ED - non solo cuore

DALLA DISFUNZIONE ERETTILE (DE) ALL’
INFARTO MIOCARDICO (IMA)
Dr. Maria Grazia Baldin
Udine 10 maggio 2014
1
DEFINIZIONE
Disfunzione Erettile
Incapacità a raggiungere o a mantenere
un'erezione idonea per una attività sessuale
soddisfacente.
Il National Institutes of Health (NIH) Consensus Development Conference on impotenza
(7-09 dicembre 1992)
MECCANISMO ANATOMICO DELL’EREZIONE PENINEA
Dilatation arterioles&arteries
expanding of sinusoids
compression of subtunical
venular plexuses
Emissary veins enclosed
increasing of intracavernous
pressure to raise the penis
Neuroanatomy of penile erection
 Supraspinal pathways
[ hypothalamus, limbic system and cerebral cortex]
dopaminergic & adrenergic recepters
promotes sexual
drive
serotonin recepters
inhibits sexual
drive
Neuroanatomy of penile erection
 Peripheral pathways
Sympa, - NE release
Parasym, + NO & Ach release
Somatic, +Ach release
 autonomic [ C. Cavenosa & C. Spongiosum]
 somatic [ Glans Penis & C. Spongiosum]
LA BIOLOGIA DELL’EREZIONE PENINEA
E 'stato stimato che la prevalenza mondiale della DE
raddoppierà da 152 milioni di uomini nel 1995 a 322
milioni di uomini nel 2025
The Massachusetts Male Aging Study
J Urol. 1994;151
THE MULTIFACTORIAL CAUSES OF ED.
Obesity
Modif.
Modif.
Regulatory Functions of the Endothelium
Normal
Dysfunction
Vasodilation
NO, PGI2, EDHF,
BK, C-NP
Vasoconstriction
ROS, ET-1, TxA2,
A-II, PGH2
Thrombolysis
tPA, Protein C, TF-I, vWF
Thrombosis
PAI-1, TF-α, Tx-A2
Platelet Disaggregation
Adhesion Molecules
NO, PGI2
CAMs, P,E Selectins
Antiproliferation
Growth Factors
NO, PGI2, TGF-, Hep
ET-1, A-II, PDGF, ILGF, ILs
Lipolysis
LPL
Inflammation
ROS,
NF-B
M.Y.A.Mawla
18
Vogel R
Risk Factors for Development
of Endothelium & Erectile
Dysfunction
 Diabetes Mellitus (DM)
 Insulin Resistance Syndrome.
 Cigarette Smoking
 Hypertension
 Atherosclerosis & Hyperlipidemia
 Obesity
Prevalence and independent risk factors for ED in Spain J Urol.2001;166
Epidemiology of ED Int. J Impot Res. 2000;12
Recommendation 1
 A significant proportion of men with erectile
dysfunction (ED) exhibit early signs of
coronary artery disease (CAD), and this group
may develop more severe CAD than men
without ED
 Independent C V D risk factor
 (Level 1, Grade A).
The Princeton III Consensus recommendations for the management of erectile dysfunction
and cardiovascular disease Mayo Clin Proc. 2012 Aug;87(8):766-78.
ED prevalence in CAD patients with 1-VD (N=27, full diamonds) or 2,3-VD (N=68, empty
circles) and controls (N=95, full triangles) according to three age decades.
Montorsi P et al. Eur Heart J 2006;27:2632-2639
© The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail:
[email protected]
ED Predicts coronary events
1400 men 40-75, with no known CAD 10yr follow up
Inman et al Mayo Clin Pr 2009;84:108-113
Age Group
ED at baseline
No baseline ED
40-49
48.52 (1.23-269.26)
0.94 (0.02-5.21)
50-59
27.15 (7.40-69.56)
5.09 (3.38-7.38)
60-69
23.97 (11.49-44.10)
10.72 (7.62-14.66)
70+
29.63 (19.37-43.75)
23.30 (17.18-30.89)
CAD events per 1000 pt years
with CI interval
ED as a Predictor for Subsequent
CVD Events: a Linked Data Study
 Retrospective 10-15 year study
 1660 men with ED
 CVD events doubled in men with ED (RR2.2)
 12.3% in 5 years, 37.3% in 10 years, 76% in 15
years
 7 fold increase in men < 40 years of age
(P<0.0001)
Chew et al JSM 2010;7:192-202
Recommendation 2
 The time interval among the onset of ED
symptoms and the occurrence of CAD
symptoms and cardiovascular events is
estimated at 2–3 years and 3–5 years
 This interval allows for risk factor reduction
 (Level 2, Grade B).
The Princeton III Consensus recommendations for the management of erectile dysfunction
and cardiovascular disease Mayo Clin Proc. 2012 Aug;87(8):766-78.
Time interval between ED onset and CAD

In 67% of the pts, symptoms of ED had started
before the symptoms of CAD (mean 39 months) –
retrospective assessment
Montorsi F, et al. Eur Urol 2003
in men with CAD, the prevalence of ED is as
high as 75%
Recommendation 3
 ED is associated with increased all-cause
mortality primarily due to increased
cardiovascular mortality
 (Level 1, Grade A).
The Princeton III Consensus recommendations for the management of erectile dysfunction
and cardiovascular disease Mayo Clin Proc. 2012 Aug;87(8):766-78.
ED predicts CVD events in high risk
patients receiving Telmisartan, Ramipril
or both-ontarget/trascend 1,549 patients with CVD
 ED at baseline, 2 years, finish
 ED predicted all cause death HR 1.84
 CVD death
 MI
 Composite
HR 1.93 (p=0.005)
HR 2.02 (p=0.16)
HR 1.42 (p=0.029)
 “ED is a potent predictor of all cause death and
the composite of CVD death, MI, stroke and
heart failure in men with CVD”
Bohm Circulation 2010;121:1439-46
Figure 2. Kaplan-Meier curves for all-cause death (A), primary outcome (B), cardiovascular
death (C),
myocardial
infarction Predicts
(D), stroke Cardiovascular
(E), and chronic heart
failurein(F)
by ED (including
Erectile
Dysfunction
Events
High-Risk
mild to moderate,
moderate,
and severeTelmisartan,
ED categories Ramipril,
by IIEF scores)
or no ED (no or mild
Patients
Receiving
or Both
ED categories) at baseline.
Böhm M et al. Circulation. 2010;121:1439-1446
Relative risk of grouped CVD admissions and all-cause mortality since baseline, according to severity of
erectile dysfunction at baseline.
Banks E, Joshy G, Abhayaratna WP, Kritharides L, et al. (2013) Erectile Dysfunction Severity as a Risk Marker for Cardiovascular Disease
Hospitalisation and All-Cause Mortality: A Prospective Cohort Study. PLoS Med 10(1): e1001372. doi:10.1371/journal.pmed.1001372
http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001372
Clinical perspective
“...erectile function is a predictor of cardiovascular
morbidity and mortality. These results remained
after adjustment for possible confounders. Thus
ED represents an early symptom of endothelial
dysfunction and atherosclerosis and patients
with ED are at particularly high cardiovascular
risk. The identification of these patients with ED
offers an opportunity for early risk-adjusted
treatment with the goal of further reducing
cardiovascular events”
Circulation 2010;121:1446
Erectile Dysfunction – Today’s concept
Penis is the barometer
of Endothelial and Cardiometabolic Health
Erectile Dysfunction is a
marker of Cardiovascular Risk
ED = ED
Recommendation 4
 All men with ED should undergo a thorough medical
assessment, including testosterone, fasting lipids, fasting
glucose and blood pressure measurement.
 Following assessment, patients should be stratified according
to the risk of future cardiovascular events.
 Those at high risk of cardiovascular disease should be
evaluated by stress testing with selective use of computed
tomography (CT) or coronary angiography (Level 1, Grade A).
The Princeton III Consensus recommendations for the management of erectile dysfunction
and cardiovascular disease Mayo Clin Proc. 2012 Aug;87(8):766-78.
MANAGEMENT OF MAN WITH ED AND NO KNOWN CVD
Sexual Enquiry of All
Men
VASCULOGENIC E.D.
(No known CVD)*
Essential Checks:
Age, BP, glucose, lipids,
testosterone, smoking
Additional Checks:
BMI, waist
circumference,
exercise, alcohol, diet,
family history
Framingham Risk†
Low (<10%)
Intermediate (10-20%)
High (>20%)
Lifestyle Advice
Lifestyle advice,
medication and noninvasive risk evaluation
(e.g. stress testing)
Lifestyle advice,
medication, and
cardiologist
*Determine ED severity based on International Index of Erectile Function (IIEF): mild 17-21; mild to moderate 12-16; moderate 8-11; severe 1-7 Consider
cardiac evaluation if severe irrespective of Framingham score.
†Incorporate age, gender, total cholesterol, HDL cholesterol, smoking, systolic BP, BP therapy (see appendix sample
calculation)
The Princeton III Consensus recommendations for the management of erectile dysfunction
and cardiovascular disease Mayo Clin Proc. 2012 Aug;87(8):766-78.
European Heart Journal (2012) 33, 1635–1701
doi:10.1093/eurheartj/ehs092
TAKE HOME MESSAGE
ED e CVD due differenti manifestazioni
della stessa malattia sistemica. Compartono
gli stessi predittori di rischio indipendenti.
ED: generalmente precede l’esordio CVD (25 anni)
ED: marker precoce di malattia
cardiovascolare sintomatica.
Team di collaborazione multidisciplinare
Take Home Message
Early Death
Early
Detection
Endothelial
Dysfunction
E.D.
EDucation
Erectile
Dysfunction

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