Screening for Familial Hypercholesterolemia: a Model for Preventive Medicine Detección de la hipercolesterolemia familiar: un modelo de medicina preventiva

The most common genetic cause of premature coronary artery disease (CAD) is familial hypercholesterolemia (FH), an autosomal dominant condition in which half the offspring of an affected individual will also be affected from birth. The causative mutations are mainly found in the LDL receptor gene (LDLR) and less frequently in the apolipoprotein B gene and the proprotein subtilisin/kexin type 9 gene (PCSK9). The prevalence of heterozygous FH ranges from 1 in 300 to 1 in 500 individuals in the general population, and this condition is estimated to affect at least 100 000 people in Spain. Furthermore, FH accelerates atherosclerotic coronary disease by 10 to 40 years. In Spain, 55% of men and 24% of women with FH between 50 and 59 years of age have had some clinical manifestation of CAD, such as myocardial infarction and chest angina. Patients with homozygous FH, which affects approximately 1 per million inhabitants, have total cholesterol levels > 500 mg/dL and very premature CAD. Untreated, these individuals die before they are 20 years old. Therefore, FH is a public health problem, and diagnosis and treatment are mandatory. Diagnosis of FH is based on high concentrations of low-density lipoprotein cholesterol (LDL-C), family history of hypercholesterolemia, presence of premature CAD, and cholesterol deposition in the form of xanthomas and/or arcus senilis. Early diagnosis allows preventive measures to be taken. If patients with FH and no history of CAD are treated with statins, the risk of CAD is reduced by 79%, to a level similar to that of the general population. Although many recent guidelines for the management of FH have highlighted the high associated cardiovascular risk, most patients with FH remain undiagnosed and untreated. There are a series of barriers to diagnosis and treatment. First, patients with most severe FH are usually first identified in specialist care or lipid clinics, whereas most patients are attended in primary care. Many individuals and family members with FH who have CAD have other common risk factors and so genetic hypercholesterolemia is not diagnosed. In the case of treatment, statin doses are insufficient and combination treatment is used too sparingly. Moreover, therapy is often started in the late stages of disease, when atherosclerosis has already developed as a result of life-long high LDL-C concentrations. Finally, health care systems are not