familial hypercholesterolemia

A new study published online in the Lancet suggests that one of the main screening plans that relies on genetic tests will fail to identify a substantial portion of people with familial hypercholesterolemia.

Investigators from the UK and Belgium analyzed DNA from several cohorts of FH and non-FH patients. Their chief finding was that a large percentage of FH patients did not have one of the single genetic mutations known to cause FH. Instead, these patients, termed “polygenic,” were found to have variants in multiple genes, each of which had a small LDL-raising effect, but when combined resulted in LDL levels similar to those in people with known FH mutations.

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According to one cholesterol expert:

The take home is that genetic screening is not a panacea and that screening based on fasting ipids makes most sense. Indeed, I never understood genetic screening for this disease anyway, since the phenotype (hypercholesterolemia) is what kills people, not the genotype, the phenotype is readily available with a blood test, the disease is not immediately fatal (It takes years to develop), and treatment is based on the numbers. It is like asking for a gene test fro sickle cell anemia. You can look at blood and make the diagnosis.

Click here to read the complete story on Forbes.

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Promising results from very early studies with an experimental new cholesterol-lowering drug, a monoclonal antibody to PCSK9, have been published in the New England Journal of Medicine. Evan Stein and colleagues report the results of two single-dose studies in which the drug, REGN727, was administered intravenously and subcutaneously to healthy subjects. In a third, randomized, placebo-controlled, dose-ranging trial, REGN727 was administered subcutaneously on days 1, 29, and 43 in adults with and without familial hypercholesterolemia (FH).

REGN727 was well tolerated and no subjects stopped taking the drug due to adverse events. Five patients had brief elevations in creatine kinase over three times the upper limit of normal. The drug had a powerful LDL-lowering effect: in the dose-ranging study in subjects already receiving atorvastatin

the 50 mg dose caused a 39% reduction of LDL cholesterol to 77.5 mg/dl,
the 100 mg dose caused a 53% reduction of LDL cholesterol to 61.3 mg/dl, and
the 150 mg dose caused a 61% reduction of LDL cholesterol to 53.8 mg/dl.

In an accompanying editorial, Stephen Young and Loren Fong write that “at this point, the status of PCSK9 therapeutics appears to be full speed ahead.” But they also express caution, noting that much work remains to be done:
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