cor et vasa 60 (2018) e296–e305

Available online at www.sciencedirect.com

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journal homepage: http://www.elsevier.com/locate/crvasa

Review article

Sexual activity and cardiovascular disease, erectile

dysfunction as a predictor of ischemic heart disease

S. Hudec, M. Spacek *, M. Hutyra, O. Moravec, M. Taborsky

Department of Internal Medicine I – Cardiology, Faculty of Medicine and Dentistry, Palacky University Olomouc and
University Hospital Olomouc, Olomouc, Czech Republic

article info abstract

Article history: Sexual activity affects the quality of life of patients with cardiovascular disease (CVD). The
Received 13 March 2017 purpose of this document is to highlight the fact that sexual activity of patients with stable
Received in revised form forms of CVD and moderate exercise tolerance is safe. Delaying resumption of sexual activity
23 June 2017 is not justified and could have a negative impact on the patient's mental status and the
Accepted 30 August 2017 quality of partner life. Vasculogenic erectile dysfunction is considered an independent risk
Available online 28 September 2017 factor for coronary heart disease.
© 2017 The Czech Society of Cardiology. Published by Elsevier Sp. z o.o. All rights reserved.
Keywords:
Hemodynamic changes
Sexual activity
Cardiovascular disease
Erectile dysfunction
Phosphodiesterase 5 inhibitors

Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e297
Hemodynamic implications of sexual activity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e297
Cardiovascular risk for developing coronary heart disease, arrhythmias and sudden cardiac death during sexual activity e297
Coronary heart disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e297
Sudden cardiac death and arrhythmias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e298
Sexual activity in specific cardiovascular disease – who is at risk and when can sexual activity be resumed . . . . . . . . . . e298
Coronary heart disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e299
Heart failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e299
Valvular heart disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e299
Arrhythmias, pacemakers, and implantable cardioverter-defibrillators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e299

* Corresponding author at: Department of Internal Medicine I – Cardiology, Faculty of Medicine and Dentistry, Palacky University Olomouc
and University Hospital Olomouc, I.P. Pavlova 6, 775 20 Olomouc, Czech Republic.
E-mail address: mildaspacek@gmail.com (M. Spacek).
http://dx.doi.org/10.1016/j.crvasa.2017.08.006
0010-8650/© 2017 The Czech Society of Cardiology. Published by Elsevier Sp. z o.o. All rights reserved.
 cor et vasa 60 (2018) e296–e305 e297

Congenital heart disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e300

Hypertrophic cardiomyopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e300
Erectile dysfunction – a predictor of coronary heart disease and a marker of its severity . . . . . . . . . . . . . . . . . . . . . . . . . . e300
Erectile dysfunction and the risk of future cardiovascular events: the window of opportunity . . . . . . . . . . . . . . . . . . . e300
Erectile dysfunction and cardiovascular disease: correlation in clinical practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e301
Cardiovascular medication deteriorating the quality of erection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e301
Managing the patient diagnosed to have organic (vasculogenic) erectile dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . e301
Pharmacotherapy of erectile dysfunction with phosphodiesterase-5 (PDE5) inhibitors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . e302
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e302
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e302
Ethical statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e302
Funding body . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e302
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e302

response to SexA has been reported [5,6]. Energy expenditure

Introduction
Sexual activity (SexA) makes an important part of life of each
individual and significantly affects its quality. For many
patients, quality of life is more important than actual survival
time. Hence, early resumption of SexA after a cardiovascular
event is of importance for the patient's psychological status
and partner life. Quite logically, concerns about cardiovascular
event recurrence result in reduced SexA. Despite these, there is
still general reluctance to address this issue in secondary
prevention. The low level of information and awareness
regarding this aspect of life or even feelings of embarrassment
in physician–patient communication results in unnecessary
delay in resuming SexA. The first document based on data
from studies conducted to date and addressing this issue is the
position paper of the American Heart Association (AHA)
published in 2012 [1]. One of the first Czech authors
systematically involved in the study of various aspects of
sex in patients with cardiovascular disease (CVD) was Prof.
Petr Niederle [2].
Erectile dysfunction (ED) affects up to 40% of men aged over
40, and is most often due to vascular causes. Based on the
finding of an analogy between atherosclerotic involvement of
the cavernous and coronary territories, it has been suggested
to use this fact in predicting development of coronary heart
disease (CHD).
Hemodynamic implications of sexual activity
A host of studies have investigated neuroendocrine and
cardiovascular changes during sexual arousal and activity.
Sexual arousal and actual intercourse (defined as heterosexual
vaginal intercourse) are associated with neuroendocrine
changes having an impact on the cardiovascular system.
Sympathetic activation elicits changes in blood pressure (BP)
and heart rate (HR). In a healthy individual at peak sexual
arousal occurring within 10–15 s of orgasm, HR rises to about
130 bpm at most, with systolic BP usually not exceeding
170 mmHg [3,4]. Foreplay is associated with only a mild
increase in HR and BP. Orgasm is immediately followed by a
quick return to baseline arterial BP and HR. No significant
difference between women and men in their cardiovascular
during SexA is usually 3–5 metabolic equivalents (METs), a
value reached, e.g., after quickly climbing 2 flights of stairs or
during fast walk [7]; hence coitus is thus equivalent to mild to
moderate exercise. While patients who have more difficulty
attaining orgasm are most likely to achieve a higher degree of
physical load, specific data are lacking. As the above values
were obtained in studies including predominantly young
married middle-aged men and their wives, the cohorts
involved in those studies were obviously by far not represen-
tative of the entire population, particularly its older-age
groups, those less physically fit as well as those with
cardiovascular disease. It should thus be remembered that
SexA requires 3–5 METs and each patient should be assessed
based on their individual ability to tolerate such a load.
Cardiovascular risk for developing coronary heart
disease, arrhythmias and sudden cardiac death
during sexual activity
Coronary heart disease
Coital angina (‘‘angina d'amour’’), angina that occurs during
the minutes or hours after sexual activity, represents <5% of
all anginal attacks. [8]. Its prevalence in physically less active,
sedentary individuals is higher than in the physically active
ones. Anginal attacks are most unlikely to occur in individuals
during SexA as long as these problems are not experienced
during a physical activity ≥3–5 METs [9].
A meta-analysis of 4 case–control crossover studies with
individuals aged 50–60 showed a 2.7-fold increase in the
relative risk (RR) of intercourse-related (coital) myocardial
infarction (MI) compared with other times [10]. While, in
sedentary individuals, the RR is as much as triple, its value in
the physically active ones is only 1.2. No significant difference
in the RR of experiencing coital MI was reported between
individuals with a history of MI and without a history of
coronary heart disease [11].
In SHEEP (Stockholm Heart Epidemiology Programme),
while the RR of physically inactive individuals was shown to
be increased by a factor of 4.4, in the physically active in was
decreased, being 0.7. The increased risk of myocardial
infarction after sexual activity and the further increase in
e298 cor et vasa 60 (2018) e296–e305

risk among the less physically fit support the hypothesis of

causal triggering by sexual activity [12].
Although SexA is associated with an increased RR of
developing MI, the absolute risk of experiencing a cardiovas-
cular event is extremely low, accounting for less than 1% of all
cases of acute MI. This can be explained by the fact that the
duration of intercourse is but a fraction of the total period of
time associated with increased risk of developing myocardial
ischemia or MI [11].
The absolute risk of MI associated with SexA (performed
over at least a total of 1 h per week) is 2–3 per 10 000 person-
years [10], and is higher in the physically inactive individuals.
Sudden cardiac death and arrhythmias
While, in an autopsy study of 5559 cases of sudden cardiac
death (SCD), 34 (0.6%) deaths were associated with SexA [13],
other authors reported a range of 0.6–1.7% [14,15]. In 82–93% of
cases, the victims were men, with the majority of them (75%)
experiencing SCD during extramarital SexA with young
partners in an unfamiliar setting, frequently after excess
consumption of food and alcohol. The absolute risk of SCD is
below 1 per 10 000 person-years [10].
The body of data on SexA-associated ventricular arrhyth-
mias is very small. Studies involving MI patients did not
document an increase in the incidence of ventricular ectopies
compared with other activities, or the incidence was even
lower [16,17]. In a small study enrolling 43 patients (of this
number, only 8 women) with an implantable cardioverter-
defibrillator (ICD), the RR of developing tachyarrhythmic
events was comparable with other forms of triggers (mental
stress, physical exercise, SexA) [18]. The general recommen-
dations regarding sexual activity in patients with cardiovas-
cular diseases are presented in Table 1.
Sexual activity in specific cardiovascular disease –
who is at risk and when can sexual activity be
resumed
Coronary heart disease patients, especially those after a MI,
are usually sexually active in only 40–45%. Reasons for sexual
abstinence include, in particular, persisting cardiac problems,
concerns about MI recurrence, and erectile dysfunction (ED).
While SexA resumption is often unnecessarily delayed (9–16
weeks), avoidance of SexA is absolutely unsubstantiated. A
frequent reason for delayed resumption of SexA is inadequate
level of information of physicians and, hence, also patients or
their partners regarding the risk of cardiovascular complica-
tions during SexA. Concerns about potential MI recurrence
may lead to reluctance to resume SexA eventually resulting in
male sexual dysfunction. Thus, the main responsibility lies
with the physician who should inform, advise and/or counsel
the patient regarding the appropriateness of resuming SexA
unless at increased risk of developing cardiovascular compli-
cations [19].
In clinical practice, stratification of the risk of CVD
patients during SexA can be based on provisions of the III
Princeton Consensus published in 2010, dividing patients into
3 groups, i.e., those at low, high and undetermined risk of
developing cardiovascular complications. The latter category
should be re-evaluated using exercise testing (e.g., bicycle
ergometry).
Low-risk individuals include those tolerating moderate
exercise with absence of symptoms, i.e., individuals after
complete revascularization, with controlled hypertension,
insignificant valve disease, NYHA Class I–II heart failure as
well as those achieving physical workloads of 5 METs without
evidence of ischemia.

Table 1 – Sexual activity and cardiovascular disease: general recommendations [1]

Recommendation Classa Levelb
Women with CVD should be advised regarding the safety and efficacy of contraceptive techniques and I C
pregnancy as appropriate
Cardiac rehabilitation and regular exercise may be useful in reducing the risk of cardiovascular IIa B
complications associated with SexA in CVD patients
SexA is advisable in patients with CVD clinically assessed as those at low risk of cardiovascular IIa B
complications
It is advisable to perform exercise testing in patients not at low cardiovascular risk or their cardiovascular IIa C
risk is unknown in order to assess their exercise capacity, development of symptoms, ischemia, or
arrhythmia
SexA is advisable for patients tolerating loads ≥3–5 MET without developing angina, excess dyspnea, IIa C
ischemic ST-segment changes, cyanosis, hypotension, or arrhythmia
Patients with CVD planning to start or resume SexA should best be assessed using a detailed history and IIa C
physical examination
Patients with unstable, decompensated and/or severely symptomatic CVD should delay SexA until their III C
condition has stabilized and is optimally managed
Patients with CVD symptomatic during SexA should delay SexA resumption until their condition has III C
stabilized and is optimally managed
Abbreviations: CVD, cardiovascular disease; MET, metabolic equivalent; SexA, sexual activity.
a
Class of recommendation.
b
Level of evidence.
 cor et vasa 60 (2018) e296–e305
High-risk individuals include unstable patients or those in a
very serious condition as they are markedly symptomatic. A
high-risk profile is present in individuals with unstable or
refractory angina, uncontrolled hypertension, NYHA Class IV
heart failure, recent MI (<2 weeks) not managed intervention-
ally, those with exercise-induced ventricular tachycardia,
arrhythmic storm (frequent ICD discharges), poorly rate-
controlled atrial fibrillation, markedly symptomatic obstruc-
tive hypertrophic cardiomyopathy, and those with moderate
to severe valve disease, in particular aortic stenosis.
A group in between the above ones includes patients at
undetermined risk of experiencing cardiovascular complica-
tions during SexA, i.e., patients who should best undergo
exercise testing prior to resuming SexA. Unless symptoms of
cardiovascular disease, arrhythmia or a decrease in systolic BP
are present at a load of 5–6 METs, these are low-risk individuals
[20–22]. Based of results of exercise testing, the patient is thus
classified as one at low or high risk. These individuals include,
in particular, those with the following conditions: mild to
moderate angina, individuals 2–8 weeks after in MI not
managed interventionally, NYHA Class III heart failure, non-
cardiac atherosclerotic involvement (peripheral arterial dis-
ease), transient ischemic attack (TIA), or stroke [23].
Coronary heart disease
While patients with stable coronary heart disease (angina) are
at minimal risk of complications, the risk is high with unstable
and refractory forms [2,24]. Patients with unclear severity of
symptoms should have exercise testing.
In the era prior to routine introduction of reperfusion
therapy, it was not advisable for patients to resume SexA
within 6–8 of experiencing an MI. More recently, stable
patients having a successful revascularization intervention
are advised to resume SexA as early as within 1 week of MI
(including STEMI); this is based on the fact that involvement of
patients in cardiovascular rehabilitation programmes 2 weeks
post MI is also safe (similar exercise) [2,24]. Here again, patients
can have exercise testing to assess their symptoms and
exercise tolerance. Patients who have had scheduled percuta-
neous coronary intervention (PCI) may resume SexA as early
as a few days postoperatively depending on the status of
vascular access (transfemoral in particular) and the presence/
absence of vascular complications (inguinal hematoma,
pseudoaneurysm, aneurysm). In patients treated using the
radial access, SexA is usually resumed earlier than in those
with transfemoral access. In patients with incomplete
revascularization, it is critical to check for the presence of
residual ischemia; the patient should preferably have exercise
testing. In patients undergoing surgical revascularization and
other procedures involving sternotomy (e.g., valve replace-
ment), it is appropriate to wait until the sternotomy wound has
healed; hence SexA should not be resumed before 6–8 weeks.
In the first postoperative months, partners should avoid
positions resulting in chest discomfort and increased pressure
on the wound. In patients having minimally invasive
procedures (MIDCAB), SexA can be resumed earlier than in
those treated by sternotomy, with no specified duration of
sexual abstinence. In the English Longitudinal Study of Ageing
(ELSA), which also compares sexual behavior and concerns in
e299
people with and without CHD in the population aged 50 and
older, SexA in men was 69% vs. 80% (with vs. without CHD,
respectively) while erectile difficulties 47% vs. 38%. Effects
were more pronounced among those diagnosed in the past 4
years. Women diagnosed <4 years ago were also less likely to
be sexually active 35% vs. 55%. This highlights the need to
educate these patients about the safety or risk of SexA, or to
provide additional care such as ED therapy or counseling [25].
Heart failure
Hemodynamic, vascular, and neurohumoral abnormalities
occurring in heart failure patients frequently lead to sexual
dysfunction [26]. Sixty to 87% of patients report sexual
problems including decreased sexual appetite and activity;
with complete sexual abstinence reported by one in four
patients. While sexual dysfunction correlates with the severity
of heart failure as determined using NYHA classification, it
does not with left ventricular ejection fraction (LVEF) [27]. The
safety of SexA depends on the severity of symptoms of heart
failure and degree of its compensation. In patients with well
compensated heart failure, SexA is safe [28,29]. Many patients
prefer better quality of life (including SexA) to survival time
[30,31]. Sexual activity is increased by proper management of
heart failure and exercise [32]. In dyspneic patients, appropri-
ate positions include a semireclining or ‘‘on-bottom’’ position
during coitus, as they are less physically demanding [33].
Valvular heart disease
To date, no studies have been published specifically addres-
sing the issue of valve disease and SexA, although recom-
mendations to regular physical activity are available [22,34,35].
Given the fact that SexA is equivalent to mild to moderate
physical activity, it is conceivable that SexA is safe for patients
with hemodynamically mild to moderate valve disease. In
patients with hemodynamically significant valve disease and
marked symptoms (even mild symptoms in the case of severe
aortic stenosis), it is reasonable to delay resumption of SexA
until the valve disease and symptoms have been managed,
either pharmacologically or surgically. By contrast, there is no
reason to discourage patients with (normally functioning)
prosthetic valves from SexA. In asymptomatic, moderate to
severe aortic stenosis, and in patients with unspecifiable
symptoms, it is advisable to perform exercise testing. Stress
echocardiography may provide additional information to
physiological response to exercise testing including estima-
tion of ventricular function, inducible increase in gradients,
and severity of pulmonary hypertension.
Arrhythmias, pacemakers, and implantable cardioverter-
defibrillators
As discussed above, sudden cardiac death due to SexA is a
most rare occurrence. The body of data related to the number
of cases of SexA-induced arrhythmia in patients with a
positive history is very small. Patients with CVD including
those with ICDs do not seem to be at increased risk of
experiencing ventricular arrhythmia as long as they tolerate
the respective physical load (3–5 METs) [17,18]. Patients able to
e300 cor et vasa 60 (2018) e296–e305
pperform common leisure-time activities can safely practise
SexA. These patients include individuals with well rate-
controlled atrial fibrillation, a history of atrioventricular re-
entry tachycardia, pacemakers, IDCs implanted both for
primary prevention unless they receive adequate discharges,
and for secondary prevention provided they tolerate physical
load while not receiving frequency adequate discharges [36–39].
In patients with frequent discharges, it is critical to first
stabilize their condition, choose optimal control of the
arrhythmia and, prior to resuming SexA, mainly to identify
the underlying cause of these discharges (ischemic substrate,
mineral dysbalance). On the other hand, a history of several
discharges itself need not be a contraindication to SexA.
Likewise, while the presence of an ICD is not a contraindi-
cation to continue practising SexA, individuals with ICD
implantation show an appreciable reduction in their SexA
due – primarily – to unjustified concerns of their partners
afraid of a discharge during SexA [40–42]. These concerns may
be dispelled by exercise testing. It is advisable to inform
patients' partners about the extremely low risk of discharge
during SexA.
Congenital heart disease
Patients with mild but, also, those with more complex disease
are at increased risk of developing atrial and ventricular
arrhythmias, stroke and, rarely, myocardial ischemia. In a
study, up to 9% of patients with congenital heart disease (VSV)
reported symptoms (dyspnea, palpitations, fatigue, or synco-
pe) during SexA. The symptoms tended to occur more often in
individuals with more severe defects, worse functional status
and those with cyanosis [43]. In a survey of males with
congenital heart disease, 9% reported dyspnea, another 9%
arrhythmia, with 5% experiencing chest pain during SexA; the
incidence was higher in patients with NYHA Class III.
Nonetheless, only very few cases of sudden death associated
with SexA have been reported.
Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy is the most frequent cause of
sudden arrhythmic death in young individuals (including
professional athletes). This condition is associated with poor
predictability of the underlying arrhythmogenic substrate. A
correlation has been demonstrated between physical load and
increased risk of SCD from ventricular tachyarrhythmia [44–
48]. While concerns have been raised that SexA may also raise
the risk of SCD, there has been no report to date of a patient
with hypertrophic cardiomyopathy dying suddenly during
SexA. This is in line with recommendations for everyday
physical activity to avoid participation in demanding compet-
itive sports and activities inconsistent with levels achieved
during SexA [39].
Erectile dysfunction – a predictor of coronary heart
disease and a marker of its severity
Erectile dysfunction is defined as permanent or repeat
inability to achieve and maintain erection sufficient to obtain
satisfactory sexual intercourse. Erectile dysfunction (of vary-
ing severity) affects close to 40% of males aged over 40 and
increases with age [49]. A survey conducted in 2001 by STEM/
MARK poll agency in the Czech Republic showed a form of ED
affected up to 54% of Czech males between 35 and 65 years of
age [50]. In 60% of cases, the etiology of ED was organic
(vasculogenic), with the remainder being psychogenic and
mixed causes.
Erectile dysfunction and CHD share the underlying cause,
i.e., atherosclerosis, whose first stage is endothelial dysfunc-
tion (impaired relaxation). In fact, ED and CHD are two
different aspects of the same condition. The same applies to
risk factors (age, hypertension, dyslipidemia, diabetes, physi-
cal inactivity, and smoking).
Further, currently available data clearly show that ED (i)
occurs frequently in men with known CVD; (ii) is an
independent risk factor of future cardiovascular events in
men both with and without known cardiovascular disease
and; (iii) coexists with coronary arterial disease [21,24,36].
From the anatomical point of view, coronary and cavernous
arteries are so-called terminal arteries, i.e., they do not contain
anastomoses.
Two main hypotheses have been put forth to explain the
pathophysiology of ED still before a cardiovascular event
occurs in the presence of subclinical CHD. The first is referred
to as artery size hypothesis [51,52]. While the penile arterial
lumen is about 1–2 mm, that of coronary and carotid arteries is
3–4 mm and approx. 5–7 mm, respectively. Moreover, while, in
larger arteries, adequate flow is obtained by 15% dilatation of
their original lumen, erection requires vasodilation of penile
arteries of up to 80%. Quite logically, the process of
atherosclerosis occurring at the same rate becomes clinically
significant in the smaller penile arteries earlier than in the
larger arteries elsewhere in the body [53]. The other hypothesis
is based on the finding of a higher proportion of endothelial
cells in the vascular tree (sinusoidal spaces of penile cavernous
bodies) than elsewhere in the body; hence, even incipient
endothelial dysfunction will manifest itself with more marked
deficiency of NO, and thus earlier tumescence impairment.
Erectile dysfunction and the risk of future cardiovascular
events: the window of opportunity
Judging from the above, one can assume that atherosclerotic
disease of cavernous veins manifesting itself in ED may predict
coronary artery disease and serve as an early marker of
coronary heart disease. It has been reported that the mean
interval between development of ED and overt CHD is 2–5
years (average 3 years) [21] or, more precisely, the interval
between development of ED and presentation of CHD
symptoms is 2–3 years, while the interval between develop-
ment of ED and a fatal cardiovascular event (stroke, myocar-
dial infarction) is 3–5 years. The risk of a cardiovascular events
within the next 10 years of development of ED is increased by a
factor of 1.3–1.6 [19].
As mentioned above, ED is an independent risk
factor for cardiovascular events. Numerous trials have
investigated the ability of ED to predict both the risk of future
fatal and non-fatal cardiovascular events (MI, stroke, revas-
cularization) and total mortality in the population of patients
 cor et vasa 60 (2018) e296–e305
at high cardiovascular risk, i.e., particularly in patients with
diabetes and those with heart failure [24,54–57]. A meta-
analysis of prospective cohort studies involving 92 757 men
followed for 6.1 years showed, in patients with ED, increased
risk of cardiovascular events by 44%, myocardial infarction by
62%, cerebrovascular events by 39%, with cardiovascular and
total mortality increased by 19% and 25%, respectively [24]. The
predictive value is further enhanced in men with known CVD
where ED increases the risk of death from any cause by
90% [24].
As age increases, so does the prognostic value of ED as a
predictor of CHD, with the predictive potential being highest in
young men with moderate to severe ED. It is just the time
interval of 2–5 years, which provides an opportunity to
further intensify disease control in terms of preventing CHD
development/progression (reduction of risk factors, lifestyle
modification).
Erectile dysfunction and cardiovascular disease: correlation in
clinical practice
The prevalence of ED in CHD patients is in the range of 47–75%
[21,35,36]. It is reported that 24% of patients with ED have a
normal coronary angiographic finding whereas up to 47% of
them show coronary artery disease (CAD). Likewise, there are
differences in the prevalence of ED depending on the clinical
form of CHD (acute/chronic) and the number of coronary
arteries with hemodynamically significant involvement. In
patients experiencing an acute coronary syndrome (ACS) and
single-vessel involvement, the prevalence of ED is 22%
whereas, in patients with chronic CHD and multiple-
vessel involvement, the prevalence is as much as triple, i.e.,
55–65% [58].
The underlying pathophysiology consists in the nature of
the atherosclerotic plaque in the individual clinical forms of
CHD. Acute CHD evolves secondary to rupture of a non-
obturating atherosclerotic plaque with an apposed thrombus,
hence the systemic atherosclerotic load may be smaller [58,59].
The severity of ED and its duration correlate with the
severity of CHD. The severity of ED is classified using the 5-
item version of the International Index of Erectile Function
(IIEF-5). An IIEF <10 and duration >24 months has been found
to be associated with a more severe coronary angiographic
finding [58].
Erectile dysfunction may be the only clinical symptom of
subclinical CHD. It has been reported that up to 22% of ED
patients have exercise-induced ischemia (e.g., in bicycle
ergometry), with a positive coronary angiographic finding in
over 90% of cases [3,36]. A prospective angiographic study
showed that 19% of patients with ED had silent CHD [3]. In
young men below 40 years of age with ED, the incidence of CHD
is up to 7 times that compared with a reference population [60].
Cardiovascular medication deteriorating the quality of erection
Numerous earlier studies reported that ED may be elicited by
drugs acting on the cardiovascular system, diuretics and beta-
blockers in particular [61–66]. However, more recent studies
evaluating newer drugs have refuted these long-held and
perpetuated paradigms [63–65,67–70]. For instance, beta-
e301
blocker therapy was shown to be associated with development
of ED at 1-year follow-up in only 5 of 1000 patients.
Furthermore, therapy using novel beta-blockers has also been
associated with what is referred to as nocebo effect (as
opposed to placebo effect, with the patient informed about the
side effects awaiting them). While thiazide diuretics and
aldosterone antagonists (spironolacton) have been consistent-
ly shown to contribute to the development of ED, no such
significant effect has been reported with loop diuretics. To
avoid the side effects of spironolacton, this drug can be
replaced by eplerenon. In conditions requiring treatment with
a beta-blocker (heart failure, previous MI) and a clear
association between development of ED and medication, the
physician may attempt to replace the beta-blocker with
nebivolol (also exerting NO-mediated vasodilator action) or,
alternatively, the patient can be switched to PDE-5 inhibitors.
While angiotensin-converting enzyme inhibitors, angiotensin
receptor blockers, and calcium-channel blockers have all been
suggested to have a neutral or even beneficial effect on erectile
function, conclusive data are lacking [71–73]. In ELSA study,
cardiovascular medication showed weak associations with
erectile dysfunction [25]. While low-dose statins rather tend to
improve erectile function, it worsens with high-dose statin
therapy (given the potential decrease in testosterone levels).
Importantly, cardiovascular drugs affecting symptoms and
mortality should not be withdrawn or discontinued because of
the potential development of ED.
Managing the patient diagnosed to have organic
(vasculogenic) erectile dysfunction
In patients with ED, it is appropriate to estimate the risk of
experiencing a fatal cardiovascular event within the next 10
years using the SCORE system. This is based on the fact that ED
is yet another independent risk factor of CHD, allowing to
reclassify the individual to a category with higher risk of
developing cardiovascular events (whether or not they have
been diagnosed to have CVD). Treatment of the other
pharmacologically modifiable risk factors of CHD should be
escalated. A desirable strategy is a marked change in lifestyle
(physical activity, Mediterranean diet, non smoking). Patients
should have their individual exercise tolerance assessed for
potential presence of CHD symptoms and/or, possibly have
exercise testing (e.g., bicycle ergometry). Further, based on the
finding, the patient can be indicated for a interventional
procedure (coronary angiography). Detailed recommendations
are discussed in the so-called Princeton Consensus and,
particularly, in the recent III Consensus published in 2012.
While some studies reported that use of specific phosphodi-
esterase 5 (PDE5) inhibitors in the treatment of ED may also
affect mortality and cardiovascular morbidity of patients with
silent CHD and diabetes [56], other authors [57] suggested that
the relative risk (RR) for developing CVD in ED patients using
sildenafil decreased from 1.7 to 1.1 at 2 years. However, when
initiating therapy, it is critical to perform checks at an interval
of 2–4 weeks to assess the efficacy of therapy, monitor any side
effects of therapy, and titrate doses. In patients with
testosterone deficiency (who are often poor responders to
therapy with PDE5) can be considered for so-called testoster-
one therapy.
e302 cor et vasa 60 (2018) e296–e305
Pharmacotherapy of erectile dysfunction with
phosphodiesterase-5 (PDE5) inhibitors
Treatment with PDE5 inhibitors has an excellent clinical effect
in most ED patients. The mode of action consists in inhibiting
cGMP degradation thus increasing NO levels and subsequent
vasodilation. Currently, three PDE5 inhibitors are available on
the Czech market; sildenafil and vardenafil (both relatively
short-acting agents with a half-life of 4 h) and tadalafil (a long-
acting agent with a half-life of 17.5 h). Sildenafil and tadalafil
have also found use in the treatment of pulmonary hyperten-
sion. The overall hemodynamic effects of these agents include
systemic vasodilation manifesting itself in mild reduction of
systolic and diastolic blood pressure (by 10 mmHg and
8 mmHg at most, respectively). This reduction may be greater
in patients with CHD and arterial hypertension [74]. While
many patients (even physicians) believe that PDE5 inhibitors
may – through hypotension – be associated with, or increase
the risk of cardiovascular events, particularly MI, they are a
safe and effective option in the treatment of vasculogenic ED
as documented by some meta-analyses [74–77]. There is only a
small additive effect in reducing blood pressure in patients co-
treated with antihypertensives (see above). Contraindications
to using PDE5 inhibitors include hypotension (<90/50 mmHg)
and use of nitrates (including molsidomin), the latter because
of the difficulty to predict the decrease in blood pressure. As
concomitant use of alpha-blockers can lead to the develop-
ment of symptomatic hypotension (orthostatic), it is advisable
to reduce alpha-blocker dose before initiating therapy with
PDE5 inhibitors [78]. Phosphodiesterase 5 inhibitors should
also not be given to patients already receiving PDE5 inhibitors
for the treatment of pulmonary hypertension. Among PDE5
inhibitors, only vardenafil prolongs the QT interval and should
not be given to patients with congenital long QT interval
syndrome and to patients with a history of torsade de pointes
or those receiving drugs prolonging the QT interval (IA and III
class antiarrhythmics in the Vaughan-Williams classification).
Nitrates should be taken within 24 h of PDE5 inhibitor
administration (with sildenafil and vardenafil) and within 48 h
of tadalafil administration. Patients experiencing chest pain to
be potentially managed with a nitrate, it is imperative to ask
about any PDE5 inhibitor use in the preceding 24–48 h. It is
appropriate to consider the rationale for long-term nitrate use
in patients after complete revascularization and in those in
whom therapy with PDE5 inhibitors is desirable to be initiated.
As with all vasodilators, special caution is to be exerted with
PDE5 inhibitors when considering therapy initiation in
patients with severe aortic stenosis and hypertrophic cardio-
myopathy, although no case of death related to PDE5 inhibitor
use in left ventricular outflow tract obstruction (fixed or
dynamic) has been reported to date.
Conclusion
Sexual activity is an important part of partner life affecting its
quality. Patients with cardiovascular disease show a higher
incidence of sexual dysfunction based both on organic and
psychogenic causes due to concerns about development of
cardiovascular complications during SexA. It should be
stressed that the physical load associated with this activity
is 3–5 metabolic equivalents thus representing a moderate one
at most. As new agents appear on the market and, given the
advances in interventional cardiology, the recommended
intervals to resuming SexA after cardiovascular events have
become shorter. Avoidance of sexual activity is only desirable
in unstable patients with severe symptoms. Patients at unclear
risk of complications should be indicated for exercise testing.
Obviously, the general awareness about this issue is inade-
quate and frequently results in avoiding SexA and partner
problems, which, in extreme cases, may culminate in a
breakup of the partnership. Due to concerns about cardiovas-
cular complications, men often experience (psychogenic)
erectile dysfunction making the problem still worse. The role
of the physician thus lies in explaining the safety and very low
potential risks of SexA and adjusting the necessary medica-
tion. The most frequent cause of ED is vessel involvement
(vasculogenic etiology), in which case ED may serve as a
predictor or marker of the severity of CHD given the similarity
between cavernous and coronary arteries. The underlying
pathology is particularly the development of atherosclerosis,
which may manifest itself by ED earlier given the smaller size
of penile arteries; hence, it is an independent risk factor of
coronary heart disease. The ability to predict within 2–5 years
the presence (yet subclinical) of atherosclerotic involvement of
coronary arteries enables us to escalate early modification of
risk factors of coronary heart disease or perform revasculari-
zation interventions. The dominant role in the treatment of
erectile dysfunction is played by PDE5 inhibitors showing, in
most cases, an excellent clinical effect and safety profile;
however, utmost caution should be exercised regarding
contraindications to their use including severe hypotension
and use of nitrates.
Conflict of interest
None.
Ethical statement
The research was conducted in compliance with the principles
of the Declaration of Helsinki.
Funding body
None.
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