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CASEBOOK CLINICAL


suffered the same in his early 50s. ‘The coronary unit said it was important that I get my cholesterol measured. And I want my teenage children checked, too.’


What patterns of hyperlipidaemia should make the GP consider familial hypercholesterolaemia (FH)? In this context, how is a ‘relevant’ family history defined? The definition (see below) is complex but FH should be suspected when total cholesterol levels are above 7.5mmol/l, especially if there is a personal or family history of premature coronary heart disease. For the purpose of inclusion of ‘family history’ in the QRISK2 calculation, a history of angina or heart attack before age 60 in a first-degree relative qualifies.


What are the diagnostic criteria for FH? Do all these patients require referral and, if so, why? In the UK, familial hyperlipidaemia is defined using the ‘Simon Broome’ criteria, which include a combination of:2 • Total cholesterol in an adult of >7.5mmol/l (>6.7mmol/l in a child) and an LDL cholesterol of >4.9mmol/l (>4.0mmol/l in a child) Along with either: • Tendon xanthomata or evidence of these signs in a first-degree or second- degree relative, or • DNA evidence of an LDL receptor mutation, familial defective apo B-100 or a PCSK9 mutation. Possible FH should be diagnosed if the cholesterol concentrations fit these criteria and the individual has one of the following: • Premature onset of MI (under 50 years in second-degree or 60 years in first- degree relatives). • Markedly elevated lipids (as above) in first- or second-degree relatives The 2014 NICE lipid modification guideline recommends referral to a specialist lipid clinic for people with total cholesterol levels above 9.0mmol/l or


72 February 2016 Pulse


Tendon xanthomata


non-HDL cholesterol of 7.5mmol/l or higher.3 Individuals and families with a clinical diagnosis of FH have very high prevalence of and mortality from CHD and should be offered investigation and counselling by a specialist in the subject, and cascade testing to identify other affected family members and optimise early treatment and follow-up.


How does this diagnosis alter standard treatment for hyperlipidaemia, and what are the goals of treatment?


Standard treatment is currently with high-intensity statins. The aim should be to achieve a reduction of at least 50% from baseline non-HDL cholesterol levels. The dose should be increased to the maximum tolerated. Ezetimibe can be used as an alternative in people with true statin intolerance or as an add-on in those not achieving the desired reduction on maximally tolerated statin alone. In those with the rare homozygous form of FH (estimated frequency of 12 in a million), specialist assessment and possible initiation of lipid-modifying therapy should occur by the time children are aged 10. Plasma apheresis is an option in homozygous FH.


Case 3


References 1 Feinman L and Leiber C. Ethanol and lipid metabolism. Am J Clin Nutr 1999; 70: 791-2 2 NICE. CG 71: Identification and management of familial hyperlipidaemia, London: NICE, 2008 3 NICE. CG181: Lipid modification. London: NICE; 2014


An 87-year-old, fit and well lady on no medication makes a rare appearance in your surgery. She has no symptoms, but is concerned because all her friends are on statins – and they think she should be, too. She has never been keen on taking pills, but wants to discuss the pros and cons.


What is the evidence base for using statins both for primary and secondary prevention in very elderly patients? How would you express these issues to a patient of this sort? There is no doubt that age per se is one of the strongest risk factors for developing cardiovascular disease manifestations,


including heart attacks and strokes, and that the prognosis in people who already have evidence of cardiovascular disease is also closely related to age. While there is currently no evidence that mortality is affected by statin therapy in people aged 80 or above – these patients are usually excluded from interventional studies – they are at high absolute risk particularly if they smoke or have hypertension, and it is highly likely that their risk of stroke and MI will be reduced by treatment with statins. However, the NICE guideline acknowledges the lack of strong evidence here and recommends future research. It is therefore important to explain to patients in jargon-free language, making use of decision aids and numerical estimates of absolute risks, that while there is no evidence at their age that treatment with statins will prolong life, there is a strong basis to indicate their risk of a heart attack or stroke is likely to be significantly reduced by treatment and even more than in younger people who are at lower absolute risk. The risk of morbidity and mortality from a heart attack or stroke needs to be weighed against the small risk of developing statin-related side-effects.


Does her age put her at increased risk of side-effects?


In general, there is no evidence that people in this age group are more likely to suffer adverse effects with statin therapy, although they do have a higher prevalence of generalised aches and pains, which may complicate therapy and if already present may increase the likelihood of muscle side-effects.


Is there an age at which you would not consider initiating statin therapy as a primary preventive measure? And is there an age at which statins given for secondary prevention should be withdrawn, or not started, because of a lack of evidence of benefit? I would not withdraw statin therapy, whether previously started for primary or secondary prevention, simply because of increasing age if the statin is tolerated. If anything, as patients become older their absolute CVD risk increases, as does the likely absolute benefit of effective lipid lowering. In terms of initiation of statins, patients with previous or new CVD events are at the highest risk of recurrent events and should be offered high-intensity statins irrespective of age. Regarding primary prevention in patients aged 85 or older, I would take biological age, other major risk factors such as smoking or hypertension, and their wishes and beliefs into account, but would generally only withhold statins in those where there is serious comorbidity leading to very limited life expectancy (less than one year) due to cancer or heart failure, for example.


Dr Rajai Ahmad is a consultant cardiologist at Sandwell and West Birmingham Hospitals NHS Trust


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