The Influence of Risk Factors on Mortality
Rates after Elective Open Repair of
Abdominal Aortic Aneurysms (AAA)
Class 5
1st Year
Mestrado Integrado em Medicina
• Abnormal widening of abdominal aorta below the renal arteries (at least 1.5-folds the normal diameter);
• 13th cause of death in the United States (US):
• 200,000 new diagnosis each year;
• 40,000 surgical repairs each year;
• 15,000 die from rupture each year.
• 3rd cause of sudden death in men >60 in US;
• 75% are asymptomatic until their rupture.
Introduction
Abdominal Aortic Aneurysm (AAA)
Risk Factors for AAA
• Age>50 y.o. and male gender
• Hypertension
• Atherosclerosis
• Chronic obstructive pulmonary disease
• Smoking
• Family history of AAA
• Previous vascular surgery
Introduction
Elective Open Repair (EOR) of AAA
• Established procedure for patients >40 years
• Invasive surgery procedure with insertion of a prosthetic tube-like graft
• Excludes aneurysm and prevents growth
• Proven, long-term results
• Considered the “gold standard”
• Operative mortality rounds 1% to 5%
Introduction
Introduction
Petr Utikala (2004), Biomed Papers 148(2), 183–187
Elective Open Repair (EOR) of AAA
Postoperative Complications of EOR
• Venous Bleeding/Haemorrhage
• Gastrointestinal ischemia and/or dysfunction
• Cardiac events (including Myocardial Infarction)
• Pulmonary insufficiency
• Organ Failure
• Renal failure
• Graft infection
Introduction
Research Question and Aims
Research Questions:
• Which risk factors mostly contribute to mortality after EOR?
• Is it possible to improve the prediction of patients’ outcome after EOR?
Aims:
• Develop a meta-analysis review;
• Summarize the risk factors, postoperative complications and mortality
rates of patients with AAA undergoing EOR;
• Analyze the influence of risk factors on patients’ outcome after EOR;
• Contribute to the improvement of the prediction of patients’ outcome.
Research Question and Aims
Participants and Methods
Participants and Methods
Participants and Methods
Meta-Analysis Review
Type of Study
Participants and Methods
All articles (n=203) published on PubMed Database considering:
•"abdominal aortic aneurysm"[Text Word] OR "aortic aneurysm,
abdominal"[MeSH Terms] OR aaa[Text Word]
•AND elective[All Fields]
•AND open[All Fields]
•AND ((("wound healing"[TIAB] NOT Medline[SB]) OR "wound
healing“[MeSH Terms] OR repair[Text Word]) OR ("surgery"[Subheading]
OR "operative surgical procedures"[Text Word] OR "surgical procedures,
operative"[MeSH Terms] OR "surgery"[MeSH Terms] OR surgery[Text
Word]))
•AND mortality[Text Word]
Study Participants
Study Design: 1st Triage Step
Participants and Methods
Inclusion Criteria
• Abdominal aortic aneurysms (AAA)
• Elective open repair/surgery (EOR)
• Mortality rates after elective open repair
• Postoperative complications
• Patient’s outcome
Exclusion Criteria
• Other types or “mixed” aortic aneurysms (n=10)
• Emergency repair of ruptured AAA (n=13)
• Patients submitted to endovascular repair (EVAR) (n=51)
• Other papers as reviews, systematic reviews, meta-analysis, letters or editorials
(n=20)
• Papers in other languages rather than English, French, Spanish or Portuguese (n=16)
• Not related studies (n=26)
Participants and Methods
Study Design: 1st Triage Step
Participants and Methods
Inclusion Criteria
• Full paper available
• Provide data about preoperative clinical variables and risk factors
• Provide data about postoperative complications
• Provide data about patients’ mortality/outcome
Exclusion Criteria
• Impossibility to obtain full article by on line request, library acquisition or e-mail
request to authors (n=13)
• Other types of articles such as, review (n=1) or meeting abstract (n=1)
• Not related to the study (n=5)
• Absence of data about risk factors (n=10)
• Absence of data about mortality (n=4)
• Absence of data combining mortality associated to risk factors (n=29)
Study Design: 2nd Triage Step
Participants and Methods
Study Design: 2nd Triage Step
Participants and Methods
Study characteristics• Name of first Author, Year of Publication
• Type of Study
• Country of Origin
• Sample Size (n)
Preoperative clinical variables• Age (mean)
• Aneurysm Diameter (mean)
• Gender (male and female %)
Risk Factors exposition• Diabetes Mellitus, DM (%)
• History of Cardiac Disease, CDH (%) – History of myocardial infarction and/or angina
• Hypertension, HT (%)
• History of Pulmonary Disease, PDH (%) – History of COPD or pulmonary embolism
• Chronic Renal Failure, CRF (%) – Creatinine levels (>2.0mg/dL)
• Smoking Habits (%)
Selected Variables
Participants and Methods
Postoperative Complications• Morbidity Events, (%)
• Venous Bleeding, (%)
• Gastrointestinal Ischemia, GIsch (%)
• MultiOrgan Failure, MOF (%)
• Renal Failure, RF (%)
• Cardiac Complications, CardiacC (%)
• Myocardial Infarction, MI (%)
• Respiratory Complications, RespC (%)
Patients Outcome• Mortality (%)
Statistical Data• Risk factor associated Odds Ratio
• Risk factor associated Confidence Interval
Selected Variables
Participants and Methods
• Data input on Database using Statistical Package for Social Sciences
(SPSS) Version 16.0 used to summarize the mean frequencies,
confidence intervals and standard deviations of all clinical variables, risk
factors exposition, postoperative complications, and mortality rates;
• Epi Info™, Version 6 to perform a χ2 analysis to determine the Odds
Ratio (OR) and 95% confidence interval for the association of risk factors
influence on patients’ outcome;
• R Version 2.6.2 to elaborate the Forest Plot graphics in order to combine
the information about the influence of risk factors on patients’ outcome.
Statistical Analysis
Results
1) Summarize risk factors and postoperative complications, as well as the
mortality rate within all studies.
2) Determine the Odds Ratio (OR) and 95% confidence interval for the
influence of risk factors on patients’ outcome and elaborate the Forest
Plots in order to combine the information from all studies.
Systematic Review
Meta-Analysis
Results
Combine data from 46 articles (29 + 17) which result in 50 individual studies
regarding the frequencies of:
• Risk Factors
• Postoperative complications
• Morbidity rates
• Mortality rates
Results
Systematic Review
Results
Number of
StudiesMedian (%) Std. Deviation Minimum (%) Maximum (%) Mean (%)
Mean Age (y.o.) 45 71,0 3,4 65,8 83,0 71,4
Mean Aneurysm Diameter (cm) 29 5,9 0,5 4,70 6,5 5,9
Frequency of Males in Patients Group 46 86,9 7,7 67,0 99,2 85,1
Frequency of Patients with DM 37 9,5 6,4 2,9 36,0 10,4
Frequency of Patients with CDH 38 44,3 18,8 2,4 76,0 41,1
Frequency of Patients with HT 36 60,0 14,8 30,0 88,6 59,2
Frequency of Patients with PDH 33 23,0 13,6 6,7 58,8 24,9
Frequency of Patients with CRF 30 9,5 6,6 1,5 26,0 11,5
Frequency of Patients with Smoking 30 54,2 26,8 4,0 97,1 53,1
Frequency of Total Morbidity events 17 31,0 19,8 0,3 68,1 31,9
Frequency of Bleeding events 16 3,8 5,6 0,4 20,0 6,1
Frequency of GIsch events 14 1,7 7,3 0,2 28,6 3,9
Frequency of MOFailure events 8 3,7 2,8 0,8 8,0 3,9
Frequency of RFailure events 18 1,5 4,6 0,2 17,1 3,8
Frequency of CardiacC events 25 5,7 6,4 1,0 25,7 7,3
Frequency of MI events 17 2,2 3,4 0,6 10,9 4,0
Frequency of RespC events 23 7,5 11,2 0,5 40,0 11,4
Frequency of Deaths 50 4,0 3,2 0,0 17,1 4,4
Systematic Review
Summary
• Median % of Male Gender is 86.9%
• Median % of patients with HT is 60.0%
• Median % of patients with Smoking habits is 54.2%
• Median % of patients with CDH is 44.3%
• Median % of Cardiac Complications is 5.7%
• Median % of Respiratory Complications is 7.5%
• Median occurrence of Morbidity events of 31.0%
• Median frequency of Mortality was 4.0%
Results
Systematic Review
Combine data regarding the influence of risk factors on patients’ outcome:
• Mean Age (y.o.)
• Mean Aneurysm Diameter (cm)
• Gender
• Diabetes Mellitus, DM
• History of Cardiac Disease, CDH
• Hypertension, HT
• History of Pulmonary Disease, PDH
• Chronic Renal Failure, CRF
• Smoking Habits
Results
Meta-Analysis
Mean Age
Results
Meta-Analysis
Rigberg DA (2006)
Hertzer NR (2005)
Hua HT (2005)
Leon LR (2005)
Zeebregts CJ (2004)
Kruger A (2002)
Lederle FA (2002)
Brady AR (2000)
Adjusted OROR=1.0795% CI (1.05 – 1.09) p<0.001
Test of heterogeneity:Q: 21,35
d.f.: 7 p.value: 0,003
1.0 2.0 5.0 10.00.5
Meta-Analysis
Mean Aneurysm Diameter Test of heterogeneity:Q: 0,19
d.f.: 2 p.value: 0,910
Results
Hertzer NR (2005)
Lederle FA (2002)
Brady AR (2000)
Adjusted OROR=1.5895% CI (1.11 – 2.25) p=0.011
0.5 1.0 2.0
Meta-Analysis
Female Gender
Results
Test of heterogeneityQ: 4,87
d.f.: 7p.value: 0,676
0.2 1.0 10.00.5 2.0 5.0 20.0
OR=1.5895% CI (1.39 – 1.80) p<0.001
Rigberg DA (2006)
Hertzer NR (2005)
Leon LR (2005)
Nesi F (2004)
Bianchari F (2003) #1
Bianchari F (2003) #2
Rayan SS (2002)
Brady AR (2000)
Adjusted OR
Diabetes Mellitus
Results
Meta-Analysis
1.0 2.0 5.0 10.0 20.00.5
Hua HT (2005)Ari
Bianchari F (2003) #1
Bianchari F (2003) #2
Rayan SS (2002)
Adjusted OROR=1.2895% CI (0.80 – 2.06) p=0.309
Test of heterogeneityQ: 1,24
d.f.: 3p.value: 0,744
Cardiac Disease History (CDH)
Results
Meta-Analysis
0.2 1.00.5 2.0 5.0 20.0 50.00.10.05
OR=1.9395% CI (1.42 – 2.62) p<0.001
Test of heterogeneityQ: 20d.f.: 6
p.value: 0,003
Conrad MF (2007)
Hirzalla O (2006)
Hua HT (2005)
Nesi F (2004)
Bianchari F (2003) #1
Bianchari F (2003) #2
Hertzer NR (2002)
Adjusted OR
Hypertension (HT)
Results
0.2 1.0 10.00.5 2.0 5.0 20.0 50.00.10.05
Test of heterogeneityQ: 51,04
d.f.: 5p.value: <0,001
OR=2.9595% CI (2.14 – 4.05) p<0.001
Bonardelli S (2007)
Hua HT (2005)
Nesi F (2004)
Bianchari F (2003) #1
Bianchari F (2003) #2
Liapis CD (2003)
Adjusted OR
Meta-Analysis
Pulmonary Disease History (PDH)
Results
Meta-Analysis
0.2 1.0 10.00.5 2.0 5.00.1
Bonardelli S (2007)
Hertzer NR (2005)
Hua HT (2005)
Nesi F (2004)
Bianchari F (2003) #1
Bianchari F (2003) #2
Hertzer NR (2002)
Adjusted OR
Test of heterogeneityQ: 6,26
d.f.: 6p.value: 0,394
OR=1.3295% CI (0.94 – 1.87) p=0.112
Chronic Renal Failure (CRF)
Results
Meta-Analysis
Bonardelli S (2007)
Conrad MF (2007)
Hirzalla O (2006)
Hertzer NR (2005)
Hua HT (2005)
Bianchari F (2003) #1
Bianchari F (2003) #2
Hertzer NR (2002)
Adjusted OR
Test of heterogeneityQ: 9,29
d.f.: 7p.value: 0,232
OR=2.7895% CI (2.21 – 3.47) p<0.001
1.0 5.0 100.02.0 10.0 50.00.5 20.0
Smoking Habits
Results
Meta-Analysis
0.1 0.5 5.00.2 1.0 2.00.05
Hirzalla O (2006)
Hua HT (2005)
Nesi F (2004)
Bianchari F (2003) #1
Bianchari F (2003) #2
Adjusted OROR=1.0095% CI (0.99 – 1.01) p=0.987
Test of heterogeneityQ: 4,29
d.f.: 4p.value: 0,368
Resuming the influence of risk factor in patient’s outcome after EOR
• Hypertension (OR=2.95; p<0.001)
• Chronic Renal Failure (OR=2.78; p<0.001)
• Cardiac Disease History (OR=1.93; p<0.001)
• Female Gender (OR=1.58; p<0.001)
• Aneurysm Diameter (OR=1.58; p=0.011)
• Pulmonary Disease History (OR=1.32; p=0.112)
• Diabetes Mellitus (OR=1.28; p=0.309)
• Mean Age (OR=1.07; p<0.001)
• Smoking (OR=1.00; p=0.987)
Results
Meta-Analysis
Discussion
Related to study design:
• Search only in ONE online Database (PubMed).
Related to the query:
• Absence of a unique MeSh term to define “elective open repair”;
• The “huge” number of risk factors and postoperative complications;
• Difficulty to define the outcome as <30 days after surgery.
Related to studies:
• Heterogeneity of the studies;
• Absence of data relative to the most common risk factors;
• Absence of data relative to risk factors associated outcome.
Limits of the Study
Epidemiological Data
Systematic review revealed:
• Increased frequency of Male Gender (median 86.9%);
• Patients are diagnosed with advanced age (mean 71.4 y.o);
• Increased Aneurism Diameter (mean 5.9 cm);
Our results show similar distribution to those shown in literature referring
that AAA are more common in men with age ranging 65-75 y.o. and
diagnosed with a diameter of the aorta below the renal arteries of >3.0
cm.
Gillum RF. J Clin Epidemiol. 1995 Nov;48(11):1289-98.
Flemming C, et al. Ann. Intern. Med. 142 (3): 203-11.
Lederle FA, et al. Arch Intern Med. 2000;160:1425-30.
Discussion of Results
Discussion
Risk Factors
The most common risk factors found were:
• Male Gender (median 86.9%);
• Advanced age (mean 71.4 y.o);
• History of Hypertension, HT (median 60.0%)
• Smoking Habits (median 54.2%)
• History of Cardiac Diseases, CDH (median 44.3%)
The great majority of studies, including the “ACC/AHA 2005 guidelines”
refer age, smoking, and gender as the most significant AAA risk factors,
although, hypertension and history of cardiac disease are also
consideredLederle FA, et al. Arch Intern Med. 2000;160:1425-30.
Hirsch AT, et al. J Am Coll Cardiol 2006 Mar 21;47(6):1239-312
Discussion of Results
Discussion
Morbidity/Postoperative Complications
The median occurrence of Morbidity events was of 31.0%, and the most
frequent postoperative complications found were:
• Respiratory Complications (median 7.5%)
• Cardiac Complications (median 5.7%)
There is a wide variety of postoperative complications, and most of them
are correlated with the healthy condition of the patient prior to the
surgery,
or also to the experience of the surgical team. Nevertheless, it is
accepted that between 5-25% of all patients will at least suffer one
complication.
Hirsch AT, et al. J Am Coll Cardiol 2006 Mar 21;47(6):1239-312
Wilt TJ, et al. Evid Rep Technol Assess (Full Rep). 2006 Aug;(144):1-113.
Discussion of Results
Discussion
Mortality Rate
The median frequency of Mortality found was 4.0%.
Mortality rates <30days after surgery for patients undergoing EOR ranges
between 1-5%, although in some surgical teams this can be 0%. Despite
the differential conditions of patients, in-hospital care conditions are
extremely important to prevent higher mortality rates.
Hirsch AT, et al. J Am Coll Cardiol 2006 Mar 21;47(6):1239-312
Moreover, mortality rates seem to be influenced by patients’ risk factor
exposition and therefore can vary within studies.
Lederle FA, et al. Arch Intern Med. 2000;160:1425-30.
Discussion of Results
Discussion
Influence of risk factor in patient’s outcome after EOR
1. Smoking is considered to represent a significant risk marker for AAA
development, although, statistical analysis revealed that patient’s
outcome was not influenced by Smoking Habits.
2. Despite statistical analysis did not provide significant data, Pulmonary
Disease History and Diabetes Mellitus may influence the outcome
since they represent an increase of 32% and 28%, respectively, in the
risk for death after EOR if present. Nevertheless, these two risk factors
require more studies to clarify its effect on patients’ outcome.
Discussion of Results
Discussion
Influence of risk factor in patient’s outcome after EOR
3. Statistical analysis revealed that Hypertension or Chronic Renal
Failure represent an almost 3-folds increased risk for death after EOR.
These risk factors are strictly correlated with patients’ health condition
and are extremely important in the recovery after any surgical procedure.
4. As expected Cardiac Disease History represent an increased risk factor
for death after EOR (almost 2-folds), since it is common that people who
suffered cardiac events may have repetitions shortly in time.
Discussion of Results
Discussion
Discussion
Influence of risk factor in patient’s outcome after EOR
5. Remarkably interesting is the fact that Female Gender revealed a 58%
increase risk of death after EOR. Male gender represent a risk factor,
however, when females develop AAA, usually it has more severe
consequences and death can occur shortly after surgery.
6. Statistical analysis also revealed that an increment of 1cm of the
Aneurysm Diameter represents a 58% increase risk of death after EOR.
7. Age has also proved to influence the risk of death after EOR, with an
increment of 7% per year.
Discussion of Results
Discussion
Despite the fact that EOR has been substituted by Endovascular Repair,
EOR has proven to have good results in AAA management, but may require
experienced surgeons and good in-hospital intensive care unites in order to
contribute for the improvement of AAA management.
Our study revealed important findings that contribute to the prediction of
patient’s outcome after EOR, by simple analysis of risk factor exposition.
Moreover, it may allow the development of a decision tree for the selection
of patients that can be submitted to EOR and expect a good outcome.
Final Conclusions
The Influence of Risk Factors on Mortality
Rates after Elective Open Repair of
Abdominal Aortic Aneurysms (AAA)
Class 5
1st Year
Mestrado Integrado em Medicina