Clouse WD, Hallett, Jr JW, Schaff HV, Gayari MM, Ilstrup DM, Melton III LJ. Improved Prognosis of Thoracic Aortic AneurysmsA Population-Based Study. JAMA. 1998;280(22):1926-1929. doi:10.1001/jama.280.22.1926
From the Divisions of Vascular Surgery (Drs Clouse and Hallett) and Cardiovascular Surgery (Dr Schaff) and the Sections of Biostatistics (Ms Gayari and Mr Ilstrup) and Epidemiology (Dr Melton), Mayo Clinic and Mayo Medical School, Rochester, Minn.
Context.— Managing thoracic aortic aneurysms identified
incidentally by increased use of computed tomography, echocardiography,
and magnetic resonance imaging is problematic, especially in the
Objective.— To ascertain whether the previously reported
poor prognosis for individuals with thoracic aortic aneurysms has
changed with better medical therapies and improved surgical techniques
that can now be applied to aneurysm management.
Design.— Population-based cohort study.
Setting and Patients.— All 133 patients with the diagnosis
of degenerative thoracic aortic aneurysms among Olmsted County,
Minnesota, residents between 1980 and 1994 compared with a previously
reported cohort of similar patients between 1951 and 1980.
Main Outcome Measures.— The primary clinical end points were
incidence, cumulative rupture risk, rupture risk as a function of
aneurysm size, and survival.
Results.— In contrast to abdominal aortic aneurysms, for
which men are affected predominately, 51% of thoracic aortic aneurysms
were identified in women who were considerably older at recognition
than men (mean age, 75.9 vs 62.8 years, respectively;
P=.01). The overall incidence rate of 10.4 per
100,000 person-years (95% confidence interval [CI], 8.6-12.2)
between 1980 and 1994 was more than 3-fold higher than the rate from
1951 to 1980. The cumulative risk of rupture was 20% after 5 years.
Seventy-nine percent of ruptures occurred in women
(P=.01). The 5-year risk of rupture as a
function of aneurysm size at recognition was 0% for aneurysms less
than 4 cm in diameter, 16% (95% CI, 4%-28%) for those 4 to 5.9 cm,
and 31% (95% CI, 5%-56%) for aneurysms 6 cm or more. Overall 5-year
survival improved to 56% (95% CI, 48%-66%) between 1980 and 1994
compared with only 19% between 1951 and 1980 (P<.01).
Conclusions.— In this population, elderly women represent an
increasing portion of all patients with clinically recognized thoracic
aortic aneurysms and constitute the majority of patients whose aneurysm
eventually ruptures. Overall survival for thoracic aortic aneurysms has
improved significantly in the past 15 years.
THERE IS renewed clinical interest in the prognosis
of thoracic aortic aneurysms.1 With the advent of computed
tomography and 2-dimensional echocardiography, recognition of such
aneurysms has increased. Many of these aneurysms are relatively small
at diagnosis (<6 cm in diameter), raising the critical question of
when surgical or endovascular repair should be recommended.
Most of the current information on the prognosis of thoracic
aortic aneurysms is provided by selected referral populations and
tertiary surgical series.1 The applicability of such data
to the initial management of thoracic aneurysms that present in
community practice is uncertain. An earlier population-based study from
Rochester, Minn, reported a dismal outlook for these patients, but it
was performed prior to routine use of computed tomography and
echocardiography and prior to recent advances in medical and surgical
management.2 In addition, the indications for elective
repair of thoracic aneurysms remain debatable because morbidity and
mortality are higher than for repair of abdominal aortic
aneurysms3- 6 (Table 1). In particular,
spinal cord and cerebral and visceral ischemia contribute to these
risks.7,8 However, no recent data are available on the risk
of rupture of thoracic aortic aneurysms among unselected patients from
the community at large.
Therefore, we used the resources of the Rochester Epidemiology Project
to conduct a population-based study of thoracic aortic aneurysm
incidence, prognosis, operative intervention, and survival among the
residents of Olmsted County, Minnesota. In addition, we investigated
factors that were associated with an increased risk of rupture. Key
findings were compared with results from an earlier study in this
population that covered from between 1951 and 1980.2
This population-based study was possible because all Olmsted County
residents with a recognized thoracic aortic aneurysm could be
identified, and their complete (outpatient and inpatient) medical
records could be retrieved for review.9 All medical records
were reviewed for each resident of Olmsted County in whom a diagnosis
of thoracic aortic aneurysm was initially made between January 1, 1980,
and December 31, 1994. A diagnosis of thoracic aortic aneurysm was
accepted if a focal aortic dilation (1.5 times larger than normal
local aorta) was identified and confirmed by
radiographic studies, operation, or autopsy. Acute aortic dissections,
traumatic aortic lacerations, annular dilatation without ascending
aortic enlargement, and penetrating atheromatous lesions without
aneurysmal change were excluded.
We obtained from the medical records data regarding patient demographic
characteristics, clinical presentation, maximal diameters of the
aneurysms, cardiovascular risk factors, operative indication, surgical
outcome, and survival. All patients were followed up through their
complete medical records until death, emigration from the community, or
to February 1, 1997, to identify aneurysm repair, rupture, or death.
Incident cases were defined as persons who were residents of Olmsted
County on the date of the diagnosis of thoracic aortic aneurysm.
Detailed age- and sex-specific population figures for 1980 through 1994
were derived by linear interpolation of decennial census figures for
1980 and 1990.10 With these denominators, age- and sex-specific incidence rates for thoracic aortic aneurysm were
calculated for both overall and 5-year periods from 1980 through 1994.
Summary rates were directly adjusted to the (5-year) age distribution
of the white population of the United States in 1990. Ninety-five
percent confidence intervals (CIs) were calculated around the point
estimates by assuming a Poisson error distribution. Secular trends were
modeled with Poisson regression.
The Kaplan-Meier method was used to estimate survival and to ascertain
the cumulative probability of rupture, which was estimated as a
function of time following initial diagnosis of the
aneurysm.11 Expected survival rates were calculated from
life tables of the Minnesota white population. Survivorship curves were
compared with log-rank tests.12 Associations between
continuous risk factors and rupture risk were evaluated with Cox
proportional hazards models.13,14 The Cox model was also
used for multivariate assessment of risk factors for rupture, including
time-dependent risk factors.
Between January 1, 1980, and December 31, 1994, 133 Olmsted
County residents were diagnosed as having a degenerative
(nondissecting) thoracic aortic aneurysm. Etiology of the aneurysms was
diverse, but medial degeneration and atherosclerosis predominated. The
anatomic location was delineated as ascending aortic or aortic arch
disease alone in 40%, descending thoracic aortic disease alone in
31%, and both in 29%. Sixty-five (49%) were men and 68 (51%) were
women. The average age at diagnosis was 69.0 years, but women were
significantly older at their initial diagnosis than men
(75.9±12.7 years vs 62.8±17.3 years,
The mean diameter (±SD) of these degenerative aneurysms was
4.9±0.2 cm (median, 4.7 cm). Size at diagnosis did not
differ by sex (mean, 4.9±1.2 cm among the women and
4.9±1.6 cm among the men). Seventy-nine percent of the
105 aneurysms were less than 6 cm at initial diagnosis, while 21% of
the 28 aneurysms were 6 cm or larger.
The 133 Olmsted County residents with thoracic aortic aneurysms were
identified from a population averaging about 100,000. The
overall incidence rate, age- and sex-adjusted to the 1990 US white
population, was 10.4 per 100,000 person-years (95% CI,
8.6-12.2). Incidence rates increased dramatically with age, and
age-adjusted rates were greater for men than women. After the 1980 to
1984 study, age-adjusted incidence rates increased more than 3-fold
compared with our previous study from 1951 to 1980 (Figure 1).
Rupture occurred in 28 (21%) of the 133 cases. The 5-year cumulative
probability of rupture was 20% (95% CI, 12%-28%), ie, survival free
of rupture was 80% at 5 years. In only 4 patients (3%), the aneurysm
was diagnosed initially at the time of rupture. Of the 24 aneurysms
that ruptured subsequent to diagnosis, the interval between initial
diagnosis and rupture was 4.3±0.7 years. Seventy-nine
percent of the ruptures were in women. The 5-year cumulative
probability of rupture was 33% (95% CI, 19%-47%) for women and 9%
(95% CI, 1%-17%) for men (P<.01).
Of the variables examined in univariate analyses, eventual
development of dissection within the aneurysm, female sex, symptoms at
diagnosis, and age at diagnosis were related significantly to aneurysm
rupture (Table 2 and
(Table 3). Hypertension was of borderline
significance. Smoking, chronic obstructive pulmonary disease,
hyperlipidemia, family history of aneurysm, and saccular configuration
were not related significantly to rupture.
When the 3 significant factors at diagnosis (sex, symptoms, and age)
were placed in a Cox multivariate model, the factors that remained
associated with increased rupture risk were female sex (risk ratio,
6.8; 95% CI, 2.3-19.9; P=.01) and symptoms at
recognition (risk ratio, 7.0; 95% CI, 2.56-19.3;
P=.01). Age at diagnosis was not associated
with rupture risk when included in the multivariate model (risk ratio,
1.03; 95% CI, 0.99-1.07; P=.16).
The relationship of size to the cumulative probability of rupture did not
achieve statistical significance in the univariate analysis
(P=.48), but the observed probabilities of
rupture risk were consistent with increasing risk with increasing size (Figure 2). The cumulative probability of rupture
at 5 years was 0% for those with aneurysms less than 4 cm in diameter,
16% (95% CI, 4%-28%) for those with aneurysm diameters between 4
and 5.9 cm, and 31% (95% CI, 5% -56%) in those with diameters 6 cm
or larger (Figure 3). Mean aneurysm diameter
documented prior to rupture was 6.3±0.3 cm.
Eighty deaths occurred among the 133 patients with degenerative
thoracic aortic aneurysms, for a 5-year survival rate of 56% (95% CI,
48%-66%) compared with an expected survival of 78% (Figure 3). This
survival rate was significantly better than the 5-year survival of 19%
between 1951 and 1980 (P<.01). Median survival was 6.6
years. The leading cause of death in this cohort was rupture of the
thoracic aortic aneurysm, which accounted for 30% of the deaths.
Cardiac events accounted for another 25%, along with pulmonary causes
in 15%, cancer in 10%, stroke in 4%, and various other causes of
death in 16%.
Among the 133 patients in this study, 35 procedures were
performed in 32 patients, for an operative intervention rate of 24%.
The 5-year cumulative probability of any operation (elective or
emergent) was 29% (95% CI, 16%-41%) for men and 19% (95% CI,
7%-32%) for women (P=.31). The 5-year
cumulative probability for elective aneurysm repair was 25% (95% CI,
13%-37%) for men and 13% (95% CI, 2%-23%) for women
(P=.14). Time from diagnosis to operation
averaged 2.9±0.6 years. Thirty-day case-fatality rates
were 8% and 57%, respectively, for elective compared with emergent
This population-based study identifies several important changes in the
natural history of thoracic aortic aneurysms. First, the incidence of
this condition has increased more than 3-fold in the past 4
decades.2 Second, we have found a strong independent
correlation of female sex with ruptures. Finally, survival for patients
with a thoracic aortic aneurysm has improved in the past 2 decades.
Multiple factors have contributed to these trends, which now have new
implications for current and future clinical management. The dramatic
increase in overall incidence was associated with enhanced recognition
of thoracic aneurysms by the introduction of computed tomography and
2-dimensional echocardiography in the 1970s and early 1980s,
respectively. Many of these aneurysms are small and consequently have
been observed. Second, the association between female sex and rupture
risk remains unexplained by our current understanding of aneurysm
pathogenesis. Although the mean age at diagnosis was 13 years older for
women than men, the mean size at recognition was similar. However, the
surgical intervention rate in women was one half the rate for men.
Because women were on average 76 years old at diagnosis compared with
men who were only 63 years old, advanced age may have influenced the
decision for less operative intervention in the female cohort.
Finally, one of the most reassuring findings of this study was the
improved 5-year survival of patients diagnosed as having a thoracic
aortic aneurysm.15- 18 What factors may be contributing to
an improved outlook in recent years? First, there may be a lead-time
bias since smaller aneurysms than what had been previously detected
were recognized in the current study. Earlier detection may also
account in part for the higher elective operative rate in this study
compared with our population-based report from 1951 to 1980 (11%
between 1951-1980 vs 24% between 1980-1994). Second, better
may have played an important role. This current
study showed a trend that hypertension was a prognostic factor for
rupture. Since β-blockers appear to slow aneurysm expansion rates,
their more prevalent use may have delayed or averted rupture in some
patients.19,20 Third, earlier recognition and more
aggressive management of coronary heart disease is likely to have had a
salutary influence on patient survival in the past 15
years.1,6,7 Finally, operative tecniques and
perioperative care have also improved.
With the increasing number of elderly patients, the trends revealed by
this population-based study are likely to continue. The relatively high
incidence of thoracic aortic aneurysms among women and the aneurysms'
propensity to rupture are important factors to be considered in future
management strategies. Decreasing rupture rates in women would require
an increased rate of elective surgery, a strategy that may or may not
be appropriate in the very elderly. The risks of surgery and the lack
of randomized trials for managing small thoracic aneurysms also
discourage mass screening of the elderly.
Currently, 3 general guidelines are suggested for all patients
with clinically recognized thoracic aortic aneurysms.
Hypertension21 is one risk factor that is known to increase
rupture risk and a factor that can be controlled in most patients.
Second, symptomatic aneurysms and those complicated by dissection are
more likely to rupture and should be evaluated urgently for repair.
Finally, asymptomatic thoracic aortic aneurysms with diameters of 6 cm
or greater are at increased risk of eventual rupture and should be
considered for elective repair in acceptable surgical candidates.