GENDER BASED DIFFERENCES IN ABDOMINAL AORTIC ANEURYSM (AAA) RUPTURE -Srikrishna Varun Malayala, MBBS...

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-aortic-aneurysm/ (05/23/13)

Disclosures

None

1. http://aorticstents.com/what-is-abdominal-aortic-aneurysm/ (05/23/13)

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

“men’s diseases.” Centers for Disease Control (CDC)-2010

Males Females

Risk factorsSmoking 21.5% 17.3%

Hypertension 61.4% 46.3%

Dyslipidemia 31 % 24 %

Diabetes 11.8 % 10.8%

Obesity 35.5% 35.8%

Cardiovascular DiseasesCoronary 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).

Background

U.S. Preventive Services Task Force-March 2009

Screening modality Grade

Risk factor modification

Smoking Counseling on cessation

A

Hypertension Blood pressuremonitoring

A

Dyslipidemia Lipid profile A

Diabetes Mellitus Fasting plasma glucose

B

Obesity Lifestyle modification

B

Prevention of Cardiovascular diseases

Aspirin B

1. http://www.uspreventiveservicestaskforce.org/uspstopics.htm

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

PerformanceImprovementProjects ??

A- Strongly RecommendedBenefit>>Risk

B-RecommendedBenefit>Risk

Introduction

-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.

1.Steinberg I, Stein HL. Arterosclerotic abdominal aortic aneurysms. report of 200 consecutive cases diagnosed by intravenous aortography. JAMA 1966;195:1025. 2. Brown LC, Powell JT (September 1999). "Risk Factors for Aneurysm Rupture in Patients Kept Under Ultrasound Surveillance". Annals of Surgery 230 (3): 289–96; discussion 296–7. doi:10.1097/00000658-199909000-00002. PMC 1420874. PMID 10493476

Non modifiable•Smoking•Hypertension•Hyperlipidemia•Atherosclerosis

-Risk factors1: Modifiable

• Age

• Male gender• White race• Family history

-My out-patient PI project: Screening for AAA in high risk patients.

-AAA rupture is a medical emergency.

-Mortality could be up to 50%2.

-Ruptured AAA is estimated to cause 5 percent of sudden deaths2.

Introduction

1.http://www.nlm.nih.gov/medlineplus/ency/article/003789.htm (05/23/2013) 2.http://www.surgical-tutor.org.uk/default-home.htm?system/vascular/aaa.htm~right (05/23/2013)3.http://www.radiologyassistant.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 1998;27:992-1003.

Normal CT scan Abdominal Aortic Aneurysm Abdominal Aortic Aneurysm Rupture

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

• Risk of rupture4:i. < 4 cm = 0.5% per yearii. 4.0 – 4.9 cm = 1% per yeariii. 5.0 – 5.9 cm = 11% per year iv. 6.0 – 6.9 cm = 26% per yearv. 7.0 – 7.9 cm = 40% per yearvi. > 8 cm = 50% year year

12 3

• Management5:i. Open repair : conventional method of repairii. Endovascular repair: faster recovery, reduced length of stay

in ICU, reduced hospital stay (no long benefits in terms of survival and mortality)5

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.

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 2005;142:203-11.2. http://www.uspreventiveservicestaskforce.org/uspstf05/aaascr/aaars.htm3. http://www.fomadistrict2.com/wp-content/uploads/2012/12/SAAAVE-ACT.pdf

• “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

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”.

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 2004;39:267-9.

• 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

Case report on aorto-enteric fistula“Time bomb in the belly”

Literature reviewEpidemiological 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.

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. 1995;142:1291–1299.

2. 2cott RAP, Bridgewater S, Ashton HA. Randomised clinical trial of screening for abdominal aortic aneurysm in women. Br J Surg. 2002;89: 283–285.

3. Katz DJ, Stanley JC, Zelenock GB. Gender differences in abdominal aortic aneurysm prevalence, treatment, and outcome. J Vasc Surg. 1997; 25:561–568.

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 Women’s Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J

Med. 2003;349:523–534.

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

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.

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. 1997;26:595– 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. 2001;154:236 –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. 1993;7:690 – 697.

• Suitability for EVAR is different: The angulation of iliacs, size of femoral

arteries and tortuosity of aortas are different in females3.

N-67,800 All of them=men

• 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

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. 2002;346:1445–1452.

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.

2002;346:1437–1444.

• 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.

1. http://www.world-heart-federation.org/press/fact-sheets/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. 2005;331:467–468.

Gender based differences in cardiovascular diseases

• “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.

Circulation 2007

British Journal of Surgery1985-1994: 873 AAA ruptures of Western Australia

Goals: 1.Emphasize the importance of screening for AAAs in high risk women.2.Emphasize the importance of “sex-specific” management guidelines of AAA.

Objectives:1.Compare the outcomes of ruptured Abdominal Aortic Aneurysms between men and women.2.Compare the characters of ruptured AAAs in men and women.

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:

i. Demographic characters ii. Co-morbidities (Hypertension, Dyslipidemia, Diabetes,

Cardiovascular diseases)iii. Previous history of AAA (size diagnosed, any surgeries and

history of rupture)iv. Medications (statins, ASA, Plavix)v. Characters of aneurysm(size, iliac arteries)vi. Hospital course (LOS ICU, LOS hospital, surgery, outcome)vii. Post-operative complicationsviii. Long term survival(SSN database)

•A total of 39 parameters were compared between males and females.

Methods

• Total no. of cases reviewed= 1538 (100%)

Results

Exclusion criteriaElective repairsEndovascular leakEndovascular revision

•Total no. of cases excluded = 1417 (92%)

• Total no. of cases included= 117 (8%)

ResultsIncidence

N (%)

Males 79 (67.6%)

Females 38 (32.4%)

Total 117

-Trends in mortality and hospital admission rates for abdominal aortic aneurysm in England and Wales. Br J Surg. 2005; 92: 968–975.

-The prevalence of AAA is 6 times lower in women but the rate of rupture is higher in females (1).

DemographicsMales Females Total p-

value

Site

0.17SOCH 52(65.8%

)20(52.6%) 72

SBMH 27(34.2%)

18(47.4%) 45

Race

N/ACaucasian 79

(100%)38(100%) 117

Others 0 0 0

BMI (n=77)

0.02Normal 15(25.8%

)11(58.0%) 26

Overweight 24(41.3%)

6(31.5%) 30

Obese 19(32.9%)

2(10.5%) 21

Smoking0.06

Yes 66(83.5%)

26(68.4%) 92

No 13(16.5%)

12(31.6%) 25

Co-morbidities and medicationsMales Females Total p-value

Hypertension

0.64Yes 66(83.5%) 33(86.8%) 99

No 13(16.5%) 5(13.2%) 18

Major co-morbidities

0.64Yes 38 (48.1%) 20(52.6%) 58

No 41(52.9%) 18(47.4%) 59

Statin

0.74Yes 40(50.6%) 18(47.4%) 68

No 39(49.4%) 20(52.6%) 59

Beta-Blocker

0.48Yes 24(30.4%) 14(36.8%) 38

No 55(69.6%) 24(63.2%) 79

Aspirin0.10Yes 40(50.6%) 18(47.4%) 58

No 39(49.4%) 20(52.6%) 59

Clopidogrel0.47Yes 7(8.9%) 5(13.1%) 12

No 72 33(86.8%) 105

Age at rupturep=0.005

N Mean(year

s)

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

<55 56-65

66-75 76-85 86-95

>95

Males 1 5 14 32 24 3

Females 0 2 1 10 20 5

Overall 1 7 15 42 44 8

Age-specific incidence (10 year intervals)

65.7 %

65.8 %

• 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.

Characters of AAAs at presentation

Males Females Total p-value

Location

0.28Infra-renal 75 (94.9%)

34 (89.5%) 109

Supra-renal 0 1 (2.6%) 1

Both 4 (5.1%) 3 (7.9%) 7

Iliac arteries

0.42

Left 6 (7.6%) 1(2.6%) 7

Right 9(11.4%) 4(10.5%) 13

Both 12(15.2%) 3(7.9%) 15

None 52 (65.8%)

30(78.9%) 82

(Parameters from the CT scan abdomen at admission)

Characters of AAAs at presentationSize at rupture

Size at rupture (cm)

<5

5-6 6-7 7-8 8-9 >9

Males 3 10 9 18 12 27

Females 1 13 5 5 8 6

Mean size (cm)

S.D.(cm)

Range(cm)

Males 8.23 1.84 4-12

Females

7.46 2.09 3-14.7

p=0.04

Size-specific incidence

50 %

50 %

Effect of gender on Hospital course

Yes No

Males 74 (93.7%)

5 (6.3%)

Females 24 (63.2%)

14 (36.8%)

Incidence of surgery

-P=0.03

-Adjusted for age and major co-morbidities (binary logistic regression)

Males Females Total p-value

EVAR 57 (72.2%)

16 (42.1%) 73

<0.01Open 17 (21.5%)

8 (21.1%) 25

None 5 (6.3%) 14 (36.8%) 19

Type of surgery performed

Use of ventilat

or+

PressorSupport

+

LOS ICU(days)

Post-opcomplications*

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(p<0.001, logistic regression)

Indicators of post-operative morbidity

+Age was a significant predictor of VDRF and use of vasopressors (p<0.001, logistic regression)

N=98, Men=74 and Women=24

Overall MortalityAlive 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

-P=0.001

-Adjusted for hypertension, smoking, statins, major co-morbidities (logistic regression)

Post-operative mortality -P=0.05

-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

EVAR OPEN

Males 17.5 % 64.7%

Females 43.8% 63%

P-value 0.02 N/A

Mortality based on type of surgery

-Adjusted for hypertension, smoking, statins, major co-morbidities (logistic regression)

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 !!

Size at previous diagnosis

Long term survival

Kaplan-Meier survival curve analysis

Males=11.0 monthsFemales=9.3 months

P= 0.41

-unadjusted data.-very small sample.

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

It is all about….….

Will the screening be cost effective?

1.http://www.123rf.com/photo_18118258_elderly-woman-suffering-with-a-belly-pain-in-the-living-room.html-05/232013

1

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

• Average re-imbursement for an ultrasound for AAA screening=97.77$1

http://www.gehealthcare.com/usen/community/reimbursement/docs/Vascular_Surgery_reimbursementv2.pdf

Will the screening be cost effective?

Conclusions: “Lower AAA prevalence is balanced by a higher rupture rate, mortality and morbidity. So screening is indeed cost-effective.”

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

•Small AAAs (Prospective trial)

•Total no. of visits (Catholic Health System) = >1500

Next steps….

Conclusions1.The overall incidence of AAA rupture was higher in males (68%) than in females(32%).

1.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, p=0.005.

1.There was a significant difference in the size of AAA rupture between females (mean=7.4 cm, SD=2.0) and males (mean=8.2 cm, SD=1.8); t (115)=2.0, p = 0.04.

1.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 (p=0.03).

Conclusions5. There was a significant effect of gender on the

overall mortality (p=0.001) and post-operative mortality after EVAR (p=0.02) from AAA rupture after controlling the effect of hypertension, co-morbidities, smoking, use of statins and previous history of aneurysm.

6. 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.

Acknowledgements

• University at Buffalo GME -- Statistical support

• Andrew Bishop (Data analyst)-- Financial analysis

• Henri Woodman, MD-- Symposium presentation

• Paul M Anain, MD—Outstanding mentorship

• Khalid J Qazi, MD, MACP--Outstanding mentorship

THANK YOU