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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:335.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Systematic Family Screening for Familial Hypercholesterolemia in Iceland

Bolli Thorsson; Gunnar Sigurdsson; Vilmundur Gudnason

From the Icelandic Heart Association Research Institute (B.T., G.S., V.G.), the University of Iceland (G.S., V.G.), and the Lipid Clinic of Landspitali University Hospital of Iceland (G.S.), Kopavogur, Iceland.

Correspondence to Vilmundur Gudnason, MD, PhD, Director of the Icelandic Heart Association Research Institute, Holtasmári 1, 201 Kopavogur, Iceland. E-mail v.gudnason{at}hjarta.is

Objective— This study compares a novel approach using systematic family screening for patients in Iceland who have familial hypercholesterolemia (FH) with conventional proband screening and assesses the sensitivity and specificity of diagnosing FH by cholesterol measurements compared with mutational testing of family members.

Methods and Results— Probands with the I4T+2C mutation were traced to common ancestors. A downtracing of each family lineage was performed back to the oldest living offspring (key individuals); these individuals were recruited for cholesterol measurement and mutation testing. The sensitivity and specificity of cholesterol measurements was assessed against mutational analysis. Eleven probands clustered into 4 families. There were 364 key individuals identified among their descendants. Eighty-four percent responded, and 11% were positive for the mutation. There were 78 offspring of the positive key individuals, and 40 of those were carriers. Compared with use of the conventional first-degree relative approach, an additional 19% of FH individuals, including key individuals and their descendants, were identified. As diagnostic criteria, cholesterol measurements in the families had 95% specificity and 94% sensitivity.

Conclusions— Tracing FH probands to common ancestors and screening the oldest offspring in each family lineage adds considerably to the conventional method of FH screening (testing first-degree relatives). This may have relevance in other founder populations.

Key Words: familial hypercholesterolemia • preventive medicine • family screening • mutational analysis • screening enrichment

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