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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?

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 achiev...

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Detalles Bibliográficos
Autores principales: Futema, M., Kumari, M., Boustred, C., Kivimaki, M., Humphries, S.E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373788/
https://www.ncbi.nlm.nih.gov/pubmed/25682026
http://dx.doi.org/10.1016/j.atherosclerosis.2015.01.028
Descripción
Sumario: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.