Sex-specific distributions and determinants of thoracic aortic diameters in the elderly

Bons, Lidia R.; Rueda‐Ochoa, Oscar L.; Ghoul, Khalid El; Rohde, Sofie; Budde, Ricardo P.J.; Leening, Maarten J.G.; Vernooij, Meike W.; Franco, Oscar H.; Lugt, Aad van der; Roos‐Hesselink, Jolien W.; Kavousi, Maryam; Bos, Daniël

doi:10.1136/heartjnl-2019-315320

Cited by 27 publications

(33 citation statements)

References 28 publications

(32 reference statements)

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“…Interestingly, the presence of DM was related to a smaller ascending and descending aortic diameter in the literature [38]. This phenomenon might be caused by high glucose levels associated with DM which inhibits intermediate-phase secretion of the matrix metalloproteinases.…”

Section: Discussionmentioning

confidence: 93%

Epicardial adipose tissue is a predictor of ascending aortic dilatation in hypertensive patients, but not paracardial adipose tissue

Argan

Avcı

Yıldırım

et al. 2020

BMC Cardiovasc Disord

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Background: Ascending aortic aneurysms are one of the major causes of mortality. In recent years, there is a growing interest of epicardial adipose tissue (EAT) and related diseases. The aim of this study was to investigate the relationship of EAT, and PAT with ascending aortic dilatation (AAD). Methods: We included 934 patients with hypertension in this study. The patients were evaluated by a complete transthoracic echocardiographic examination, including measurements of EAT, PAT, and aortic dimensions. Aortic size index (ASI) was used for diagnosing AAD. The patients were divided into two groups: dilated ascending aorta diameter (ASI ≥ 21 mm / m 2 , n = 102) or normal aortic diameter (ASI < 21 mm / m2, n = 832) according to the ASI. Characteristics of these patients were compared before and after propensity score matching analysis. Results: Patients with AAD were older (72.3 ± 11.6 vs. 61.7 ± 12.7 years, p < 0.001), had more female gender (66% vs. 54%,p = 0.021) than patients with normal ascending aorta (AA). After propensity score matching analysis (77 vs. 77), EAT [OR:1.461, %95CI (1.082-1.974), p = 0.013] was independently associated with AAD in multivariate logistic regression analysis. In ROC curve analysis, EAT > 0.45 cm had 51.9% sensitivity and 62.3% specificity [AUC = 0.617, P = 0.012, 95% CI (0.529-0.707)]. Conclusion: Based on our findings, increased EAT may be suggested as an independent risk factor for AAD due to local or systemic effects in hypertensive patients.

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Section: Discussionmentioning

confidence: 93%

Epicardial adipose tissue is a predictor of ascending aortic dilatation in hypertensive patients, but not paracardial adipose tissue

Argan

Avcı

Yıldırım

et al. 2020

BMC Cardiovasc Disord

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“…1 ) following instructions from Jackson Labs. Since the incidence of thoracic aortic disease (including aneurysm and dissection) is higher in men than in women [ 23 , 24 ], male mice have been used for experimentation.…”

Section: Methodsmentioning

confidence: 99%

Targeting feed-forward signaling of TGFβ/NOX4/DHFR/eNOS uncoupling/TGFβ axis with anti-TGFβ and folic acid attenuates formation of aortic aneurysms: Novel mechanisms and therapeutics

et al. 2021

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In the present study we aimed to identify novel mechanisms and therapeutics for thoracic aortic aneurysm (TAA) in Fbn1 C1039G/+ Marfan Syndrome (MFS) mice. The expression of mature/active TGFβ and its downstream effector NOX4 were upregulated while tetrahydrobiopterin (H 4 B) salvage enzyme dihydrofolate reductase (DHFR) was downregulated in Fbn1 C1039G/+ mice. In vivo treatment with anti-TGFβ completely attenuated NOX4 expression, restored DHFR protein abundance, reduced ROS production, recoupled eNOS and attenuated aneurysm formation. Intriguingly, oral administration with folic acid (FA) to recouple eNOS markedly alleviated expansion of aortic roots and abdominal aortas in Fbn1 C1039G/+ mice, which was attributed to substantially upregulated DHFR expression and activity in the endothelium to restore tissue and circulating levels of H 4 B. Notably, circulating H 4 B levels were accurately predictive of tissue H 4 B bioavailability, and negatively associated with expansion of aortic roots, indicating a novel biomarker role of circulating H 4 B for TAA. Furthermore, FA diet abrogated TGFβ and NOX4 expression, disrupting the feed-forward loop to inactivate TGFβ/NOX4/DHFR/eNOS uncoupling axis in vivo and in vitro, while PTIO, a NO scavenger, reversed this effect in cultured human aortic endothelial cells (HAECs). Besides, expression of the rate limiting H 4 B synthetic enzyme GTP cyclohydrolase 1 (GTPCHI), was downregulated in Fbn1 C1039G/+ mice at baseline. In cultured HAECs, RNAi inhibition of fibrillin resulted in reduced GTPCHI expression, while this response was abrogated by anti-TGFβ, indicating TGFβ-dependent downregulation of GTPCHI in response to fibrillin deficiency. Taken together, our data for the first time reveal that uncoupled eNOS plays a central role in TAA formation, while anti-TGFβ and FA diet robustly abolish aneurysm formation via inactivation of a novel TGFβ/NOX4/DHFR/eNOS uncoupling/TGFβ feed-forward pathway. Correction of fibrillin deficiency is additionally beneficial via preservation of GTPCHI function.

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“…In their Heart paper, Bons and colleagues report the results of the Rotterdam Study 9. They provide us with population based, sex-specific distributions values of thoracic aortic diameters in the elderly.…”

mentioning

confidence: 99%

“…Their findings9 suggest the need to reassess commonly used reference values, considering older age and sex. They provided part of the missing data needed to reassess reference values and inspire future research into the prognostic implications of their findings.…”

mentioning

confidence: 99%

Sex-specific thoracic aortic dimensions and clinical implications

Groepenhoff

Ruijter

2019

Heart

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Patients with a dilated thoracic aorta are at risk for aortic complications such as aortic dissection or rupture. While these aortic complications result in high mortality rates, aortic dilatation often remains asymptomatic for a long period of time. Therefore, identification and treatment of individuals with a dilated aorta is of paramount importance. This is specifically relevant given that the diagnostic techniques and therapeutic options are available. Currently, the European Society of Cardiology guidelines define an aorta dilated if the diameter exceeds 40 mm. In addition, preventive surgery is indicated for aortic diameters above 55 mm for both women and men. 1 Even though thoracic aortic aneurysms are less prevalent in women as compared with men, the consequences are worse for women. Female patients with an aortic dissection have a poorer surgical outcome and die more frequently than men. Also, the growth rate of a thoracic aneurysm is greater in women as compared with men. 2 Currently, as medicine advances, personalised medicine has become emerging. The most relevant patient characteristics that have been considered relevant in medicine are age, sex and comorbidities such as diabetes. However, for aortic complications, information on subgroups is limited as data in older patients is sparse, and currently used cutoff values are based on a cohort of relatively young people. 3 In addition to lack of data on age, thoracic aortic diameters values have been determined regardless of sex. As a result, one-size fits all cut-off values are used, while the Framingham Heart Study had indicated that age and sex matter for vascular dimensions such as thoracic aortic diameter. 4 Since more attention is being paid to sex differences within arterial vascular disease, 5 it has been described that women have smaller carotid and coronary arteries 6 and have smaller abdominal aortic aneurysms as compared with men (summarised in figure 1). As smaller abdominal aortic aneurysms in women are more prone to rupture, 5 the currently used uniform threshold for dilated abdominal aortic aneurysm repair has been under debate. 7 For the coronary vasculature, smaller vessels in women have been hypothesised to be one of the underlying reasons for the higher risk of coronary complications in women undergoing coronary artery revascularisation. 6 8 In their Heart paper, Bons and colleagues report the results of the Rotterdam Study. 9 They provide us with population based, sex-specific distributions values of thoracic aortic diameters in the elderly. In addition, they identify relevant determinants for the aortic diameters in men and women. Of the 2505 participants, approximately half is female that allowed for an equally powered study in men and women. The population underwent non-enhanced multidetector computed tomography (CT) to measure ascending and descending aortic diameters. As it is still undecided whether aortic diameters should be evaluated using body surface area (BSA) corrected values or absolute values, the authors assessed bo...

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Sex-specific distributions and determinants of thoracic aortic diameters in the elderly

Cited by 27 publications

References 28 publications

Epicardial adipose tissue is a predictor of ascending aortic dilatation in hypertensive patients, but not paracardial adipose tissue

Epicardial adipose tissue is a predictor of ascending aortic dilatation in hypertensive patients, but not paracardial adipose tissue

Targeting feed-forward signaling of TGFβ/NOX4/DHFR/eNOS uncoupling/TGFβ axis with anti-TGFβ and folic acid attenuates formation of aortic aneurysms: Novel mechanisms and therapeutics

Sex-specific thoracic aortic dimensions and clinical implications

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