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Genetic Screening for Familial Hypercholesterolemia

Genetic screening for definite Familial Hypercholesterolemia (FH) looks for pathogenic variants in the LDLR, APOB, or PCSK9 genes, as not everyone with a family history of high cholesterol or heart disease has FH. Health professionals recommend genetic testing when an individual’s relatives have been previously diagnosed with FH or based upon physical examination for symptoms mentioned earlier. As FH is also on tier 1 recommended list for genetic screening by the Centers for Disease Control and Prevention (CDC), many large-scale population genomics programs, like ones offered in partnership with Helix, offer no-cost genetic screening for all participants, regardless of family history or existing symptoms.

Genetic screening is vital for early diagnosis to provide possible treatments or measures for affected individuals and their potential asymptomatic family members. Potential treatments include a combination of low-fat diets, adequate exercise, and pharmacotherapy. Generally, pharmacotherapy involves drugs called statins, which usually reduce LDL-C levels by 50%. If the maximum tolerated dose of statin does not bring LDL-C to satisfactory levels in an individual, a combination of statin and ezetimibe is used. Ezetimibe is usually utilized for patients who cannot tolerate high statin dosages as it has lower efficacy rates. The lower efficacy rates come from the fact that ezetimibe only inhibits cholesterol absorption and not cholesterol production in the liver. Ezetimibe alone only reduces LDL-C levels by around 10-18% compared to a combination of ezetimibe and statin, which reduce LDL-C levels by an additional 20-25%. Another therapeutic option is Lipoprotein apheresis or LDL apheresis, which is used for patients with persistent levels of LDL-C even after intensive drug therapies. LDL apheresis is a non-surgical procedure in which the portion of the blood that contains the cholesterol (plasma) is separated and run through a machine to be filtered out.

Familial Hypercholesterolemia Outlook

Scientists estimate that 85% of males and 50% of females will suffer a cardiac event before age 65 if left untreated. This high incidence of mortality and morbidity has led many to consider FH a global problem. Follow-up studies have shown that the leading cause of death for those afflicted with FH is coronary heart disease (CHD). The good news is that with enough long-term treatments, researchers estimate that FH patients could potentially increase their life expectancy by 10-30 years. By expanding community participation in large-scale population genomics programs, Helix and its partners are also doing further research to understand better and discover new genetic risk factors associated with FH, as well as the impact of identifying FH proactively on society as a whole.