In this study, we investigated the association
between coexisting systemic diseases and PIS
development after EVAR. The results showed that
CAD, heart failure, and COPD were significant risk
factor for PIS. We also observed that other systemic
diseases, such as hypertension, renal failure, diabetes
mellitus and hyperlipidemia, that are likely to be found in patients with aortic aneurysms were not related to
PIS. Although the lack of randomized controlled trials
and the low number of patients make the findings
argumentative, this controversy is decreasing due to
the fact that the number of researches is increasingly,
particularly in COPD, hypertension, and diabetes
mellitus compared to other coexisting diseases.
Due to the older ages of patients undergoing
EVAR, it seems to be reasonable that this age group
would have many coexisting diseases. Researches
included in our study did not found a significant
difference between developed and undeveloped PIS
groups in terms of systemic coexisting diseases, other
than one study. In terms of ischemic heart disease
and COPD, Sartipy et al.[3] observed a significant
difference between the groups, contrary to the other
studies. Additionally, the differences for diabetes
mellitus and renal failure were not significant in this
study. No additional statistical analysis (univariate or multivariate analysis) was performed in this research
other than comparisons between the groups. Kwon
et al.[9] evaluated diabetes mellitus and hypertension
as variables in univariate and multivariate analysis;
however, results were not significant. Contrary to the
findings of five researches[5-9] which did not observe a
significant difference between the groups in terms of
CAD, COPD, and heart failure, we found that these
three systemic diseases were closely associated with the
development of PIS.
In 1992, the systemic inflammatory response
syndrome (SIRS) was defined at the American College
of Chest Physicians/Society of Critical Care Medicine
Consensus Conference.[10] This old definition consisted
of the following criteria: a body temperature of >38°C
or <36°C, heart rate of >90 bpm, respiratory rate of
>20 breath/min, and WBC of >12,000 cells/mm3
or <4,000 cells/mm3. Current sepsis guidelines have
abandoned the SIRS definition.[11] In spite of this, PIS is usually accepted as a systemic inflammatory
response occurring after EVAR. The published studies
defined PIS as fever and leukocytosis in conditions
without an infection.[12] This definition is different to
the diagnostic criteria for SIRS.[13] While the criteria
for SIRS have four points, PIS only encompasses
leukocytosis and fever from these criteria. Respiration
or heart beats per minute are outside the definition of
PIS. The remaining leukocytosis and fever appear to
be findings that may be confused with other causes. As
a result, Spanos et al.[14] were of the opinion that there
was a need to consider anaphylaxis, particularly in the
differential diagnosis.
There are three criteria used as the general
definition for PIS: fever, leukocytosis, and elevated
CRP. However, although all of the studies included
in our study agreed fever and leukocytosis as the main
criteria, CRP was added to the definition only by
Gorla et al.[8]
Diabetes mellitus, frequently encountered in those
with cardiovascular diseases, increases the risk of
infection and sepsis. Also, up to 22% of all sepsis
patients are known to have diabetes mellitus.[15,16] The
main reason for this susceptibility toward infection
can be attributed to the effect of hyperglycemia and
is considered to be related to defects in adhesion,
neutrophil chemotaxis, and intercellular death.[17]
Although there is a direct correlation between the
inflammatory process and sepsis with diabetes
mellitus, the cause of the lack of a significant link
between PIS and diabetes mellitus in our analysis
is not consistent with this situation. However, we
believe that, at this point, it is necessary to investigate
whether other comorbid disease are the risk factors.
Also, other variables related to diabetes mellitus
such as duration and antidiabetic medications should
be analyzed. Investigation of patients in subgroups
according to years of diabetes mellitus, type of
diabetes mellitus, and treatment options may reveal
the correlation between PIS and diabetes mellitus
more clearly.
Inflammation is shown to be effective in the
development of many cardiac diseases including
atherosclerosis and CAD and in the formation of
complications.[18] In atherosclerotic lesions, a
chronic inflammatory process, balloon angioplasty
administration induces inflammation, leading to the
release of inflammatory biomarkers by the interleukin-6
and tumor necrotizing factor-alpha.[19]
Inflammation and heart failure are strongly linked
with each other.[20] Indeed, they often mutually
strengthen each other. This situation supports our
results about that there is a relationship between PIS
with both CAD and heart failure. A similar situation
for heart disease exists in COPD which is associated
with chronic inflammation affecting pulmonary
parenchyma and peripheral airways, resulting in
inflammation characterized by increased alveolar
macrophages, neutrophils and T-lymphocytes.[21] This
relationship shows positive correlation, reaching the
highest points during acute exacerbations.[21]
The exact etiology of PIS still remains to be
elucidated. Endograft material, bacterial translocation,
contrast use, and thrombus are thought to be the
potential factors.[22] Endograft material (polyester and
polytetrafluoroethylene) is the most investigated factor.
Kakisis et al.[23] found that polyester-based endograft
was an independent risk factor for PIS according to the
multivariable model. On the contrary, Moulokakis et
al.[24] were unable to find any difference between these
two materials.
In particular, considering the patient group to
which EVAR would be applied, accompanying
systemic diseases constitute an important clinical
situation. Therefore, it is important to identify and
control coexisting diseases before the procedure. At
the same time, identification of diseases that may
be a risk factor for PIS would form the basis for the
measures to be taken. Thus, factors that increase the
cost of treatment such as complications and length of
hospital stay can be prevented.
There are some limitations to this meta-analysis.
First, PubMed, Scopus, and Web of Science were
used for database screening. Since the other databases
were not examined, the number of articles available
remained low. Second, only English publications
were selected. Third, a population of 947 patients
was reached, which may be an insufficient sample
size. Finally, we were unable to evaluate syndromes
such as Marfan. In the literature, EVAR in patients
with connective tissue disorders has been shown
to be associated with a high risk of early and midterm
complications and reinterventions and an open
surgical approach should be reserved for patients with
acceptable risks.[25]
In conclusion, there is a significant correlation
between PIS with CAD, heart failure, and COPD.
Although the endograft material is the most known etiological factor for PIS, coexisting diseases should
be also considered. This may be helpful for planning
the preventive therapies of PIS. Nevertheless, further
large-scale, prospective, randomized-controlled
studies are warranted to reveal the possible relationship
between other frequently encountered diseases such as
diabetes mellitus.
Declaration of conflicting interests
The authors declared no conflicts of interest with respect
to the authorship and/or publication of this article.
Funding
The authors received no financial support for the research
and/or authorship of this article.