Imputation of Baseline LDL Cholesterol Concentration in Patients with Familial Hypercholesterolemia on Statins or Ezetimibe.

TitleImputation of Baseline LDL Cholesterol Concentration in Patients with Familial Hypercholesterolemia on Statins or Ezetimibe.
Publication TypeJournal Article
Year of Publication2017
AuthorsRuel, I, Aljenedil, S, Sadri, I, de Varennes, É, Hegele, RA, Couture, P, Bergeron, J, Wanneh, E, Baass, A, Dufour, R, Gaudet, D, Brisson, D, Brunham, LR, Francis, GA, Cermakova, L, Brophy, JM, Ryomoto, A, Mancini, GBJ, Genest, J
JournalClinical Chemistry
Paginationpii: clinchem.2017.279422
Date Published10/2017
ISSNPrint: 0009-9147; Online: 1530-8561


Familial hypercholesterolemia (FH) is the most frequent genetic disorder seen clinically and is characterized by increased LDL cholesterol (LDL-C) (>95th percentile), family history of increased LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) in the patient or in first-degree relatives, presence of tendinous xanthomas or premature corneal arcus, or presence of a pathogenic mutation in the LDLR, PCSK9, or APOB genes. A diagnosis of FH has important clinical implications with respect to lifelong risk of ASCVD and requirement for intensive pharmacological therapy. The concentration of baseline LDL-C (untreated) is essential for the diagnosis of FH but is often not available because the individual is already on statin therapy.


To validate a new algorithm to impute baseline LDL-C, we examined 1297 patients. The baseline LDL-C was compared with the imputed baseline obtained within 18 months of the initiation of therapy. We compared the percent reduction in LDL-C on treatment from baseline with the published percent reductions.


After eliminating individuals with missing data, nonstandard doses of statins, or medications other than statins or ezetimibe, we provide data on 951 patients. The mean ± SE baseline LDL-C was 243.0 (2.2) mg/dL [6.28 (0.06) mmol/L], and the mean ± SE imputed baseline LDL-C was 244.2 (2.6) mg/dL [6.31 (0.07) mmol/L] (P = 0.48). There was no difference in response according to the patient's sex or in percent reduction between observed and expected for individual doses or types of statin or ezetimibe.


We provide a validated estimation of baseline LDL-C for patients with FH that may help clinicians in making a diagnosis.