CLINICAL RESEARCH
Characterizing the young patient with aortic dissection: results from the international registry of aortic dissection (IRAD)
James L. Januzzi, MD, FACC*,
Eric M. Isselbacher, MD, FACC*,
Rossella Fattori, MD, FACC ,
Jeanna V. Cooper, MS ,
Dean E. Smith, PhD,
Jianming Fang, MD,
Kim A. Eagle, MD, FACC,
Rajendra H. Mehta, MD, FACC,
Christoph A. Nienaber, MD, FACC and
Linda A. Pape, MD, FACC||,*
* Thoracic Aorta Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, USA
University Hospital S. Orsola, Bologna, Italy
Cardiology Division and Coordinating Center for the IRAD Investigators, University of Michigan Medical Center, Ann Arbor, Michigan, USA
Cardiology Division, University of Rostock, Rostock, Germany
|| Cardiology Division, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Manuscript received January 24, 2003;
revised manuscript received July 17, 2003,
accepted August 11, 2003.
* Reprint requests and correspondence: Dr. Linda A. Pape, University of Massachusetts Medical School, 55 Lake Avenue North, S3-850, Worcester, Massachusetts 01655, USA.
Linda.pape{at}umassmed.edu
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Abstract
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OBJECTIVES: The goal of this study was to better characterize the young patient with aortic dissection (AoD).
BACKGROUND: Aortic dissection is unusual in young patients, and frequently associated with unusual presentations.
METHODS: Data were collected on 951 patients diagnosed with AoD between January 1996 and November 2001. Two categories of patients, <40 years and  40 years, were compared using chi-square cross tabulations for categorical and Student t test for continuous data.
RESULTS: Sixty-eight patients (7%) with AoD were <40 years of age. Compared with patients 40 years, younger patients were less likely to have a prior history of hypertension (p < 0.05); however, younger patients were more likely to have Marfan syndrome, bicuspid aortic valve, and prior aortic surgery (all, p < 0.05). Clinical presentations in the two age groups were similar; however, younger patients were less likely to be hypertensive (25% vs. 45%, p = 0.003). The proximal aortas of young AoD patients were larger (all, p < 0.05) compared with older patients. These differences in aortic size between age groups were not entirely related to Marfan syndrome. Mortality among young patients was similar to patients 40 years of age (22% vs. 24%, p = NS), irrespective of the site of dissection.
CONCLUSIONS: Compared with older patients with AoD, young patients have unique risk factors for dissection: Marfan syndrome, bicuspid aortic valves, and larger aortic dimensions. Surprisingly, the mortality risk for young AoD patients is not lower than older AoD patients.
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Abbreviations and Acronyms
| | AoD | = aortic dissection | | BAV | = bicuspid aortic valve | | IRAD | = International Registry of Aortic Dissection |
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In the setting of dissection of the thoracic aorta, arriving at a prompt diagnosis is critical for a favorable outcome. Despite advances in the accuracy of diagnostic imaging modalities, a high level of clinical suspicion remains the most important factor in recognizing aortic dissection (AoD). Numerous studies have delineated "typical" risk factors, symptoms/signs, and outcomes of AoD (1–3); however, the usefulness of these "typical" characteristics is limited. Anecdotal observations have suggested that younger patients with AoD represent a group prone towards both unusual risk factors and atypical presentations (2,4,5). In order to study these potentially age-related differences among patients with AoD, we used the resources of the International Registry of Aortic Dissection (IRAD).
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Methods
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Patient selection and data collection.
The design and initial results from IRAD have been previously described in detail (3). At the time of our study, 951 patients with classic AoD had been enrolled at 18 institutions between January 1996 and November 2001. The diagnosis of AoD was based on history, imaging studies, direct visualization at surgery, and/or postmortem findings. Clinical data were collected via a standardized data form, using standard definitions. Variables of interest included demographics, history, physical examination, imaging results, management strategies, and outcomes. Patients were then divided into age categories of <40 and 40 years for the purposes of this analysis.
Data analysis.
Data analysis was performed using the SPSS statistical analysis software (SPSS Inc., Chicago, Illinois). Univariate analyses between groups (including internal comparisons among young patients with or without Marfan syndrome) were done using chi-square cross tabulations for categorical data and the Student t test for continuous data. All p values are two-sided, with values <0.05 considered significant. Multivariate logistic regression was used to estimate the odds ratio of factors related to in-hospital mortality. The final model only kept factors with p < 0.1. The analysis was performed using SAS 8.2 (SAS Institute, Cary, North Carolina).
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Results
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Sixty-eight patients (7%) <40 years of age were identified in the registry. The demographics of younger versus older patients presenting with AoD are detailed in Table 1. Compared with older patients, patients <40 years of age demonstrated a similar incidence of type A AoD. Young AoD patients were less likely to have a prior history of hypertension (34% vs. 72%, p < 0.001) or atherosclerosis (1% vs. 30%, p < 0.001). Marfan syndrome was much more prevalent among patients <40 years of age, relative to patients 40 years (50% vs. 2%, p < 0.001). Additionally, younger patients were more likely to have a bicuspid aortic valve (BAV) (9% vs. 1%, p < 0.001) or prior aortic valve replacement surgery (12% vs. 5%, p = 0.008).
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Table 1 Baseline Demographics of Patients in the International Registry of Aortic Dissection Based on Age Categories of <40 and 40 Years of Age
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At presentation, signs and symptoms of AoD were similar in both age groups and were largely independent of age (Table 2). However, younger patients were more likely to complain of abrupt pain onset after AoD (96% vs. 82%, p = 0.004), and were significantly less likely to be hypertensive at first hospital presentation (25% vs. 45%, p = 0.003).
The characteristics of AoD in relation to age at presentation are detailed in Table 3. In younger patients, the origin of type A dissection was more proximally located, either in the sinuses of Valsalva or at the sinotubular junction. In comparison, the origin of type A dissection among older patients was more likely to be in the ascending aorta. Additionally, younger patients were more often found to have a patent false lumen than were older patients (87% vs. 71%, p = 0.006).
While aortic dilation was common among all dissection patients, among those from whom aortic measurements were available, we noted even greater aortic diameters in the young (Table 3). Relative to patients 40 years of age, younger AoD patients demonstrated more dilation at the aortic annulus, sinuses of Valsalva, sinotubular junction, and ascending aorta (all, p  0.05). Aortic arch and descending aortic diameters did not differ significantly between the two groups, but there was a nonsignificant trend towards larger arch and descending aortic dimensions among older patients.
An analysis of dissection characteristics of patients <40 years with (n = 34) or without (n = 34) Marfan syndrome suggested that young dissection patients without Marfan syndrome had proximal aortic diameters as large as those patients with the syndrome (Table 4). No significant differences were found among the dissection characteristics of young patients when compared based on the presence or absence of Marfan syndrome (data not shown).
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Table 4 Aortic Dimensions Among Patients <40, With or Without Marfan Syndrome in the International Registry of Aortic Dissection
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With respect to management, younger patients were more likely than older patients to undergo surgical repair of their AoD (81% vs. 60%, p = 0.001). Moreover, aortic root replacement was more likely among patients <40 years of age compared with the older cohort (59% vs. 21%, p < 0.001), as was aortic valve replacement (33% vs. 16%, p = 0.001).
The outcomes of patients in the age categories of <40 years and 40 years were similar (Table 5), except for a higher incidence of limb ischemia among younger patients (18% vs. 10%, p = 0.06). In univariate analyses, the overall mortality rates were similar for both age categories (22% vs. 24%, p = NS). In a multivariate model obtained by stepwise regression, there were no significant differences in mortality when examining age as a dichotomous variable (odds ratio for age <40 = 0.70, 95% confidence intervals = 0.36 to 1.35, p = NS). There was no age-related difference in mortality when examining different types of AoD (type A: 23% vs. 31%; type B: 18% vs. 12%, <40 vs. 40 years, respectively; all, p = NS).
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Discussion
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Dissection of the thoracic aorta remains the most lethal condition involving the aorta (2,3). Furthermore, survival after the onset of symptoms is time-dependent and, therefore, early and accurate diagnosis is crucial. Numerous studies have emphasized "typical" risk factors and presenting characteristics of AoD. However, it has been suggested that younger patients may be more likely to have an atypical presentation of acute AoD. Accordingly, we utilized the resources of IRAD to examine the potential differences between young patients and an older cohort from IRAD.
We found that younger and older AoD patients generally presented with similar symptoms and signs, although, compared with older patients, younger patients were less likely to have a history of prior hypertension, and were less likely to be hypertensive at presentation. Notably, however, the prevalence of either prior or present hypertension among young AoD patients is still higher than expected for an age-matched population, underscoring the importance of elevated arterial blood pressure in the etiology of AoD across age groups. Finally, the risk factors we identified for early-onset AoD included Marfan syndrome and prior BAV, although many young patients with AoD had neither diagnosis.
Complications involving the aorta are highly prevalent among patients with Marfan syndrome. Accordingly, as expected, 50% of our young AoD patients had a prior history of this diagnosis. However, a significant number of patients did not have a history of Marfan syndrome, yet still presented with significant aortic enlargement and AoD. These data lend support to prior observations of histologic findings similar to the classic cystic medial necrosis among young patients with sporadic AoD (4,6,7), and suggest an underlying genetic defect of connective tissue, resulting in dissection at an early age in such patients.
The association between BAV, aortic dilation, and AoD has been recognized for decades (7–11), with a risk of dissection 5 to 18 times higher in the presence of a bicuspid (compared with a trileaflet) aortic valve. The mechanism underlying the aortic dilation and increased risk for dissection among BAV patient is thought to be secondary to a coinherited developmental defect of the proximal aorta (12), an increased predilection towards apoptosis of the cellular components of the aortic media, with resultant medial weakening, and dilation of the aorta (13). Pathologic findings of dilated aortas in the presence of a BAV are frequently similar to those in patients with Marfan syndrome (7,8).
That the overall complication rate, especially mortality, of patients <40 years of age were similar to older patients in our study was an unexpected finding. Advancing age is generally associated with a higher mortality in cases of AoD (14). Indeed, the significantly higher prevalence in the older age group of comorbid conditions such as hypertension and atherosclerosis would have predicted increased mortality compared with younger patients, but this was not the case. Delays in diagnosis as the cause of the differences between groups also were not a factor. Though speculative, the reasons for a lack of better outcome in the <40-year age group might be explained if aortic tissue integrity is more often impaired in young AoD patients, resulting in more extensive dissections, a higher risk for complications, and more challenging surgical repairs.
Study limitations.
While the IRAD database allowed the largest systematic analysis of AoD in young patients to date, there are limitations to our study. Although our findings were significant, and consistent with other studies, the absolute number of young AoD patients in our study is small. Another limitation is that the diagnosis of Marfan syndrome in our study was based on historical data, and we cannot preclude that some of the young patients had this, or other connective tissue disorders, which would, in turn, have influenced our results. Finally, although we found more significant proximal aortic enlargement among our younger type A AoD subjects, not every patient in this subgroup had aortic dimensions available for analysis.
Conclusions.
Compared with older AoD patients, patients <40 years have unique risk factors, including a higher prevalence of Marfan syndrome and BAV. Hypertension, either historically or at presentation, was less common in the young than in older AoD patients. Young patients frequently demonstrated significant proximal aortic dilation suggesting abnormalities of aortic medial integrity, even in the absence of Marfan syndrome or BAV. Mortality from AoD among young patients was surprisingly high, similar to patients 40 years of age, irrespective of the site of dissection, and did not appear to be related to missed diagnosis or delays in diagnosis. Further studies of the underlying genetic predisposition(s) leading to early onset AoD are necessary.
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Footnotes
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Supported by a grant from the Varbedian Fund.
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Abstract
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