Published Online
on November 29, 2004

A more recent version of this article appeared on January 1, 2005

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Submitted on August 5, 2004
Revised on September 28, 2004
Accepted on October 1, 2004

Heritability of Carotid Artery Atherosclerotic Lesions. An Ultrasound Study in 154 Families

Susanna Moskau MD; Astrid Golla PhD; Christoph Grothe MD; Monika Boes MD; Christoph Pohl MD; and Thomas Klockgether MD^*

From the Department of Neurology (S.M., C.G., M.B., C.P., T.K.) and the Institute of Medical Informatics (A.G.), Biometrics and Epidemiology, University Hospital Bonn, Germany.

^* To whom correspondence should be addressed. E-mail: klockgether{at}uni-bonn.de.

Background and Purpose--Ultrasound examination of the carotid arteries yields several quantitative measures that may serve as intermediate phenotypes in genetic studies. This study was undertaken to compare the heritabilities of 3 ultrasound measures: intima-media thickness (IMT), plaque score, and maximal stenosis.

Methods--We studied 565 individuals from 154 families ascertained by an affected parent with carotid artery atherosclerosis. IMT, plaque score, and maximal stenosis of the carotid arteries were examined by B-mode ultrasound and analyzed quantitatively. Heritability estimates were obtained by variance component analysis as implemented in the program SOLAR (sequential oligogenic linkage analysis routines). Covariates were age, sex, weight, height, body mass index (BMI), arterial hypertension, diabetes mellitus, amount of nicotine consumed, and plasma levels of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, LDL/HDL ratio, lipoprotein(a) [Lp(a)], triglycerides, factor VIII, factor XIII, fibrinogen, and von Willebrand factor (vWF).

Results--After accounting for the covariables age, sex, hypertension, diabetes mellitus, and Lp(a), heritability of IMT was estimated as h²=0.61±0.17 (P=0.001). Variation of plaque score was influenced by age, sex, hypertension, diabetes mellitus, hypercholesterolemia, amount of nicotine consumed, factor VIII, and vWF. When these were considered, no significant heritability could be detected. Heritability of stenosis was estimated as h²=0.47±0.07 (P=0.006), with age, sex, BMI, hypertension, diabetes mellitus, amount of nicotine consumed, and LDL/HDL ratio as covariates.

Conclusions--Among the 3 ultrasound measures studied, IMT had the highest heritability. IMT was strongly influenced by genetic determinants other than those influencing known risk factors. This makes IMT a promising candidate for use as an intermediate phenotype in genetic studies aiming to identify novel genes for atherosclerosis.

Key words: atherosclerosis • carotid arteries • genetics • ultrasonography

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