Dataset Information

Aortic Dimensions, Biophysical Properties, and Plasma Biomarkers in Children and Adults with Marfan or Loeys-Dietz Syndrome.

ABSTRACT:

Background

Aortic dilation, stiffening, and dissection are common and potentially lethal complications of Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS), which involve abnormal transforming growth factor beta (TGF-β) signalling. The relation of aortic dimensions, stiffness, and biomarker levels is unknown. The objective of this study was to measure aortic dimensions, stiffness, TGF-β and matrix metalloproteinase (MMP) levels, and endothelial function in patients with MFS, and to compare TGF-β levels in patients with MFS receiving different therapeutic regimens.

Methods

This was a cohort study of 40 MFS and 4 LDS patients and 87 control participants. Aortic dimension and stiffness indexes, including pulse wave velocity (PWV), were measured using echocardiography and Doppler. Total and free TGF-β and MMP blood levels were measured using Quantikine (R&D Systems, Inc, Minneapolis, MN) and Quanterix (Billerica, MA) kits. Endothelial function was measured using brachial artery flow-mediated dilation.

Results

PWV was increased in patients with MFS. There were increased MMP-2 levels in those with MFS but no increase in free or total TGF-β or MMP-9 levels compared with control participants. There was no difference in TGF-β levels between MFS patients receiving no medications, angiotensin receptor blockers, and β-blockers. PWV correlated most strongly with age. Endothelial function showed premature gradual decline in patients with MFS.

Conclusions

Despite the increased PWV, monitoring aortic stiffness or TGF-β levels would not be helpful in patients with MFS. TGF-β levels were not increased and the increased MMP-2 levels suggest consideration of a different therapeutic target.

SUBMITTER: Cui JZ

PROVIDER: S-EPMC8134910 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAortic aneurysm and aortic dissection can have a major impact on the life expectancy of Marfan syndrome (MFS) or Loeys-Dietz syndrome (LDS) patients. Although obesity can influence the development of aortic complications, evidence on whether obesity influences the development of aortic aneurysm or dissection in MFS and LDS is limited. The aim of the present study was to elucidate the relationship between aortic size and body composition, assessed by modern bioelectrical impedance analysis (BIA) in MFS/LDS-patients.MethodsIn this exploratory cross-sectional study in MFS or LDS patients, enrolled between June 2020 and May 2022, 34 patients received modern BIA and magnetic resonance imaging (MRI) (n=32) or computed tomography (CT) imaging (n=2) of the entire aorta. A P value of <0.05 was considered significant.ResultsFifty-one patients (66% female; mean age: 37.7±11.7; range, 17-68 years) with MFS or LDS were enrolled; 34 patients, 27 with MFS and 7 with LDS, underwent aortic MRI or CT scanning. The mean aortic length was 503.7±58.7 mm, and the mean thoracic aortic length and abdominal aortic length were 351.5±52.4 and 152.2±27.4 mm, respectively. The aortic bulb and the ascending aorta were measured only in the non-surgically repaired patients. Fifteen MFS (88.2%) and two LDS (40.0%) patients had an aortic aneurysm. In these, the aortic bulb tended to be larger in MFS than in LDS patients [42.6×41.9×41.2 vs. 37.8×37.4×36.8 mm; P=0.07 (-1.1; 9.1); P=0.07 (-1.2; 8.4); P=0.07 (-1.5; 7.9)]. BIA revealed mean body fat levels of 31.6%±8.7% (range, 9.5-53.5%), indicating that 18 patients (52.9%) were obese. There was a significant correlation between body fat content and thoracic aortic length (R=-0.377; P=0.02), muscle mass and total aortic length (R=0.359; P=0.03), thoracic aortic length (R=0.399; P=0.02), extracellular mass (ECM), and total aortic length (R=0.354; P=0.04), and connective tissue and aortic diameters at the aortic arch (R=0.511; P=0.002), aortic isthmus (R=0.565; P<0.001), and abdominal aorta (R=0.486; P=0.004). Older age was correlated with wider aortic arch, isthmus, and abdominal aorta. Male patients had a longer aorta.ConclusionsWhile a slender habitus is commonly known for MFS and LDS patients, our data show that many MFS and LDS patients (especially female) do not fit this phenotypic characteristic and are obese, which is associated with a more severe aortic phenotype. This topic should be included in the clinical assessment of affected MFS and LDS patients, in addition to measurement of the aortic diameters. Physicians should systematically screen MFS and LDS patients for obesity, educate them about the potential risk of resulting aortic complications, and encourage them to adopt a healthy lifestyle, that includes (mild) exercise and a balanced diet.

Project description:BACKGROUND AND PURPOSE:Loeys-Dietz syndrome (LDS) is a recently described entity that has the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Its neuroradiologic manifestations have not been well delineated. We sought to describe the neuroradiologic features of LDS and to assess the manifestations that would warrant follow-up imaging. MATERIALS AND METHODS:Two neuroradiologists retrospectively reviewed CT angiography (CTA), MR imaging, and plain film studies related to the head and neck in 25 patients ranging from 1 to 55 years of age, all of whom had positive genetic testing and clinical characteristics of LDS. Arterial tortuosity was evaluated by subjective assessment of 2D and 3D volumetric CTA and MR angiography data. Craniosynostosis and spinal manifestations were assessed by using plain films and CT images. MR images mostly of the head were reviewed for associated findings such as hydrocephalus, Chiari malformation, etc. Clinical manifestations were collated from the electronic patient record. RESULTS:All patients had extreme arterial tortuosity, which is characteristic of this syndrome. Thirteen patients had scoliosis, 12 had craniosynostosis, 8 had intracranial aneurysms, 6 had spinal instability, 3 had dissections of the carotid and vertebrobasilar arteries, 3 had hydrocephalus, 4 had dural ectasia, 2 had a Chiari malformation, and 1 had intracranial hemorrhage as a complication of vascular dissection. CONCLUSIONS:Significant neuroradiologic manifestations are associated with LDS, predominantly arterial tortuosity. Most of the patients in this series were young and, therefore, may require serial CTA monitoring for development of intra- and extracranial dissections and aneurysms, on the basis of the fact that most of the patients with pseudoaneurysms and dissection were older at the time of imaging. Other findings of LDS such as craniosynostosis, Chiari malformation, and spinal instability may also need to be addressed.