SCIENTIFIC PAPERS
`
`ANNALS OF SURGERY
`Vol. 230, No. 3, 289 –297
`© 1999 Lippincott Williams & Wilkins, Inc.
`
`Risk Factors for Aneurysm Rupture in Patients
`Kept Under Ultrasound Surveillance
`
`The U.K. Small Aneurysm Trial Participants, with Louise C. Brown, MSc,* and Janet T. Powell, MD*
`
`From the *Department of Vascular Surgery, Imperial College at Charing Cross, London, United Kingdom
`
`Objective
`To investigate risk factors associated with aneurysm rupture
`using patients randomized into the U.K. Small Aneurysm Trial
`(n 5 1090) or monitored for aneurysm growth in the associ-
`ated study (n 5 1167).
`
`Summary Background Data
`The U.K. Small Aneurysm Trial has shown that ultrasound
`surveillance is a safe management option for patients with
`small abdominal aortic aneurysms (4.0 to 5.5 cm in diameter),
`with an annual rupture rate of 1%.
`
`Methods
`In the cohort of 2257 patients (79% male), aged 59 to 77
`years, 103 instances of abdominal aortic aneurysm rupture
`were identified during the 7-year period of follow-up (1991–
`1998). Almost all patients (98%) had initial aneurysm diame-
`ters in the range of 3 to 6 cm, and the majority of ruptures
`(76%) occurred in patients with aneurysms $5 cm in diame-
`ter. Kaplan-Meier survival and Cox regression analysis were
`
`used to identify baseline risk factors associated with aneu-
`rysm rupture.
`
`Results
`After 3 years, the annual rate of aneurysm rupture was 2.2%
`(95% confidence interval 1.7 to 2.8). The risk of rupture was
`independently and significantly associated with female sex
`(p , 0.001), larger initial aneurysm diameter (p , 0.001),
`lower FEV1 (p 5 0.004), current smoking (p 5 0.01), and
`higher mean blood pressure (p 5 0.01). Age, body mass in-
`dex, serum cholesterol concentration, and ankle/brachial
`pressure index were not associated with an increased risk of
`aneurysm rupture.
`
`Conclusions
`Within this cohort of patients, women had a threefold higher
`risk of aneurysm rupture than men. Effective control of blood
`pressure and cessation of smoking are likely to diminish the
`risk of rupture.
`
`Rupture of an abdominal aortic aneurysm (AAA) is a
`catastrophic event. Many patients die without reaching the
`operating table, and only 50% of those undergoing surgical
`repair survive beyond 30 days.1,2 Therefore, most surgeons
`offer elective repair to fit patients with an asymptomatic
`AAA. The benefits of such a strategy for patients with a
`small aneurysm (4.0 to 5.5 cm in diameter) have been
`challenged recently:
`the U.K. Small Aneurysm Trial
`
`Presented by Roger M. Greenhalgh, MD, at the 119th Annual Meeting of
`the American Surgical Association, April 15–17, 1999, Hyatt Regency
`Hotel, San Diego, California.
`The U.K. Small Aneurysm Trial was supported by the Medical Research
`Council, the British Heart Foundation, and the Camelia Botnar Foun-
`dation.
`Reprints will not be available from the authors.
`Correspondence: Janet T. Powell, MD, Dept. of Vascular Surgery, Imperial
`College at Charing Cross, St. Dunstan’s Road, London W6 8RP,
`United Kingdom.
`Accepted for publication April 1999.
`
`showed that early elective surgery conferred no long-term
`survival benefit.3 Uncertainty concerning the risk of rupture
`of AAAs of different sizes and the absence of appropriate
`evidence compound the difficulties of decision making,
`particularly for patients of marginal fitness.4 Autopsy stud-
`ies have indicated that aneurysm diameter is an important
`determinant of rupture, with larger aneurysms having the
`greatest risk.5,6 However, diameter as measured at autopsy
`does not reflect diameter in vivo.7 Studies in living patients
`also may suffer from the poor reproducibility of measuring
`aneurysm diameter by different scanning modalities,8 par-
`ticularly for retrospective data. A further complicating issue
`is the confirmation of AAA rupture in patient or population
`studies. Not surprisingly,
`the rupture rates reported for
`aneurysms ,5.0 cm in diameter vary widely, from 0%7 or
`1% per annum3,9,10 to as high as 6% per annum.11 The data
`for larger aneurysms are even more difficult to interpret,
`although modeling studies have suggested that the risk of
`rupture is 9% and 12.5% per annum for AAAs with diam-
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`U.K. Small Aneurysm Trial Participants
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`Ann. Surg. c September 1999
`
`eters of 6.5 and 7.5 cm, respectively.12 Size apart, other
`factors such as hypertension may influence the risk of
`aneurysm rupture.11 Knowledge of these other factors
`should allow a more informed approach to management,
`particularly in patients of marginal fitness.
`The U.K. Small Aneurysm Trial and the associated study,
`for patients ineligible or refusing randomization,13 provided
`the opportunity to investigate prospectively, in a large co-
`hort (n 5 2257) of carefully monitored patients, the param-
`eters that influence rupture of AAAs.
`
`METHODS
`The methods have been described elsewhere.3,13 Briefly,
`patients (age 60 –76 years) were entered into either the U.K.
`Small Aneurysm Trial or the Small Aneurysm Study from
`93 hospitals across Britain. Fit patients who consented to
`randomization in the trial had an AAA 4.0 to 5.5 cm in
`diameter. In total, 1090 patients were randomized in the
`4-year period from September 1991, and 527 of these were
`allocated to serial ultrasonographic surveillance.3 The 563
`patients randomized to surgery were included up to the time
`of surgery. These 563 patients may have been followed
`since before the aneurysm reached 4.0 cm (the Small An-
`eurysm Study), or had to wait several months before elec-
`tive surgery, contributing 706 person-years of follow-up. In
`addition, the trial coordinators followed the progress of a
`further 1167 patients who were ineligible for randomization
`for the following reasons: the aortic diameter was ,4.0 cm
`(n 5 507) or .5.5 cm (n 5 100), the patient refused
`randomization (n 5 122), the patient was considered unfit
`for surgery (n 5 340), or other reason, such as with a long
`wait before elective surgery (n 5 98). All these patients
`were monitored at regular intervals by the trial coordinators,
`who measured the AAA diameter with an Aloka SSD500
`scanner equipped with a 3.5-MHz transducer (Keymed,
`Southend, United Kingdom). The repeatability of measure-
`ment of aneurysm diameter was 60.2 cm. All patients were
`flagged at the Office of National Statistics to enable us to
`receive automatic notification of emigration, death, place of
`death, underlying cause of death, and whether an autopsy
`was performed. For this study, our primary end-point was
`rupture of the AAA; this was ascertained either from the
`death certificate or from imaging and surgical details.
`Statistical analysis was undertaken according to a pre-
`defined plan. Patients were censored at June 30, 1998 (the
`end of the trial), or if the earlier events of emigration,
`aneurysm repair, aneurysm rupture, or death had occurred.
`Kaplan-Meier survival curves for time from initial AAA
`diameter were used to evaluate rupture rates. We used Cox’s
`proportional hazards regression to estimate hazard ratios
`and to adjust these for age, sex, and initial aneurysm diam-
`eter. Aneurysm growth rates were calculated by linear re-
`gression analysis.
`To investigate how the risk of aneurysm rupture varied
`with aortic diameter, we used measurements obtained
`
`within the 12 months preceding rupture (available for
`82/103 [80%] of the ruptures). For the further 21 patients
`who died from aneurysm rupture, we estimated an aneu-
`rysm diameter at the time of rupture based on the last
`measurement (.1 year previously) and the aneurysm
`growth rate in that patient. This estimated diameter was
`used to allocate these 21 patients to the size categories
`used for analysis. For the 2154 patients not known to
`have AAA rupture, the person-years of follow-up were
`calculated to the time of censorship (AAA repair, cessa-
`tion of follow-up, or death).
`
`RESULTS
`
`Rupture Rates According to Baseline
`Variables
`
`Among the 1090 randomized patients, there were 25
`recorded AAA ruptures. In 8 patients the event was verified
`at surgical repair, and 17 died without surgical repair and
`the event was recorded on the death certificate (including 10
`autopsies). To increase the number of events (AAA rupture)
`identified, we included 1167 nonrandomized patients,
`among whom there was a higher proportion of ruptures
`(78/1167). This yielded a cohort of 2257 patients (Fig. 1)
`with 103 recorded aneurysm ruptures. Twenty-four ruptures
`were confirmed at surgical repair, 34 were confirmed by
`autopsy, a further 30 patients died in the hospital from
`aneurysm rupture, and 15 of the deaths attributed to rup-
`tured aneurysm occurred outside the hospital without an
`autopsy. Of the 103 patients with AAA rupture, 26 (25%)
`patients died without ever reaching the hospital, 53 (51%)
`died in the hospital without undergoing surgery, 13 (13%)
`died within 30 days of surgery (46% operative mortality
`rate), and 11 (11%) survived beyond 30 days. In total, 502
`deaths (occurring before June 30, 1998) were recorded.
`Ruptured AAA was the underlying cause of death in 92
`patients (18%), including 13 who did not survive emer-
`gency surgical repair. The autopsy rate was 21%. A further
`51% of these patients died in the hospital, and the remainder
`died elsewhere without evidence of an autopsy being per-
`formed. The progress of patients is shown in Figure 1.
`Altogether, there were 4102 patient-years of follow-up.
`The baseline characteristics of the trial and study patients
`are compared in Table 1 and the baseline characteristics of
`the patients with and without aneurysm rupture in Table 2.
`The study group was in many respects similar to the trial
`group, although there was an increased proportion of
`women and the study group was slightly older, had smaller
`aneurysms, and, as might be expected, had poorer lung and
`renal function (see Table 1). The mean initial AAA diameter
`was higher among the patients with rupture, and this group
`had a high proportion of women (38%) and current smokers
`(49%) (see Table 2). The mean blood pressure also was
`higher in the patients with aneurysm rupture. The other
`variables in Table 2 all had a moderate number of missing
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`Vol. 230 c No. 3
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`U.K. Small Aneurysm Trial
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`291
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`Figure 1. Profile of patients with respect to rupture of abdominal aortic aneurysm (AAA).
`
`values. There was no association between use of aspirin or
`beta-blockers and AAA rupture. Ruptures occurred during
`every month of the year, but with a seasonal nadir in
`September and October.
`
`The overall survival without AAA rupture in this cohort
`of 2257 patients is shown in Figure 2. In the first 3 years, the
`annual rupture rate was 2.2% (95% confidence interval 1.7
`to 2.8). The estimated hazard ratios identified the possibility
`
`Table 1. BASELINE CHARACTERISTICS OF RANDOMIZED (TRIAL) AND STUDY
`(NONRANDOMIZED) PATIENTS
`
`Variable
`
`Randomized Patients (n 5 1090)
`
`Study Patients (n 5 1167)
`
`Age (years)
`Sex
`Initial AAA diameter (cm)
`Smoking status
`
`History of diabetes
`
`History of hypertension
`
`Electrocardiogram
`(Minnesota coding for presence
`of ischemic heart disease)
`
`FEV1 (L)
`ABPI (average of both legs)
`Body mass index (kg/m2)
`Systolic blood pressure (mmHg)
`Mean blood pressure (mmHg)
`Total cholesterol (mmol/L)
`Creatinine (mmol/L)
`Hemoglobin (g/L)
`White cell count (3 109/L)
`
`69.3 6 4.4
`902 (83%) male
`4.6 6 0.4
`Current 5 404 (37%)
`Ex 5 622 (57%)
`Never 5 64 (6%)
`Yes 5 30 (3%) [2]
`No 5 1058 (97%)
`Yes 5 419 (39%) [4]
`No 5 667 (61%)
`[19]
`Unlikely, 0 5 634 (59%)
`Possible, 1 5 289 (27%)
`Probable, 2 5 148 (14%)
`2.16 6 0.7 [27]
`0.95 6 0.2 [27]
`25.0 6 3.6 [12]
`156 6 27 [3]
`118 6 15 [3]
`6.15 6 1.2 [15]
`109 6 37 [37]
`14.1 6 1.5 [6]
`7.9 6 3.1 [16]
`
`69.8 6 4.4
`890 (76%) male
`4.3 6 0.9
`Current 5 437 (38%) [15]
`Ex 5 639 (55%)
`Never 5 76 (7%)
`Yes 5 69 (6%) [23]
`No 5 1075 (94%)
`Yes 5 510 (44%) [20]
`No 5 637 (56%)
`[122]
`Unlikely, 0 5 538 (51%)
`Possible, 1 5 314 (30%)
`Probable, 2 5 193 (19%)
`1.99 6 0.8 [108]
`0.91 6 0.2 [84]
`25.0 6 4.0 [56]
`158 6 28 [30]
`110 6 17 [32]
`6.24 6 1.3 [135]
`116 6 57 [108]
`13.8 6 1.6 [44]
`8.0 6 2.8 [45]
`
`The number of missing values for each variable is shown in square brackets.
`
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`Ann. Surg. c September 1999
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`Table 2. BASELINE CHARACTERISTICS OF PATIENTS WITH AND WITHOUT
`ANEURYSM RUPTURE
`
`Rupture Group (n 5 103;
`median follow-up
`22 [IQR 12–42] months)
`
`Nonrupture Group (n 5 2154;
`median follow-up
`18 [IQR 6–34] months)
`
`Age (years)
`Males (%)
`Initial AAA diameter (cm)
`Smoking status [15]
`
`FEV1 (L) [135]
`Mean blood pressure (mmHg) [35]
`ABPI (average of both legs) [111]
`Body mass index (kg/m2) [78]
`Total cholesterol (mmol/L) [150]
`
`70.6 6 4.5
`64 (62%)
`5.0 6 1.1
`Current 5 49 (49%)
`Ex 5 46 (45%)
`Never 5 6 (6%)
`1.69 6 0.76
`113 6 16.3
`0.90 6 0.21
`24.3 6 4.5
`6.31 6 1.3
`
`69.3 6 4.4
`1728 (80%)
`4.4 6 0.7
`Current 5 792 (37%)
`Ex 5 1215 (57%)
`Never 5 134 (6%)
`2.11 6 0.76
`109 6 16.1
`0.93 6 0.21
`25.0 6 3.8
`6.19 6 1.2
`
`The number of missing values is given in square brackets.
`* Probability values were obtained using the Mann-Whitney test, except for sex and smoking status, where chi-square tests were used.
`
`p*
`
`0.038
`,0.001
`,0.001
`0.06
`
`,0.001
`0.037
`0.082
`0.056
`0.47
`
`that female sex, higher mean arterial blood pressure, current
`smoking, and FEV1, in addition to initial AAA diameter,
`increased the risk of aneurysm rupture (Table 3). Although
`height was inversely associated with the risk of rupture in
`univariate analysis, after adjustment for age and sex the
`association was no longer significant. The fitness status
`(electrocardiogram, creatinine measurement) of men and
`women was similar, but the mean diameter preceding rup-
`ture was smaller in women (5.0 6 0.8 cm) than men (6.0 6
`1.4 cm) (p 5 0.001). The Kaplan-Meier curves comparing
`rupture-free survival in men and women (Fig. 3) also clearly
`indicate the threefold increased risk of AAA rupture in
`women (log rank test, p , 0.001).
`The large cohort of 2257 patients included significant
`proportions of patients whose AAA diameter never ex-
`ceeded 4.0 cm or who, although the AAA diameter ex-
`
`ceeded 5.5 cm, were considered unfit or refused surgery.
`The inclusion of these patients could have biased the results.
`Therefore, we repeated the analysis using only the more
`homogenous group of 1090 fit patients with AAAs 4.0 to
`5.5 cm in diameter randomized in the U.K. Small Aneurysm
`Trial (with 25 known ruptures). This analysis of trial pa-
`tients identified current smoking as having borderline sig-
`nificance, with initial AAA diameter, female sex, and higher
`mean blood pressure being independently and significantly
`associated with aneurysm rupture (Table 4). We have long
`suspected that self-reporting of smoking status may be
`inaccurate. Baseline plasma cotinine (a long-lived metabo-
`lite of nicotine) was measured in the 1090 trial patients.
`When cotinine instead of self-reported smoking status was
`used as the index of smoking habit, the clear significance of
`smoking was observed (p 5 0.045).
`
`Risk of Rupture and Last AAA Diameter
`
`To obtain further insight into how the risk of rupture
`varied according to the most recent aortic diameter, pa-
`tients were categorized into four groups with diameters of
`#3.9 cm, 4.0 to 4.9 cm, 5.0 to 5.9 cm, and $6.0 cm. In
`82/103 patients with AAA rupture, the aortic diameter
`had been measured within the preceding 12 months. An
`estimate of AAA diameter at rupture, based on last
`known diameter and individual growth rate, was made for
`the remaining 21 cases. Based on known (known 1
`estimated) diameter at rupture, there were 2 (3), 18 (24),
`33 (40), and 29 (36) ruptures in diameter categories #3.9
`cm, 4.0 to 4.9 cm, 5.0 to 5.9 cm, and $6.0 cm, respec-
`tively. The total number of person-years in each size
`range was calculated from the first AAA diameter mea-
`surement
`in that size range to the first measurement
`recorded in the next size range. The number of ruptures
`
`Figure 2. Overall survival without abdominal aortic aneurysm rupture.
`Kaplan-Meier estimate; patients were censored at death, aneurysm
`repair, or last follow-up.
`
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`
`Table 3. CRUDE RUPTURE RATES, ADJUSTED HAZARD RATIOS, AND p VALUES FOR
`BASELINE VARIABLES
`
`Variable
`
`Age (years by tertile group)
`59–66
`67–71
`72–77
`Sex
`Men
`Women
`Initial AAA diameter (cm)
`3.0–3.9
`4.0–5.5
`5.6–9.7
`Smoking status
`Current
`Ex
`Never
`BMI (kg/m2 by tertile group)
`15.0–23.3
`23.4–26.3
`26.4–42.1
`Mean blood pressure (mmHg by
`tertile group)
`57–102
`103–116
`117–193
`ABPI (mean by tertile group)
`0.02–0.86
`0.87–1.03
`1.04–1.90
`FEV1 (L by tertile group)
`0.1–1.7
`1.7–2.4
`2.5–4.0
`Cholesterol (mmol/L by tertile group)
`1.6–5.6
`5.7–6.6
`6.7–16.9
`
`* Adjusted for age, sex, and initial AAA diameter
`
`Number of
`Ruptures/Number
`of Patients
`
`Crude Rupture Rate
`(per 100 Person-Years)
`
`Adjusted Hazard Ratio
`(95% CI)*
`
`p*
`
`30/752
`26/752
`47/752
`
`64/1792
`39/464
`
`14/648
`69/1509
`20/100
`
`49/841
`46/1261
`6/140
`
`41/727
`29/732
`25/720
`
`28/760
`36/796
`36/666
`
`36/716
`38/715
`19/715
`
`51/728
`26/707
`16/687
`
`32/719
`24/702
`34/686
`
`2.2
`1.9
`3.5
`
`2.0
`4.6
`
`0.9
`2.7
`27.8
`
`3.3
`2.0
`2.4
`
`3.1
`2.1
`1.9
`
`2.0
`2.4
`3.1
`
`2.6
`2.9
`1.5
`
`3.8
`2.0
`1.2
`
`2.5
`1.8
`2.5
`
`1.03 (0.98–1.08) per year
`
`0.23
`
`1.0
`3.0 (1.99–4.53)
`
`,0.001
`
`2.94 (2.49–3.48) per cm
`
`,0.001
`
`1.0
`0.59 (0.39–0.89)
`0.65 (0.27–1.53)
`
`0.01
`
`0.99 (0.94–1.04) per kg/m2
`
`0.67
`
`1.02 (1.00–1.03) per mmHg
`
`0.01
`
`0.93 (0.34–2.58) per unit
`
`0.89
`
`0.62 (0.45–0.86) per L
`
`0.004
`
`0.92 (0.78–1.08) per mmol/L
`
`0.32
`
`per 100 patient-years increased from 0.3 for AAA #3.9
`cm to 1.5 and 6.5 for patients with AAAs in the diameter
`ranges 4.0 to 4.9 cm and 5.0 to 5.9 cm, respectively. The
`person-years of follow-up for patients with AAAs $6.0
`cm was so restricted by censorship at surgery that no
`estimate of rupture rate was calculated, although the rate
`of rupture appeared very high. The alternate analysis
`displaying survival without AAA rupture from the last
`measurement of aortic diameter up to the time of aneu-
`rysm repair, death, AAA rupture, or cessation of follow-
`up9 is shown in Figure 4. This analysis does not provide
`an estimate of rupture rates but allows assessment of how
`the risk of rupture varies with the last known AAA
`diameter. The much-higher risk of rupture in patients
`with aneurysms $6.0 cm is shown clearly.
`
`DISCUSSION
`
`The prognosis of AAA has been uncertain, mostly be-
`cause it has remained difficult to predict which aneurysms,
`in a given size range, are at highest risk of rupture. Our
`study shows that even very small aneurysms may rupture,
`but the risk and rate of rupture is very low. Previous cohort
`and population studies, like the present study, have been
`complicated by the uncertainty of diagnosis: no study has a
`full autopsy rate. Imaging and operative details and autopsy
`all permit an accurate diagnosis of rupture. The diagnosis of
`ruptured AAA, unconfirmed by these modalities, after a
`hospital death can be viewed with confidence but is less
`secure. In this study, a large number of deaths occurred
`outside the hospital, 15 in the rupture arm and 119 in the
`
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`Ann. Surg. c September 1999
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`Table 4. VARIABLES ASSOCIATED WITH
`ANEURYSM RUPTURE IN 1090
`RANDOMIZED TRIAL PATIENTS
`
`Baseline Variable
`
`Hazard Ratio (95% CI)
`
`p
`
`Age (years)
`Female sex
`AAA diameter (cm)
`Current smoker
`Mean blood pressure
`(mmHg)
`
`1.02 (0.93–1.13)
`4.50 (1.98–10.2)
`2.51 (1.08–5.80)
`2.11 (0.95–4.67)
`1.04 (1.02–1.07)
`
`0.67
`0.000
`0.032
`0.066
`0.002
`
`Cox regression analysis, all baseline variables adjusted for one another. For smok-
`ing, never-smokers and exsmokers were combined and compared with current
`smokers.
`
`surgery, providing potential bias, whereas current smoking
`habit is not. It has been known for a long time that smoking
`is the most important risk factor for the development of
`AAA.16,17 Now, for the first time, we have shown that
`current smoking also increases the risk of AAA rupture.
`These findings indicate that for patients of marginal fitness,
`those who refuse surgery, or those in whom a wait before
`surgery is anticipated, the surgeons and physicians should
`collaborate to provide adequate control of blood pressure
`and counseling and replacement therapy to help the patient
`stop smoking.
`Surgeons would like to know how to stratify the risk of
`rupture according to aneurysm diameter and growth rate.
`All previous studies have indicated that the risk of rupture
`escalates as the aortic diameter increases.5,6,9,10 In the co-
`hort studied here, the paucity of data for larger AAAs ($6
`cm) is mainly attributable to surgery and makes it difficult
`to provide accurate information. The highest proportion of
`ruptures occurred in those who were unfit for surgery or
`refused surgery. For these reasons, the figures we provide
`for ruptures per 100 patient-years and rupture-free survival
`after the last measurement of aortic diameter must be inter-
`preted cautiously. Although small AAAs do rupture, the risk
`for an aneurysm smaller than 5 cm in diameter is very low.
`The risk for AAAs 5.0 to 5.9 cm in diameter also is low but
`
`Figure 4. Survival without abdominal aortic aneurysm (AAA) rupture by
`size category of last measured aortic diameter.
`
`Figure 3. Overall survival without AAA rupture by gender. Kaplan-
`Meier estimates; patients were censored at death, aneurysm repair, or
`last follow-up. Log rank values, p , 0.001.
`
`nonrupture arm (see Fig. 1); in these patients, the diagnosis
`of aneurysm rupture is insecure, providing the possibility of
`significant amounts of both false-positive and false-negative
`information. However, this study has the advantages of
`being prospective, based on very reproducible physiologic
`measurements (including AAA diameter), and providing
`accurate censorship at the time of AAA repair. This latter
`event may be difficult to ascertain in large population stud-
`ies.
`Screening studies have shown that the prevalence of
`AAA is much lower in women than men.10 Women form
`only a small proportion of the surgical caseload for this
`condition. One of the most important and surprising find-
`ings of our study is that the rate of aneurysm rupture was
`three times higher in women than in men (see Fig. 3). This
`difference remained after adjustment for age, initial AAA
`diameter, and body mass index or height. The mean AAA
`diameter at rupture was 5 cm in women and 6 cm in men.
`There is evidence to indicate that women have smaller-
`diameter, more compliant aortas than men.14 This might
`suggest that the ratio of infrarenal/suprarenal diameter is the
`important determinant of AAA stability or rupture, although
`suprarenal diameters cannot be measured reproducibly by
`ultrasonography.8
`Higher mean blood pressure and current smoking (asso-
`ciated with a low FEV1) are the risk factors for AAA
`rupture that can be altered. Previously, we have shown that
`small aneurysms appeared to grow faster in smokers,15 and
`others have indicated that poor lung function and increased
`diastolic blood pressure are associated with AAA rupture.11
`Mean blood pressure reflects the continuing hemodynamic
`burden on the aortic wall, always present to weaken the
`aneurysmal section. Among the cohort of patients we stud-
`ied, there was a very significant correlation between current
`smoking habit and lung function: both were associated with
`AAA rupture. The data on smoking habit were more com-
`plete than lung function measurements. Moreover, poor
`lung function is a valid reason to declare a patient unfit for
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`appears to escalate sharply for aneurysms $6 cm in diam-
`eter. Unfortunately, the annual rate of rupture for these large
`aneurysms cannot be estimated, because the length of fol-
`low-up was very limited. The analysis of factors associated
`with AAA growth and whether rapid aneurysm growth
`predicts rupture will be the focus of a separate analysis.
`This study has shed new light on the risk factors associ-
`ated with the rupture of AAAs, particularly smaller aneu-
`rysms. Recently, endovascular repair has become a man-
`agement option for patients considered unfit for open repair,
`but it is not known how this will influence rupture rates in
`such patients. Whether or not marginally fit patients are
`treated by endovascular repair, we shall need to know
`whether smoking cessation and improved blood pressure
`control will diminish the risk of rupture. Our data also
`suggest that when considering the indications for aneurysm
`repair, different thresholds should apply to women than
`men.
`
`U.K. Small Aneurysm Trial
`Steering Committee: Prof. RM Greenhalgh (Chairman); Prof. JT Pow-
`ell (Imperial College at Charing Cross); Prof. FGR Fowkes, Dr. JF Forbes,
`Prof. CV Ruckley (University of Edinburgh).
`Writing Committee: Prof. JT Powell (Chair); LC Brown, Prof. RM
`Greenhalgh, Prof. FGR Fowkes, Prof. CV Ruckley.
`Monitoring Committee: Prof. PA Poole-Wilson (Chair); Sir N.
`Browse, Prof. CJ Bulpitt, Prof. K. Burnand, Dr. EC Coles, Dr. A. Fletcher.
`Trial Coordinators: Sue Blair, Rebecca Clark, Carol Devine, Karen
`Ferguson, Sheila Hearn, Eileen Kerracher, Sarah Logan, Anna McCabe,
`Razia Meer-Baloch, Michelle Mossa, Anna Rattray, Katie Wilson.
`ECG Coding: Mrs. N. Keen, Mrs. C. Rose.
`Blood Analysis: R. Mir Hassaine.
`TRIAL PARTICIPANTS (number of randomized patients recruited in
`brackets)
`S.W. ENGLAND AND SOUTH WALES—Prof. M. Horrocks, Regional
`Trial Director: Royal United Hospital: Mr. J. Budd (6), Prof. M. Horrocks
`(23); Bristol Royal Infirmary: Mr. RN Baird (12), Mr. P Lamont (10);
`Derriford Hospital: Mr. DC Wilkins (6), Mr. S Ashley (3); Dorset
`County Hospital: Mr. K. Flowerdew (9); Frenchay Hospital: Mr. A.
`Baker (7); Gloucester Royal Infirmary: Mr. J. Earnshaw (4), Mr. B.
`Heather (3); Morriston Hospital: Mr. C. Gibbons (14); Neville Hall
`Hospital: Mr. RL Blackett (8); New Royal Bournemouth General Hos-
`pital: Mr. SD Parvin (30); North Devon District General Hospital: Mr.
`DR Harvey (1); Princess of Wales Hospital: Mr. R. Hedges (1); Princess
`Margaret Hospital: Mr. D. Finch (6), Mr. DB Hocken (2); Southampton
`General Hospital: Mr. GE Morris (1), Mr. CP Shearman (4); Southmead
`Hospital: Mr. P. Lear (4); Torbay Hospital: Mr. P. Lewis (5); Yeovil
`District General Hospital: Mr. RJ Clarke (5).
`SCOTLAND & N.E. ENGLAND—Prof. CV Ruckley, Regional Trial
`Director: Edinburgh R.I.: Mr. AM Jenkins (1), Prof. CV Ruckley (28);
`Aberdeen R.I.: Mr. GG Cooper (18), Mr. J. Engeset (38), Mr. R. Naylor
`(1); Ayr Hospital: Mr. G. Stewart (16); Dryburn Hospital, Durham: Mr.
`J. Cumming (10); Dumfries & Galloway Royal Infirmary: Mr. J. Mc-
`Cormick (8); Dunfermline & West Fife Hospital: Miss A. Howd (9), Mr.
`A. Turner (6); Falkirk & District Infirmary: Mr. DR Harper (5), Mr. RC
`Smith (6); Freeman Hospital: Mr. J. Chamberlain (10), Mr. AG Jones
`(12), Mr. MG Wyatt (2); Gartnavel General Hospital: Mr. AJ McKay
`(13); Ninewells Hospital: Mr. JC Forrester (3), Mr. P. McCollum (30), Mr.
`PA Stonebridge (3); Perth Royal Infirmary: Mr. AIG Davidson (2);
`Queen Elizabeth Hospital: Mr. R. Baker (4); Royal Victoria Infirmary:
`Mr. JLR Forsythe (1), Mr. D. Lambert (8); Royal Northern Infirmary:
`Mr. JL Duncan (11).
`
`THE MIDLANDS—Prof. PRF Bell, Regional Trial Director: Leicester
`Royal Infirmary: Prof. PRF Bell (25), Mr. D. Ratliff (1); Derbyshire
`Royal Infirmary: Mr. KG Callum (16), Mr. JR Nash (17); Glenfield
`General Hospital: Mr. DS McPherson (7); Kettering & General District
`Hospital: Mr. RE Jenner (4), Mr. R. Stewart (5); Kidderminster General
`Hospital: Mr. PR Armitstead (8); Leicester General Hospital: Mr. WW
`Barrie (5); Northampton General Hospital: Mr. DB Hamer (6), Mr. S.
`Powis (5); Northern General Hospital: Mr. LD Coen (2); Mr. J. Michaels
`(4), Mr. CL Welsh (3); Nottingham Queen’s Medical Centre: Mr. BR
`Hopkinson (5), Mr. PW Wenham (14); Royal Hallamshire Hospital: Mr.
`J. Beard (25); Sandwell District General Hospital: Mr. A. Auckland (3);
`Worcester Royal Infirmary: Mr. J. Black (7), Mr. R. Downing (6);
`Worcester Royal Infirmary: Mr. NC Hickey (3).
`LONDON & S.E. ENGLAND—Prof. RM Greenhalgh, Regional Trial
`Director: Charing Cross Hospital: Mr. AH Davies (2), Prof. RM Green-
`halgh (39), Mr. D. Nott (5); Colchester General Hospital: Mr. ARL May
`(33); Epsom District Hospital: Mr. R. McFarland (11); Guy’s Hospital:
`Mr. P. Taylor (15); Hillingdon Hospital: Mr. JWP Bradley (3), Mr. T.
`Paes (9); Ipswich Hospital: Mr. AEP Cameron (7); Joyce Green Hospi-
`tal: Mr. A. McIrvine (18); Lewisham Hospital: Mr. D. Negus (4), Mr. PR
`Taylor (10); Medway Hospital: Mr. CM Butler (2), Mr. RW Hoile (1);
`Newham General Hospital: Mr. B. Pardy (11); Princess Alexandra
`Hospital: Miss J. Ackroyd (9); Royal Free Hospital: Mr. G. Hamilton (4);
`Royal Hampshire County Hospital: Mr. R. Lane (1); Royal Surrey
`County Hospital: Mr. AEB Giddings (21); St. Georges’s Hospital: Mr. J.
`Dormandy (5), Mr. R. Taylor (9); St. Peter’s Hospital: Mr. M. Thomas
`(18); St. Thomas’ Hospital: Mr. KJ Burnand (7); University College
`Hospital: Mr. M. Adiseshiah (3); West Middlesex Hospital: Mr. P.
`Pattison (1); West Norwich Hospital: Mr. J. Clarke (8), Mr. J. Colin (9);
`Wexham Park Hospital: Mr. P. Rutter (4); Whipps Cross Hospital: Mr.
`S. Brearley (14), Mr. M. Pietroni (1).
`N. ENGLAND AND NORTH WALES—Prof. CN McCollum, Regional
`Trial Director: University Hospital South Manchester: Prof. CN McCol-
`lum (12); Arrowe Park Hospital: Mr. MG Greaney (2), Mr. D. Reilly (7);
`Blackburn Royal Infirmary: Mr. WG Paley (1); Blackpool, Victoria
`Hospital: Mr. M. Lambert (16); Burnley General Hospital: Mr. R.
`Hughes (16); Clatterbridge Hospital: Mr. S. Blair (2); Cumberland
`Infirmary: Mr. JEG Shand (1); Grimsby District General Hospital: Mr.
`LA Donaldson (1); Hull Royal Infirmary: Mr. JMD Galloway (2), Mr.
`AR Wilkinson (21); Leeds District General Hospital: Mr. M. Gough
`(16); Leigh Infirmary: Mr. J. Mosley (1); Macclesfield General Hospi-
`tal: Mr. DM Matheson (19); Manchester Royal Infirmary: Mr. M.
`Walker (4); Oldham Royal Hospital: Mr. N. Hulton (4); Pontefract
`General Infirmary: Mr. MI Aldoori (4), Mr. CK Yeung (1); Royal
`Preston Hospital: Mr. AR Hearn (6); Royal Lancaster Infirmary: Mr. J.
`Kelly (18); Stafford General Hospital: Mr. D. Durrans (2), Mr. B. Gwynn
`(3); Stoke City General Hospital: Mr. GB Hopkinson (13); Telford
`General Hospital: Mr. RGM Duffield (18); The Infirmary Rochdale:
`Mr. IG Schraibman (3); York District Hospital: Mr. R. Hall (3), Mr. SH
`Leveson (4); Glan Clwyd Hospital, Rhyl: Mr. J. Clark (3), Mr. O.
`Klimach (23).
`
`References
`
`1. Bradbury AW, Makhdoomi KR, Adam DJ, et al. Twelve-year expe-
`rience of the management of ruptured abdominal aortic aneurysm. Br J
`Surg 1997; 84:1705–1707.
`2. Johnson KW. Ruptured abdominal aortic aneurysm. 6-year follow-up
`results of a multicenter prospective study. J Vasc Surg 1994; 19:888 –
`900.
`3. U.K. Small Aneurysm Trial Participants. Mortality results for random-
`ised controlled trial of early elective surgery or ultrasonographic
`surveillance for small abdominal aortic aneurysms. Lancet 1998; 352:
`1649 –1655.
`4. Lederle FA. Risk of rupture of large abdominal aortic aneurysm. Arch
`Intern Med 1996; 156:1007–1009.
`
`

`

`296
`
`U.K. Small Aneurysm Trial Participants
`
`Ann. Surg. c September 1999
`
`5. Darling RC. Ruptured arteriosclerotic abdominal aortic aneurysms: a
`pathologic and clinical study. Am J Surg 1970; 119:397– 401.
`6. Turk KAD. The post-mortem incidence of abdominal aortic aneurysm.
`Proc Roy Soc Med 1965; 58:869 – 870.
`7. Nevitt MP, Ballard DJ, Hallett JW. Prognosis of abdominal aortic
`aneurysms: a population-based study. N Engl J Med 1989; 321:1009 –
`1014.
`8. Ellis M, Powell JT, Greenhalgh RM. The limitations of ultrasonogra-
`phy in surveillance of abdominal aortic aneurysms. Br J Surg 1991;
`78:614 – 616.
`9. Reed WW, Hallett JW, Damiano MA, Ballard DJ. Learning from the
`last ultrasound. A population-based study of patients with abdominal
`aortic aneurysm. Arch Intern Med 1997; 157:2064 –2068.
`10. Scott RA, Tisi PV, Ashton MA, Allen DR. Abdominal aortic aneurysm
`rupture rates: a 7-year follow-up of the entire abdominal aortic aneu-
`rysm population detected by screening. J Vasc Surg 1998; 28:124 –
`128.
`11. Cronenwett JL, Murphy TF, Zelenock GB, et al. Actuarial analysis of
`variables associated with rupture of small abdominal aortic aneurysms.
`Surgery 1985; 98:472– 483.
`12. Michaels JA. The management of small abdominal aortic aneurysms:
`a computer simulation using Monte Carlo methods. Eur J Vasc Surg
`1992; 6:551–557.
`13. U.K. Small Aneurysm Trial Participants. The U.K. Small Aneurysm
`Trial: design, methods and progress. Eur J Vasc Endovasc Surg 1995;
`9:42– 48.
`14. Sonesson B, Hansen F, Stale H, Lanne T. Compliance and diameter in
`the human abdominal aorta—the influence of age and sex. Eur J Vasc
`Surg 1993; 7:690 – 697.
`15. MacSweeney STR, Ellis M, Worrell PC, Greenhalgh RM, Powell JT.
`Smoking and growth rate of small abdominal aortic aneurysms. Lancet
`1994; 344:651– 652.
`16. Hammond EC, Garfinkel