Back to Search
Start Over
Aggressive Cardiovascular Phenotype of Aneurysms-Osteoarthritis Syndrome Caused by Pathogenic SMAD3 Variants
- Source :
- Journal of the American College of Cardiology, 60(5), 397-403. Elsevier USA, Journal of the American College of Cardiology, 60, 397-403, Journal of the American College of Cardiology, 60, 5, pp. 397-403, Journal of the American College of Cardiology, Journal of the American College of Cardiology, 60(5), 397-403, Journal of the American College of Cardiology, 60(5), 397-403. Elsevier Inc.
- Publication Year :
- 2012
-
Abstract
- Objectives The purpose of this study was describe the cardiovascular phenotype of the aneurysms-osteoarthritis syndrome (AOS) and to provide clinical recommendations. Background AOS, caused by pathogenic SMAD3 variants, is a recently described autosomal dominant syndrome characterized by aneurysms and arterial tortuosity in combination with osteoarthritis. Methods AOS patients in participating centers underwent extensive cardiovascular evaluation, including imaging, arterial stiffness measurements, and biochemical studies. Results We included 44 AOS patients from 7 families with pathogenic SMAD3 variants (mean age: 42 +/- 17 years). In 71%, an aortic root aneurysm was found. In 33%, aneurysms in other arteries in the thorax and abdomen were diagnosed, and in 48%, arterial tortuosity was diagnosed. In 16 patients, cerebrovascular imaging was performed, and cerebrovascular abnormalities were detected in 56% of them. Fifteen deaths occurred at a mean age of 54 +/- 15 years. The main cause of death was aortic dissection (9 of 15; 60%), which occurred at mildly increased aortic diameters (range: 40 to 63 mm). Furthermore, cardiac abnormalities were diagnosed, such as congenital heart defects (6%), mitral valve abnormalities (51%), left ventricular hypertrophy (19%), and atrial fibrillation (22%). N-terminal brain natriuretic peptide (NT-proBNP) was significantly higher in AOS patients compared with matched controls (p < 0.001). Aortic pulse wave velocity was high-normal (9.2 +/- 2.2 m/s), indicating increased aortic stiffness, which strongly correlated with NT-proBNP (r = 0.731, p = 0.005). Conclusions AOS predisposes patients to aggressive and widespread cardiovascular disease and is associated with high mortality. Dissections can occur at relatively mildly increased aortic diameters; therefore, early elective repair of the ascending aorta should be considered. Moreover, cerebrovascular abnormalities were encountered in most patients. (J Am Coll Cardiol 2012;60:397-403) (C) 2012 by the American College of Cardiology Foundation
- Subjects :
- Male
Heart disease
Cardiomyopathy
Bioinformatics
SMAD3
Cohort Studies
Aortic aneurysm
Fibrosis
Pregnancy
Cause of Death
Natriuretic Peptide, Brain
genetics
Cause of death
Genes, Dominant
Cardiovascular diseases [NCEBP 14]
Syndrome
Middle Aged
Phenotype
Cardiovascular Diseases
Cardiology
cardiovascular system
Female
Cardiology and Cardiovascular Medicine
Adult
medicine.medical_specialty
Adolescent
Aortography
Genomic disorders and inherited multi-system disorders [IGMD 3]
Young Adult
Aneurysm
Imaging, Three-Dimensional
Vascular Stiffness
SDG 3 - Good Health and Well-being
Internal medicine
Image Interpretation, Computer-Assisted
Osteoarthritis
medicine
Humans
Smad3 Protein
Survival analysis
Aged
Chromosome Aberrations
Aortic Aneurysm, Thoracic
business.industry
medicine.disease
Survival Analysis
Peptide Fragments
aorta
Aortic Dissection
Cerebrovascular Disorders
Genomic Structural Variation
Human medicine
business
Subjects
Details
- ISSN :
- 07351097
- Volume :
- 60
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of the American College of Cardiology
- Accession number :
- edsair.doi.dedup.....d1ab66fc39dc826102517d6d8987ed01