© The Canadian Journal of Urology™; 21(Supplement 2); June 2014
their relative costs and availabilities. Although most
of these markers have not undergone rigorous enough
study to achieve guideline endorsement, prognostic
markers represent a rapidly growing area of clinical
research.
Vlachopoulos et al
64
investigated arterial prognostic
markers in ED patients. The study employed carotid-
femoral pulse wave velocity (PWV), a measure
of aortic stiffness, and CIMT. Both indices were
significantly increased inmenwith ED versus without,
suggesting an increased CVS risk inmenwith ED. The
European Society of Cardiology/European Society of
Hypertension guidelines recommends PWV for the
evaluation of the hypertensive patient.
65
Recent data
show an independent predictive ability of PWV for
future CVD events specifically in ED patients.
66
Pulse
pressure, a crude index of aortic stiffness, was also
found to be predictive of CVD events in ED patients.
66
Prognostic markers that can be evaluated from
routine blood sampling are particularly useful, and
several candidates have been evaluated in men with
ED. Total testosterone (TT) is a relatively low cost
option, and a meta-analysis of seven population-
based studies concluded that there was a (borderline-
significant) 25% increased risk in CVD mortality
associated with a 2.18 standard deviation decrease in
serumtestosterone. The authors highlighted significant
between-study heterogeneity and concluded that low
testosterone is likely to be a marker of poor general
health.
67
Among patients with ED, Corona et al
reported that TT levels < 8 nmol/L (230 ng/dL) were
associated with a significant increase in fatal major
adverse cardiovascular events versus those with
levels ≥ 8 nmol/L.
68
This finding was supported by a
recent analysis of data from the European Male Aging
Study showing that TT < 8 nmol/L (230 ng/dL) and
sexual symptoms were independently and additively
associatedwith increased all-cause and CVDmortality
in men between 40 and 79 years of age.
69
Although an
observational cohort study of male US veterans with
low TT levels (≤ 250 ng/dL) showed that testosterone
treatment was associated with decreased mortality
compared with no testosterone treatment,
70
it cannot
be concluded that testosterone treatment reduced
mortality.
71
In agreement with the British Society of
Sexual Medicine,
72
Third International Consultation on
Sexual Medicine,
73
and Princeton III Consensus,
11
we
recommend that TT levels be measured as a potential
cause and prognosticator of ED, particularly in those
for whom phosphodiesterase type 5 inhibitors have
failed. Although there are no generally accepted
lower limits of normal TT, there is general agreement
that TT > 350 ng/dL (12 nmol/L) does not usually
require substitution and, based on data from young
hypogonadal men, those with TT < 230 ng/dL
(8 nmol/L) usually benefit from testosterone treatment.
A 3 to 6 month trial of testosterone therapy should be
considered for symptomatic patients with TT 230 ng/
dL-350 ng/dL (8 nmol/L-12 nmol/L).
74
Testosterone
replacement improves sexual desire
75
and may
improve and erectile function
76
and quality-of-life
77
but requires careful monitoring.
Waist circumference (intra-abdominal adiposity)
(IAA) inmenwithEDdrives the progression ofmultiple
risk factors directly, through the secretion of excess free
fatty acids and inflammatory adipokines, anddecreased
secretion of adiponectin. The important contributions
of IAA to dyslipidemia and insulin resistance provide
an indirect, though clinically important, link to the
genesis and progression of atherosclerosis andCVD.
78-80
Presence of excess IAA is an important determinant of
cardiometabolic risk. IAA is associated with insulin
resistance, hyperglycemia, dyslipidemia, hypertension,
and prothrombotic/proinflammatory states. Excess
IAA typically is accompanied by elevated levels of
C-reactive protein and free fatty acids (FFAs), as well
as decreased levels of adiponectin. Abdominal obesity
has been shown to be associatedwith the inflammation
cascade, with adipose tissue expressing a number of
inflammatory cytokines. Inflammation is nowbelieved
to play a role in the development of atherosclerosis and
type 2 DM. Elevated levels of CRP are considered to be
predictive of CVD and insulin resistance.
80,81
These components help to explain why excess
abdominal adiposity is considered to be a great threat
to CVS and metabolic health. Abdominal obesity is
associated with multiple cardiometabolic risk factors,
including dyslipidemia,
82
elevated blood glucose,
83
and
inflammation
84
– all factors leading to the development
of CVD and DM in male ED patients. DM is, after age,
the greatest risk factor for ED.
2
Patients with DMwere
three times more likely to develop ED than those who
did not have DM.
84,85
The prevalence for ED in these
patients was as high as 75%.
86-88
The Cologne Male
Survey noted a 4-fold increase in ED in men with DM
as compared to the general population.
89
In the Health
Professionals Follow-up Study, which involved greater
than 30,000 subjects, Bacon et al
90
found duration of
DM strongly associatedwith incidence of ED. Rhoden
et al
91
found higher glycosolated hemoglobin levels in
patients with DM to be significantly associated with
more severe ED (p < 0.05). The risk of ED in men with
DM is also significantly associated with other diabetic
complications such as diabetic neuropathy (p < 0.05).
92
Adipocytes generate inflammatory cytokines, and
patients with obesity and T2DM tend to have a higher
31
Erectile dysfunction in primary care: a focus on cardiometabolic risk evaluation and stratification for future
cardiovascular events
