class 5 1 st year mestrado integrado em medicina

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



Meta-Analysis Review

Type of Study


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


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)


Study Design: 1st Triage Step


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


Study Design: 2nd Triage Step


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


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


• 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


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



Rayan SS (2002)



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)



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


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)



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)



Hertzer NR (2002)

Adjusted OR


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)



Hertzer NR (2002)

Adjusted OR


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)





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

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.


Wilt TJ, et al. Evid Rep Technol Assess (Full Rep). 2006 Aug;(144):1-113.


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.


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

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


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

Discussion


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

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

class 5 1 st year mestrado integrado em medicina

Documents

mortality rates of patients

mixed aortic aneurysms

portuguese n

influence of risk factors

editorials n

patients mortalityoutcom

prediction of patients

endovascular repair