Familial hypercholesterolaemia: A global call to arms.
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).
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) and. 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. Although early detection and treatment with statins and other LDL-C lowering therapies can improve survival, FH remains widely underdiagnosed and undertreated, thereby representing a major global public health challenge.

Whilst the prevalence of heterozygous FH has been traditionally estimated as ∼1:500, contemporary data suggest an overall frequency of ∼1:200–300, implying that >30 million individuals could be affected worldwide. Furthermore, the burden of the disease is even higher in subpopulations with gene founder effects or within communities where consanguineous marriages are common. Available information suggests that <5% of those affected are diagnosed, with higher detection rates reported among countries with formal screening programmes. Similarly, homozygous FH is now considered to have a higher prevalence of 1:160,000–300,000 (calculations based on suggested heterozygous frequency of ∼1:200–300) instead of the historical figure of 1:1,000,000. Additionally, FH is either insufficiently treated or treated late and, even with current best therapies (high-dose statins and cholesterol absorption inhibitors), only ∼20% of individuals attain guideline-recommended LDL-C goals. These factors are also compounded by a general lack of public health policies aimed specifically at FH, lack of uniformity among various initiatives for remediating the gaps in care, and the absence of a specific WHO “International Classification of Diseases” code for FH itself (currently included together with other disorders within the heading “pure hypercholesterolaemias” [ICD-10 code E78.0]). For example, the identification of new FH subjects is mainly based on clinical criteria in most regions, whereas in others genetic confirmation of the diagnosis in index cases and relatives according to a cascade testing strategy is utilised; additionally, although a cascade screening strategy has been found to be cost-effective and may promote risk reduction by early initiation of therapy, only a few regions/nations have implemented it widely (...)

The full test of the paper is available here: [FULL TEXT]
The supplemental material is available here: [Suppl. Material]
 
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