Simon Broome FH Register

History

Dr Joan Slack first instigated the idea of a register of familial hyperlipidaemias in 1976 and the register was set up by Professor Jim Mann in 1980. It was funded initially by the Simon Broome Heart Research Trust which was a charity set up by Mrs Katherine Broome, widow of Simon Broome who had died prematurely of heart disease. In recognition of this support, the register was named “The Simon Broome Familial Hyperlipidaemia Register”. From its inception the work was overseen by a Scientific Steering Committee (SSC) and Professors Jim Mann and Gil Thompson were among its earliest members. The Register has been, and continues to be, co-ordinated from Oxford - initially by Professor Margaret Thorogood and from 1990 directed by Professor Andrew Neil.

Current Situation

The register continues to be overseen by its Scientific Steering Committee (SSC) which is chaired by Dr. Nigel Capps (Warwickshire) who reports to HEART UK . The secretary is Dr. Mary Seed ( Charing Cross Hospital , London ) and other academic clinicians include Professor John Betteridge (UCL), Dr. Rossi Naoumova (Hammersmith), Professor Paul Durrington ( Manchester ), and Professor Andrew Neil ( Oxford ). Following the development of DNA technology in the 1980s and the recognition of the potential usefulness of genetic testing in FH, Professor Steve Humphries (UCL) joined the SSC to provide molecular biological expertise.

Current Research

One of the major interests of the register at present is 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 already resulted in several publications. 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. Further work on identifying risk factors in FH patients is continuing 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.

Papers from the Simon Broome Registry

•  Simon Broome Steering Committee. Risk of fatal coronary heart disease in familial hypercholesterolaemia. Scientific Steering Committee on behalf of the Simon Broome Register Group. BMJ 1991;303:893-6.

First paper from the Simon Broome Study showing a roughly nine-fold higher risk of fatal coronary heart disease (CHD) in FH patients aged less than 60 years before the introduction of effective treatment with HMG Co-A reductase inhibitors (statins).

•  Simon Broome Steering Committee. Steering committee on behalf of the Simon Broome Register Group. Mortality in treated heterozygous familial hypercholesterolaemia: implications for clinical management. Atherosclerosis 1999;142:105-12.

Follow-up study showing that the increased risk of fatal CHD in FH is substantially reduced by treatment with statins, especially in young individuals.

•  Huxley RR, Hawkins MH, Humphries SE, Karpe F, Neil HAW, for the Simon Broome Familial Hyperlipidaemia Register Group and Scientific Steering Committee. Risk of fatal stroke in patients with treated familial hypercholesterolemia. Stroke 2003;34:22-27

A study showing that the risk of stroke in patients with FH is not significantly higher after treatment than in the general population.

•  Neil HAW, Huxley RR, Hawkins MM, Durrington PN, Betteridge DJ, Humphries SE, Simon Broome Familial Hyperlipidaemia Register Group and Scientific Steering Committee. Comparison of the risk of fatal coronary heart disease in treated xanthomatous and non-xanthomatous heterozygous familial hypercholesterolaemia: a prospective registry study. Atherosclerosis 2003;170:73-78

Patients with tendons xanthomas are classified on diagnosis as having “definite FH” and those without xanthomas as “possible FH”. This study compared the risk of heart disease in the two groups and found that although it were slightly lower in the patients without xanthomas, the risk was still significantly higher than the general population, indicating that both groups of patients would clearly benefit from statin treatment.

•  Neil HAW, Seagroatt V, Betteridge DJ, Cooper MP, Durrington PN, Miller JP, Seed M, Naoumova RP, Thompson GR, Huxley R, Humphries SE. Established and emerging coronary risk factors in patients with heterozygous familial hypercholesterolaemia. Heart 2004;90:1431-1437

A British Heart Foundation-funded study showing that increasing age, being male, smoking cigarettes, and having low HDL, particularly in women, were all associated with increased risk of heart disease in FH patients, but that “novel” cardiovascular risk factors such as homocysteine or leucocyte count were not associated with a significant excess risk.

•  Neil HAW, Hawkins MM, Durrington PN, Betteridge DJ, Capps NE, Humphries SE, for the Simon Broome Familial Hyperlipidaemia Register Group and Scientific Steering Committee. Non-coronary heart disease mortality and risk of fatal cancer in patients with treated heterozygous familial hypercholesterolaemia: a prospective registry study. Atherosclerosis 2005;179:293-297

A study showing that although mortality from heart disease is increased in FH, cancer mortality is reduced by nearly half, so that the overall mortality is no higher than in the general population of England and Wales. Although the study cannot exclude the possibility that statins have anti-cancer activity, the results strongly suggest that giving advice to consume a healthy diet, increase physical activity and stop smoking is associated with a substantial reduction in mortality from cancer.

Other papers of Interest

•  Neil HAW, Hammond T, Huxley R, Matthews DR , Humphries SE. Extent of underdiagnosis of familial hypercholesterolaemia in routine practice: prospective registry study. BMJ 2000;321:148

A study to estimate the prevalence of diagnosed FH and the extent of under-diagnosis in the general population in Oxfordshire. FH patients were identified using both the Simon Broome Register and the Oxford lipid clinic computerised patient register and, from the size of the resident population of Oxfordshire, it was possible to calculate that about 1 in 2,000 individuals were affected which indicated that nearly a quarter of all expected patients had been diagnosed. Interestingly, the frequency in men and women between the ages of 55-65 was closer to one in 600 and the study showed considerable under-diagnosis of FH in young subjects. Since these individuals would benefit most from treatment, it is crucially important to be able to identify them early.

•  Marks D, Wonderling D, Thorogood M, Lambert H, Humphries SE, Neil AW. Cost-effectiveness analysis of different approaches of screening for familial hypercholesterolaemia. BMJ 2002;324:1303-1306

•  Marks D, Thorogood M, Neil HAW, Wonderling D, Humphries SE. Comparing costs and benefits over a ten year period of strategies for familial hypercholesterolaemia screening. J Public Health Med 2003;25(1):47-52

These two studies examined the relative cost of identifying FH patients through different methods. The methods included screening all 16-year-olds, identifying patients who had just had a heart attack, and conducting family tracing from probands known to have FH. Overall, the most cost-effective way of finding FH patients appeared to be through cascade testing from known probands. These findings were presented to the Department of Health and, in response, the recent White Paper on Genetics in the NHS committed funding to pilot a national cascade screening programme in five sites in England .

•  Neil HAW, Hammond T, Mant D, Humphries SE. Effect of statin treatment for familial hypercholesterolaemia on life assurance: results of consecutive surveys in 1990 and 2002. BMJ 2004;328:500-501

A study assessing to what extent insurance companies charge a policy excess on life assurance premiums for FH patients due to the increased risk of coronary disease. Interestingly, when an application for term life assurance was made by a hypothetical patient with FH, whose cholesterol levels had been well controlled with statins, most companies quoted premiums that were lower than for an untreated patient and in some cases no excess was applied.

•  Marks D, Thorogood M, Farrer M, Humphries SE. Census of clinics providing specialist lipid services in the United Kingdom . J Public Health Med 2004;26(4):353-4

Results of a survey of all the Lipid Clinics in Britain to try to identify how many FH patients are currently known. At the present there are 113 Lipid Clinics operating throughout mainland UK and it would appear that, at most, 15,000 FH patients have been identified and are on their databases. These patients, however, constitute a large enough group from whom to carry out cascade testing in any future national cascade screening programme.