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(Hypertension. 2001;38:1190.)
© 2001 American Heart Association, Inc.

Fourth Workshop on Structure and Function of Large Arteries: Part II

Carotid and Femoral Artery Stiffness in Relation to Three Candidate Genes in a White Population

Elisabeth J. Balkestein; Jan A. Staessen; Ji-Guang Wang; Janneke J. van der Heijden-Spek; Luc M. Van Bortel; Cristina Barlassina; Giuseppe Bianchi; Eva Brand; Stefan-Martin Herrmann; Harry A. Struijker-Boudier

From the Cardiovascular Research Institute Maastricht, Department of Pharmacology and Toxicology, Maastricht University (E.J.B., J.J. van der H.-S., L.M. Van B., H.A.S.-B.), Maastricht, The Netherlands; Hypertensie en Cardiovasculaire Revalidatie Eenheid, Departement Moleculair en Cardiovasculair Onderzoek, Katholieke Universiteit Leuven (J.A.S., J.-G.W.), Leuven, Belgium; Heymans Institute of Pharmacology, Ghent University (L.M. Van B.), Ghent, Belgium; Divisione di Nefrologia Dialisi e Ipertensione, Ospedale San Raffaele, Dipartimento di Scienze en Tecnologie Biomediche, Universitá degli Studi di Milano (C.B., G.B.), Milano, Italy; and Departments of Nephrology (E.B.) and Clinical Pharmacology (S.-M.H.), Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany.

Correspondence to E.J.M. Balkestein, MD, Cardiovascular Research Institute Maastricht, Maastricht University, Department of Pharmacology and Toxicology, PO Box 616, 6201 MD Maastricht, The Netherlands. E-mail e.balkestein{at}farmaco.unimaas.nl

Abstract

Abstract—— Different genetic polymorphisms influence cardiovascular disease. We recently discovered a relationship between the intima-media thickness of the muscular femoral artery, but not the elastic common carotid artery, and the combined ACE (ACE, I/D), -adducin (Gly460Trp),and aldosterone synthase (AS, C-344T) gene polymorphisms. To investigate the relationship between these polymorphisms and functional properties of the carotid artery and femoral artery, a sample of 756 subjects enrolled in a population study were genotyped for the presence of the ACE D, -adducin 460Trp, and aldosterone synthase -344T alleles. Vessel wall properties were assessed using a vessel wall movement detector system in combination with applanation tonometry. Statistical analysis allowed for confounders and interaction among genes. Cross-sectional compliance of the common carotid artery was negatively associated with the ACE D allele. ACE II versus ACE DD homozygotes differed, expressed as a percentage of the population mean (7.0%; 95% confidence interval [CI], 1.6% to 12.4%; P=0.02). In multigene analysis, ACE DD subjects also deviated significantly from the population mean for the distensibility coefficient of the common carotid artery when carrying the AS/T allele (-5.5%; 95% CI, -9.3% to -1.7%; P<0.01), without a change in cross-sectional compliance. ACE DD subjects, when homozygote for -adducin Gly460, had a lower femoral cross-sectional compliance (-10.4%; 95% CI, -1.9% to -18.9%; P<0.03) and a lower distensibility (-9.7%; 95% CI, -2.1% to -17.3%; P<0.02) compared with the population mean. These data show that functional large artery properties are influenced by the ACE I/D polymorphism. Cross-sectional compliance and distensibility coefficients are influenced by the ACE I/D genotype, but this influence depends on the vascular territory and genetic background.

Key Words: angiotensin-converting enzyme • genes • polymorphism • race • arteries • population

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