Coronary heart disease mortality in severe vs. non-severe familial hypercholesterolaemia in the Simon Broome Register

Steve E Humphries,Jackie A Cooper,Nigel Capps,Paul N Durrington,Ben Jones,Ian F.W Mcdowell,Handrean Soran,Andrew H.W Neil

doi:10.1016/j.atherosclerosis.2018.11.014

Abstract

Background and aimsThe International Atherosclerosis Society (IAS) has proposed that patients with “severe” FH (SFH) would warrant early and more aggressive cholesterol-lowering treatment such as with PCSK9 inhibitors. SFH is diagnosed if LDL-cholesterol (LDLC) > 10 mmol/L, or LDLC >8.0 mmol/L plus one high-risk feature, or LDLC >5 mmol/L plus two high-risk features. Here we compare CHD mortality in SFH and non-SFH (NSFH) patients in the UK prospective Simon Broome Register since 1991, when statin use became routine. Methods2929 definite or possible PFH patients (51% women) aged 20–79 years were recruited from 21 UK lipid clinics and followed prospectively between 1992 and 2016. The excess CHD standardised mortality ratio (SMR) compared to the England and Wales population was calculated (with 95% confidence intervals). Results1982 (67.7%) patients met the SFH definition. Compared to the non-SFH, significantly (p < 0.001) more SFH patients had diagnosed CHD at baseline (24.6% vs. 17.5%), were current smokers (21.9% vs 10.2%) and had a BMI > 30 kg/m2 (14.9% vs. 7.8%). The SMR for CHD mortality was significantly (p = 0.007) higher for SFH (220 (184–261) (34,134 person years, 129 deaths observed, vs. 59 expected) compared to NSFH of 144 (98–203) (15,432 person years, 32 observed vs. 22 expected). After adjustment for traditional risk factors, the Hazard Ratio for CHD mortality in SFH vs. NSFH was 1.22 (0.80–1.87) p = 0.36, indicating that the excess risk was largely accounted for by these factors. ConclusionsCHD mortality remains elevated in treated FH, especially for SFH, emphasising the importance of optimal lipid-lowering and management of other risk factors.

Highlights

Familial hypercholesterolaemia (FH) is a common autosomal dominant disorder caused by carriage of a mutation in one of several genes known to be involved in clearance of low-density lipoprotein cholesterol (LDL-C) particles from the blood [1,2]
We examine whether the coronary heart disease (CHD) risk associated with severe” FH (SFH) is similar in men and women, and we estimate the risk of CHD in SFH in different age groups, and to what extent the CHD standardised mortality ratio (SMR) rates fall over time in SFH as potent statins become available
High levels of Lp(a) and creatinine are components of the SFH definition [6], but were not available for this cohort, and a proportion of the NSFH patients would be moved to the SFH category if this data were available, so this figure is an underestimate of the true prevalence of SFH in this cohort

Summary

Introduction

Familial hypercholesterolaemia (FH) is a common autosomal dominant disorder caused by carriage of a mutation in one of several genes known to be involved in clearance of low-density lipoprotein cholesterol (LDL-C) particles from the blood [1,2]. We compare the standardised mortality ratio (SMR) for CHD in SFH and non-SFH patients in the UK prospective Simon Broome Register, which has been following FH patients since 1988 for CHD and non-CHD causes of death [7,8,9,10]. We use this data to estimate the SMR for CHD in SFH vs Non-SFH (NSFH). Conclusions: CHD mortality remains elevated in treated FH, especially for SFH, emphasising the importance of optimal lipid-lowering and management of other risk factors

Methods

Results

Conclusion