Background: In 2016 the International Atherosclerosis Society (IAS) proposed that patients with “severe” FH (SFH) should be identified since they might 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 patients in the UK Simon Broome Register since 1991, when statin use became routine.
Methods: 2929 Definite or Possible patients (51% women) aged 20-79 years recruited from 21 UK lipid clinics were followed between 1992-2016.  The excess CHD standardised mortality ratio (SMR) compared to the population in England and Wales was calculated (95% Confidence intervals). 
Results: (67.7%) patients met the SFH definition. Post 1991, 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 non-SFH 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 non-SFH was 122 (80-187) p=0.36. Applying UK guidelines for the use of PCSK9i agents, overall ~24% of those in the register are likely to be eligible, but if this were restricted to those with SFH, overall ~16% would qualify. 
Conclusions: CHD mortality remains elevated in treated FH, especially for SFH, emphasising the importance of optimal lipid-lowering, including the use of novel agents, and management of other risk factors.

01 - CORONARY HEART DISEASE MORTALITY IN SEVERE AND NON-SEVERE FAMILIAL HYPER-CHOLESTEROLAEMIA : DATA FROM THE UK SIMON BROOME FH REGISTER.