EURURO Vol. 71 No. 4

E117 692

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
Gacci et al recently presented a remarkable review of the
relationship between male lower urinary tract symptoms
(LUTS) and major adverse cardiac events (MACE). Consid-
ering the rates of LUTS/benign prostatic hyperplasia (BPH)
and cardiovascular disease (CVD) associated with non-
communicable diseases and the use of holistic health care in
this era of aging societies, this is an important issue.
Although the authors’ review was thorough and included
scientific analysis, some points remain to be clarified.
First, although there is no controversy about the
relationship between metabolic syndrome (MS) and CVD
aggravation, the link between MS and LUTS remains
inconclusive. Besides the well-known complicated relation-
ship between male LUTS and MS, which includes factors
such as prostate enlargement, insulin resistance, dyslipide-
mia, hyperinsulinemia, autonomic sympathetic overactivity,
and consequent endothelial and smoothmuscle dysfunction,
MS itself is a combination of multiple diseases or conditions
influenced by multiple factors, including age, obesity, fatty
liver, and hormonal factors There is mixed evidence
regarding the relationship between male LUTS and MS.
Second, the authors focused heavily on BPH to explain
the link between LUTS and MACE, but mounting evidence
suggests that storage symptoms are the dominant symp-
toms in patients with obesity or MS via ischemic mecha-
nisms related to atherosclerosis . Increasing evidence is
revealing that among LUTS, storage symptoms are closely
related to obesity, MS, and atherosclerosis.
Lastly, the interpretation of the meta-regression should
include a more objective discussion of the impact of mean
age on MACE. Meta-regression during meta-analysis could
not provide information on potent risk factors, as could
ordinary multiple regression analysis. In order for age to
be an independent factor in meta-regression analysis,
the age range of the patients also has to be considered
because mean age itself is a secondary data point. Although
the meta-regression analysis showed that age had a
negative effect on MACE in moderate to severe LUTS, it
may also be the case that patients in weighted studies were
simply relatively younger in mean age than those in
nonweighted studies.
To address these questionable points and to clarify
the consistency of the relationship between male LUTS
and CVD, a meta-analysis using continuous variables
(eg, questionnaire scores for LUTS and CVD risk scores for
MACE) is needed, as continuous variables would provide
firmer information than discrete variables Another
solution involves studying healthy cohorts or performing
well-designed randomized controlled trials (RCTs). The
fundamental reason for analyzing healthy cohorts is to
avoid the complicated effects of confounding factors,
which cannot be controlled for except in an RCT. To
explain the role of LUTS in predicting CVD aggravation,
C-reactive protein (CRP), a validated marker for the
degree of MS and atherosclerosis, could be examined
Kim et al reported that healthy men with low CRP
levels have a greater tendency to have lower storage
symptom scores after adjustment for age, obesity, prostate
size, and metabolic risk factors in comparison to men
with normal CRP levels, which implies that subclinical
inflammation plays a role in the pathophysiology of storage
symptoms.
Conflicts of interest: The author has nothing to disclose.
Acknowledgments: This work was supported by the Soonchunhyang
University Research Fund.
References
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DOI of original article: .
0302-2838/# 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.