Familial hypercholesterolemia (FH) is the most common genetic cause of premature coronary heart disease (CHD). This cardiological problem manifests itself at birth and is transmitted to half of the offspring.
The prevalence of heterozygous FH is 1 in 300-500 people in the general population, and it is estimated that more than 100,000 people in Spain have FH.
FH accelerates coronary atherosclerotic disease by one to four decades, causing a significant decrease in life expectancy. Figures show that 55% of men and 24% of women with FH in their 50s have presented symptoms of coronary disease, such as myocardial infarction and angina pectoris. We are therefore facing a public health problem and its diagnosis and treatment are mandatory.
Diagnosis of Familial Hypercholesterolemia
The diagnosis of FH is based on the finding of elevated cholesterol concentrations (generally > 220 mg/dL), family history of hypercholesterolemia, history of premature CD and cholesterol deposits in the form of xanthomas and/or corneal arcus (tendinous xanthomas although pathognomonic of FH are found in less than 30% of cases).
We know that early diagnosis and treatment has been shown to markedly reduce coronary risk and prolong life. But the vast majority of patients with FH remain undiagnosed and untreated.
There are a number of barriers to adequate diagnosis and treatment:
- patients with more severe FH are usually detected in specialized care or lipid clinics; however, most patients are found in primary care;
- many individuals and families with FH are often overlooked among those with CHD caused by the most common risk factors and are therefore not diagnosed with genetic hypercholesterolemia;
- most treated patients have insufficient statin doses or little combination therapy and, in addition, treatment is often started late in life when atherosclerosis has already developed, due to lifetime exposure to elevated LDL-C levels;
- there is insufficient awareness in health systems and there is a lack of screening programs and registries that help to follow up patients, to know their evolution and adherence to treatment.
Familial Hypercholesterolemia in Spain
In Spain, since obtaining free chronic treatment for FH in 2004, there has been greater awareness and a boost in its diagnosis. It is estimated that 20% of the population is diagnosed, 60% of which by clinical criteria.
Since 2004, the Spanish Familial Hypercholesterolemia Foundation has launched a national program (in collaboration with specialized hospitals) to detect FH in the family cascade.
To date, 4,155 people belonging to 771 families have been recruited, with an average of more than 5 people per family. Some 3,000 individuals in this study, conducted by Safeheart, have a positive genetic diagnosis. An important finding in this study is that despite being an inherited disorder, approximately 25% of the detected family members were unaware that they had FH and 20% did not receive lipid-lowering treatment.
Treatment of Familial Hypercholesterolemia
International and national guidelines consider patients with FH to be at high CV risk and, therefore, the target for LDL-C should be
However, there is little information on the lipid-lowering therapy used and the attainment of targets achieved in LDL-C in actual clinical practice in follow-up studies. On the other hand, national registries are useful tools to provide information on lipid-lowering treatment and to learn about the health status of the population studied.
We analyzed patient data from the Spanish SAFEHEART study, which enrolled a total of 3,745 individuals aged 18 years or older, of whom 2,752 had a genetically confirmed diagnosis of FH between January 2004 and November 2013. Follow-up data, including complete lipid profile, were obtained in 2,168 patients. The mean age was 49.5 years: 1,264 were male (45.9%). The mean follow-up time was 5.1 years. CV disease was 13% and premature CV disease 9.4%.
The results obtained in the study show that there is still room for improvement in lipid-lowering treatment, in terms of using more combination therapy and higher doses of highly effective statins. However, these results also show the enormous difficulty that FH patients have in achieving LDL-C targets, despite using the best lipid-lowering therapy available.
These data highlight the medical need for new cholesterol-lowering options in combination with current treatment to achieve low cLDL levels that will help us prevent the development of premature CV disease.
Recommendations and conclusion
The lack of a diagnosis poses a problem for the effective prevention of premature CD, and affects the quality of life and the economic and social contribution of individuals and families with FH. It also causes enormous healthcare costs.
Improving the diagnosis and treatment of individuals and families with FH requires greater awareness on the part of those responsible for healthcare systems. At a time when resources need to be prioritized in health interventions, biases that sometimes lead to funding expensive, high-tech interventions to the detriment of prevention programs should be avoided. HF has become the paradigm of a preventable and easily treatable chronic disease.
FH is a public health challenge that affects the family and is easily diagnosed and treated. Since most people with FH are asymptomatic, primary care physician involvement and training is needed to ensure adequate care of families with FH.
Most people with FH should be treated in primary care, preferably in a family setting, while more complex cases including children should be managed in specialized centers or lipid clinics.
Patient support organizations have taken an increasingly active role in raising public awareness and monitoring the functioning of registries to facilitate diagnosis and treatment.