The Statin Conundrum
The Statin Conundrum

NICE Lipid Modification Guidance has been revised to enable doctors to offer statin treatment to people at lower 10 year risk but high lifetime risk of CVD.  See our responses to the questions this raises.  

Key findings from the register 

At least 120,000 people in the UK are thought to be affected with heterozygous FH, of whom more than 75% are undiagnosed.

Diagnosis is based on the Simon Broome criteria of elevated LDL-cholesterol levels (>4.9mmol/l in adults, > 4.0 mmol/L if < 16 yo), and a family history of early CHD and/or elevated cholesterol levels, when patients are given a diagnosis of Possible FH.  In the presence of the clinical feature of tendon xanthomas, or if they have a positive genetic test, patients are given a diagnosis of Definite FH.

Patients with FH have elevated LDL cholesterol levels from birth and carotid intimal media thickness can be shown to be significantly increased in affected heterozygous children by the age of 11 years.  Early retrospective epidemiological studies had shown that the cumulative incidence of fatal or non-fatal myocardial infarction Encouragingly, follow up of this finding in 1999 (2) after the introduction of statin lowering therapy showed a significant reduction in coronary heart disease and improved life expectancy, though as illustrated in the figure above, patients in the 20-59 year age range still had a coronary death rate that was 3.7 fold higher than the general population of England and Wales (the “Standardised Mortality Ratio”). However, by 2008 (9) longer follow up demonstrated that in patients identified and treated with statins before they develop heart disease (primary prevention) there was no excess mortality, although patients with evidence of heart disease (for example having had a heart attack already) the death rate was still elevated. Interestingly, treated FH patients had a lower death rate from cancer, mainly due to the lower than average rate of smoking in identified patients and so lower risk of, for example, lung cancer. without treatment is about 50% by the age of 50 years in men and about 30% by the age of 60 years in women and the first paper from the register in 1991 confirmed this high risk with a nearly 100-fold excess mortality from coronary heart disease in patients aged 20-39 years. 

One of the major interests of the register has been to try to identify factors which predispose patients with FH to develop early heart disease.  A five-year grant from the British Heart Foundation was obtained in 1998 to carry out this work which has resulted in several publications.  This project involved recruitment of over 500 patients with FH and to allow analysis of collected plasma samples and DNA samples. Perhaps not surprisingly, the research demonstrated that risk factors known to increase cardiovascular risk in the general population are also important in FH.  The most significant are increasing age, and being male, but smoking cigarettes is a particularly important risk factor, whilst having low levels of the “good” cholesterol – HDL - increase risk, especially in women (5).  Further work on identifying risk factors in FH patients is continuing (14) together with epidemiological analyses to assess the extent to which the prognosis has improved as more effective lipid-modifying drug therapy becomes available and as patients are identified and treated earlier.

See references