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Journal Article

Would raising the total cholesterol diagnostic cut-off from 7.5 mmol/L to 9.3 mmol/L improve detection rate of patients with monogenic familial hypercholesterolaemia?


Publication date

Apr 2015


A previous report suggested that 88% of individuals in the general
population with total cholesterol (TC) > 9.3 mmol/L have familial
hypercholesterolaemia (FH). We tested this hypothesis in a cohort of
4896 UK civil servants, mean (SD) age 44 (±6) years, using next
generation sequencing to achieve a comprehensive genetic diagnosis. 25
(0.5%) participants (mean age 49.2 years) had baseline
TC > 9.3 mmol/L, and overall we found an FH-causing mutation in the LDLR
gene in seven (28%) subjects. The detection rate increased to 39% by
excluding eight participants with triglyceride levels over 2.3 mmol/L,
and reached 75% in those with TC > 10.4 mmol/L. By extrapolation, the
detection rate would be ∼25% by including all participants with
TC > 8.6 mmol/L (2.5 standard deviations from the mean). Based on the
1/500 FH frequency, 30% of all FH-cases in this cohort would be missed
using the 9.3 mmol/L cut-off. Given that an overall detection rate of
25% is considered economically acceptable, these data suggest that a
diagnostic TC cut-off of 8.6 mmol/L, rather than 9.3 mmol/L would be
clinically useful for FH in the general population.

Published in


Volume and page numbers

239 , 295 -298





Medicine, Health, and Biology


Open Access article; Open Access funded by Medical Research Council; Under a Creative Commons license


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