Published Online
on March 17, 2003

A more recent version of this article appeared on March 25, 2003

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Submitted on October 9, 2002
Revised on December 19, 2002
Accepted on January 2, 2003

Family History and Cardiovascular Risk in Familial Hypercholesterolemia. Data in More Than 1000 Children

Albert Wiegman MD, Jessica Rodenburg MD, Saskia de Jongh MD, Joep C. Defesche PhD, Henk D. Bakker MD, PhD, John J.P. Kastelein MD, PhD^*, and Eric J.G. Sijbrands MD, PhD

From the Departments of Pediatrics and Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands (A.W., J.R., S.d.J., J.C.D., H.D.B., J.J.P.K); and the Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands (E.J.G.S.).

^* To whom correspondence should be addressed. E-mail: e.vandongen{at}amc.uva.nl.

Background--Elevated LDL cholesterol (LDL-C) levels in childhood predict cardiovascular disease (CVD) later in life. Familial hypercholesterolemia (FH) represents the paradigm of this relation.

Methods and Results--The objectives of this study were to (1) establish the LDL-C level that provides the most accurate diagnosis of FH in children from families with known FH and (2) assess whether lipoprotein variation in these children is associated with premature CVD in relatives. Foremost, however, it was our objective to identify children with FH who are at high risk and in need of early intervention. A total of 1034 consecutive children from FH kindreds were investigated. First, LDL-C levels >3.50 mmol/L had a 0.98 post-test probability (95% CI, 0.96 to 0.99) of predicting the presence of an LDL receptor mutation. Second, children with FH in the highest LDL-C tertile (>6.23 mmol/L) had a 1.7-times higher incidence (95% CI, 1.24 to 2.36) of having a parent with FH suffering from premature CVD (P=0.001). In addition, such a parent was found 1.8 times more often (95% CI, 1.20 to 2.59) among children with FH who had HDL-C <1.00 mmol/L (P=0.004). Last, children with FH whose lipoprotein(a) was >300 mg/L had a 1.45-times higher incidence (95% CI, 0.99 to 2.13) of having a parent with FH suffering from premature CVD (P=0.05).

Conclusions--In FH families, LDL-C levels allow accurate diagnosis of FH in childhood. Moreover, increased LDL-C and lipoprotein(a) and decreased HDL-C levels in children identify FH kindreds with the highest CVD risk.

Key words: lipoproteins • hypercholesterolemia • cardiovascular diseases • cholesterol

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