Characterizing the young patient with aortic dissection: results from the international registry of aortic dissection (IRAD)

Methods

Results

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).

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).

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).

Discussion

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.