Raising Awareness: EAS Says FH Underdiagnosed and Undertreated

August 27, 2013

COPENHAGEN, DENMARK A consensus statement from the European Atherosclerosis Society (EAS) on the underdiagnosis and undertreatment of familial hypercholesterolemia (FH), first presented during the EAS 2013 Congress in June, is now published in the European Heart Journal [1].

Chaired by Dr John Chapman (Hôpital de la Pitié, Paris, France) and Dr Henry Ginsberg (Columbia University, New York, NY), the consensus statement cites data suggesting that despite a theoretical prevalence of heterozygous FH in the general population of one per 500 individuals, the true prevalence might be closer to one in 200. Overall, less than 1% of individuals with FH are diagnosed in most countries.

Based on the range of these estimates, as many as 14 million to 34 million individuals worldwide have heterozygous FH.

Speaking with heartwire , Dr Amit Khera (University of Texas Southwestern, Dallas), who was not a member of the writing committee but who treats FH patients in his clinic, agreed with the EAS opinion that FH is underdiagnosed and undertreated. FH, he said, is one the most common genetic cardiovascular disorders, with approximately 600 000 US citizens having the lipid abnormality.

"At one in 500, maybe not directly but indirectly, we should all know somebody who has FH," said Khera. "Yet most people would have no idea what we're talking about. Said another way, most physicians should have some of these patients in their practice, but I bet that most wouldn't even know. And this is not a brand-new disease. At my institution, Dr Michael Brown and Dr Joseph Goldstein won the Nobel Prize for characterizing this disease in 1985."

A combination of patient advocacy, medical breakthroughs, and the introduction of newer medications for treatment of FH is helping to raise the profile of the disorder, however. Two new drugs, mipomersen sodium (Kynamro, Genzyme, Cambridge, MA) and lomitapide (Aegerion Pharmaceuticals, Cambridge, MA) were both approved by the Food and Drug Administration (FDA) for the rarer form of the disease, homozygous FDA. Although theEuropean Medicines Agency recently voted against approving mipomersen, the Committee for Medicinal Products for Human Use gave a green light to lomitapide.

On the whole, the timing of the EAS consensus statement, which corresponds with the recent availability of these new drugs, might give some physicians reason to be skeptical. While the statement is supported by educational grants from these pharmaceutical companies, Khera said that good things are going to happen as a result of the document.

"There have been a lot of resources put behind awareness," he said. "There are some diseases, like [low-testosterone disorder] low-T, where it could be argued they've been created or backed by large marketing campaigns, but FH is not one of those diseases. It is a largely unknown disease, and yet given the prevalence and our ability to do something about it, all of the notoriety or press that it is currently getting is well needed."

Life-Altering Therapy for the Kids

As reported by heartwire , the EAS document states that adults, children, and families are screened for FH if a family member presents with diagnosed FH. In addition, other criteria for screening include plasma cholesterol >310 mg/dL in adults, plasma cholesterol in children >230 mg/dL, premature coronary heart disease, tendon xanthomas, or premature sudden cardiac death in a family member.

To heartwire , Khera said the importance of diagnosing FH is because the disease is so common and because patients are at a heightened risk for cardiovascular disease. Also, it's treatable. One important aspect is that FH is generally an autosomal dominant genetic disorder, so diagnosing FH in a parent means there is a 50% chance that the children will also have FH.

"When we make a diagnosis, we have just potentially instituted life-altering, lifesaving therapy for their kids," said Khera. "If we identify the children early, and whenever you agree that treatment should be started, whether that's eight, nine, 10, or 13 years of age, we can help avoid some of the complications of FH."

All individuals with FH should undergo intensive lifestyle modification, and cholesterol-lowering drugs should be started immediately upon diagnosis, according to the EAS. For adults, treatment can include a maximally tolerated potent statin, ezetimibe (Zetia, Merck), bile acid-binding resins, and lipoprotein apheresis in homozygotes and treatment-resistant heterozygotes. For children ages eight to 10 years old, treatment can include a statin, ezetimibe, bile acid-binding resins, and lipoprotein apheresis in homozygotes.

In terms of treatment targets, the EAS recommends an LDL target of <135 mg/dL for children with FH. For adults, LDL-target levels are the same as those recommended for adults without FH, that being <100 mg/dL and <70 mg/dL for adults with known coronary heart disease or diabetes. The optimal age for screening children is between two and 10 years old, according to the EAS, although there are no safety data available on statins in children younger than eight years, it cautions.

Khera said that patients often have difficulty getting to treatment goal with one pill and will often require polypharmacy to reduce LDL-cholesterol levels sufficiently. Given the smaller numbers of patients, the treatment algorithm is largely based on expert consensus, he noted. Because heterozygous FH patients can have LDL-cholesterol levels in the 200- to 300-mg/dL range, this often requires a >50% reduction, which means an additional drug often needs to be added to the high-potency statin.

Overall, risk scoring with algorithms like the Framingham Risk Score (FHS) are not helpful in FH patients because they have had high cholesterol levels since birth. "This also changes the calculus when treating patients," said Khera.

The EAS consensus statement was supported by unrestricted educational grants from Amgen, Aegerion, AstraZeneca, Genzyme, Hoffman-La Roche, Kowa Europe, Novartis, and Sanofi/Regeneron. These companies were not present at the consensus panel meetings, had no role in the design or content of the consensus statement, and had no right to approve or disapprove the final document. Khera reports no conflicts of interest.

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