Why is the aortic wall so thick

During a recent longitudinal prospective study to evaluate aortic wall thickness in intrauterine growth restricted fetuses and infants, 12 we planned additional analyses to determine whether aortic thickening was predictive of higher BP during infancy.

Therefore, the aim of the present study was twofold: i to measure in utero and postnatally at a mean follow-up of 18 month of life the abdominal aortic intima-media thickness aIMT and BP in IUGR and adequate for gestational age AGA fetuses; and ii to assess the correlation between aIMT and BP development to test the hypothesis of the existence of vascular dysfunction in IUGR fetuses and children, and determine whether the fetal aortic thickening in IUGR infants required surveillance for cardiovascular risk in childhood.

This secondary prospective analysis of IUGR patients was performed as part of a multicenter collaboration. Written informed consent was obtained from each woman before the enrollment, and the project was approved by the University Hospital Committee for Research on Human subjects. The women included in the study were all between 24 and 30 weeks of gestation.

The data concerning the women and their pregnancies were recorded according to the established procedures of our Department. The maternal smoking status current smoker, yes or no was obtained from the medical history. The exclusion criteria were a twin pregnancy, major congenital anomalies, pregnancies complicated by maternal history of cardiovascular disease or endocrine disorders such as diabetes, hypercholesterolemia, pre-eclampsia, thyroid or adrenal problems, clinical chorioamnionitis or perinatal infections.

Additionally, mothers who had received alcohol or drugs, such as ritodrine and corticosteroids except for fetal lung maturation were excluded.

In nine cases, the parents declined consent. For each matched fetus, we recorded the aIMT and anthropometrical and sonographic features. Three independent measurements for each participant were taken; the arithmetic mean was considered for the study, as proposed by current guidelines. The anthropometrical, sonographic and clinical characteristics of the study population are shown in Table 1.

We found no differences for the measurements with respect to the maternal age at delivery, parity, nicotine abuse or the delivery mode. No gender disparity was encountered comparing the IUGR vs.

The mean aIMT at the postnatal age of 18 months was 2. Certain prenatal factors may affect neonate blood pressure, but the existing evidence is inconclusive and the mechanisms behind these factors are unclear. Even when measured at the mean postnatal age of 18 months, the values were still significantly correlated.

Increasing evidence reveals an inverse association between birth weight and blood pressure in children, adolescents and adults, 1 which provides a new perspective for hypertension etiology and prevention. Furthermore, in addition to the postnatal events, atheromatous changes have been documented histopathologically in early childhood, particularly in the abdominal aorta, 16 and it is now possible, thanks to external ultrasonography, to measure the aortic wall thickness in vivo during fetal 12 and early postnatal life 13 in an accurate and reproducible manner.

Moreover, the ultrasound measurement of aIMT in IUGR fetuses was found to be a sensitive marker of hypertension in young children and of atherosclerosis risk in adults, 11 which supported the epidemiological link between impaired fetal growth and later cardiovascular disease risk.

Although the mechanisms, which underlie these associations remain unclear, these data represent another step in understanding IUGR and the related cardiovascular disease risk. Further studies should focus on additional factors that impact on the early endothelial dysfunction, 10 in addition to placenta-induced developmental disorders and Doppler umbilical artery vasculopathy. More importantly, the biological mechanisms through, which these prenatal factors are associated with offspring BP remain unclear.

Poor knowledge of these mechanisms is a critical barrier for causal interpretation, as well as safe and effective intervention. This is the first study to examine the potential mediation of both IUGR and prenatal aortic stiffening and developing BP.

Repeated aIMT measures facilitated the identification of the critical growth periods fetal, infancy and early childhood that impact offspring BP. Adjusting for maternal and family factors can remove substantial confounding. Despite the standard protocol, the single measure of blood pressure could introduce measurement errors. We could not distinguish between the impacts of the different components and the rates of both fetal or maternal pregnancy weight gain on infant BP. Despite clear temporality prenatal aortic stiffening exposures affected IUGR fetuses, which affected childhood BP , the observed associations can be interpreted as causal pathways only by assuming no residual confounding, which is nearly impossible for observational studies.

In conclusion, our new findings can advance current poor knowledge on mechanisms for fetal programming of blood pressure. Evidence from this analysis indicates that, instead of limiting our focus on fetal or neonatal size, monitoring in utero aortic wall thickness may be more important for long-term cardiovascular health.

Persistent aortic thickening may predispose patients to later cardiovascular risk, and may influence vasomotor tone and arterial compliance from early in life.

Risk of high blood pressure among young men increases with the degree of immaturity at birth. Circulation ; : — Article Google Scholar. The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature.

J Hypertens ; 18 : — Mechanisms of disease: in utero programming in the pathogenesis of hypertension. Nat Clin Pract Nephrol ; 2 : — Fetal and placental size and risk of hypertension in adult life.

BMJ ; : — Initiation of hypertension in utero and its amplification throughout life. BMJ ; : 24— Data from the International Registry of Acute Aortic Dissection showed that aortic diameter is an imperfect predictor of acute type A aortic dissection.

The observation that this condition occurs in patients with only mildly dilated or even normal aortas led us to search for an additional marker of risk to assist in the timing of elective aortic root surgery in patients at risk of aortic dissection. Aortic diameter and systemic hypertension have classically been considered as the principal determinants of wall stress. It has recently been reported that the aortic medial wall is significantly thinner in Marfan syndrome patients with acute aortic dissection compared with those undergoing elective aortic root surgery for indications other than dissection [ 7 ].

These observations have led us to suggest that wall thinning might also be an important contributing factor that increases wall stress.

Therefore, we retrospectively examined our database of patients who underwent aortic root replacement at our institution, either for acute type A dissection or for other indications elective surgery.

It was the goal of this study to assess the possible value of medial wall thickness and the relation of aortic diameter to medial wall thickness as markers of risk for aortic dissection. Data were obtained from hospital records of patients who had undergone aortic root repair at our centre University Hospital Leuven, Belgium between and The Ethical Committee of the hospital granted approval for this data collection and the need for individual patient consent was waived.

Patients were identified by a search of the surgical database for all cases of acute dissection involving the ascending aorta and all cases of prophylactic aortic root surgery. Patients without preoperative imaging or without an aortic specimen available for histology were excluded.

Patients with poor quality histological specimens that precluded quantitative analysis were excluded. This resulted in patients being included in the final analysis, 94 in the aneurysm group and 87 in the dissection group.

Information regarding demographics, anthropometric data and medical history was collected from an institutional computerized database, and body surface area was calculated using the Dubois and Dubois formula [ 8 ]. Maximum aortic diameters were measured on cross-sectional tomograms perpendicular to the long axis of the ascending aorta. The aortic specimens were stained with haematoxylin and eosin and microscopically evaluated by a pathologist. For each patient, the results of these histological studies were available in a computerized database, from which they were retrieved.

These studies were retrospectively analysed for the presence and degree of four histological features: cystic medial necrosis, elastic fragmentation, inflammation and atherosclerotic features.

These stained histological specimens were available in an institutional database from which they were retrieved to allow for digitalization of the specimens. Digital image processing software AxioVision, Carl Zeiss Meditec AG, Jena, Germany was utilized by two independent observers to each conduct a minimum of three manual measurements of the medial wall thickness.

Using these measurements, the average medial wall thickness of each aortic specimen was determined Fig. Measuring medial wall thickness WT on a digitalized histological specimen.

The medial wall thickness of the true lumen is added to the medial wall thickness of the false lumen to determine the predissection medial wall thickness.

Basic data analysis was performed with the use of Statistica Dell, Inc. The variables were compared using the unpaired Student's t -test. Linear regression analysis was used to detect a correlation between aortic wall thickness and aortic diameter. Table 1 reports the demographic and clinical characteristics of the patient population.

Our study included individuals; of these patients, The average patient age was One patient was affected by Turner syndrome and 2 patients were affected by Marfan syndrome. There was no statistically significant difference between subjects with aortic dissection and those without, except for an increased prevalence of aortic valve disease and bicuspid aortic valve morphology in the aneurysm group. The results of the histopathology studies are summarized in Table 2. The mean ascending aortic diameter was Among all patients in the dissection group, the mean ascending aortic diameter was Between the two groups, there was no statistically significant difference with regard to aortic size.

A small percentage of patients in the aneurysm group underwent elective surgery unrelated to aortic dilatation; however, because of the poor quality of the ascending aortic tissue as assessed intraoperatively, they underwent aortic root repair. There was no significant difference between the two groups. Distribution of the aortic size by the number of observed cases No of obs at the time of presentation.

A black line depicting the traditional cut-off for elective aortic root replacement. Regression model demonstrating the medial wall thickness in elective aortic root replacement left and acute aortic dissection right incorporating the aortic diameter. The medial wall thickness was inversely associated with the aortic diameter in patients with an acute aortic dissection. Note the significantly lower wall thickness for acute dissection patients.

Figure 5 demonstrates the aortic diameter to medial wall thickness ratio, compared between the two groups for all patients with an aortic diameter of more than 45 mm. Note the significantly higher aortic diameter to medial wall thickness ratio for acute dissection patients. Acute type A aortic dissection is a relatively rare cause of cardiovascular death with a suggested incidence of 2.

The only effective prophylactic treatment for aortic dissection, aside from treatment of systemic hypertension, remains an elective aortic root replacement in patients with established clinical risk factors. Current guidelines for prophylactic aortic root repair are founded on the knowledge of experienced clinicians and on data from clinical series. Taking into account these guidelines, surgery to prevent dissection of the dilated ascending aorta should be suggested when the ascending aortic diameter reaches 55 mm in patients without coexistent risk factors and 45 mm in patients with connective tissue disease or a bicuspid aortic valve [ 1—5 ].

For this study, we examined the aortic size after dissection had occurred. This methodology could potentially lead to an overestimation of the aortic diameter in the dissection patients as there is increasing evidence in the literature that the ascending aortic diameter increases as a result of aortic dissection [ 18 ]. However, there are also reports stating that the aortic diameter is minimally affected by the formation of aortic dissection [ 19 ]. These patients would not qualify for prophylactic aortic root replacement according to the currently established indications and, therefore, aortic dissection would not have been prevented even if they had undergone aortic imaging prior to their presentation with an aortic dissection.

In the future, we will be faced with the challenge of establishing a follow-up strategy for an increasing number of patients with an incidental finding of mild aortic dilatation because of the widespread application of high-quality echocardiography, high-resolution computed tomography and magnetic resonance imaging.

Hence, there is a need for a new clinical index that helps delineate the subjects at higher risk of dissection even at mildly dilated aortic diameters. To identify additional parameters that affect the risk of dissection, Shiran et al. They concluded that the medial wall thickness was significantly thinner in connective tissue disorder patients with aortic dissection compared with those undergoing prophylactic aortic root surgery [ 7 ].

We therefore suggest that wall thinning might play an important role in the pathogenesis of acute aortic dissection in all patients with smaller aortic diameters. In contrast to the data presented by Shiran et al. However, the structural weakening of the aortic wall in patients with a connective tissue disorder might have amplified the effect of wall thinning in the patients involved in that study. What we did find was that patients with an aortic dissection revealed a significant inverse association between medial wall thickness and aortic diameter, while in the aneurysm group there was no relation.

When we specifically looked at those patients with a moderately dilated aorta of more than 49 mm, we see a clearly thinner wall in dissection patients, compared with the patients with an aortic aneurysm. Cardiovascular disease CVD is a leading cause of death [ 1 ], and its pathological basis is arterial damage resulting in the development of arteriosclerosis.

Arteriosclerosis describes diffuse thickening and stiffening of both the intima and media of large- and medium-size arteries. Atherosclerosis is a form of arteriosclerosis characterized by focal lesions in the intima of large- and medium-size arteries.

Originally, atherosclerosis was believed to arise only in adulthood. Recent studies, however, have demonstrated that although the clinical complications of atherosclerosis occur in adult life, the process of atherogenesis begins as a young child [ 2 ] or even as a fetus [ 3 ].

Cosmi et al [ 4 , 5 ] have shown that fetuses and children with intrauterine growth restriction IUGR have a greater aortic intima-media thickness aIMT than appropriate for gestational age AGA fetuses. Furthermore, low birthweight, caused by preterm birth or IUGR, is associated with a thicker aIMT and increased rates of CVD that are similar to those seen with major environmental risk factors, such as cigarette smoking, hypertension [ 6 ], hypercholesterolemia, and diabetes [ 7 ].

Theories proposing a fetal origin of atherosclerosis suggest that vascular lesions arise as a fetal adaptation to a state of malnutrition, such as IUGR. These adaptive processes may be cardiovascular, metabolic, or endocrine and may permanently alter structure and physiology [ 8 , 9 , 10 ]. The mechanisms placing IUGR fetuses at increased cardiovascular risk have not been clarified. Theoretical explanations include increased blood pressure, dyslipidemia, or reduced insulin-like growth factor [ 11 ].

There remains, however, no direct evidence that the changes observed in the structure of the aortic wall in fetuses and children are the precursors of arterial plaques, although they share the same physical sites [ 12 ]. Nevertheless, early identification of those infants at increased risk of atherosclerosis should allow for timely interventions that may delay or prevent the onset of cardiovascular events in adulthood.

The latter comparison will evaluate whether these potential cardiovascular risk factors are present in all small fetuses or only those with placental insufficiency.

Written informed consent was obtained from each patient before undergoing any study-related procedures. The study protocol was approved by the Institutional Review Board of Barcelona University Hospital, and there were no conflicts of interest. Study participants were recruited after a routine third trimester fetal ultrasound was obtained. The inclusion criteria were singleton pregnancies and parental willingness to participate in the study.

The exclusion criteria were a lack of consent, multiple pregnancies, congenital anomalies, diabetes, hypercholesterolemia, chronic hypertension, gestational hypertension, preeclampsia, thyroid or adrenal pathology, alcohol use, medication use e. Corticosteroids were permitted when administered for lung maturation only. Ultrasound examinations were performed at a mean gestational age of All parameters were measured using a Siemens linear ultrasound probe S 9L4 3.

Fetal biometries were measured and the estimated fetal weight was determined, followed by Doppler velocimetry of the umbilical artery, middle cerebral artery, cerebro-placental ratio and ductus venous only in fetuses with an estimated fetal weight below the 10 th percentile. Measurements of aIMT and AD were obtained in the fetal abdominal aorta between the renal arteries and iliac arteries.

Coronal and sagittal projections of the fetus were used to localize and subsequently magnify the area of the vessel to be measured. The image was frozen at the end of the systole to minimize variability. AIMT, defined as the distance between blood-intima interface and media-adventitia interface Fig 1 , and AD, defined as the distance between blood-intima interface at both ends of the vessel Fig 2 , were measured in this image.

Each measurement was performed three times and the arithmetic mean was calculated. Fetal examination was easy but an experimented sonographer was required to perform it.

Each measurement was obtained three times by a single observer EV during the initial ultrasound study. The measurements were repeated in a blinded manner by the original observer. After this, the images were unfrozen and new ones were obtained by a second observer.

The second observer also repeated the measurements three times. Both observers had advanced experience in fetal ultrasound. In addition to the fetal measurements, the maternal and fetal medical history, maternal and paternal anthropometric data, and other ultrasound and neonatal data were compiled.

After calculating intraobserver and interobserver variability for the aIMT and AD measurements, the first observer measurements were used for the main data analyzed in the study.

Chicago Power analysis calculations indicated the need for a sample size of 33 patients in each group to detect significant differences for the primary endpoint: differences greater than 0. Normal distribution was tested using a combination of techniques, including application of the Kolmogorov-Smirnov test, histogram analysis, coefficient of skewness, and kurtosis.