© The Canadian Journal of Urology™; 21(Supplement 2); June 2014
TABLE 2.
Summary of evidence supporting emerging prognostic markers of cardiovascular disease in men
with erectile dysfunction
13
Biomarkers
LOE
a
: association LOE
a
: CVD Availability
Cost
With CVD
Prognostic
Prevalence in ED Value in ED
CIMT
81
2b
NE
Somewhat limited
Medium
CACS
60,82
2b
NE
Limited
High
ABI
22
2b
NE
High
Low
Testosterone
67,68
NE
2c
High
Low
Aortic stiffness (ie, PWV)
64
NE
2c
Somewhat limited
Medium
Albuminuria
7
NE
2c
High
Low
a
per Center for Evidence-Based Medicine (
); 2b = exploratory cohort study with
good reference standards; 2c = outcomes research
ABI = ankle-brachial index; CACS = coronary artery calcium scoring; CIMT = carotid intima-media thickness;
CVD = cardiovascular disease; ED = erectile dysfunction; LOE = level of evidence; NE = no evidence; PWV = pulse-wave velocity
Ruijter et al
58
performed a meta-analysis of 14 studies
(mean patient age, 58 years [range, 35-75]) that showed
little improvement in 10 year risk prediction of first-
time myocardial infarction or stroke when common
CIMT measurements were added to the FRS. The
incorporation of CIMT into CVS risk assessment is
further complicated by the fact that thresholds for
abnormal CIMT must be adjusted for age, sex, and
race and are operator dependent.
59
Ankle brachial index (ABI)
CVD has been identified in men with established ED
by using various measures of general atherosclerotic
burden, which are also considered surrogatemarkers of
CVD. For example, ABI, the ratio of blood pressure in
the dorsalis pedis artery to that in the brachial artery, is
widely used to detect PAD. TheACCF/AHAconsiders
measurement of ABI to be reasonable for CVS risk
assessment in asymptomatic adults at intermediate
risk.
53
In a study evaluating the relationship between
ED and peripheral arterial disease (PAD), Polonsky et
al showed that ABI successfully identified PAD inmen
with ED and suggested that menwith EDundergoABI
examination.
60
ACCF/AHA guidelines state that ABI
< 0.9 indicates the presence of PAD.
53
Coronary artery calcium scoring (CACS)
CACS is another measure that has been prospectively
validated as a predictor of CVD,
61
and for which
the literature provides limited support in the ED
population. Similar to ABI and CIMT, the ACCF/
AHA considers CACS reasonable for CVS risk
assessment in intermediate risk adults.
53
Jackson
and Padley performed maximal treadmill EST and
CACS in 20 men aged 39 to 69 years with ED and
no cardiac symptoms.
62
CACS were > 50 in 11 men,
all of whom had angiographic CAD on coronary
computed tomography, and 9 of whom had normal
ESTs.
62
This study suggests that ED is a predictor of
subclinical, non–flow-limiting CAD not detectable by
EST, and that methods such as CACS and coronary
computed tomography angiography may help detect
CAD in patients with normal EST. More recently,
in a comparison of the ability of six risk markers
(CACS, CIMT, ABI, brachial flow-mediated dilation,
high-sensitivity C-reactive protein [hsCRP], and
family history of coronary heart disease) to improve
prediction of incident coronary heart disease/
CVD in FRS intermediate risk patients (10 year
risk, > 5% and < 20%) enrolled in the Multi-Ethnic
Study of Atherosclerosis, CACS provided superior
improvements in risk estimation versus the other
risk markers.
63
Noninvasive CVS evaluation may
include other emerging prognostic markers, which are
discussed in the next section.
Role of additional emerging prognostic
markers inpredictingCVS risk inmenwithED
Although we recommend EST, CIMT, ABI, and/
or CACS for noninvasive evaluation of subclinical
CVD in intermediate risk patients, additional
emerging prognosticmarkers may providemeaningful
information pertinent to CVS risk in some patients.
Table 2 summarizes evidence supporting thesemarkers
for assessment of CVS risk inmen with ED, along with
30
Miner ET AL.
