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GENDER BASED DIFFERENCES IN ABDOMINAL AORTIC ANEURYSM (AAA) RUPTURE

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.

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GENDER BASED DIFFERENCES IN ABDOMINAL AORTIC ANEURYSM (AAA) RUPTURE

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

  2. Disclosures None 1. http://aorticstents.com/what-is-abdominal-aortic-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“men’s diseases.” • 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. • 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. A- Strongly Recommended Benefit>>Risk B-Recommended Benefit>Risk Performance Improvement Projects ?? 1. http://www.uspreventiveservicestaskforce.org/uspstopics.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 50%2. -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 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

  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: • < 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 • > 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-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.

  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 • 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. • http://www.uspreventiveservicestaskforce.org/uspstf05/aaascr/aaars.htm • http://www.fomadistrict2.com/wp-content/uploads/2012/12/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 • 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 • Kent KC, Zwolak RM, Jaff MR, et al. Screening for abdominal aortic aneurysm: A consensus statement. J Vasc Surg 2004;39:267-9.

  9. 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. • 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. • 2cott RAP, Bridgewater S, Ashton HA. Randomised clinical trial of screening for abdominal aortic aneurysm in women. Br J Surg. 2002;89: 283–285. • Katz DJ, Stanley JC, Zelenock GB. Gender differences in abdominal aortic aneurysm prevalence, treatment, and outcome. J Vasc Surg. 1997; 25:561–568. • 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.

  11. 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. 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.

  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 them=men • 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. • 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.

  13. 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. • http://www.world-heart-federation.org/press/fact-sheets/women-and-cardiovascular-disease/ • American Heart Association. 1997 Heart and Stroke Facts: Statistical Update. Dallas, Tex: American Heart Association; 1996. • Mikhail GW. Coronary heart disease in women is underdiagnosed, under- treated, and under-researched. BMJ. 2005;331:467–468.

  14. 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%)

  18. Results Incidence -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: 968–975.

  19. Demographics

  20. Co-morbidities and medications

  21. Age at rupture p=0.005 • 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) 65.8 % 65.7 % Figure 2. Mean age (years) p<0.001 Figure 2. Mean age (years) p<0.001

  22. Characters of AAAs at presentation (Parameters from the CT scan abdomen at admission)

  23. Characters of AAAs at presentation Size at rupture p=0.04 Size-specific incidence 50 % 50 %

  24. Effect of gender on Hospital course Incidence of surgery -P=0.03 -Adjusted for age and major co-morbidities (binary logistic regression) Type of surgery performed

  25. Indicators of post-operative morbidity N=98, Men=74 and Women=24 *Major co-morbidities was a significant predictor of post-operative complications, VDRF and use of vasopressors (p<0.001, logistic regression) +Age was a significant predictor of VDRF and use of vasopressors (p<0.001, logistic regression)

  26. Overall Mortality -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) Mortality based on type of surgery -Adjusted for hypertension, smoking, statins, major co-morbidities (logistic regression)

  27. Size at previous diagnosis 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 Males=11.0 months Females=9.3 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-woman-suffering-with-a-belly-pain-in-the-living-room.html-05/232013

  30. Will the screening be cost effective? • Average re-imbursement for an ultrasound for AAA screening=97.77$1 • Summary of financials from previous 3 years (All Catholic Health sites) • Average profit for surgical repair after a AAA rupture is 8500$ more for male patients over female patients • Average profit for AAA rupture admissions is 7500$ more for male patients over female patients http://www.gehealthcare.com/usen/community/reimbursement/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) = >1500

  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, p=0.005. 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. 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).

  34. Conclusions • 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. • 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, MD—Outstanding mentorship • Khalid J Qazi, MD, MACP--Outstanding mentorship

  36. THANK YOU

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