International Journal of Cardiology 198 (2015) 178–179
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International Journal of Cardiology
journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Association between sildenafil and inflammation markers/mediators
Shou-Guo Zhao a, Ji-Min Wang b, Qian-Feng Han c, Tai Li c, Heng-Chen Yao c,⁎
a
Department of Andrology, Liaocheng People's Hospital and clinical school of Taishan Medical University, Liaocheng 252000, PR China
b
Clinical laboratory, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng, 252000 PR China
c
Department of Cardiology, Liaocheng People's Hospital and clinical school of Taishan Medical University, Liaocheng 252000, PR China
a r t i c l e i n f o
Article history:
Received 28 June 2015
Accepted 30 June 2015
Available online 3 July 2015
We have recently read with great interest Dr Vlachopoulos and
colleagues' article entitled “Acute effect of sildenafil on inflammato-
ry markers/mediators in patients with vasculogenic erectile dysfunc-
tion” that was published in the International Journal of Cardiology
[1]. In this article, Dr Vlachopoulos and colleagues reported the
results of 27 patients who were medically treated with sildenafil
for vasculogenic erectile dysfunction (ED). In this investigation,
blood samples were collected at baseline and at 2 and 4 h after sil-
denafil or placebo administration to determine the levels of fibrino-
gen, high sensitivity C-reactive protein (hsCRP), high sensitivity
interleukin-6 (hsIL-6) and tumor necrosis factor α (TNF-α). The
authors concluded that administration of sildenafil could produce a
significant sustained acute reduction of fibrinogen, hsCRP and hsIL-
6 and TNF-α. Furthermore, the authors also stated the effects of sil-
denafil on fibrinogen, hsCRP and hsIL-6 and TNF-α was independent
of the baseline values of these markers/mediators or the baseline
testosterone levels.
In this paper, the authors come to a conclusion that there is an acute
effect of sildenafil administration on pro-inflammatory markers/media-
tors in men with vasculogenic ED and that means an implication in ED
patients who are considered to be at increased cardiovascular risk.
Yes, indeed, there is actually a link between sildenafil treatment and
the reduction of inflammatory markers However, we do think that
there is a need for further discussion or clarification about the conclu-
sions and the potential clinical implications stated by the authors of
this well-written article.
Firstly, in the recruitment of the patients, although diabetes,
coronary artery disease, stroke or peripheral artery disease, acute
inflammatory diseases, collagen disease, and malignant neoplasms
have been excluded, no information about ventricular function of
⁎ Corresponding author.
E-mail address: yaohc66@126.com (H.-C. Yao).
http://dx.doi.org/10.1016/j.ijcard.2015.06.183
0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
these patients was considered. The rates of ED in heart failure (HF)
are extremely high. The levels of a number of pro-inflammatory
cytokines are influenced by heart dysfunction. Both HF and ED are
associated with increased levels of proinflammatory cytokines,
such as TNF-α, IL-6 and IL-8 [2]. Recently, one study recruited
40 well-trained endurance athletes that underwent evaluation
prior to and immediately following one of four endurance sporting
events ranging from 3 to 11 hour duration. Cytokines (IL-1β, IL-6,
IL-8, IL-10, IL-12p70 and TNF-α) were analyzed by flow cytometry
from serum samples collected within 50 min of race completion.
They found that cardiac dysfunction following intense endurance exer-
cise was associated with increased expression of pro-inflammatory
cytokines [3]. Therefore, without considering ventricular function,
one of the major influencing factors of proinflammatory cytokines,
the conclusion reported by Dr Vlachopoulos et al. may require some
cautious interpretation.
Furthermore, sildenafil, as a phosphodiesterase type (PDE-5)
inhibitor, has time-dependent mild to moderate anti-inflammatory ef-
fects, at least partially via activation of the decreasement of fibrinogen
[4]. Recently, one meta-analysis, includes six randomized clinical trials
(recruited 476 diabetic men, 239 randomized to sildenafil, and 237 to
placebo respectively), suggests that chronic administration of sildenafil
seems to reduce serum pro-inflammatory markers (IL-6) in men with
diabetes [5]. On the contrary, one study, recruited 292 diabetic
patients with ED (148 patients given sildenafil daily for 16 weeks),
indicated that serum levels of IL-6 were unchanged after a so long
period of treatment [6]. Also, in another animal study, the results
showed that plasma TNF-α levels were not modified by the daily
sildenafil treatment [7]. Whereas, the expression of vascular cell
adhesion molecule (VCAM) could be reduced by the treatment of
sildenafil [8]. But, in Dr Vlachopoulos's study, the authors had only
enrolled 27 patients with ED, the results of acute effect of sidenafil on
inflammatory markers/mediators in patients with vasculogenic ED
may be causal. Therefore, the conclusions in Dr Vlachopoulos's report
are not entirely clear and may need to recruit a large scale samples of
patients with vasculogenic ED for further analysis or investigation,
which can help us to know well about the effects of sildenafil on
inflammatory markers/mediators in patients with ED.
Conflict of interest
No conflict of interest to declare.
 Letter to the Editor
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