An interview with Prof Tony Wierzbicki #NationalCholesterolMonth

Do you know your cholesterol number?

National Cholesterol Month is an entire month devoted to raising awareness of the dangers of high cholesterol. We interviewed Professor Tony Wierzbicki, consultant in Metabolic Medicine and Chemical Pathology at Guy’s and St Thomas’ NHS Foundation Trust.

Can you tell us a bit about Familial Hypercholesterolaemia?

Familial Hypercholesterolaemia (FH) is caused by a gene mistake, and causes the LDL-cholesterol level to be very high. It is one of the most common autosomal dominant diseases, with a prevalence of somewhere between 1 in 300 and 1 in 500 depending on the population. It is associated with early onset heart disease, previously age 50-60, but now typically occurring in people in their 60s or 70s. We sometimes see patients presenting in their 30s and 40s with heart disease.

If you have high cholesterol and we find a gene mistake in you confirming that you have FH, then a nurse or the Clinical Genetics team will suggest testing other members of your family to see if anyone else has the same gene mistake.

Because FH is associated with a high cholesterol from birth, children begin to show early signs of artery damage from about the age of 6; and it is detectable upon artery scanning at about age 12. If you treat FH from youth, those changes go away and arteries revert back to normal.

Is FH the only cause of high cholesterol?

Not all high cholesterol levels are caused by a single gene (monogenic) mistake which causes FH. Some cases of high cholesterol are caused by lots of different gene variants working together (we call this ‘polygenic’).

There are implications for treatment, prognosis and the need and timing of any family testing, depending on whether you have a monogenic or polygenic form of high cholesterol.

People with monogenic FH, on the whole, tend to get heart disease earlier, and it tends to be more severe than the polygenic form for any given cholesterol level. If you have monogenic disease, then you need to be treated with a cholesterol lowering agent from the moment of diagnosis whereas if you have polygenic disease, we use a standard cardiovascular disease risk equation to calculate people’s cardiovascular disease risk – and in our case at Guy’s at St Thomas’, we do imaging as well. We can then make a decision on whether you should be treated or not. In about 30% of cases of polygenic disease we will say ‘Fine; the cholesterol level is this, there is nothing else wrong, come back to us in five or 10 years and we will recheck your arteries.’

Because of the very cost-effective nature of screening for FH, the fact that we’ve got effective treatments and it being very easy to detect, NICE recommended FH identification as a good use of taxpayer’s money. The Department of Health has added FH screening to the national cardiovascular plan and has asked the NHS to detect 25% of cases by 2025.

"Genomic medicine gives us an absolute confirmatory diagnosis."

How is genomic medicine informing the treatment of FH? Have you identified any especially interesting cases through the 100,000 Genomes Project?

The distribution of cholesterol in FH is a lot wider than people think it is. We have found that genomic medicine gives us an absolute confirmatory diagnosis.

Via the 100,000 genomes Project, we found that some gene mistakes cause the LDL cholesterol to go up significantly and cause FH. We found other gene mistakes that actually cause cholesterol to fall quite dramatically. 

Some patients have both of these gene mistakes so their cholesterol level is normal, but when you go into the family, you find relatives with ultra-low cholesterol who inherited the cholesterol-dropping gene mistake, and other relatives who had inherited the cholesterol-rising gene mistake, and their cholesterol was sky high.

The availability of gene testing for FH has allowed us to build a large service and to contribute to the worldwide data on the condition, particularly around the use of imaging (artery scanning) and other diagnostics in FH such as which tests are actually worth doing (and which are not). For instance, imaging is worth doing. Recently, we have been looking at large scale data analysis of our patient group as a means of clarifying pathways for identifying FH in other situations.

What do you think will be the biggest changes in the next five or ten years ?

One, genetic testing for FH will become universal. We know it works; we know that it is very efficient; we know that it does not take a lot of time or effort; and that we can come up with nice, simple protocols that can be done by hospital doctors and GPs. 

The next thing will be to try to use the information that we get from genomics to identify those people who are likely to get heart disease early but do not have FH. We will develop a way of using genomic data to develop a genetic risk score to identify patients who are most likely to develop severe heart disease, and then we will be able to target those patients aggressively for imaging and early therapy. 

I think the integration of genetics with imaging in cardiovacular disease will be where the big developments occur is in the next decade.

"Genetic testing for FH will become universal. We know it works; we know that it is very efficient"

What would be your key message to healthcare professionals during National Cholesterol Month?
Measure it!

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With any Whole Genome Sequencing (WGS) test ordered, a Record of Discussion (RoD) form will also need to be submitted. This document is to record the patient’s consent for genomic testing and their choice on taking part in research. Guidance on the patient choice conversation can be found here
This RoD form will be available for clinicians to download from this webpage. Once completed with the patient, it can be send to the lab with the corresponding test order form and sample.
Tests available to order will be listed in the National Genomic Test Directory. A test order form will soon be made available for clinicians on this webpage to download and complete. This form will include the address of the laboratory that the appropriate sample and completed form needs to be sent to.
Until the new Genomic Laboratory Service goes live, please continue to follow existing test order processes.
Later this year, the online test ordering tool for Whole Genome Sequencing will be integrated into the National Genomics Informatics System (NGIS) and clinicians will be able to search or filter to find a clinical indication, confirm eligibility criteria and start the test request process for their patient.