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Fibrillin-1 genotype is associated with aortic stiffness and disease severity in patients with coronary artery disease.

Abstract：

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.

journal_name

Circulation

journal_title

Circulation

authors

Medley TL,Cole TJ,Gatzka CD,Wang WY,Dart AM,Kingwell BA

doi

10.1161/hc0702.104129

subject

Has Abstract

pub_date

2002-02-19 00:00:00

pages

810-5

issue

eissn

0009-7322

issn

1524-4539

journal_volume

105

pub_type

临床试验,杂志文章

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Fibrillin-1 genotype is associated with aortic stiffness and disease severity in patients with coronary artery disease.