New EAS Consensus Document Tackles Familial Hypercholesterolemia

Shelley Wood

June 04, 2013

LYON, France — The European Atherosclerosis Society (EAS) writing group will soon publish a new consensus document tackling the underdiagnosis and undertreatment of heterozygous familial hypercholesterolemia (FH), said Dr Børge Nordestgaard (University of Copenhagen, Denmark).

Speaking here today during a session on new initiatives at the EAS 2013 Congress, Nordestgaard explained that Dr John Chapman (Hôpital de la Pitié, Paris, France) and Dr Henry Ginsberg (Columbia University, New York, NY) are the cochairs for the writing group, which also includes a wide array of other experts from around the world.

The EAS has previously published consensus statements on screening for lipoprotein (a) and another on what to do for patients with high triglycerides in the setting of low HDL cholesterol.

A Bigger Problem

The document will provide a brief introduction to the pathophysiology and genetics of heterozygous FH, then review the evidence supporting the group's conclusion that the disease is both underdiagnosed and undertreated, Nordestgaard said. The writing group was able to find data on diagnosis rates from only 20 countries. Using the accepted estimate of one FH case for every 500 individuals, the number of actual diagnosed cases ranged from 33 000 in the Netherlands (a 71% FH diagnosis rate), to 620 000 in the US and 68 000 in Canada, both diagnosis rates of <1%, Nordestgaard stated.

Moreover, he continued, a Copenhagen study that screened 69 000 members of the general population found a much higher prevalence of definite or probable FH: one in every 200 screened. Based on that finding, said Nordestgaard, the number of undiagnosed FH cases in the entire world ranges between 13.7 to 34.3 million. In Europe, the range is 1.8 to 4.5 million.

"And only 1% of these are treated today," Nordestgaard noted.

Screening and Diagnosis

The group determined that children, adults, and families should be screened for FH if one of the following criteria is met:

  • A family member presents with diagnosed FH

  • Plasma cholesterol in an adult >8mmol/L (>310 mg/dL)

  • Plasma cholesterol in a child >6mmol/L (>230 mg/dL)

  • Premature CHD

  • Tendon xanthomas

  • Sudden premature cardiac death

Physicians are encouraged to draw up the "family pedigree" tracking age, LDL level, and presence or absence of FH, using the offspring of a diagnosed patient as the index case at which time cascade screening should be started.

Although a number of FH diagnostic criteria have been devised, the EAS writing group recommend the Dutch Lipid Clinic Network Criteria [1], which uses a simple scoring system out of eight. Definite FH is a score greater than eight, probable FH is a score of six to eight, etc.

The next sections of the document deals with clinical vs mutation diagnosis, offering recommendations on who and how to treat, based on whether patient or family-member diagnosis was based on clinical symptoms or genetic testing. For example, in the setting of a clinical diagnosis without mutation confirmation, the group recommends treating the patient, but only monitoring the family and considering treatment. By contrast, in a patient with a mutation diagnosis but no clinical diagnosis, the patient and his or her family should have their LDL monitored only, with treatment considered as needed.

Treatment Targets

In terms of treatment targets, the group settled on an LDL target of <3.5 mmol/L (<135 mg/dL) for children with FH (age 8–10), a more "relaxed" target than for adults, to take into account normal growth. For adults with FH, LDL target levels are the same as those recommended for adults without FH: <2.5 mmol/L (<100 mg/dL) and <1.8 mmol/L (<70 mg/dL) for adults with known CHD or diabetes.

Children, Nordestgaard observed, should be started on a "less-potent statin" in addition to lifestyle and dietary counseling; adults, by contrast, should be started on the maximal potent statin dose. "Don't start low and titrate up," Nordestgaard said. "That would be a sin in these patients."

The evidence supporting the treatment priorities, he added, come primarily from studies of patients without FH.

Expert Advice, in the Absence of Large Studies

In the Q&A following his presentation, Nordestgaard stressed that the aim of the document is simplicity, and that it is based on expert consensus in the absence of extensive literature in this patient population. Moreover, the writing group intentionally steered clear of a graded recommendation/level of evidence format in order to make the document as accessible as possible, he said.

The target cholesterol levels, in particular, were a source of hours of debate, he explained, because although some of the only existing evidence in FH patients suggests that halving LDL levels is likely best, the writing group determined that it would be best to align their recommendations with the more general European guidance on dyslipidemias. Otherwise, he said, physicians might mistakenly get the idea that lowering LDL to a specific target is less important in FH than in someone without FH.

Session cochair and current EAS President, Professor Alberico L Catapano (University of Milan, Italy) reiterated that the consensus document is not a guidelines document, but rather consensus advice. As such, the text accompanying the specific recommendations makes the point that in this unique group of patients, the target given is universal, but "in fact, you should go as low as possible."

Speaking with heartwire after the session, Catapano, who was a member of the consensus writing panel, stressed that the primary aim of the document was to raise awareness of the scope of the problem and give physicians simple tools for diagnosis and treatment.

"This will be the first step for people in different nations in Europe and perhaps around the world to get the knowledge that FH is not as infrequent as people thought. So what we have to do now is build on this with dedicated programs to help people diagnose FH."

As it is now, he continued, "doctors see a patient and they think, oh, he's just hypercholesterolemic, and they treat them on the basis of that, perhaps not being as aggressive as they should. The problem with these patients is that they've had a lifelong exposure to high levels of cholesterol, so they are not at the same risk in the next few years as someone who develops hypercholesterolemia at aged 40. They've had hypercholesterolemia since they were zero."

The consensus document has been submitted for publication "and it hopefully will be accepted in a matter of weeks," said Catapano.

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