on January 22, 2002
Published online before print January 22, 2002, doi: 10.1161/hc0702.104129
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 23, 2001
From the Alfred and Baker Medical Unit (T.L.M., C.D.G., A.M.D., B.A.K.) and Molecular Genetics Laboratory (T.J.C.), Baker Medical Research Institute Prahran, Victoria, Australia, and the Department of Medical Genetics and Cambridge Institute for Medical Research (W.Y.S.W.), University of Cambridge, Cambridge, UK. * To whom correspondence should be addressed. E-mail: b.kingwell{at}alfred.org.au.
Background—Elevated pulse pressure is associated strongly with adverse cardiovascular outcome; however, the genetic basis of this condition is unknown. This study examined whether genotypic variation in the extracellular matrix protein fibrillin-1, the Marfan gene, was associated with aortic stiffening and therefore could contribute to cardiovascular risk associated with pulse pressure elevation in coronary disease. Methods and Results—Patients (n=145; 113 men), 62±9 years of age (mean±SD), with angiographically confirmed coronary disease, were studied. Carotid applanation tonometry was used to assess central blood pressures, and in conjunction with Doppler velocimetry, to assess aortic input and characteristic impedance. Fibrillin-1 genotype was characterized by a variable nucleotide tandem repeat and 2 single-nucleotide polymorphisms. The variable nucleotide tandem repeat was a good predictor of underlying haplotypes with 3 genotypes (2-2, 2-4, and 2-3) accounting for 86% of the population. The 2-3 genotype had higher input impedance (P=0.002), characteristic impedance (P=0.005), and carotid pulse pressure (P=0.002) compared with the 2-2 and 2-4 genotypes. Disease severity assessed by previous angioplasties and the number of patients with a stenosis >90% was also greater in the 2-3 genotype. Furthermore, in a multivariate analysis, fibrillin-1 genotype and central pulse pressure were independent of conventional risk factors in determining coronary disease severity. There was no difference in age, sex ratio, body mass index, smoking status, cholesterol level, or medication among the 3 genotypes. Conclusions—Although a causative link has not been shown, these data are consistent with an important role for fibrillin-1 genotype in cardiovascular risk associated with large-artery stiffening and pulse pressure elevation in individuals with coronary disease.
Revised on December 11, 2001
Accepted on December 19, 2001
Fibrillin-1 Genotype Is Associated With
Aortic Stiffness and Disease Severity in Patients With Coronary
Artery Disease
Key words: mechanics • coronary disease • arteries • blood pressure • aorta
This article has been cited by other articles:
 |
|
 |
|
  S. S. DeLoach and R. R. Townsend Vascular Stiffness: Its Measurement and Significance for Epidemiologic and Outcome Studies Clin. J. Am. Soc. Nephrol., January 1, 2008; 3(1): 184 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Gonzalez, A. M. Briones, B. Somoza, C. J. Daly, E. Vila, B. Starcher, J. C. McGrath, M. C. Gonzalez, and S. M. Arribas Postnatal alterations in elastic fiber organization precede resistance artery narrowing in SHR Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H804 - H812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J De Backer, G J Nollen, D Devos, G Pals, P Coucke, K Verstraete, E E van der Wall, A De Paepe, and B J M Mulder Variability of aortic stiffness is not associated with the fibrillin 1 genotype in patients with Marfan's syndrome. Heart, July 1, 2006; 92(7): 977 - 978. [Full Text] [PDF]
|
|
|
|
 |
|
 Yasmin, I. B. Wilkinson, K. M. O'Shaughnessy, T. Lanne, R. De Basso, and J. T. Powell Influence of fibrillin-1 genotype on aortic stiffness in men: a note of caution J Appl Physiol, April 1, 2006; 100(4): 1431 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Powell, R. J. Turner, M. Sian, R. Debasso, and T. Lanne Influence of fibrillin-1 genotype on the aortic stiffness in men J Appl Physiol, September 1, 2005; 99(3): 1036 - 1040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Mitchell, A. L. DeStefano, M. G. Larson, E. J. Benjamin, M.-H. Chen, R. S. Vasan, J. A. Vita, and D. Levy Heritability and a Genome-Wide Linkage Scan for Arterial Stiffness, Wave Reflection, and Mean Arterial Pressure: The Framingham Heart Study Circulation, July 12, 2005; 112(2): 194 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Laurent, P. Boutouyrie, and P. Lacolley Structural and Genetic Bases of Arterial Stiffness Hypertension, June 1, 2005; 45(6): 1050 - 1055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Medley, T. J. Cole, A. M. Dart, C. D. Gatzka, and B. A. Kingwell Matrix Metalloproteinase-9 Genotype Influences Large Artery Stiffness Through Effects on Aortic Gene and Protein Expression Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1479 - 1484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Hadjinikolaou, K Kotidis, and M Galinanes Relationship between reduced elasticity of extracardiac vessels and left main stem coronary artery disease Eur. Heart J., March 2, 2004; 25(6): 508 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Medley, B. A. Kingwell, C. D. Gatzka, P. Pillay, and T. J. Cole Matrix Metalloproteinase-3 Genotype Contributes to Age-Related Aortic Stiffening Through Modulation of Gene and Protein Expression Circ. Res., June 13, 2003; 92(11): 1254 - 1261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Oliver and D. J. Webb Noninvasive Assessment of Arterial Stiffness and Risk of Atherosclerotic Events Arterioscler. Thromb. Vasc. Biol., April 1, 2003; 23(4): 554 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Kingwell, T. K. Waddell, T. L. Medley, J. D. Cameron, and A. M. Dart Large artery stiffness predicts ischemic threshold in patients with coronary artery disease J. Am. Coll. Cardiol., August 21, 2002; 40(4): 773 - 779. [Abstract] [Full Text] [PDF]
|
|