New FH guidance signals the shift into the era of genetic medicine according to specialists who foresee increased numbers of individuals being identified with heritable gene mutations from publicly funded genetic testing.

The full guidelines published in summary form this week in Internal Medicine Journal cover updates in detection together with diagnosis and genetic testing , risk stratification and management as well as strategies for implanting care into practice.

Speaking to the limbic Professor Gerald Watts, chair of the FH-Australasia Network, says there have been many aspects of work that necessitated the updated guidance, including new epidemiological data suggesting the condition is more common than previously thought.

“The population prevalence of FH is much more common than the 1 in 500 that’s quoted – so it’s not a rare condition, meaning to say that in Australia we’ve probably got 100,0000 people with FH, about 10% of whom are children.”

And with genetic testing for heritable mutations associated with FH receiving an MBS listing back in May 2020, Professor Watts says detection has become a central feature of the guidance with recommendations for multiple approaches to screening that requires specialists and primary care to work together.

“There are new diagnostic technologies particularly MBS-listed genetic testing and I think the important point here is that GPs and cardiologists can work conjointly. The requesting for a DNA test for FH needs to be done by a non-treating specialist, but once the diagnosis is made the GP, or series of GPs that cover the family in question, can use the DNA to make a precise diagnosis of the condition.”

Shared care

Professor Watts says FH treatment is also no longer the providence of cardiologists, suggesting that up to 70% of patients could be treated in primary care.

“I’d say on average about 10-15% of people need to be in a specialised centre,” he notes, referring to very severe cases such as patients diagnosed with homozygous FH.

“Another 20% can be in shared care but I think the large bulk of people can be managed in primary care,” he said of patients typically with an LDL cholesterol level of around six with a good family history and demonstrating no other risk factors.

“The important point is to regularly follow these patients up to make certain they are on statin therapy, which is particularly important in children with FH, and that there is regular surveillance of adherence to therapy and that treatment targets are reached.”

A simple treatment target is a 50% reduction in LDL cholesterol and for very high risk patients an LDL cholesterol less that 1.8 mm/L, he suggests.

Meanwhile statin intolerant patients were another important group who should be in specialist care, at least initially, according to Professor Watts.

“If someone is not at target or is statin intolerant with a LDL cholesterol greater than five they need a PCSK9 monoclonal antibody or another PCSK9 inhibitor. And these people need to be seen by a specialist to initiate treatment. But once they are stable the GP, now as a streamlined authority, can continue to repeat the prescription of PSKC9 inhibitors,” he says.

The updated guidance also recommends doing away with a fasting blood glucose sample for diagnosis.

“You don’t need a fasting sample to actually screen for hypercholesterolaemia and FH. If you’ve really got very high cholesterol you don’t have to fast for 24 hours to diagnose it so a non fasting sample will do. Two samples are important particularly in children but they can be non fasting samples.”

Statin treatment for children

The use of statins as an important aspect of care for children also receives a strong focus in the updated guidance.

According to Professor Watts, both Australian registry data and international data show that 50% of children with FH are not treated with statins, which he describes as ‘a pity’ because the condition, which starts from conception, poses a cumulative risk.

Children between the ages of 8-10 years who have an adverse family history should be started on statin therapy with appropriate lifestyle measures while patients with homozygous FH should be on treatment as soon as possible, says Professor Watts.

“Certainly by the age of two to four years but unfortunately our registry data do show that whilst there is agreement for tests in children genetically in FH there is still under treatment with statin therapy with many parents reluctant to start their children on the therapy.”

But Professor Watts adds that the therapy is ‘very well tolerated’ by children.

“Our own Australian registry has shown that very few children cannot tolerate statins – in the 700 patients we’ve seen only one had statin related myositis so they are tolerable, they’re safe and adherence is important.”

Another important update is a new recommendation that non-invasive imaging for atherosclerosis and the coronary artery calcium score could be used to apportion risk.

“We considered that there certainly is a role for CT angiography here. And particularly so in the most severe forms of FH such as homozygous FH or compound heterozygous FH, which may have some clinical occult and dangerous underlying coronary disease,” notes Professor Watts.

For risk stratification there is also a recommendation that Lipoprotein (a), which Professor Watts stresses is a ‘very powerful predictor of outcome’, be measured in all people with FH at least once.

Meanwhile, guidance on homozygous FH points to the fact that lipoprotein apheresis should be undertaken in the most severe cases with room for new therapies such as PCSK9 inhibitors and more advanced therapies under compassionate use.

You can access the full recommendations, released earlier in Heart Lung and Circulation here.