P1448 Thoracic aorta and circulating transforming growth factor-b in marfan syndrome and marfanoid habitus

Abstract

Abstract Purpose Current understanding of the pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MS) focuses upon abnormal activity of the transforming growth factor beta (TGF-β) signalling pathway. Circulating TGF-β predicts cardiovascular events in patients with MS and is elevated in the entire spectrum of aortic syndromes. Marfanoid habitus (MH) patients not meeting the MS criteria (TAA, ectopia lentis, family history), but share the same skeletal features and are the part of the Marfan continuum. Our aim was to evaluate the possible role of elevated TGF-β level in the aortic dilatation at mid-term follow-up in Marfanoid habitus patients. Methods 33 consecutive patients with a presumptive clinical diagnosis of Marfan syndrome were referred to Almazov centre and enrolled in our observational, prospective, single-center study. Nine of them (mean age 27.9 ± 9.3) fulfilled diagnosis of MS according to revised Ghent criteria. 24 subjects (mean age 21.8 ± 3.4) with skeletal features of Marfanoid habitus have had no major findings of MS. Proximal aortic segments were visualized in the parasternal long-axis and suprasternal views. Concentration of TGF-β1 and TGF-β2 in serum was determined using a test system Human Platinum ELISA. End points analyzed during 5 years of follow-up were mortality, aortic-related events, and aortic dimension changes. Results During 122 person-years of the follow-up (median 5.1 years) no deaths or aortic-related events occurred in Marfanoid habitus patients. TGF-β1 and TGF-β2 serum levels were elevated in patients with Marfanoid habitus (14.2 ± 27.6 and 2.1 ± 1.7 ng/ml, respectively) but were lower than in MS group (44.6 ± 47.3 ng/ml, p = 0.03 and 2.7 ± 1.7 ng/ml, p = 0.39, respectively). A high TGF-β1 serum level (cutoff >14.75 ng/ml, provided by the manufacturer of our TGF-β assay) was detected in 44% and TGF-β2 (>2.0 ng/ml) in majority patients (67%) of the MS group. In Marfanoid habitus group we found a high TGF-β1 serum level only in 4 (17%) patients and TGF-β2 in 9 (38%) patients. Aortic diameter at the sinuses of Valsalva and Z-score were significantly lower in Marfanoid habitus group (29.2 ± 2.8 mm and 1.56 ± 0.93) than in MS patients (43.1 ± 15.1 mm, p = 0.0007 and 6.86 ± 5.83, p = 0.004) at the beginning of study and significantly increased during the follow-up (31.3 ± 2.9 mm and 1,69 ± 0,15, p < 0.001 for both). There was no correlation between TGF-β level and aortic dimensions in patients with MS and marfanoid habitus. Conclusion In young adults with Marfanoid habitus and the current absence of ascending aortic aneurysm we found the increased TGF-β level and aortic root enlargement during the follow-up. High TGF-β serum level may contribute to the excessive progression of aortic dilatation later over mid-to-late aging and requires further investigation to establish its role in the aortic aneurysm pathogenesis.