EURURO Vol. 71 No. 4

E119 692

Letter to the Editor
Reply to Jae Heon Kim’s Letter to the Editor re:
Mauro Gacci, Giovanni Corona, Arcangelo Sebastianelli,
et al. Male Lower Urinary Tract Symptoms and
Cardiovascular Events: A Systematic Review and
Meta-analysis. Eur Urol 2016;70:788–96
We would like to thank Dr. Kim for the interest in our review
and for his comments. The concerns he raised warrant
further clarifications.
Kim states that the link between metabolic syndrome
(MS) and lower urinary tract symptoms (LUTS) remains
inconclusive and that there is mixed evidence. However,
several systematic reviews in the literature support the
strength of the correlation between MS and LUTS at the
highest level of evidence (level 1A) . As reported in our
recently published meta-analysis , obese, dyslipidemic,
and aged men have a higher risk of having MS as a
determinant of their prostate enlargement.
Moreover, evidence summarized in a recent article
indicated a role of MS as a construct, as well as each of the
individual components, in the pathogenesis of benign
prostatic hyperplasia (BPH)/LUTS. In particular, some
MS-related conditions, such as dyslipidemia, hypogonad-
ism, and chronic low-grade inflammation, are emerging as
determinants for BPH/LUTS . There are many lines of
evidence showing that not only the prostate but also the
bladder can be directly affected by MS-related factors
. Higher serum levels of C-reactive protein (CRP), a
nonspecific marker of systemic inflammation, have been
associated with higher risk of not only incident symptom-
atic BPH but also storage LUTS. Preclinical studies demon-
strated that sex steroid imbalance (high estrogen and low
testosterone levels) as well as inflammation can directly
affect bladder contractility . This current evidence
suggests that important factors such as chronic low-grade
inflammation and hormonal imbalance could play a role in
linking LUTS and cardiovascular disease (CVD).
We agree with Dr. Kim’s remark that use of mean age
could have represented a methodological bias in the data
analysis. However, this issue represents a problem for all
meta-analyses. The take home message from the present
study is not that LUTS represent a risk factor for CVD. Our
data show that LUTS should not merely be considered a
hydraulic problem; the presence of LUTS might alert
clinicians that these individuals deserve a more holistic
approach, since they have several metabolic risk factors for
CVD. This is particularly true for younger subjects, whereas
in older patients the specific contribution of LUTS in
predicting forthcoming CVD is reduced by the presence of
other traditional CVD risk factors. It is important to
remember that the majority of CVD events occur in subjects
who would be classified as ‘‘lower risk’’ using conventional
parameters. Similar results have been reported for the
significance of erectile dysfunction in the stratification of
CVD risk .
Finally, as we reported in our sections on eligibility
criteria and study selection, we only analyzed men with
moderate to severe LUTS compared to those with mild or
without LUTS. We believe that the use of continuous
variables instead of discrete variable scores could provide
further information. However, for the data available in the
literature, this subanalysis is not feasible. As stated in our
conclusions, we agree that further RCTs with healthy
control groups are needed to confirm our data.
Conflicts of interest: The authors have nothing to disclose.
References
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DOIs of original articles: , .
0302-2838/# 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.