Familial hypercholesterolemia (FH): saving lives with better screening and better medicines

David Taylor, Emeritus Professor of Pharmaceutical and Public Health Policy, University College London

The West African Ebola epidemic – which so far has killed at least 6,000 people – is a dramatic reminder that infectious diseases still threaten humanity, especially in poorer countries. Malaria, for instance, currently accounts for over 600,000 deaths a year, the majority of which occur amongst African children. We ignore such threats at humanity’s peril.

Yet in overall terms vascular disease and occurrences such as heart attacks and strokes are today the biggest cause of death in not only ‘developed’ regions like Europe, but also in many lower and middle income countries. In China alone, for example, they cause approaching 3 million adult deaths a year. The world-wide total is about 20 million.

However, the good news is that we now know enough to prevent most vascular disease deaths in people aged under 80, should we choose to put modern knowledge into practice as robustly as possible. In countries like the US and the UK age standardised vascular disease mortality already stands at well under half the rate recorded in the 1950s. This is mainly due to cuts in smoking and the introduction and use of pharmaceuticals like beta-blockers, ACE inhibitors and statins.

If we go on supporting public health initiatives aimed at curbing problems like obesity and through using polypill technologies extend population-wide use of established low cost medicines to reduce blood pressure and LDL cholesterol levels in everyone in their 50s and above, vascular disease death rates could be halved again. Associated disability rates (including those for forms of dementia) in older people will also fall if irrational fears of optimal ‘public health’ medicines taking can be overcome.

Yet even if this achieved some sections of the population will without additional efforts miss out on the health progress such policies offer. There are, for instance, in the order of 12-14 million individuals across the world living with familial hypercholesterolemia (FH). Although the precise numbers are uncertain some 600,000 live in the US and around a million in the EU.

As a result of this genetically rather than purely lifestyle determined set of linked pathologies, which are normally said to affect at least 1 in 500 people but can be twice  prevalent in some communities, many people with FH  suffer myocardial infarctions and other vascular events before or not long after the age of 50. Some with the most severe forms even fall victim in childhood.

Because people with FH lack receptors which keep their low density cholesterol levels in check they are at high risk of premature death, even in communities with relatively healthy life styles and good access to health care. At present most people with FH do not know they have it, even though they may well have lost relatives due to early heart disease or strokes. Often such deaths are seen as random events to be endured rather than lessons to be learned from.

FH in The Netherlands

FH detection rate data is limited. In countries such as the US, France, Germany and the UK it is unlikely that more that 10-15 cent of the affected population is fully diagnosed and being treated adequately. But in The Netherlands a national screening programme based on genetic testing at birth coupled with a ‘cascade’ approach aimed finding other family members at risk has since its inception the 1990s radically improved performance. Only about half of those with FH can be identified with gene tests alone. Yet even so some sources indicate that 7 in every 10 individuals has been appropriately diagnosed in Holland. This improves the chance of effective treatment.

Professionals and patients everywhere should learn from this important example of best practice. The screening of all new-borns for FH has advantages. But even if this is not available the falling cost of mutation testing coupled with more traditional ways of case finding (such as identifying tendon xanthomas – soft cholesterol filled swellings – and allied eye abnormalities in young adults) means that this is a notable example of the type of condition modern health care systems and well informed service users should together be increasingly able to pick up, in part through convenient self testing and diagnosis in community pharmacies.

More effective medicines

Because FH is not caused by the same mix of factors responsible for most cases of vascular disease in later life it has not proved as amenable to treatment as ‘normal’ cases of atherosclerosis. However, better therapies are increasingly available.  For example, a new class of treatments known as PCSK-9 inhibitors is currently being developed. These medicines should for some individuals and families with FH provide a means of safely increasing their LDL receptor expression rates to much safer levels.

In the past some doctors and service users may have feared discovering FH because of the limited prospects for effective and/or affordable care. This was probably always unduly fatalistic. But with the growing prospect of treatments that address fundamental disease mechanisms there is now every reason to fight to increase rates of diagnosis.

New therapies are also becoming available for improving outcomes in other areas of vascular ill-health, including – for instance – atrial fibrillation. There are more opportunities than ever before for identifying and providing tailored treatments for FH and its consequences, as opposed to passively accepting early life individual or multiple family deaths as being due to mere chance.

Despite calls for austerity and cost restraint, service users and health professionals alike should I believe be doing everything they can to employ established and new medicines to best effect. This could in future ensure near universal freedom from the threat of premature disability and death resulting from conditions such as atherosclerosis and events like strokes. If the Dutch can find FH effectively, why don’t the rest of us elect to do so?

Professor David Taylor's picture

Professor David Taylor

David Taylor is Emeritus Professor of Pharmaceutical and Public Health Policy, University College London

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