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2/23/2015

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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


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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.


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+)


15


Important Age Interaction!!

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Does ED Provide a “Window of Opportunity” for

Detecting and Treating Otherwise Unheralded CVD

Risk?

February 23, 2015 16

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.

23

Miner et al. Am J Med. 2014;127:174-82.

ASSOCIATION OF SUBCLINICAL VASCULAR DISEASE WITH SELF-

REPORTED ERECTILE DYSFUNCTION: THE MESA STUDY

February 23, 2015 24

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

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