Imputation of untreated LDL-C in treated subjects with homozygous familial hypercholesterolaemia: An international collaboration

Diagnosis of Homozygous Familial Hypercholesterolaemia (HoFH) relies on untreated low-density lipoprotein-cholesterol (LDL-C) which is often unknown. We determine whether untreated LDL-C can be imputed from treated LDL-C in HoFH. Two groups with HoFH were identified: Group 1 (n = 193) from Canada, B...

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Veröffentlicht in:	Atherosclerosis Jg. 412; S. 120590
Hauptverfasser:	John Mancini, G.B., Ryomoto, Arnold, Ruel, Isabelle, Iatan, Iulia, Raal, Frederick J., Santos, Raul D., Marte, Ana Paula, Hegele, Robert A., Kennedy, Brooke A., Brunham, Liam R., Gaudet, Daniel, Larouche, Miriam, Brisson, Diane, Schonck, Willemijn, Reeskamp, Laurens F., Genest, Jacques
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Ireland Elsevier B.V 01.01.2026
Schlagworte:	Estimated untreated low-density lipoprotein-cholesterol Homozygous familial hypercholesterolaemia Imputation LDL-Receptor Lipid lowering therapy Low density lipoprotein-cholesterol Low density lipoprotein-cholesterol Lipid lowering therapy Estimated untreated low-density lipoprotein-cholesterol Imputation Homozygous familial hypercholesterolaemia LDL-Receptor
ISSN:	0021-9150, 1879-1484, 1879-1484
Online-Zugang:	Volltext
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Zusammenfassung:	Diagnosis of Homozygous Familial Hypercholesterolaemia (HoFH) relies on untreated low-density lipoprotein-cholesterol (LDL-C) which is often unknown. We determine whether untreated LDL-C can be imputed from treated LDL-C in HoFH. Two groups with HoFH were identified: Group 1 (n = 193) from Canada, Brazil and South Africa; Group 2 (n = 206) from the HoFH International Clinical Collaboration. Pre- and post-treatment LDL-C and lipid lowering therapy (LLT) intensity from Group 1 were used to develop a regression model and applied to treated LDL-C in Group 2 to impute pre-treatment LDL-C. The same process was performed in reverse. A final imputation model was created from combining both groups. There was a curvilinear relationship between the expected and observed % lowering of LDL-C on LLT (r = 0.3923, p < 0.0001, Standard Error [SE] = 23 %). Using this relationship, LDL-C was imputed from treated values and showed significant correlation with pre-treatment LDL-C (r = 0.71, p < 0.001; mean values 13.4 ± 4.7 [Standard Deviation] and 13.6 ± 7.3 mmol/L, respectively, ns). Concordance between actual and imputed values ≥ 10 or <10 mmol/L was 80 %. Whereas 36 % of patients had treated LDL-C ≥ 10 mmol/L, 64 % had treated or imputed pre-treatment LDL-C ≥ 10 mmol/L. In HoFH, the response to LLT can be quantified and used to impute untreated LDL-C from treated LDL-C. Imputation may augment awareness of possible HoFH in treated subjects lacking records of untreated LDL-C. [Display omitted] •Subjects with Homozygous Familial Hypercholesterolemia have biallelic mutations affecting LDL-C clearance.•They respond to LDL-C lowering therapy in a variable and diminished fashion compared to other patients.•Despite this, there is a quantifiable, relationship between intensity of therapy and resulting LDL-C.•This relationship was validated from international cohorts of patients with Homozygous Familial Hypercholesterolemia.•If baseline LDL-C is missing, imputed LDL-C can raise the possibility of underlying Homozygous Familial Hypercholesterolemia.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0021-9150 1879-1484 1879-1484
DOI:	10.1016/j.atherosclerosis.2025.120590