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February 23, 2015 1
Erectile Dysfunction: An Early Sign of Cardiovascular Disease
Recommendations for the Evaluation of CVD Risk in Patients with Vascular ED
Presented by: Michael J. Blaha MD MPH
Penile Anatomy
Vascular Causes of ED
ArterialStenosis
ImpairedVasodilation
AtherosclerosisImpairment of
endothelium-dependentrelaxations
Smooth muscleAtrophy and fibrosis
Impairedrelaxation
Hypertension
Hypercholesterolemia
Diabetes
Arterial insufficiency
Reduced inflow
Excessive outflow
Arteries
Corporo-venoocclusive disease
ImpairmentOf neurogenic
relaxations
TrabeculaeTrabeculae
Arteries
Adapted from: Saenz de Tejada I, et al. Erectile Dysfunction. Plymbridge Distributors; 2000;65-102
Functional ChangesStructural Changes
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Vascular ED: Early Marker of More Diffuse Vascular DiseaseVascular ED: Early Marker of More Diffuse Vascular Disease
Smaller penile arteries suffer obstruction from plaque burden earlier than the larger arteries
• Penile 1-2 mm• Coronary 3-4 mm• Carotid 5-7 mm• Iliofemoral 6-8 mm
• Penile 1-2 mm• Coronary 3-4 mm• Carotid 5-7 mm• Iliofemoral 6-8 mm
Jackson et al. J Sex Med. 2006;3:28-36.
ED may be silent to the patient and healthcare prov ider — BUT THE VASCULAR DISORDER LINK WITH ED IS NOT CLINICALLY SI LENT
Vascular ED: Early Marker of Endothelial Dysfunction
Arteriole
lumen
Endothelium
SmoothSmooth
musclemuscle
Erectile Dysfunction & Cardiometabolic
RiskDyslipidemia
HBP
Diabetes CAD
Dyslipidemia
PENIS
HBP
Diabetes CAD
PENIS
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Erectile Dysfunction and Subsequent Cardiovascular Disease
Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA. JAMA. 2005;294:2996-3002.
Erectile Dysfunction and Subsequent Cardiovascular Disease
Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA. JAMA. 2005;294:2996-3002.
Does ED Predict CVD in an Asymptomatic Male?
Study PopulationStudy Population
• 9457 men age 55+ in the Prostate Cancer Prevention Trial randomized to placebo
– 8063 (85%) men with no CVD at study entry• 3816 (47%) reported some level of ED
at study entry• 4247 (53%) reported no erectile
dysfunction at study entry
Thompson et al. JAMA. 2005;294:2996-3002.
Study ResultsStudy Results
• 2420/4247 (57%) of men with no ED at study entry reported incident ED after 5 years.
• This increased to 65% at 7 years.• Incident ED was statistically significantly
associated with subsequent angina, myocardial infarction, and stroke relative to men without reported ED after adjusting for potential confounders (HR 1.25 – 1.45).
• Risk ~ smoking or a family history of CHD
Thompson et al. JAMA. 2005;294:2996-3002.
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10Thompson et al. JAMA. 2005;294:2996-3002.
Study Results
Does ED Precedes CVD?Does ED Precedes CVD?Prostate Cancer Prevention Trial (PCPT): Placebo Gr oupProstate Cancer Prevention Trial (PCPT): Placebo Gr oup
Time to Any Cardiovascular Event From Initial Repor t of ED for those with Incident ED and No Previous Cardiovascul ar Event.
Per
cent
age
With
Car
diov
ascu
lar
Eve
nt
At risk, n = 2495; number of cardiovascular events, 255; 5-year estimate of cardiovascular events, 11% .
No. at Risk 2495 2096 1551 776
Time Since Initial Erectile Dysfunction, y
20
15
10
5
01 2 3 4 5 6 7
The longer patients have had ED, the higher the likelihood of CVD event.
Thompson et al. JAMA. 2005;294:2996-3002.
A Population-Based, Longitudinal Study of Erectile Dysfunction and Future Coronary Artery Disease
Inman B, St. Sauver J, Jacobson D, McGree M, Nehra A, Jacobsen S. Mayo Clinic Proceedings. 2009;84:108-13.
Are the Same Associations Seen in a Community-Based Sample?
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• 1,402 community-dwelling men, enrolled in an Olmsted County (Minnesota) substudy, with regular sexual partners without known CAD were screened biennially for presence of ED
• Occurred from January 1996 to December 2005, a period of 10 years
• Adjusted CAD Incidence was calculated after age stratification and adjustment for cofounders
Study Population
Inman B, et al. Mayo Clinic Proceedings. 2009;84:108-13.
Study ResultsStudy Results
• Prevalence of ED was 2%, 6%, 17% and 39% in men aged 40-49, 50-59, 60-69, and 70+ years respectively.
• CAD incidence per 1000 person-years for men without ED was 0.94 (age 40-49), 5.09 (age 50-59), 10.72 (age 60-69), and 23.3 (age 70+).
• For men with ED: incidence of CAD was 48.52(age 40-49), 27.15 (age 50-59), 23.97 (age 60-69), and 29.63 (age 70+)
Inman B, et al. Mayo Clinic Proceedings. 2009;84:108-13.
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Inman B, et al. Mayo Clinic Proceedings. 2009;84:108-13.
Important Age Interaction!!
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Does ED Provide a “Window of Opportunity” for
Detecting and Treating Otherwise Unheralded CVD
Risk?
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Focused on clearing a patients for sexual activity and ED treatment
Princeton I Guidelines
Initiate or resumeInitiate or resume
dysfunctiondysfunction
Initiate or resumeInitiate or resumesexual activitysexual activity
ororTxTx* for sexual * for sexual dysfunctiondysfunction
Sexual activitySexual activitydeferred untildeferred untilstabilization ofstabilization ofcardiac conditioncardiac condition
Sexual InquirySexual Inquiry
EvaluationEvaluationClinicalClinical
EvaluationEvaluation
Low RiskLow Risk Indeterminate RiskIndeterminate Risk High RiskHigh Risk
CardiovascularCardiovascular
restratificationrestratification
CardiovascularCardiovascularassessment andassessment andrestratificationrestratification
From DeBusk et al. Am J Cardiol. 2000;86:175-181.
The guidelines, updated in 2005, recommend that:
� All men who have a CV evaluation also be assessed for sexual function,
� All patients presenting with ED be assessed for CV risk factors
� Emphasize the importance of lifestyle changes, such as weight loss and exercise, for patients with ED and CVD
Princeton II Guidelines
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19
Princeton II Guidelines
Cardiometabolic Risk and Men’s Sexual Health(Princeton Consensus Conference III)
• Convened in November 2010• Demonstrated predictive value of vasculogenic ED
in assigning cardiovascular disease risk in men of all ages
• Developed approach for cardiovascular disease risk assessment in younger patients with no known cardiovascular disease
• Emphasis on men with ED who need additional, cost effective cardio-metabolic workup
Nehra A et al.
Princeton III Risk Assessment Algorithm
for ED with No Known CVD
Princeton III Consensus Panel, 2010.
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22
Miner et al. Am J Med. 2014;127:174-82.
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Miner et al. Am J Med. 2014;127:174-82.
ASSOCIATION OF SUBCLINICAL VASCULAR DISEASE WITH SELF-
REPORTED ERECTILE DYSFUNCTION: THE MESA STUDY
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Feldman DI, Blaha MJ. Manuscript in preparation.
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0%
10%
20%
30%
40%
50%
60%
70%
CA
C=
0
0 <
CA
C <
10
0
CA
C >
10
0
Q1
Q2
Q3
Q4
CP
=0
0 <
CP
< 2
CP
>2
AB
I <
0.9
0.9
< A
BI <
1.0
1.0
< A
BI <
1.4
AB
I >
1.4 Q1
Q2
Q3
Q4
Q1
Q2
Q3
Q4
Q1
Q2
Q3
Q4
Coronary Artery Calcium cIMT Carotid Plaque ABI Aortic Distensibility Distensibility Coefficient FMD
Pre
va
len
ce
ATHEROSCLEROSIS STIFFNESS & DYSFUNCTION
Coronary Artery Calcium Is Most Closely Associated with Erectile Dysfunction
1
1.5
2
2.5
3
Atherosclerosis Vascular Stiffness & Dysfunction
Unadjusted Model 1 Model 2 Model 3
Model 1: Age, race, SES; Model 2: Model 1 + smoking, diabetes, family history, systolic blood
pressure, LDL-C, HDL-C, lipid-lowering medications, anti-hypertensive medications,
triglycerides* and waist circumference; Model 3: Model 2 + beta-blockers, depression scale,
non-tricyclic antidepressants, tricyclic antidepressants, anti-psychotic medications.
*
*
*
*
*
* * p<0.05
ED is More Closely Associated with Atherosclerosis
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* Using the ACC/AHA 2013 10-Year-Risk Cardiovascula r Risk Calculator based on the ACC/AHA 2013 Pooled Cohort Equations.
Updated Algorithm for CVD Risk Assessment in Asymptomatic Men >40 with Vascular Erectile Dysfunc tion
Conclusions
• Vascular ED can be a warning sign for significant CVD Risk
• Work with your local Men’s Health specialist• All patients with vascular ED deserve further
risk assessment, usually with direct measurement of subclinical atherosclerosis
• Current best evidence suggests coronary artery calcium (CAC) best predicts ED, and best identifies risk in patients with vascular ED