S.
- Watts G.F.
- et al.
Familial hypercholesterolaemia in children and adolescents: gaining decades of life
by optimizing detection and treatment.
Eur. Heart J. 2015; (pii: ehv157, First published online: 25 May 2015)https://doi.org/10.1093/eurheartj/ehv157
2
,
3
,
- Wiegman A.
- Gidding S.S.
- Watts G.F.
- et al.
Familial hypercholesterolaemia in children and adolescents: gaining decades of life
by optimizing detection and treatment.
Eur. Heart J. 2015; (pii: ehv157, First published online: 25 May 2015)https://doi.org/10.1093/eurheartj/ehv157
4
,
5
]. Although early detection and treatment with statins and other LDL-C lowering therapies
can improve survival, FH remains widely underdiagnosed and undertreated [
- Huijgen R.
- Kindt I.
- Defesche J.C.
- Kastelein J.J.
Cardiovascular risk in relation to functionality of sequence variants in the gene
coding for the low-density lipoprotein receptor: a study among 29,365 individuals
tested for 64 specific low-density lipoprotein-receptor sequence variants.
Eur. Heart J. 2012; 33: 2325-2330
[1]
], thereby representing a major global public health challenge.Keywords
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References
- Familial hypercholesterolemia is underdiagnosed and undertreated in the general population: guidance to clinicians to prevent coronary artery disease.Consensus Statement Eur. Atheroscler. Soc. Eur. Heart J. 2013; 34: 3478-3490
- Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management.A Position Pap. Consensus Panel Fam. Hypercholesterolaemia Eur. Atheroscler. Soc. Eur. Heart J. 2014; 35: 2146-2157
- Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment.Eur. Heart J. 2015; (pii: ehv157, First published online: 25 May 2015)https://doi.org/10.1093/eurheartj/ehv157
- Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction.Nature. 2015; 518: 102-106
- Cardiovascular risk in relation to functionality of sequence variants in the gene coding for the low-density lipoprotein receptor: a study among 29,365 individuals tested for 64 specific low-density lipoprotein-receptor sequence variants.Eur. Heart J. 2012; 33: 2325-2330
- Familial hypercholesterolemia in the danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication.J. Clin. Endocrinol. Metab. 2012; 97: 3956-3964
- Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review.Am. J. Epidemiol. 2004; 160: 407-420
- Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype-phenotype relationship, and clinical outcome.Eur. Heart J. 2015; 36: 560-565
- Reductions in all-cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: a prospective registry study.Eur. Heart J. 2008; 29: 2625-2633
- Efficacy of statins in familial hypercholesterolaemia: a long term cohort study.BMJ. 2008; 337: a2423
- International Classification of Diseases (ICD) – 10.Version.2015 (Last consult 20 August, 2015)
- A systematic review of economic evaluations of the detection and treatment of familial hypercholesterolemia.Int. J. Cardiol. 2013; 167: 2391-2396
Article info
Publication history
Published online: September 17, 2015
Accepted:
September 14,
2015
Received:
September 14,
2015
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
