Paolo Salvi1, Andrea Grillo1,2, Susan Marelli3, Lan Gao4, Lucia Salvi5, Maurizio Viecca3, Anna Maria Di Blasio6, Renzo Carretta7, Alessandro Pini3, Gianfranco Parati1,2. 1. Department of Cardiovascular Neural and Metabolic Sciences, IRCCS Istituto Auxologico Italiano. 2. Department of Medicine and Surgery, University of Milano-Bicocca. 3. Department of Cardiology, Rare Disease Center 'Marfan Clinic', ASST Fatebenefratelli Sacco, Milan, Italy. 4. Department of Cardiology, Peking University First Hospital, Beijing, China. 5. Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia. 6. Department of Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milan. 7. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
Abstract
OBJECTIVE: Marfan syndrome (MFS) is an autosomal dominant genetic disorder characterized by aortic root dilation and dissection and an abnormal fibrillin-1 synthesis. In this observational study, we evaluated aortic stiffness in MFS and its association with ascending aorta diameters and fibrillin-1 genotype. METHODS: A total of 116 Marfan adult patients without history of cardiovascular surgery, and 144 age, sex, blood pressure and heart rate matched controls were enrolled. All patients underwent arterial stiffness evaluation through carotid-femoral pulse wave velocity (PWV) and central blood pressure waveform analysis (PulsePen tonometer). Fibrillin-1 mutations were classified based on the effect on the protein, into 'dominant negative' and 'haploinsufficient' mutations. RESULTS: PWV and central pulse pressure were significantly higher in MFS patients than in controls [respectively 7.31 (6.81-7.44) vs. 6.69 (6.52-6.86) m/s, P = 0.0008; 41.3 (39.1-43.5) vs. 34.0 (32.7-35.3) mmHg, P < 0.0001], with a higher age-related increase of PWV in MFS (β 0.062 vs. 0.036). Pressure amplification was significantly reduced in MFS [18.2 (15.9-20.5) vs. 33.4 (31.6-35.2)%, P < 0.0001]. Central pressure profile was altered even in MFS patients without aortic dilatation. Multiple linear regression models showed that PWV independently predicted aortic diameters at the sinuses of Valsalva (ß = 0.243, P = 0.002) and at the sinotubular junction (ß = 0.186, P = 0.048). PWV was higher in 'dominant negative' than 'haploinsufficient' fibrillin-1 mutations [7.37 (7.04-7.70) vs. 6.60 (5.97-7.23) m/s, P = 0.035], although this difference was not significant after adjustment. CONCLUSION: Aortic stiffness is increased in MFS, independently from fibrillin-1 genotype and is associated with diameters of ascending aorta. Alterations in central hemodynamics are present even when aortic diameter is within normal limits. Our findings suggest an accelerated arterial aging in MFS.
OBJECTIVE:Marfan syndrome (MFS) is an autosomal dominant genetic disorder characterized by aortic root dilation and dissection and an abnormal fibrillin-1 synthesis. In this observational study, we evaluated aortic stiffness in MFS and its association with ascending aorta diameters and fibrillin-1 genotype. METHODS: A total of 116 Marfan adult patients without history of cardiovascular surgery, and 144 age, sex, blood pressure and heart rate matched controls were enrolled. All patients underwent arterial stiffness evaluation through carotid-femoral pulse wave velocity (PWV) and central blood pressure waveform analysis (PulsePen tonometer). Fibrillin-1 mutations were classified based on the effect on the protein, into 'dominant negative' and 'haploinsufficient' mutations. RESULTS: PWV and central pulse pressure were significantly higher in MFSpatients than in controls [respectively 7.31 (6.81-7.44) vs. 6.69 (6.52-6.86) m/s, P = 0.0008; 41.3 (39.1-43.5) vs. 34.0 (32.7-35.3) mmHg, P < 0.0001], with a higher age-related increase of PWV in MFS (β 0.062 vs. 0.036). Pressure amplification was significantly reduced in MFS [18.2 (15.9-20.5) vs. 33.4 (31.6-35.2)%, P < 0.0001]. Central pressure profile was altered even in MFSpatients without aortic dilatation. Multiple linear regression models showed that PWV independently predicted aortic diameters at the sinuses of Valsalva (ß = 0.243, P = 0.002) and at the sinotubular junction (ß = 0.186, P = 0.048). PWV was higher in 'dominant negative' than 'haploinsufficient'fibrillin-1 mutations [7.37 (7.04-7.70) vs. 6.60 (5.97-7.23) m/s, P = 0.035], although this difference was not significant after adjustment. CONCLUSION: Aortic stiffness is increased in MFS, independently from fibrillin-1 genotype and is associated with diameters of ascending aorta. Alterations in central hemodynamics are present even when aortic diameter is within normal limits. Our findings suggest an accelerated arterial aging in MFS.
Authors: Eusebio García-Izquierdo; Vanessa Moñivas-Palomero; Alberto Forteza; Carlos Martín-López; Mario Torres-Sanabria; Xabier Cia-Mendioroz; Consuelo Olivo-Rodríguez; Sara Navarro-Rico; Andrés Sánchez-Gómez; Jesús G Mirelis; Miguel A Cavero; Susana Mingo-Santos Journal: Int J Cardiovasc Imaging Date: 2021-04-19 Impact factor: 2.357
Authors: Zoe White; Nadia Milad; Arash Y Tehrani; Jennifer Lamothe; James C Hogg; Mitra Esfandiarei; Michael Seidman; Steven Booth; Tillie-Louise Hackett; Mathieu C Morissette; Pascal Bernatchez Journal: Am J Pathol Date: 2019-05-22 Impact factor: 4.307
Authors: Constance G Weismann; Joanna Hlebowicz; Anna Åkesson; Petru Liuba; Katarina Hanseus Journal: Front Physiol Date: 2022-04-25 Impact factor: 4.755
Authors: Catherine Tcheandjieu; Matthew Aguirre; Stefan Gustafsson; Priyanka Saha; Praneetha Potiny; Melissa Haendel; Erik Ingelsson; Manuel A Rivas; James R Priest Journal: PLoS Genet Date: 2020-11-23 Impact factor: 5.917
Authors: Giuseppina Laganà; Nicolò Venza; Arianna Malara; Claudio Liguori; Paola Cozza; Calogera Pisano Journal: Int J Environ Res Public Health Date: 2021-03-16 Impact factor: 3.390