GENDER BASED DIFFERENCES IN ABDOMINAL AORTIC ANEURYSM (AAA) RUPTURE

1
GENDER BASED DIFFERENCES IN ABDOMINAL AORTIC
ANEURYSM (AAA) RUPTURE
-Srikrishna Varun Malayala, MBBS
Mentors -Khalid J Qazi, MD, MACP -Paul M
Anain, MD
1. http//aorticstents.com/what-is-abdominal-aorti
c-aneurysm/ (05/23/13)
2
Disclosures
None
1. http//aorticstents.com/what-is-abdominal-aorti
c-aneurysm/ (05/23/13)
3
Background

• Cardiovascular disease is the number one cause of
  death for both men and women in the United
  States1.
• Traditionally, all the cardiovascular diseases
  were considered as mens diseases.

Centers for Disease Control (CDC)-2010 Centers for Disease Control (CDC)-2010 Centers for Disease Control (CDC)-2010
Males Females
Risk factors Risk factors Risk factors
Smoking 21.5 17.3
Hypertension 61.4 46.3
Dyslipidemia 31 24
Diabetes 11.8 10.8
Obesity 35.5 35.8
Cardiovascular Diseases Cardiovascular Diseases Cardiovascular Diseases
Coronary Artery Diseases 2.2 1
Cerebrovascular Diseases 2.7 2.6
Peripheral Vascular Diseases 11 8
Carotid Artery Diseases 3.8 2.7

1. Cardiovascular Health Branch, Division of Chronic
   Disease Control and Community Intervention,
   National Center for Chronic Disease Prevention
   and Health Promotion, CDC. Trends in ischemic
   heart disease mortality United States,
   1980-1988.
2. Petersen S, Peto V, Scarborough P, Rayner M,
   British Heart FoundationHealth Promotion Research
   Group. Coronary heart disease statistics
   2005.Oxford British Heart Foundation, 2005.
   www.heartstats.org/temp/ CHD_2005_Whole_spdocument
   .pdf (accessed 15 Aug 2005).

4
Background

• Preventive medicine - screening tests, counseling
  and preventive medications.

U.S. Preventive Services Task Force-March 2009 U.S. Preventive Services Task Force-March 2009 U.S. Preventive Services Task Force-March 2009
Screening modality Grade
Risk factor modification Risk factor modification Risk factor modification
Smoking Counseling on cessation A
Hypertension Blood pressure monitoring A
Dyslipidemia Lipid profile A
Diabetes Mellitus Fasting plasma glucose B
Obesity Lifestyle modification B
Prevention of Cardiovascular diseases Aspirin B
A- Strongly Recommended BenefitgtgtRisk B-Recommen
ded BenefitgtRisk
Performance Improvement Projects ??
1. http//www.uspreventiveservicestaskforce.org/us
pstopics.htm
5
Introduction
-My out-patient PI project Screening for AAA in
high risk patients.
-Dilatation or widening of the abdominal
aorta. -Definition An abdominal aortic diameter
of 3 cm or more, which is usually more than 2
standard deviations above the mean diameter1.

• -Risk factors1
• Modifiable
• Age
• Male gender
• White race
• Family history

• Non modifiable
• Smoking
• Hypertension
• Hyperlipidemia
• Atherosclerosis

-AAA rupture is a medical emergency. -Mortality
could be up to 502. -Ruptured AAA is estimated
to cause 5 percent of sudden deaths2.
1.Steinberg I, Stein HL. Arterosclerotic
abdominal aortic aneurysms. report of 200
consecutive cases diagnosed by intravenous
aortography. JAMA 19661951025. 2. Brown LC,
Powell JT (September 1999). "Risk Factors for
Aneurysm Rupture in Patients Kept Under
Ultrasound Surveillance". Annals of Surgery 230
(3) 28996 discussion 2967. doi10.1097/0000065
8-199909000-00002. PMC 1420874. PMID 10493476
6
Introduction

• The strongest risk factor for the rupture of an
  AAA is maximal aortic diameter4.

Normal CT scan
Abdominal Aortic Aneurysm
Abdominal Aortic Aneurysm Rupture
1
2
3

• Risk of rupture4
• lt 4 cm 0.5 per year
• 4.0 4.9 cm 1 per year
• 5.0 5.9 cm 11 per year
• 6.0 6.9 cm 26 per year
• 7.0 7.9 cm 40 per year
• gt 8 cm 50 year year

• Management5
• Open repair conventional method of repair
• Endovascular repair faster recovery, reduced
  length of stay in ICU, reduced hospital stay
• (no long benefits in terms of survival and
  mortality)5

1.http//www.nlm.nih.gov/medlineplus/ency/article/
003789.htm (05/23/2013) 2.http//www.surgical-tut
or.org.uk/default-home.htm?system/vascular/aaa.htm
right (05/23/2013) 3.http//www.radiologyassistan
t.nl/en/p4530b48a07dbd/aaa-rupture-1.html
(05/24/13) 4. Brewster DC, Geller SC, Kaufman JA,
Cambria RP, Gertler JP, LaMuraglia GM, et al.
Initial experience with endovascular aneurysm
repair comparison of early results with outcome
of conventional open repair. J Vasc Surg
199827992-1003.
7
Screening guidelines

• USPSTF recommends one-time screening for
  abdominal aortic aneurysm (AAA) by
  ultrasonography in men aged 65 to 75 who have
  ever smoked (100 cigarettes in life time)2.
  Ultrasound has 90 sensitivity and 100
  specificity.

• Effective for services furnished on or after
  January 1, 2007, payment may be made for a
  one-time ultrasound screening for AAA for
  beneficiaries who meet the following criteria2
• Men aged 65-75 who ever smoked.
• Men and women with a family history of AAA
• As a part of Welcome to Medicare within the
  first year of enrollment

1. Fleming C, Whitlock EP, Beil T, Lederle F.
   Screening for abdominal aortic aneurysm a
   best-evidence systematic review for the U.S.
   Preventive Services Task Force. Ann Intern Med
   2005142203-11.
2. http//www.uspreventiveservicestaskforce.org/uspst
   f05/aaascr/aaars.htm
3. http//www.fomadistrict2.com/wp-content/uploads/20
   12/12/SAAAVE-ACT.pdf

8
Management guidelines

• Indications of elective surgery1
• Diameter of 5.5 cm for an average patient.
• Symptomatic AAA (irrespective of the size)
• Rapid expansion-1 cm in one year (irrespective of
  the size)
• Decision on repair must be individualized for
  each patient.

• Surveillance2
• Less than 3 cm No repeat ultrasound
• 3-4 cm Ultrasound every 2-3 years
• 4-5.5 cm Ultrasound every 6 months to one year

1. David C. Brewster,a MD, Jack L. Cronenwett, MD,b
   John W. Hallett, Jr, MD,c K. Wayne Johnston, MD,d
   William C. Krupski, MD,e and Jon S. Matsumura,
   MD,f Boston, Mass Lebanon, NH Bangor, Me
   Toronto, Canada Denver, Colo and Chicago, Ill
   Guideliens for treatment of Abdominal Aortic
   Aneurysms, Journal of Vascular Surgery, 2007
2. Kent KC, Zwolak RM, Jaff MR, et al. Screening for
   abdominal aortic aneurysm A consensus statement.
   J Vasc Surg 200439267-9.

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• Night float-PGY-2 3 female patients in the same
  rotation.
• Aorto-enteric fistula
• 7 cm AAA with elective repair and admitted to ICU
• Multiple aneurysms (aorto-iliacs) with rupture

Case report on aorto-enteric fistula Time bomb
in the belly
10
Literature review

• Epidemiological differences
• Prevalence 7.6 in males vs 1.3 in
  females1
• Overall prevalence is increasing in women (could
  be attributed to smoking)2.
• Risk of rupture for any given size is higher in
  females3.

• Women with AAA have a stronger familial
  association than men4.
• Estrogen does have a protective effect on the AAA
  in women4.

1. Pleumeekers HJCM, Hoes AW, van der Does E, van
   Urk H, Hofman A, de Jong PTVM, Grobbee DE.
   Aneurysms of the abdominal aorta in older adults.
   Am J Epidemiol. 199514212911299.
2. 2cott RAP, Bridgewater S, Ashton HA. Randomised
   clinical trial of screening for abdominal aortic
   aneurysm in women. Br J Surg. 200289 283285.
3. Katz DJ, Stanley JC, Zelenock GB. Gender
   differences in abdominal aortic aneurysm
   prevalence, treatment, and outcome. J Vasc Surg.
   1997 25561568.
4. Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf
   AR, Lasser NL, Trevisan M, Black HR, Heckbert SR,
   Detrano R, Strickland OL, Wong ND, Crouse JR,
   Stein E, Cushman M, for the Womens Health
   Initiative Investigators. Estrogen plus progestin
   and the risk of coronary heart disease. N Engl J
   Med. 2003349523534.

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Biological differences

• At any given age, males have larger abdominal
  aortic diameters than women1.
• There is marked age-dependent increase in
  diameter observed after 45 to 54 years in men
  than in women2.

• Suitability for EVAR is different The angulation
  of iliacs, size of femoral
• arteries and tortuosity of aortas are
  different in females3.

1. Lederle FA, Johnson GR, Wilson SE, Gordon IL,
Chute EP, Littooy FN, Krupski WN, Brandyk D,
Barone GW, Graham LM, Hye RJ, Reinke DB, Aneurysm
Detection and Management Investigators.
Relationship of age, gender, race, and body size
to infrarenal aortic diameter. J Vasc Surg.
199726595 601. 2. Singh K, Bonaa KH, Jacobsen
BK, Bjork L, Soldberg S. Prevalence of and risk
factors for abdominal aortic aneurysms in a
population-based study. Am J Epidemiol.
2001154236 244. 3. Sonesson B, Hansen F, Stale
H, Lanne T. Compliance and diameter in the human
abdominal aorta the influence of sex and age.
Eur J Vasc Surg. 19937690 697.
12

• UK Small Aneurysm trial
• Multicentre, randomised controlled trial
  conducted across 93 UK hospitals
• 83 males
• ADAM study (Aneurysm Detection and Management)
• 73451 veterans aged 50 to 79
• 99 males

N-67,800
All of themmen

1. The United Kingdom Small Aneurysm Trial
   Participants. Long-term outcomes of immediate
   repair compared with surveillance of small
   abdominal aortic aneurysms. N Engl J Med.
   200234614451452.
2. Lederle F, Wison S, Johnson G, Reinke D, Litooy
   F, Acher C, Ballard D, Messina L, Gordon I, Chute
   E, Krupski W, Bradyk D. Immediate repair compared
   with surveillance of small abdominal aortic
   aneurysms. N Engl J Med. 200234614371444.

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Gender based differences in cardiovascular
diseases

• Cardiovascular diseases (CVDs) are the number one
  killer of women1.
• Mortality is more than all forms of cancers
  combined (breast , cervical and lung cancer)2.

• Women continue to be under-represented in
  research on heart disease. 3.
• Still women continue to receive similar
  treatments to men on the basis of trials that
  include mainly male participants3.

1. http//www.world-heart-federation.org/press/fact-s
   heets/women-and-cardiovascular-disease/
2. American Heart Association. 1997 Heart and Stroke
   Facts Statistical Update. Dallas, Tex American
   Heart Association 1996.
3. Mikhail GW. Coronary heart disease in women is
   underdiagnosed, under- treated, and
   under-researched. BMJ. 2005331467468.

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Circulation 2007
British Journal of Surgery 1985-1994 873 AAA
ruptures of Western Australia
15

• Goals
• Emphasize the importance of screening for AAAs in
  high risk women.
• Emphasize the importance of sex-specific
  management guidelines of AAA.
• Objectives
• Compare the outcomes of ruptured Abdominal Aortic
  Aneurysms between men and women.
• Compare the characters of ruptured AAAs in men
  and women.

16
Methods

• Sample All the AAA ruptures in Sisters and Mercy
  Hospitals admitted from January 1 2007 to present
  date (6 years).
• Type of study Retrospective review of paper
  charts and Electronic Medical Records.
• Data collection
• Demographic characters
• Co-morbidities (Hypertension, Dyslipidemia,
  Diabetes, Cardiovascular diseases)
• Previous history of AAA (size diagnosed, any
  surgeries and history of rupture)
• Medications (statins, ASA, Plavix)
• Characters of aneurysm(size, iliac arteries)
• Hospital course (LOS ICU, LOS hospital, surgery,
  outcome)
• Post-operative complications
• Long term survival(SSN database)
• A total of 39 parameters were compared between
  males and females.

17
Results

• Total no. of cases reviewed 1538 (100)

• Exclusion criteria
• Elective repairs
• Endovascular leak
• Endovascular revision

• Total no. of cases excluded 1417 (92)

• Total no. of cases included 117 (8)

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Results
Incidence
N ()
Males 79 (67.6)
Females 38 (32.4)
Total 117
-The prevalence of AAA is 6 times lower in women
but the rate of rupture is higher in females (1).
-Trends in mortality and hospital admission rates
for abdominal aortic aneurysm in England and
Wales. Br J Surg. 2005 92 968975.
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Demographics
Males Females Females Total p-value
Site 0.17
SOCH 52(65.8) 52(65.8) 20(52.6) 72 0.17
SBMH 27(34.2) 27(34.2) 18(47.4) 45 0.17
Race N/A
Caucasian 79 (100) 79 (100) 38(100) 117 N/A
Others 0 0 0 0 N/A
BMI (n77) 0.02
Normal 15(25.8) 15(25.8) 11(58.0) 26 0.02
Overweight 24(41.3) 24(41.3) 6(31.5) 30 0.02
Obese 19(32.9) 19(32.9) 2(10.5) 21 0.02
Smoking 0.06
Yes 66(83.5) 66(83.5) 26(68.4) 92 0.06
No 13(16.5) 13(16.5) 12(31.6) 25 0.06
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Co-morbidities and medications
Males Females Total p-value
Hypertension Hypertension Hypertension Hypertension 0.64
Yes 66(83.5) 33(86.8) 99 0.64
No 13(16.5) 5(13.2) 18 0.64
Major co-morbidities Major co-morbidities Major co-morbidities 0.64
Yes 38 (48.1) 20(52.6) 58 0.64
No 41(52.9) 18(47.4) 59 0.64
Statin Statin Statin Statin 0.74
Yes 40(50.6) 18(47.4) 68 0.74
No 39(49.4) 20(52.6) 59 0.74
Beta-Blocker Beta-Blocker Beta-Blocker Beta-Blocker 0.48
Yes 24(30.4) 14(36.8) 38 0.48
No 55(69.6) 24(63.2) 79 0.48
Aspirin Aspirin Aspirin Aspirin 0.10
Yes 40(50.6) 18(47.4) 58 0.10
No 39(49.4) 20(52.6) 59 0.10
Clopidogrel Clopidogrel Clopidogrel Clopidogrel 0.47
Yes 7(8.9) 5(13.1) 12 0.47
No 72 33(86.8) 105 0.47
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Age at rupture
p0.005
N Mean (years) S.D. (years) Range (years)
Males 79 75.75 10.0 50-97
Females 38 82.39 8.6 59-103
Overall 117 77.91 10.1 50-103

• Gender is an independent predictor of age of
  rupture after controlling the effects of
  hypertension, co-morbidities, smoking, use of
  statins and previous history of aneurysms.

Age-specific incidence (10 year intervals)
lt55 56-65 66-75 76-85 86-95 gt95
Males 1 5 14 32 24 3
Females 0 2 1 10 20 5
Overall 1 7 15 42 44 8
65.8
65.7
Figure 2. Mean age (years) plt0.001
Figure 2. Mean age (years) plt0.001
22
Characters of AAAs at presentation
(Parameters from the CT scan abdomen at admission)
Males Females Females Total p-value
Location Location Location Location Location 0.28
Infra-renal 75 (94.9) 75 (94.9) 34 (89.5) 109 0.28
Supra-renal 0 0 1 (2.6) 1 0.28
Both 4 (5.1) 4 (5.1) 3 (7.9) 7 0.28
Iliac arteries Iliac arteries Iliac arteries Iliac arteries Iliac arteries 0.42
Left 6 (7.6) 6 (7.6) 1(2.6) 7 0.42
Right 9(11.4) 9(11.4) 4(10.5) 13 0.42
Both 12(15.2) 12(15.2) 3(7.9) 15 0.42
None 52 (65.8) 52 (65.8) 30(78.9) 82 0.42
23
Characters of AAAs at presentation
Size at rupture
p0.04
Mean size (cm) S.D. (cm) Range (cm)
Males 8.23 1.84 4-12
Females 7.46 2.09 3-14.7
Size-specific incidence
Size at rupture (cm) lt5 5-6 6-7 7-8 8-9 gt9
Males 3 10 9 18 12 27
Females 1 13 5 5 8 6
50
50
24
Effect of gender on Hospital course
Incidence of surgery
Yes No
Males 74 (93.7) 5 (6.3)
Females 24 (63.2) 14 (36.8)
-P0.03 -Adjusted for age and major
co-morbidities (binary logistic regression)
Type of surgery performed
Males Females Total p-value
EVAR 57 (72.2) 16 (42.1) 73 lt0.01
Open 17 (21.5) 8 (21.1) 25 lt0.01
None 5 (6.3) 14 (36.8) 19 lt0.01
25
Indicators of post-operative morbidity
N98, Men74 and Women24
Use of ventilator Pressor Support LOS ICU (days) Post-op complications
Males 59.5 54.1 4.1 48.6
Females 75 70.8 5.5 58.3
Major co-morbidities was a significant predictor
of post-operative complications, VDRF and use of
vasopressors (plt0.001, logistic regression)
Age was a significant predictor of VDRF and use
of vasopressors (plt0.001, logistic regression)
26
Overall Mortality
-P0.001 -Adjusted for hypertension, smoking,
statins, major co-morbidities (logistic
regression)
Alive Dead Total
Males 54 (68.4) 25 (31.6) 79
Females 12 (31.6) 26 (68.4) 38
Overall 66 (56.4) 51 (43.6) 117
Post-operative mortality
-P0.05 -Adjusted for
hypertension, smoking, statins,
major co-morbidities (logistic regression)
Alive Dead Total
Males 53 (71.6) 21 (21.4) 74
Females 12 (50.0) 12 (50.0) 24
Overall 65 (66.3) 33 (33.7) 98
Mortality based on type of surgery
EVAR OPEN
Males 17.5 64.7
Females 43.8 63
P-value 0.02 N/A
-Adjusted for hypertension, smoking, statins,
major co-morbidities (logistic regression)
27
Size at previous diagnosis
Mean size (cm) S.D. (cm) Range (cm)
Males 4.0 3.3 4-10
Females 5.0 2.6 3-9.3
Elective surgery could have been performed !!
28
Long term survival

• Patients discharged alive were followed for a
  period of 2 years.
• Date of death was procured from ssdmf.com (SSN
  database)

Kaplan-Meier survival curve analysis
Males11.0 months Females9.3 months P
0.41 -unadjusted data. -very small sample.
29
It is all about..
1
Will the screening be cost effective?
1.http//www.123rf.com/photo_18118258_elderly-woma
n-suffering-with-a-belly-pain-in-the-living-room.h
tml-05/232013
30
Will the screening be cost effective?

• Average re-imbursement for an ultrasound for AAA
  screening97.771

• Summary of financials from previous 3 years (All
  Catholic Health sites)
• Average profit for surgical repair after a AAA
  rupture is 8500 more for male patients over
  female patients
• Average profit for AAA rupture admissions is
  7500 more for male patients over female patients

http//www.gehealthcare.com/usen/community/reimbur
sement/docs/Vascular_Surgery_reimbursementv2.pdf
31
Conclusions Lower AAA prevalence is balanced
by a higher rupture rate,
mortality and morbidity. So screening is indeed
cost-effective.
32
Limitations

• Study could not comment on the current guidelines
  of elective surgery at 5.5 cm
• Single center study
• Missing co-variates COPD, family history, age at
  menopause

Next steps.

• Small AAAs (Prospective trial)
• Total no. of visits (Catholic Health System)
  gt1500

33
Conclusions

• The overall incidence of AAA rupture was higher
  in males (68) than in females(32).
• There was a significant effect of gender on the
  age of death from AAA rupture after controlling
  the effect of hypertension, co-morbidities,
  smoking, use of statins and previous history of
  aneurysms F (1,110)8, p0.005.
• There was a significant difference in the size of
  AAA rupture between females (mean7.4 cm, SD2.0)
  and males (mean8.2 cm, SD1.8) t (115)2.0, p
  0.04.
• The probability to undergo surgery for ruptured
  AAA was significantly lower for women as
  compared to men, even after adjusting for age at
  admission and major co-morbidities (p0.03).

34
Conclusions

• There was a significant effect of gender on the
  overall mortality (p0.001) and post-operative
  mortality after EVAR (p0.02) from AAA rupture
  after controlling the effect of hypertension,
  co-morbidities, smoking, use of statins and
  previous history of aneurysm.
• Gender was an independent predictor of length of
  ICU stay, incidence of post-operative
  complications, use of pressors and use of
  ventilator.
• Using a similar threshold of size of AAA for
  elective surgery for both males and females might
  not be appropriate.
• AAA screening might be warranted for high risk
  females owing to the higher morbidity and
  mortality.

35
Acknowledgements

• University at Buffalo GME -- Statistical support
• Andrew Bishop (Data analyst)-- Financial analysis
• Henri Woodman, MD-- Symposium presentation
• Paul M Anain, MDOutstanding mentorship
• Khalid J Qazi, MD, MACP--Outstanding mentorship

36
THANK YOU