OBJECTIVE:Despite a voluminous literature on aortopathy, comparatively little attention has been paid to the lamellar architecture of the aortic wall, including the number and distribution of these layers. This study compares the lamellar organization of the developing aorta in individuals with a bicuspid (BAV) versus tricuspid aortic valve (TAV) and includes a literature review on aortic lamellae in mammals and adult humans. METHODS:Non-dilated ascending aortic wall samples (n = 83) were analyzed from individuals aged embryonic to 72 years, categorized into six age groups. Additionally, a literature review was carried out on lamellar counts across species. RESULTS:The elastic lamellae in preterm aortas were well-structured with no pathological features. Conversely, adult aortas showed progressive elastic fiber pathology. The number of lamellae increased with age; neonates had the lowest count, peaking in young children, and gradually decreasing in adolescents. Furthermore, compared to TAV patients, BAV patients showed patterns of thinner intimal layers and fewer elastic lamellae. Our literature review showed that the quantity of lamellae in mammals is correlated with both body size and aortic radius, with smaller animals having fewer lamellae. The ascending thoracic aorta in humans had between 45 and 78 elastic lamellae, while the descending and abdominal aortas had fewer layers. CONCLUSION:The number of elastic lamellae in the aortic wall is influenced by both age and valve morphology. BAV patients had less lamellae than TAV patients, which could contribute to the disparity in clinical outcomes. In older adults, age-related lamellar degeneration likely increases the risk of aortopathy.

Prenatal development of autonomic innervation of sinus venosus-related structures might be related to atrial arrhythmias later in life. Most of the pioneering studies providing embryological background are conducted in animal models. To date, a detailed comparison with the human cardiac autonomic nervous system (cANS) is lacking. The aim of this study was to compare the morphological and functional development of the cANS between mouse and human, specifically aimed at the venous pole. Wildtype mouse embryos (E9.5–E18.5) and healthy human fetuses (6–38 weeks gestational age (WGA)) were studied at sequential stages to obtain a comparative developmental series. Cardiac autonomic function was assessed through heart rate variability (HRV) analysis using ultrasound. Morphological assessment of the venous pole was performed using immunohistochemical stainings for neural crest cells and autonomic nerve markers. Murine cANS function did not definitively establish in utero as HRV parameters depicted no trend prior to birth. In contrast, human HRV parameters greatly increased from 20 to 30 WGA, indicating that human cANS function is established prenatally around 20 WGA and matures thereafter. Morphologically, cANS development followed a similar sequence with neural crest-derived nerves entering the venous pole in proximity to the developing pulmonary vein in both species. However, the timing of differentiation into sympathetic or parasympathetic phenotype was markedly distinct, as human autonomic markers emerged relatively later when related to major cardiogenesis. Structures related to arrhythmogenicity in humans, such as the ligament/vein of Marshall and the myocardium surrounding the pulmonary veins, become highly innervated during embryonic development in both mice and humans. Although early morphological cANS development at sinus venosus-related structures follows a similar sequence in mice and humans, there are substantial differences in the timing of functional establishment and differentiation in sympathetic and parasympathetic phenotypes, which should be taken into account when extrapolating mouse studies of the cANS to humans. The abundant innervation of sinus venosus-related structures may play a modulatory role in arrhythmogenesis under pathological conditions.

The venous pole of the heart where the pulmonary veins will develop encompasses the sinus venosus and the atrium. In the fourth week of development, the sinus venosus consists of a left and a right part receiving blood from the common cardinal vein, the omphalomesenteric and umbilical veins. Asymmetrical expansion of the common atrium corresponds with a rightward shift of the connection of the sinus to the atrium. The right-sided part of the sinus venosus including its tributing cardinal veins enlarges to form the right superior and inferior vena cava that will incorporate into the right atrium. The left-sided part in human development largely obliterates and remodels to form the coronary sinus in adults. In approximately the same time window (4th-fifth weeks), a splanchnic vascular plexus surrounds the developing lung buds (putative lungs) with a twofold connection. Of note, during early developmental stages, the primary route of drainage from the pulmonary plexus is toward the systemic veins and not to the heart. After lumenization of the so-called mid-pharyngeal endothelial strand (MPES), the first anlage of the pulmonary vein, the common pulmonary vein can be observed in the dorsal mesocardium, and the primary route of drainage will gradually change toward a cardiac drainage. The splanchnic pulmonary venous connections with the systemic cardinal veins will gradually disappear during normal development. In case of absence or atresia of the MPES, the pulmonary-to-systemic connections will persist, clinically resulting in total anomalous pulmonary venous return (TAPVR). This chapter describes the developmental processes and molecular pathways underlying anomalous pulmonary venous connections.

The prevalence of coronary artery disease (CAD) in bicuspid aortic valve (BAV) patients is a debatable topic. Several studies have indicated that BAV patients have a lower prevalence of CAD compared with patients with a tricuspid aortic valve (TAV), but the effects of age and gender have not always been considered. This systematic review provides an overview of articles which report on CAD in BAV and TAV patients. Searches were executed in April 2021 and January 2022 according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines in three online databases: Medline, Embase, and Scopus. Screening and data extraction was done by two investigators separately. Primary and secondary outcomes were compared between BAV and TAV patients; a fixed effects model was used for correcting on confounders. Literature search yielded 1,529 articles with 44 being eligible for inclusion. BAV patients were younger (56.4 ± 8.3 years) than TAV patients (64 ± 10.3 years, p < 0.001). All CAD risk factors and CAD were more prevalent in TAV patients. No significant difference remained after correcting for age and gender as confounders. BAV patients have a lower prevalence of CAD and CAD risk factors compared with TAV patients. However, when the age differences between both groups are considered in the analyses, a similar prevalence of both CAD and CAD risk factors is found.

Patients with a bicuspid aortic valve carry an increased risk for developing an ascending aortic aneurysm due to intrinsic aortic wall alterations. A lower threshold for aortic surgery may therefore be considered in these patients, especially in those who require aortic valve surgery. This study aimed to compare the outcomes of an isolated aortic valve replacement with that of an aortic root replacement in bicuspid aortic valve patients with an indication for aortic valve surgery. Patients were included in retrospect from a tertiary academic hospital. Included patients received an elective aortic valve (AVR) or a composite valve-graft conduit (both mechanical and biological) between 2006 and 2021 without any concomitant procedure. Mortality data were retrieved from a national database and comparisons, including survival analyses, were performed between both groups. A total of 132 isolated AVR and 149 aortic root replacements were included. Patients who received an isolated AVR were significantly older than the aortic root replacement group (62.9 vs. 57.7 year respectively, p < 0.001). Survival analyses showed a comparable long-term mortality between both groups (8.1

Partial anomalous pulmonary venous connections (PAVC) have been found after abnormal gene expressions involving several syndromes. Total anomalous pulmonary venous connection (TAPVC) is found in conjunction with heterotaxia syndrome as well as several other syndromes. It has been reported with an autosomal dominance with variable expression and incomplete penetrance. The occurrence is also related to environmental factors which may superimpose on a familial susceptibility for TAPVC. Many pathways are involved in the normal development of the pulmonary venous connections and as a consequence disturbance of many genetic and epigenetic pathways lead to partial or total pulmonary venous misconnections. In this chapter, an overview of current knowledge regarding human genetics of anomalous venous connections is provided.

Background Although sex-related differences in cardiovascular surgery outcomes have increasingly garnered attention in the past decades, knowledge about sex disparities in the pathophysiology of acute type A aortic dissections (ATAADs) remains sparse. In this study, we evaluate the histopathologic and atherosclerotic lesions in female and male ATAAD patients. Methods A total of 68 patients were studied: 51 ATAAD patients (mean age: 62.5 +/- 10.8 years; 49% women) and 17 control patients (mean age: 63 +/- 5.5 years; 53% women). Cardiovascular risk factors were assessed clinically. Intimal and medial histopathological features were systematically evaluated in all. Results Compared to the control group, all ATAAD patients showed significantly more elastic fiber pathology, mucoid extracellular matrix accumulation, smooth muscle cell nuclei loss, and overall medial degeneration ( p < 0.0001). The tunica intima was significantly thinner in the ATAAD patients than in the control group ( p < 0.023), with the latter exhibiting significantly more progressive atherosclerotic lesions than the former. No difference in medial vessel wall pathology was seen between female and male patients. As compared to male ATAAD patients, atherosclerotic lesions were more severe in female ATAAD patients, independent of age and the cardiovascular risk factor hypertension. Conclusion All ATAAD patients had a significantly thinner tunica intima and significantly diseased tunica media compared to the control patients. Our results suggest that the severity of medial aortic pathology is not sex specific in ATAAD patients. Intimal differences between females and males could, however, be considered a potential risk factor for the development of an aortic dissection.

Nanoplastics can cause severe malformations in chicken embryos. To improve our understanding of the toxicity of nanoplastics to embryos, we have studied their biodistribution in living chicken embryos. We injected the embryos in the vitelline vein at stages 18-19. We injected polystyrene nanoparticles (PS-NPs) tagged with europium- or fluorescence. Their biodistribution was tracked using inductively-coupled plasma mass spectrometry on tissue lysates, paraffin histology, and vibratome sections analysed by machine learning algorithms. PS-NPs were found at high levels in the heart, liver and kidneys. Furthermore, PS-NPs crossed the endocardium of the heart at sites of epithelial-mesenchymal transformation; they also crossed the liver endothelium. Finally, we detected PS-NPs in the allantoic fluid, consistent with their being excreted by the kidneys. Our study shows the power of the chicken embryo model for analysing the biodistribution of nanoplastics in embryos. Such experiments are difficult or impossible in mammalian embryos. These findings are a major advance in our understanding of the biodistribution and tissue-specific accumulation of PS-NPs in developing animals.

Development of the heart is a very intricate and multiplex process as it involves not only the three spatial dimensions but also the fourth or time dimension. Over time, the heart of an embryo needs to adapt its function to serve the increasing complexity of differentiation and growth towards adulthood. It becomes even more perplexing by expanding time into millions of years, allocating related species in the tree of life. As the evolution of soft tissues can hardly be studied, we have to rely on comparative embryology, supported heavily by genetic and molecular approaches. These techniques provide insight into relationships, not only between species, but also between cell populations, signaling mechanisms, molecular interactions and physical factors such as hemodynamics. Heart development depends on differentiation of a mesodermal cell population that - in more derived taxa - continues in segmentation of the first and second heart field. These fields deliver not only the cardiomyocytes, forming the three-dimensionally looping cardiac tube as a basis for the chambered heart, but also the enveloping epicardium. The synchronized beating of the heart is then organized by the conduction system. In this Review, the epicardium is introduced as an important player in cardiac differentiation, including the conduction system.

A bicuspid aortic valve (BAV) is the most prevalent congenital cardiac deformity, which is associated with an increased risk to develop a thoracic aortic aneurysm and/or an aortic dissection as compared to persons with a tricuspid aortic valve. Due to the high prevalence of a BAV in the general population and the associated life-long increased risk for adverse vascular events, BAV disease places a considerable burden on the public health. The aim of the present review is to discuss the role of transforming growth factor beta (TGF-β) signaling in the development of the vascular wall and on how this complex signaling pathway may be involved in thoracic aortic aneurysm formation in tricuspid and BAV patients.

Background: Patients with a bicuspid aortic valve (BAV) have an increased risk to develop aortic complications. Many studies are pointing towards a possible embryonic explanation for the development of both a bicuspid aortic valve as well as a defective ascending aortic wall in these patients. The fetal and newborn ascending aortic wall has however scarcely been studied in bicuspid aortic valve patients. We hypothesize that early histopathological defects might already be visible in the fetal and pediatric ascending aortic wall of bicuspid aortic valve patients, indicating at an early embryonic defect.Methods: Non-dilated BAV ascending aortic wall samples were collected (n = 40), categorized in five age groups: premature (age range 17.5 weeks + days GA till 37.6 weeks + days GA) 2. neonate (age range 1 - 21 days) 3. infant (age range 1 month - 4 years) 4. adolescent (age range 12 years - 15 years) and 5. adult (age range 41 - 72 years). Specimen were studied for intimal and medial histopathological features.Results: The premature ascending aortic wall has a significantly thicker intimal and significantly thinner medial layer as compared to all other age categories (p < 0.05). After birth the intimal thickness decreases significantly. The medial layer increases in thickness before adulthood (p < 0.05) with an increasing number of elastic lamellae (p < 0.01) and interlamellar mucoid extracellular matrix accumulation (p < 0.0001). Intimal atherosclerosis was scarce and medial histopathological features such as overall medial degeneration, smooth muscle cell nuclei loss and elastic fiber fragmentation were not appreciated in the BAV ascending aortic wall of any age.Conclusions: The main characteristics of a bicuspid ascending aortic wall are already present before adulthood, albeit not before birth. Considering the early manifestations of ascending aortic wall pathology in bicuspid aortic valve patients, the pediatric population should be considered while searching for markers predictive for future aortopathy.

COPYRIGHT © 2023 Grewal, Klautz and Poelmann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Commentary: Transforming growth factor serum concentrations in patients with proven non-syndromic aortopathy

ObjectivePatients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) have a significantly increased risk to develop thoracic aortopathy. Both conditions share many pathophysiological mechanisms leading to aortic complications. Bicuspidy is known to have a low risk for acquired coronary artery sclerosis. The aim of this study is to determine the risk of coronary sclerosis in MFS patients.MethodsMarfan syndrome patients with an aortic root dilatation, which were surgically treated between 1999 and 2017, were included and matched with BAV and tricuspid aortic valves (TAV) patients based on sex and age. Cardiovascular risk profiles were determined in all three groups. Coronary sclerosis was graded in all patients on coronary imaging (coronary angiography or computed tomography) using a coronary artery scoring method, which divides the coronaries in 28 segments and scores non-obstructive (20–49% sclerosis) and obstructive coronary sclerosis (>49% sclerosis) in each segment.ResultsA total of 90 matched patients (30 within each group) were included. MFS patients showed less cardiovascular risk factors compared to BAV and TAV patients. TAV patients had higher amounts of obstructive coronary sclerosis as compared to BAV patients (p = 0.039) and MFS patients (p = 0.032). No difference in non- and obstructive coronary artery disease (CAD) was found between the MFS and BAV population.ConclusionMarfan syndrome and bicuspid aortic valve patients have a significantly lower risk for, and prevalence of CAD as compared to TAV individuals.

Background An aortic dissection is the most devastating complication of thoracic aortic disease. Several non- and syndromic conditions such as a bicuspid aortic valve (BAV) and Marfan syndrome (MFS) have a severely increased risk to develop a thoracic aortic aneurysm and dissection. To date, the medial layer has been extensively studied in search of the pathogenetic mechanisms leading to aortic complications. Objective We aim to determine whether intimal layer pathology is characteristic in all thoracic aortopathy regardless of the underlying etiology. Method A total of 176 aortic wall specimen were studied for the intimal layer architecture including the intimal thickness, endothelial cell morphology, and atherosclerosis. Specimens were derived from four patient groups: BAV ( n = 70, age 57 ± 8.9 years), isolated tricuspid aortic valve (TAV) ( n = 38, age 64.9 ± 11.0 years), MFS with a TAV ( n = 8, age 34.2 ± 11.0 years), type A dissections with a TAV ( n = 60, age 62.7 ± 10 years). Results The intimal layer is significantly thinner in BAV, MFS, and type A aortic dissection as compared to the isolated TAV patients ( p < 0.001). Intimal atherosclerosis was also significantly less present in the three groups as compared to the isolated TAV ( p < 0.05). Discussion A thin intimal layer is a common finding in the thoracic aortopathy patients. Studies aiming at preventing future aortic complications should focus on the intimal pathology as a common effector pathway in thoracic aortopathy.

Background Type A aortic dissections (TAAD) are devastating aortic complications. Patients with Marfan syndrome, a bicuspid aortic valve or a thoracic aortic aneurysm have an increased risk to develop a TAAD. These predisposing conditions are characterized by a histologically thin intimal layer and hardly any atherosclerosis. Little is known about the susceptibility for atherosclerosis in patients with a type A aortic dissection. Objective We aim to systematically describe atherosclerotic lesions in TAAD patients. Materials and methods A total of 51 patients with a TAAD (mean age 62.5 ± 10.8 years, 49% females) and 17 control patients (mean age 63 ± 5.5 years, 53% females) were included in this study. Cardiovascular risk factors were assessed clinically. All sections were stained with Movat pentachrome and hematoxylin eosin. Plaque morphology was classified according to the modified AHA classification scheme proposed by Virmani et al. Results In the TAAD group thirty-seven percent were overweight (BMI > 25). Diabetes and peripheral arterial disease were not present in any of the patients. Fifty-nine percent of the patients had a history of hypertension. The intima in TAAD patients was significantly thinner as compared to the control group (mean thickness 143 ± 126.5 μm versus 193 ± 132 μm, p < 0.023). Seven TAAD patients had a normal intima without any form of adaptive or pathological thickening. Twenty-three TAAD patients demonstrated adaptive intimal thickening. Fourteen had an intimal xanthoma, also known as fatty streaks. A minority of 7 TAAD patients had progressive atherosclerotic lesions, 4 of which demonstrated pathological intimal thickening, 3 patients showed early fibroatheroma, late fibroatheroma and thin cap fibroatheroma. In the control group the majority of the patients exhibited progressive atherosclerotic lesions: three pathologic intimal thickening, two early fibroatheroma, six late fibroatheroma, one healed rupture and two fibrotic calcified plaque. Discussion This study shows that TAAD patients hardly exhibit any form of progressive atherosclerosis. The majority of TAAD patients showcase non-progressive intimal lesions, whereas the control group mostly demonstrated progressive intimal atherosclerotic lesions. Findings are independent of age, sex, or the presence of (a history of) hypertension.

Patients with a bicuspid aortic valve have an extreme high risk to develop a thoracic aortic aneurysm and dissection (TAAD). TAADs form a leading cause of death worldwide, with the majority of deaths being preventable if individuals at risk are identified and properly managed. Risk stratification for TAADs in bicuspidy is so far solely based on the aortic diameter. Exclusive use of aortic wall dimension, as in the current guidelines, is however not sufficient in selecting patients vulnerable for future aortic wall complications. Moreover, there are no effective medical treatments for TAADs to retain progressive aortic dilatation and thus prevent or delay aortic complications. Only surgical replacement of the aorta increases life expectancy in patients with a risk for a TAAD. Therefore, the next major challenge in the management of TAADs is the development of a personalized patient-tailored risk stratification for early detection of patients with an increased risk for TAADs, who will benefit from surgical resection of the aorta. Several signaling pathways have been studied in recent times to develop a patient specific risk stratification model. In this paper we discuss TGF-β signaling and downstream signalers as potential markers for future aortic complications in bicuspid aortic valve patients.

Background: A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. The development of the aortic valve is closely related to the development of the ascending aorta, associated with structural differences in the bicuspid aorta. Here we describe the non-dilated ascending aortic wall in bicuspid aortic valve patients.Methods: BAV (n = 41) and tricuspid aortic valve (TAV) (n = 18) non-dilated ascending aortic wall samples were studied. We investigated the following features of the aortic wall: vessel wall thickness, endothelial cell morphology, atherosclerosis, and elastic lamellae organization. Medial pathologic features encompass-ing elastic fiber thinning, fragmentation and degeneration, overall medial degeneration, mucoid extracel-lular matrix accumulation, and smooth muscle cell nuclei loss were studied. Furthermore, we included apoptosis, periaortic inflammation, and the level of expression of differentiated vascular smooth muscle cells.Results: The non-dilated BAV ascending aortic wall is characterized by a significantly thinner intimal layer, without features of atherosclerosis ( P < .001). The medial layer is significantly thicker ( P < .001) with more mucoid extracellular matrix accumulation ( P < .001). All other medial pathologic features were more prominent in the TAV ( P < .001). The media has significantly less differentiated vascular smooth muscle cells ( P < .001) between the neatly regulated elastic lamellae which are thinner in the BAV as compared to the TAV ( P < .0 0 01).Conclusions: The BAV ascending aorta without dilatation is characterized by a differentiation def ect of vascular smooth muscle cells in the media and a significantly thinner intimal layer without overt patho-logic features.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Background Thoracic aortopathy is a serious complication which is more often seen in patients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) than in individuals with a tricuspid aortic valve (TAV). The identification of common pathological mechanisms leading to aortic complications in non-syndromic and syndromic diseases would significantly improve the field of personalized medicine. Objective This study sought to compare thoracic aortopathy between MFS, BAV, and TAV individuals. Materials and methods Bicuspid aortic valve (BAV; n = 36), TAV ( n = 23), and MFS ( n = 8) patients were included. Ascending aortic wall specimen were studied for general histologic features, apoptosis, markers of cardiovascular ageing, expression of synthetic and contractile vascular smooth muscle cells (VSMC), and fibrillin-1 expression. Results The MFS group showed many similarities with the dilated BAV. Both patient groups showed a thinner intima ( p < 0.0005), a lower expression of contractile VSMCs ( p < 0.05), more elastic fiber thinning ( p < 0.001), lack of inflammation ( p < 0.001), and a decreased progerin expression ( p < 0.05) as compared to the TAV. Other features of cardiovascular ageing differed between the BAV and MFS. Dilated BAV patients demonstrated less medial degeneration ( p < 0.0001), VSMC nuclei loss ( p < 0.0001), apoptosis of the vessel wall ( p < 0.03), and elastic fiber fragmentation and disorganization ( p < 0.001), as compared to the MFS and dilated TAV. Conclusion This study showed important similarities in the pathogenesis of thoracic aortic aneurysms in BAV and MFS. These common mechanisms can be further investigated to personalize treatment strategies in non-syndromic and syndromic conditions.

Introduction Bicuspid aortic valve (BAV) patients have an increased risk to develop thoracic aortic complications. Little is known about the prevalence and severity of atherosclerosis in the BAV ascending aortic wall. This study evaluates and compares the prevalence of thoracic aortic atherosclerosis in BAV and tricuspid aortic valve (TAV) patients. Methods Atherosclerosis was objectified using three diagnostic modalities in two separate BAV patient cohorts (with and without an aortic dilatation). Within the first group, atherosclerosis was graded histopathologically according to the modified AHA classification scheme proposed by Virmani et al. In the second group, the calcific load of the ascending aorta and coronary arteries, coronary angiographies and cardiovascular risk factors were studied. Patients were selected from a surgical database (treated between 2006–2020), resulting in a total of 128 inclusions. Results Histopathology showed atherosclerotic lesions to be more prevalent and severe in all TAV as compared to all BAV patients (OR 1.49 (95%CI 1.14 – 1.94); p = 0.003). Computed tomography showed no significant differences in ascending aortic wall calcification between all BAV and all TAV patients, although a tendency of lower calcific load in favor of BAV was seen. Coronary calcification was higher in all TAV as compared to all BAV (OR 1.30 (95%CI 1.06 – 1.61); p = 0.014). Conclusion Ascending aortic atherosclerotic plaques were histologically more pronounced in TAV as compared to the BAV patients, while CT scans revealed equal amounts of calcific depositions within the ascending aortic wall. This study confirms less atherosclerosis in the ascending aortic wall and coronary arteries of BAV patients as compared to TAV patients. These results were not affected by the presence of a thoracic aortic aneurysm.

Objectives: Abdominal aortic aneurysms are associated with a sharply increased cardiovascular risk. Cardiovascular risk management is therefore recommended in prevailing guidelines for abdominal aneurysm patients. It has been hypothesized that associated risk relates to loss of aortic compliance. If this hypothesis is correct, observations for abdominal aneurysms would also apply to thoracic aortic aneurysms. The objective of this study is to test whether thoracic aneurysms are also associated with an increased cardiovascular risk burden. Methods: Patients who underwent aortic valve or root surgery were included in the study (n = 239). Cardiovascular risk factors were studied and atherosclerosis was scored based on the preoperative coronary angiographies. Multivariate analyses were performed, controlling for cardiovascular risk factors and aortic valve morphology. Comparisons were made with the age- and gender-matched general population and non-aneurysm patients as control groups. A thoracic aortic aneurysm was defined as an aortic aneurysm of ≥45 mm. Results: Thoracic aortic aneurysm was not associated with an increased coronary atherosclerotic burden (p = 0.548). Comparison with the general population revealed a significantly higher prevalence of hypertension (61.4% vs. 32.2%, p < 0.001) and a lower prevalence of diabetes (1.4% vs. 13.1%, p = 0.001) in the thoracic aneurysm group. Conclusions: The extreme cardiovascular risk associated with abdominal aortic aneurysms is location-specific and not explained by loss of aortic compliance. Thoracic aortic aneurysm, in contrast to abdominal, is not part of the atherosclerotic disease spectrum and, therefore, cardiovascular risk management does not need to be implemented in treatment guidelines of isolated thoracic aneurysms. Hypertension should be treated.