Transcript Slide 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)
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 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
1.
2.
Coronary Artery
Diseases
2.2%
1%
Cerebrovascular
Diseases
2.7%
2.6%
Peripheral Vascular
Diseases
11%
8%
Carotid Artery
Diseases
3.8%
2.7%
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, 19801988.
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
• Preventive medicine - screening tests, counseling and preventive medications.
U.S. Preventive Services Task Force-March 2009
Screening modality
Grade
Risk factor modification
Smoking
Counseling on
cessation
A
Hypertension
Blood pressure
monitoring
A
Dyslipidemia
Lipid profile
A
Fasting plasma
glucose
B
Lifestyle modification
B
Aspirin
B
Diabetes Mellitus
Obesity
Prevention of
Cardiovascular
diseases
1. http://www.uspreventiveservicestaskforce.org/uspstopics.htm
A- Strongly
Recommended
Benefit>>Risk
B-Recommended
Benefit>Risk
Performance
Improvement
Projects ??
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
Introduction
• The strongest risk factor for the rupture of an AAA is maximal aortic
diameter4.
Normal CT scan
Abdominal Aortic Aneurysm
1
Abdominal Aortic Aneurysm Rupture
2
• Risk of rupture4:
i.
< 4 cm = 0.5% per year
ii. 4.0 – 4.9 cm = 1% per year
iii. 5.0 – 5.9 cm = 11% per year
iv. 6.0 – 6.9 cm = 26% per year
v. 7.0 – 7.9 cm = 40% per year
vi.
> 8 cm = 50% year year
5
• Management :
i. Open repair : conventional method of repair
ii. 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)
3.http://www.radiologyassistant.nl/en/p4530b48a07dbd/aaa-rupture-1.html (05/24/13)
4. Brewster
2.http://www.surgical-tutor.org.uk/default-home.htm?system/vascular/aaa.htm~right (05/23/2013)
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.
3
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.
2.
3.
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
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.
2.
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.
• 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”
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.
2.
3.
4.
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.
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.
• 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
1.
2.
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.
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.
2.
3.
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.
Circulation 2007
British Journal of Surgery
1985-1994: 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.
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:
i.
ii.
Demographic characters
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 complications
viii. Long term survival(SSN database)
• A total of 39 parameters were compared between males and females.
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%)
Results
Incidence
N (%)
38
79
Males
Females
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:
968–975.
Demographics
Males
Females
Total
p-value
SOCH
52(65.8%)
20(52.6%)
72
0.17
SBMH
27(34.2%)
18(47.4%)
45
Caucasian
79 (100%)
38(100%)
117
0
0
0
Normal
15(25.8%)
11(58.0%)
26
Overweight
24(41.3%)
6(31.5%)
30
Obese
19(32.9%)
2(10.5%)
21
Site
Race
Others
N/A
BMI (n=77)
Smoking
Yes
66(83.5%)
26(68.4%)
92
No
13(16.5%)
12(31.6%)
25
0.02
0.06
Co-morbidities and medications
Males
Females
Total
Yes
66(83.5%)
33(86.8%)
99
No
13(16.5%)
5(13.2%)
18
p-value
Hypertension
0.64
Major co-morbidities
Yes
38 (48.1%)
20(52.6%)
58
No
41(52.9%)
18(47.4%)
59
Yes
40(50.6%)
18(47.4%)
68
No
39(49.4%)
20(52.6%)
59
Yes
24(30.4%)
14(36.8%)
38
No
55(69.6%)
24(63.2%)
79
Yes
40(50.6%)
18(47.4%)
58
No
39(49.4%)
20(52.6%)
59
Yes
7(8.9%)
5(13.1%)
12
No
72
33(86.8%)
105
0.64
Statin
0.74
Beta-Blocker
Aspirin
Clopidogrel
0.48
0.10
0.47
Age at rupture
84
N
Males
79
Mean
(years)
S.D.
(years)
Range
(years)
82
75.75
10.0
50-97
78
Females
38
82.39
8.6
59-103
Overall
117
77.91
10.1
50-103
p=0.005
82.39
80
75.75
76
74
72
70
Males
Females
• 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)
<55
56-65
66-75
76-85
86-95
>95
Males
1
5
14
32
24
3
65.8 %
Females
0
2
1
10
20
5
65.7 %
Overall
1
7
15
42
44
8
Characters of AAAs at presentation
(Parameters from the CT scan abdomen at admission)
Males
Females
Total
p-value
75 (94.9%)
34 (89.5%)
109
0.28
0
1 (2.6%)
1
4 (5.1%)
3 (7.9%)
7
Location
Infra-renal
Supra-renal
Both
Iliac arteries
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
0.42
Characters of AAAs at presentation
Size at rupture
p=0.04
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)
<5
5-6
6-7
7-8
8-9
>9
Males
3
10
9
18
12
27
50 %
Females
1
13
5
5
8
6
50 %
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%)
-P=0.03
-Adjusted for age and major
co-morbidities (binary logistic
regression)
Type of surgery performed
Males
Females
Total
EVAR 57 (72.2%)
16 (42.1%)
73
Open 17 (21.5%)
8 (21.1%)
25
None
14 (36.8%)
19
5 (6.3%)
p-value
<0.01
Indicators of post-operative morbidity
N=98, Men=74 and Women=24
Use of
Pressor
ventilator+ 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
(p<0.001, logistic regression)
+Age
was a significant predictor of VDRF and use of
vasopressors (p<0.001, logistic regression)
Overall Mortality
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
Alive
-Adjusted for hypertension, smoking,
statins, major co-morbidities (logistic
regression)
Post-operative mortality
Dead
Total
-P=0.05
53
(71.6%)
21
(21.4%)
74
Females
12
(50.0%)
12
(50.0%)
24
Overall
65
(66.3%)
33
(33.7%)
98
Males
-P=0.001
-Adjusted for hypertension,
smoking, statins, major co-morbidities
(logistic regression)
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)
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 !!
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.
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
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
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
Next steps….
• Small AAAs (Prospective trial)
• Total no. of visits (Catholic Health System) = >1500
Conclusions
1. 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).
Conclusions
5. 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