Publication type
Journal Article
Authors
Publication date
April 15, 2015
Summary:
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
Atherosclerosis
Volume and page numbers
Volume: 239 , p.295 -298
DOI
http://dx.doi.org/10.1016/j.atherosclerosis.2015.01.028
ISSN
219150
Subjects
Notes
Open Access article
Open Access funded by Medical Research Council
Under a Creative Commons license
#523011