A population-based case-control study of the familial risk of abdominal aortic aneurysm

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DOI: 10.1016/j.jvs.2008.08.012 · Source: PubMed
Abstract
Several studies have reported a familial clustering of abdominal aortic aneurysm (AAA) supporting that AAA is an inheritable disease, but few population-based studies can be found. Possible gender differences regarding hereditary patterns have been reported. The aim of this study was to investigate the risk of developing an AAA for first-degree relatives of patients with AAA in Sweden and compare them with matched controls and their relatives. All persons (3183) born after 1932, diagnosed with AAA between 2001 and 2005, and a random selection of 15,943 age-, gender-, and region-matched controls were included. First-degree relatives of cases and controls were identified via the Multigeneration Register. Family history of AAA for cases and controls was assessed by linking the relatives to the Hospital Discharge Register and Cause of Death Register. The data were analyzed by conditional logistic regression. The overall relative risk of AAA associated with family history compared to no family history was 1.9 (95% confidence interval [CI] 1.6-2.2). Comorbidities were more common among the cases than the controls (P < .0001) but the relative risks remained unchanged after adjustment for comorbidities. Stratification for absence or presence of comorbidities showed no significant difference between the two groups (P = .29). The relative risk of AAA for first-degree relatives was similar for women and men (P = .22 for gender differences), ie, the relative risk of AAA was not dependent on the gender of the index person. In this nationwide survey, the relative risk of developing AAA for first-degree relatives to persons diagnosed with AAA was approximately doubled compared to persons with no family history. Neither the gender of the index person nor the first-degree relative influenced the risk of AAA.
From the Society for Vascular Surgery
A population-based case-control study of the
familial risk of abdominal aortic aneurysm
Emma Larsson, MD,
a,b
Fredrik Granath, PhD, Asst. Prof,
c
Jesper Swedenborg, MD, PhD,
a,b
and
Rebecka Hultgren, MD, PhD,
a,b
Stockholm, Sweden
Background: Several studies have reported a familial clustering of abdominal aortic aneurysm (AAA) supporting that AAA
is an inheritable disease, but few population-based studies can be found. Possible gender differences regarding hereditary
patterns have been reported.
Objective: The aim of this study was to investigate the risk of developing an AAA for first-degree relatives of patients with
AAA in Sweden and compare them with matched controls and their relatives.
Methods and Materials: All persons (3183) born after 1932, diagnosed with AAA between 2001 and 2005, and a random
selection of 15,943 age-, gender-, and region-matched controls were included. First-degree relatives of cases and controls were
identified via the Multigeneration Register. Family history of AAA for cases and controls was assessed by linking the relatives
to the Hospital Discharge Register and Cause of Death Register. The data were analyzed by conditional logistic regression.
Results: The overall relative risk of AAA associated with family history compared to no family history was 1.9 (95%
confidence interval [CI] 1.6-2.2). Comorbidities were more common among the cases than the controls (P < .0001) but
the relative risks remained unchanged after adjustment for comorbidities. Stratification for absence or presence of
comorbidities showed no significant difference between the two groups (P .29). The relative risk of AAA for
first-degree relatives was similar for women and men (P .22 for gender differences), ie, the relative risk of AAA was not
dependent on the gender of the index person.
Conclusion: In this nationwide survey, the relative risk of developing AAA for first-degree relatives to persons diagnosed
with AAA was approximately doubled compared to persons with no family history. Neither the gender of the index person
nor the first-degree relative influenced the risk of AAA. ( J Vasc Surg 2009;49:47-51.)
Familial clustering of abdominal aortic aneurysm (AAA)
was described more than 30 years ago.
1
Case series have
reported increased familial risk for AAA and several studies
have reported a high prevalence of AAA among siblings of
AAA patients.
2-4
Case-control studies have shown an ap-
proximately four-fold increased risk being affected for first-
degree relatives of AAA patients.
5,6
These studies are
mostly based on consecutive patient series from one or few
centers, and few population-based reports covering the
subject can be found.
Possible gender differences regarding hereditary pat-
terns have been reported, but the results from these studies
are probably not possible to generalize.
7,8
Other important
gender differences are known for AAA; men have a higher
prevalence and are younger at onset of disease compared to
women.
9,10
In order to perform a population-based case-control
study, longitudinal data from nationwide registers is neces-
sary. Sweden has a Multigeneration Register including
first-degree relatives of persons born after 1931. This reg-
ister, together with the Cause of Death Register and the
In-patient Register, was utilized to perform a case-control
study with the aim of investigating the risk to develop an
AAA associated with a positive family history and possible
gender differences.
METHODS
National registries. All Swedish citizens have a
unique 12-digit personal identification number, enabling
identification of patients in national registries. The Swedish
National Hospital Discharge Register, managed by the
Swedish Board of Health and Welfare (NBHW), covers all
information regarding public in-patient care. The Cause of
Death Register is managed by the Centre for Epidemiol-
ogy, NBHW, and covers data for cause and time of death
for all deceased persons. The Multigeneration Register,
managed by Statistics Sweden, contains linkages between
children and parents and consists of persons in Sweden
born after 1931 and their parents. The extraction of data
was based on the diagnostic codes classified by the Interna-
tional Classification of Diseases (ICD) (Table I).
Study population. Cases (n 3183) were defined as
all persons found in the Swedish National Hospital Dis-
charge Register with a first admission under the diagnosis
of AAA or an aortic aneurysm without a given localization
From the Department of Molecular Medicine and Surgery,
a
the Department
of Internal Medicine, Clinical Epidemiology Unit, Karolinska Institutet,
c
and the Department of Vascular Surgery, Karolinska University Hospital.
b
The study was funded by financial support provided by the Swedish Heart-
Lung Foundation (Go Red), by the European Society of Vascular Sur-
gery, and through the regional agreement on medical training and clinical
research (ALF) between Stockholm County Council and the Karolinska
Institutet.
Competition of interest: none.
Presented at the Sixty-second Vascular Annual Meeting, San Diego, Calif,
Jun 4-8, 2008.
Correspondence: Emma Larsson, MD, Department of Vascular Surgery,
N2:06, Karolinska University Hospital, 171 76 Stockholm, Sweden
(e-mail: emma.larsson@ki.se).
0741-5214/$36.00
Copyright © 2009 Published by Elsevier Inc. on behalf of The Society for
Vascular Surgery.
doi:10.1016/j.jvs.2008.08.012
47
(I71.3, I71.4, I71.8, or I71.9) between 2001 and 2005,
and all persons deceased during the same period with the
corresponding underlying or contributing cause of death
that not was found in the hospital register. A random selection
of 15,943 age-, gender-, calendar year-, and region-matched
controls were identified from the Register of Total Popula-
tion. The Swedish population was 8.9 million (50.5% women)
in 2001 and 9.0 million (50.4% women) in 2005.
Exposures. First-degree relatives of cases and controls
were identified via the Multigeneration Register. Family
history of aortic aneurysm for cases and controls was as-
sessed by linking the relatives to the Hospital Discharge
Register and Cause of Death Register (for codes used see
Table I). Comorbidity for cases and controls was assessed
by the prevalence of admissions with selected diagnoses 5
years prior to the diagnosis date for the case and the
corresponding period for the matched controls (for codes
used see Table I).
Statistics. Crude comparisons of proportions were
performed by
2
tests. Significance was defined as P .05.
The risk of AAA in relation to family history was estimated
by means of conditional logistic regression and odds ratios
(ORs) with corresponding 95% confidence intervals (CIs).
Risks associated with family history were assessed with
respect to number of affected relatives and the gender of
affected relatives. In stratified analyses with respect to the
subjects’ age, gender, and diagnosis the potential effect
modification of these factors were investigated and tested
by likelihood ratio tests.
Risks in relation to family history were adjusted for
presence of comorbidity. The categorization of the comor-
bidity according to the different comorbidities alone and
combinations of two, three, or four comorbidities was
chosen due to the lack of multiplicative effects of the
different comorbidities. We also performed an interaction
analysis of the effect of family history among cases and
control with and without any comorbidity; this interaction
was tested by a likelihood ratio test. The study was ap-
proved by the Regional Ethics Committee.
RESULTS
Among the 3183 cases with AAA, 479 were identified
in the Cause of Death Register and 2704 in the Swedish
National Hospital Discharge Register. A total of 840 cases
were diagnosed with ruptured AAA. Baseline characteristics
are listed in Table II.
A positive family history for AAA was significantly more
common among cases than controls (8.4 vs 4.6%, P
.0001). The cases had a significantly higher prevalence of
comorbidities compared to the controls. The proportion of
cases with family history was similar in patients with rup-
tured and non-ruptured AAA (Table II).
The overall relative risk of AAA associated with family
history compared to no family history was approximately
doubled (OR 1.9, 95% CI 1.6-2.2) (Table III). The risk
increased further if more than one first-degree relative had
AAA. The relative risks remained unchanged after adjust-
ment for comorbidities (Table III).
In a logistic regression analysis stratified for absence or
presence of comorbidities, there was no significant differ-
ence between the two groups, ie, the relative risk of AAA
associated with family history was similar for cases suffering
from comorbidities or not (P .29) (Table IV).
Table I. Diagnostic codes classified by the International
Classification of Diseases (ICD)
ICD
78910
AAA 451.00 441.20 441.3 I71.3
441.4 171.4
Aortic aneurysm* 452 442 441.5 171.8
441.6 171.9
COPD 500-502 490-492 491.2 J44
491.8
496
IHD 420 410-414 410-414 I20-I25
Heart failure 431.10 428.99 428 I50
Hypertension 440-447 440-404 401-405 I10-I15
AAA, Abdominal aortic aneurysm; COPD, chronic obstructive pulmonary
disease; IHD, ischemic heart disease.
*Without given localization.
Table II. Characteristics for cases and controls
Characteristics
Cases
(n 3183)
Controls
(n 15,943)
PNo (%) No (%)
Gender
Females 535 (16.8) 2679 (16.8) .9951
Age
40 29 (0.9) 145 (0.9) .999
41-49 54 (1.7) 269 (1.7)
50-59 509 (16.0) 2531 (15.9)
60-69 2031 (63.8) 10,196 (64.0)
70-73 560 (17.6) 2802 (17.6)
Family history
Yes 268 (8.4) 743 (4.6) .0001
Number of affected
relatives
0 2915 (91.6) 15,200 (95.3) .0001
1 254 (8.0) 728 (4.6)
2 12 (0.4) 14 (0.1)
3 2 (0.1) 1 (0.01)
Comorbidity
No comorbid
condition 2215 (69.6) 14,179 (88.9) .0001
IHD 297 (9.3) 652 (4.1)
Hypertension 229 (7.2) 483 (3.0)
Heart failure 50 (1.6) 88 (0.6)
COPD 45 (1.4) 77 (0.5)
Any 2 comorbidities 269 (8.5) 375 (2.4)
Any 3 comorbidities 72 (2.3) 83 (0.5)
All 4 comorbidities 6 (0.2) 6 (0.04)
Diagnosis
Rupture 840
With family history 61 (7.3)
Non-rupture 2343
With family history 207 (8.8)
IHD, Ischemic heart disease; COPD, chronic obstructive pulmonary disease.
JOURNAL OF VASCULAR SURGERY
January 2009
48 Larsson et al
In a subgroup analysis, no significant gender difference
in the relative risk of AAA associated with family history
could be demonstrated (P .22 for differences between
genders), ie, the relative risk of AAA was not dependent on
the gender of the index person (Table V). No differences
between age groups in the relative risk of AAA associated
with family history were recorded (P .75) (Table V).
Patients treated for rupture and non-rupture had similar
relative risks of positive family history of AAA (P .42 for
differences between rupture and non-rupture) (Table V).
There was a tendency towards a higher risk of being
affected with AAA when having a male relative with AAA,
compared to having a female relative (P .07) (Table VI).
DISCUSSION
It is of major importance for families and the society to
clarify whether first-degree relatives of AAA patients have
an increased risk to develop AAA compared to the general
population. We found that a positive family history of AAA
was associated with an approximately doubled risk of AAA.
Comorbidities and gender of the index person did not
modify the relative risk associated with family history.
Familial tendency of AAA was first described by Clifton
in 1977.
1
Since then, several studies have reported a high
prevalence of AAA among siblings of AAA patients, sup-
porting that AAA is an inheritable disease.
2-4
In a case-
control study of 98 AAA cases and 102 controls, a positive
family history of AAA was associated with an increased risk
of AAA (OR 4.77, 95% CI 1.26-18.1).
5
Similar risk rates
were confirmed in a Finnish study of relatives of 150 AAA
patients, but only 29% of the first-degree relatives were
included in the study.
6
In a Canadian report, an approxi-
mately four-fold higher prevalence of AAA was found in
siblings of 126 AAA patients compared to siblings of a
control group.
11
The doubled risk of AAA associated with
a positive family history in the present study confirms
previously reported familial aggregation, but is lower than
previously reported four-fold increase. Since AAA is a dis-
ease affecting the elderly, one concern with the present
study is that the upper age limit of the included AAA cases
was 73-years-old, but there were no age restrictions
regarding the relatives. The present study covers the
entire Swedish population; still misclassification is possible
due to unknown relatives, eg, immigrants. The Swedish
Multigeneration Register includes all persons born after
1931 and their parents; the coverage is 86% for known
mothers and 83% for known fathers. The main effect of
unknown relatives would be an underestimation of the
effect of family history. There is also a risk of unreported
cases with ruptured AAA due to low autopsy rates (14% in
2005) which is likely to add to the underestimation of the
risk.
In a previous Swedish report by Hemminki regarding
AAA from 1987 to 2001 using the same registers as in the
present study, an increased standardized incidence ratio for
siblings of AAA patients was found.
12
Their study design
only included 71 affected sib-pairs between 0 and 69-years-
old and included all types of aortic aneurysm.
In the present study, the risk of AAA associated with
family history was neither influenced by the gender of the
Table III. Relative risk of AAA
Odds ratio (95% CI)
Unadjusted
Adjusted for
comorbidity
Family history
No 1.0 (ref) 1.0 (ref)
Yes 1.9 (1.6-2.2) 1.9 (1.6-2.2)
Number of affected relatives
0 1.0 (ref) 1.0 (ref)
1 1.8 (1.6-2.1) 1.8 (1.6-2.1)
2 4.7 (2.1-10.2) 4.3 (1.9-9.8)
3 10.0 (0.9-110.3) 12.2 (1.1-137.0)
AAA, Abdominal aortic aneurysm; CI, confidence interval.
Table IV. Relative risk of AAA associated with family
history stratified for comorbidity or not
Odds ratio (95% CI)
Number of affected
relatives Comorbidity no Comorbidity yes
0 1.0 (ref) 1.0 (ref)
1 1.7 (1.5-2.1) 2.4 (1.7-3.3)
2 4.8 (2.0-11.5) 4.2 (0.8-21.8)
AAA, Abdominal aortic aneurysm; CI, confidence interval.
Table V. Relative risk of AAA for subgroups given family
history (ref: no family history in the specific subgroups)
Odds ratio (95% CI)
Unadjusted Adjusted for comorbidity
Gender
Male 1.8 (1.5-2.1) 1.9 (1.6-2.2)
Female 2.3 (1.6-3.3) 2.1 (1.5-3.1)
Age
49 2.7 (1.0-7.3) 2.4 (0.8-7.1)
50-64 1.8 (1.5-2.3) 1.9 (1.5-2.3)
65-73 1.9 (1.5-2.3) 1.9 (1.5-2.3)
Diagnosis
Rupture 1.7 (1.3-2.4) 1.8 (1.3-2.4)
Non rupture 1.9 (1.6-2.3) 1.9 (1.6-2.3)
AAA, Abdominal aortic aneurysm; CI, confidence interval.
Table VI. Relative risk of AAA given a certain gender of
the index person and the first-degree relative (ref: no
family history)
Odds ratio (95% CI)
Female relative Male relative
Male index person 1.6 (1.3-2.0) 2.1 (1.7-2.5)
Female index person 1.8 (1.1-2.9) 3.1 (1.9-5.0)
AAA, Abdominal aortic aneurysm; CI, confidence interval.
JOURNAL OF VASCULAR SURGERY
Volume 49, Number 1
Larsson et al 49
index person nor the gender of the first-degree relative.
This indicates that presence of family history should be
taken into consideration regardless of gender when evalu-
ating the risk to develop an AAA. It is, however, important
to stress that our findings are based on index cases aged 73
years or younger. Since women develop AAA at an older
age than men, a possible underestimation would be more
pronounced for women. In two previous studies regarding
the occurrence of AAA in relatives of AAA patients, the
highest prevalence was found in brothers of female patients,
but the differences were not significant.
3,13
A retrospective
study on multiplex aneurysms without any control group
reported a higher percentage of females among the affected
relatives than among AAA probands.
8
In a prospective
case-control study, there was an increased prominence of
women in the familial AAA group.
7
However, the study
group of 542 patients was from one center and the control
group consisted of 500 spouses, non-blood relatives, and
vascular patients without aneurysms which could have in-
fluenced the finding. Screening for AAA is cost effective for
men above the age of 65, but this has not been shown to be
the case for women. It is possible, and even likely, that the
increased risk for women with a positive family history
makes screening cost effective also for this group.
AAA is a multifactorial disease involving environmental
and genetic risk factors. The present study design did not,
however, address the genetic mechanisms. The increased
risk for patients with more than one affected relative com-
pared to only a single relative with AAA in our study
supports that AAA is a multigenic disease. A recent study
reported that a sequence variant on chromosome 9 (9p21)
was associated with myocardial infarction, intracranial an-
eurysm, and AAA. The estimated degree of the effect
differed and was most pronounced for AAA.
14
Kuivaniemi
et al
15
performed a DNA linkage study for familial AAA in
233 families with more than one individual diagnosed with
AAA. Linkage to chromosomes 19p13 and 4q31 were
found, indicating that these regions could possess genetic
risk factors for AAA. When investigating the manners of
inheritance, they found that autosomal recessive inheri-
tance was most common.
Patients with AAA often have manifestations of athero-
sclerotic disease, such as hypertension and coronary artery
disease.
9,16
In the present study, AAA cases had more
comorbidities which reflects that AAA patients often share
the same risk factors as patients with other manifestations of
cardiovascular disease. Since most AAAs are asymptomatic,
the probability for detection will be influenced by contacts
with healthcare providers. The occurrences of comorbidi-
ties obviously affect the frequency of such contacts, leading
to an increasing number of diagnostic procedures. Regard-
less of the occurrence of comorbidities, the relative risk of
AAA for first-degree relatives remained doubled in a strat-
ified analysis. This emphasizes that family history is of major
concern regardless if the person suffers from other cardio-
vascular diseases or not, as shown by others.
5
In conclusion, in this nationwide survey the relative risk
to develop AAA for first-degree relatives to persons diag-
nosed with AAA was doubled compared to persons with no
family history. Neither the gender of the index person nor
the first-degree relative influenced the risk of AAA.
AUTHOR CONTRIBUTIONS
Conception and design: EL, FG, JS, RH
Analysis and interpretation: EL, FG, RH
Data collection: EL, FG
Writing the article: EL, RH
Critical revision of the article: EL, FG, JS, RH
Final approval of the article: EL, FG, JS, RH
Statistical analysis: EL, FG
Obtained funding: JS, RH
Overall responsibility: RH
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AC, Cambria RP, et al. Are familial abdominal aortic aneurysms differ-
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8. Le Hello C, Koskas F, Cluzel P, Tazi Z, Gallos C, Piette JC, et al. French
women from multiplex abdominal aortic aneurysm families should be
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Jong PT, et al. Aneurysms of the abdominal aorta in older adults. The
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repair and effect of gender on treatment of ruptured abdominal aortic
aneurysm. J Vasc Surg 2004;39:784-7.
11. Baird PA, Sadovnick AD, Yee IM, Cole CW, Cole L. Sibling risks of
abdominal aortic aneurysm. Lancet 1995;346:601-4.
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The low prevalence of abdominal aortic aneurysm in relatives in North-
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Steinthorsdottir V, Manolescu A, et al. The same sequence variant on
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JOURNAL OF VASCULAR SURGERY
January 2009
50 Larsson et al
DISCUSSION
Dr Matthew Mell (Madison, Wis). Could you speculate on
the influence of smoking in your patient cohort and whether it may
have acted as a confounding variable if a family smoking history was
more prevalent?
Dr Hultgren. Well, that’s impossible to say, since it’s a
register-based study. Looking at the comorbid conditions, you get
a hint that probably smoking prevalence is much higher in the case
group than in the control group. It’s well known that smoking
habits as well as dietary habits is inherited too through a social
pattern. So probably it is much more prevalent in the case group.
Dr Louis Nguyen (Boston, Mass). I have a question regard-
ing aneurysm screening in Sweden, because I am concerned that
the likelihood for detection of AAA is different in your case group
versus control group. A patient with a known aneurysm will more
likely be told to have his relatives checked for an aneurysm as well.
This scenario would then produce a higher incidence of relatives
with AAA. For patients with no known AAA, their relatives would
not have any reason to be screened unless there was a broad
program in place. Can you tell us if AAA screening is routine and
widespread in Sweden? Also, could you comment on whether or
not the likelihood for detection of aneurysms in the relatives of
your two groups was equivalent?
Dr Hultgren. Yes, I think that’s an important point, and
we’ve discussed that quite a lot. But we think at least by adjusting
for the comorbid conditions you get rid of some of the problem
with over-diagnosing comorbid patients. Maybe it isn’t that bad
that we actually do screen first-degree relatives more, because they
are probably at a much higher risk, so maybe that’s actually quite
motivated.
Dr J. Black (Baltimore, Md). Did you look at the age of
presentation of the index cases with aneurysms and the number of
affected relatives? The implication being that younger patients with
more affected relatives might have a genetic syndrome and would
prompt referral. Do you have that data available within the set?
Dr Hultgren. In the analysis of subgroups, we did get a
higher odds ratio (OR) for younger patients having a higher risk
for the first-degree relative, it didn’t become significant compared
to the OR of 1.8 in the older age groups. In the analysis of the
thoracic patients, younger age was a higher risk to develop disease
than in the AAA group.
Dr K.W. Johnston (Toronto, Ontario, Canada). What ge-
netic testing do you consider doing in a patient with a positive
family history of aneurysm to try and determine if they do indeed
have an increased risk?
Dr Hultgren. Well, there have been some studies internation-
ally looking at genes and genetic pathways, and nobody has really
succeeded in finding one or two especially important genes. We
will start a national screening program in a couple of years, and we
are going to do a genetic screening based on that, let me come back
in 3 years and I’ll tell you more about it.
JOURNAL OF VASCULAR SURGERY
Volume 49, Number 1
Larsson et al 51
    • "A possible explanation for this fact is based on the two genes model, proposed byTilson et al., that defends the existence of a susceptibility factor in the X chromosome and of an autosomal mutation in another gene. This X chromosome susceptibility might be able to clarify why there[21]defend the existence of a multigenic model, with mutations in more than one gene; on the other side, Sandford et al.[22]defend a multifactorial model, in which is stated that there is a probable relation between genetic factors and environmental factors (like smoking habits)202122. "
    Article · Nov 2015 · BMC Cardiovascular Disorders
    • "AAAs are a multifactorial disease, and we know that there is a significant genetic contribution to their formation [2]. Since the 1970s, clinicians have observed that an important risk factor for AAA formation is a positive family history for the disease with an estimated increased individual risk between two and eleven fold34567. Several studies have described familial aggregation of AAA78910 , the largest one of these studies with 233 multiplex families [11] . The AAA families displayed multiple forms of inheritance patterns suggesting that AAA is a complex, multifactorial disease. "
    [Show abstract] [Hide abstract] ABSTRACT: Recent technological advances have allowed researchers to interrogate the genetic basis of abdominal aortic aneurysms in great detail. The results from these studies are expected to transform our understanding of this complex disease with both multiple genetic and environmental risk factors. Clinicians need to keep abreast of these genetic findings and understand the implications for their practice. Patients will become increasingly informed on genetic risk, and a new era of individualized risk assessment for AAA is just beginning. This brief update aims to provide the clinician with a succinct précis of the recent progress in this area.
    Full-text · Article · Feb 2015
    • "Generalizability of the results to other populations is unknown, although it is encouraging that all the known major risk factors found in previous studies in other populations were detected in our study. Previous studies have indicated that family history is a significant risk factor [30,39,51,68,69] but family history of AAA was not recorded in the Geisinger EMR. "
    [Show abstract] [Hide abstract] ABSTRACT: Using abdominal aortic aneurysm (AAA) as a model, this case-control study used electronic medical record (EMR) data to assess known risk factors and identify new associations. The study population consisted of cases with AAA (n =888) and controls (n =10,523) from the Geisinger Health System EMR in Central and Northeastern Pennsylvania. We extracted all clinical and diagnostic data for these patients from January 2004 to December 2009 from the EMR. From this sample set, bootstrap replication procedures were used to randomly generate 2,500 iterations of data sets, each with 500 cases and 2000 controls. Estimates of risk factor effect sizes were obtained by stepwise logistic regression followed by bootstrap aggregation. Variables were ranked using the number of inclusions in iterations and P values. The benign neoplasm diagnosis was negatively associated with AAA, a novel finding. Similarly, type 2 diabetes, diastolic blood pressure, weight and myelogenous neoplasms were negatively associated with AAA. Peripheral artery disease, smoking, age, coronary stenosis, systolic blood pressure, age, height, male sex, pulmonary disease and hypertension were associated with an increased risk for AAA. This study utilized EMR data, retrospectively, for risk factor assessment of a complex disease. Known risk factors for AAA were replicated in magnitude and direction. A novel negative association of benign neoplasms was identified. EMRs allow researchers to rapidly and inexpensively use clinical data to expand cohort size and derive better risk estimates for AAA as well as other complex diseases.
    Full-text · Article · Dec 2014
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