Coronary heart disease mortality in treated familial hypercholesterolaemia: Update of the UK Simon Broome FH register (2018)

Type of publication:
Journal article

Author(s):
Humphries S.E.; Cooper J.A.; Seed M.; *Capps N.; Durrington P.N.; Jones B.; McDowell I.F.W.; Soran H.; Neil H.A.W.

Citation:
Atherosclerosis; Jul 2018; vol. 274 ; p. 41-46

Abstract:
Background and aims: Patients with familial hypercholesterolaemia (FH) have an elevated risk of coronary heart disease (CHD). Here we compare changes in CHD mortality in patients with heterozygous (FH) pre 1992, before lipid-lowering therapy with statins was used routinely, and in the periods 1992-2008 and 2008-2016. Methods: 1903 Definite (DFH) and 1650 Possible (PFH) patients (51% women) aged 20-79 years, recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980 and 2016 for 67,060 person-years. The CHD standardised mortality ratio (SMR) compared to the population in England and Wales was calculated (with 95% Confidence intervals). Results: There were 585 deaths, including 252 from CHD. Overall, the observed 2.4-fold excess coronary mortality for treated DFH post-1991 was significantly higher than the 1.78 excess for PFH (35% 95% CI 3%-76%). In patients with DFH and established coronary disease, there was a significant excess coronary mortality in all time periods, but in men it was reduced from a 4.83-fold excess (2.32-8.89) pre-1992 to 4.66 (3.46-6.14) in 1992-2008 and 2.51 (1.01-5.17) post-2008, while in women the corresponding values were 7.23 (2.65-15.73), 4.42 (2.70-6.82) and 6.34 (2.06-14.81). Primary prevention in men with DFH resulted in a progressive reduction in coronary mortality over the three time-periods, with no excess mortality evident post-2008 (0.89 (0.29-2.08)), although in women the excess persisted (post-2008 3.65 (1.75-6.72)). Conclusions: The results confirm the benefit of statin treatment in reducing CHD mortality, but suggest that FH patients with pre-existing CHD and women with FH may not be treated adequately.

Coronary heart disease mortality in treated Familial Hypercholesterolaemia: Update of the UK Simon Broome FH Register (2017)

Type of publication:
Conference abstract

Author(s):
Humphries S.E.; Cooper J.A.; Seed M.; *Capps N.; Durrington P.N.; Jones B.; McDowell I.F.W.; Soran H.; Neil

Citation:
Atherosclerosis Supplements; 2017; vol. 28, Pages 41-46

Abstract:
Background: Guidelines for the management of patients with Familial Hypercholesterolaemia (FH) recommend the use of high intensity statin therapy to reduce subsequent risk of Coronary Heart Disease (CHD). Here we compare changes in CHD mortality in patients with heterozygous (FH) pre 1992 before lipid-lowering therapy with statins was used routinely, and in the periods 1992-2008 and 2008 till the present. Methods: Analysis used 1903 Definite (DFH) and 1650 Possible (PFH) patients (51% women) aged 20-79 years, recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980-1991 (6627 personyears) 1992-2008 (43117 person-years) and 2009-2016 (17317 person-years). The excess CHD standardised mortality ratio (SMR) compared to the population in England and Wales was calculated (with 95% Confidence intervals). Results: There were 252 deaths from CHD. Overall, treated DFH patients had a higher CHD SMR than PFH patients (post 1991 35% higher 2.40 (2.00-2.86) vs 1.78 (1.44-2.19) p = 0.03). In treated DFH patients with previous CHD the CHD SMR was significantly elevated at all time periods but in men fell from a 4.83-fold excess (2.32-8.89) pre-1992 to 4.66 (3.46-6.14) in 1992-2008 and 2.51 (1.01-5.17) post 2008, while in women these values were 7.23 (2.65-15.73), 4.42 (2.70-6.82) and 6.34 (2.06-14.81)). In treated DFH men with no previous CHD the CHD SMR fell over the three time periods, and was not significantly elevated post 2008 (0.89 (0.29-2.08), but in women the SMR remained significantly elevated (post 2008 3.65 (1.75-6.72)). Conclusions: The data confirm the major benefit in CHD mortality associated with statin treatment, but suggest that FH patients with pre-existing disease, and women with FH may not be being treated adequately.

Knowledge gaps in the management of familial hypercholesterolaemia. A UK based survey (2016)

Type of publication:
Journal article

Author(s):
Jonathan Schofield, See Kwok, Michael France, *Nigel Capps, Ruth Eatough, Rahul Yadav, Kausik Ray, Handrean Soran

Citation:
Atherosclerosis (2016) [article in press]

Abstract:
Background and aims: Untreated individuals with familial hypercholesterolaemia (FH) are at increased
risk of developing premature cardiovascular disease (CVD). Early diagnosis and treatment can result in a
normal life expectancy. A recent survey commissioned by the European Atherosclerosis Society (EAS)
reported a lack of awareness of FH in the general population.We conducted a survey to assess knowledge
among healthcare professionals involved in the assessment and management of cardiovascular risk and
disease in the United Kingdom.
Methods: A survey designed to assess knowledge of diagnostic criteria, risk assessment, the role of
cascade screening, and management options for patients with FH was distributed to 1000 healthcare
professionals (response rate 44.3%). The same survey was redistributed following attendance at an
educational session on FH.
Results: 151 respondents (40.5%) reported having patients under their care who would meet the diagnostic criteria for FH, but just 61.4% recognized that cardiovascular risk estimation tools cannot be
applied in FH, and only 22.3% understood the relative risk of premature CVD compared to the general
population. Similarly, just 65.9% were aware of recommendations regarding cascade screening.
Conclusions: The prevalence and associated risk of FH continue to be underestimated, and knowledge of
diagnostic criteria and treatment options is suboptimal. These results support the recent Consensus
Statement of the EAS and production of quality standards by the National Institute for Health and Care
Excellence. Further work is required to formulate interventions to improve FH awareness and knowledge, and to determine the effect these interventions have on patient outcomes.