This Article Full Text Full Text (PDF) All Versions of this Article: 23/2/335    most recent 01.ATV.0000051874.51341.8Cv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thorsson, B. Articles by Gudnason, V. Search for Related Content PubMed PubMed Citation Articles by Thorsson, B. Articles by Gudnason, V. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL Genetics Home Reference Related Collections Clinical genetics Lipids Genetics of cardiovascular disease Lipid and lipoprotein metabolism

(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

This article has been cited by other articles:

				Authors/Task Force Members, I. Graham, D. Atar, K. Borch-Johnsen, G. Boysen, G. Burell, R. Cifkova, J. Dallongeville, G. De Backer, S. Ebrahim, et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts) Eur. Heart J., October 1, 2007; 28(19): 2375 - 2414. [Full Text] [PDF]

				A. J. Lusis, A. M. Fogelman, and G. C. Fonarow Genetic Basis of Atherosclerosis: Part II: Clinical Implications Circulation, October 5, 2004; 110(14): 2066 - 2071. [Full Text] [PDF]

				A. J. Lusis, A. M. Fogelman, and G. C. Fonarow Genetic Basis of Atherosclerosis: Part I: New Genes and Pathways Circulation, September 28, 2004; 110(13): 1868 - 1873. [Full Text] [PDF]

				M. A. Austin, C. M. Hutter, R. L. Zimmern, and S. E. Humphries Genetic Causes of Monogenic Heterozygous Familial Hypercholesterolemia: A HuGE Prevalence Review Am. J. Epidemiol., September 1, 2004; 160(5): 407 - 420. [Abstract] [Full Text] [PDF]