© The Canadian Journal of Urology™; 21(Supplement 2); June 2014
men age 40-59 will have a low 10 year risk.
10
Lifetime
risk is not determined in the FRS. Incorporating
some assessment of lifetime risk has been proposed
as an added step to evaluate CVS risk in this young
middle-age population noted by Inman with ED to be
at particularly elevated CVS risk.
3
New data have emerged to justify a new version,
though controversial, to better target both risk and
lipid management therapies for the reduction of CVS
events in the adult population.
11
New guidelines
have attempted to address the shortcomings of older
risk models. ED guidelines such as Princeton III
12
have attempted to utilize evidence-based evaluation
to further stratify men for CVS risk following the
utilization of keen history taking and traditional risk
models to establish the presence of predominantly
vasculogenic ED and the volume of subclinical
atherosclerotic burden which are markers for
subsequent CVS events of MI and CVA in men.
13
Key questions in ED management
• Is a history of largely organic ED a harbinger for
future CVS risk? If so, does a timeframe or
“window of opportunity” exist to lower the risk
of future CVD events?
• Are there cost-effective, sensitive, and specific
metabolic or imaging tests that might indicate
increased CVS risk?
• Will these tests delineate treatment based
on identification of either obstructive CAD or
atherosclerotic burden and thereby lower future
CVS risk and improve erectile function?
The metabolic syndrome (MetS): a cluster
of findings increasing risk of type 2 DM and
CVD-the cardiometabolic nexus of ED
MetS is a complex disorder with high socioeconomic
cost that is considered a worldwide epidemic. MetS
is defined by a cluster of interconnected factors that
directly increase the risk of coronary heart disease
(CHD), other forms of atherosclerotic cardiovascular
disease (ASCVD), and type 2 DM.
14
Its main
components are dyslipidemia [elevated triglycerides
and apolipoprotein B (apoB)-containing lipoproteins
(small dense LDL subparticles), and low high density
lipoproteins (HDL)], hypertension, and deregulated
glucose homeostasis.
14
While abdominal obesity
and/or insulin resistance (IR) have gained increasing
attention as the core manifestations of the syndrome,
other abnormalities such as chronic proinflammatory
and prothrombotic states, non-alcoholic fatty liver
disease and sleep apnea have been added to the entity
of the syndrome, making its definition even more
complex.
15
Besides the many components and clinical
implications of MetS, there is still no universally
accepted pathogenic mechanism or clearly defined
diagnostic criteria. Furthermore, there is still debate as
to whether this entity represents a specific syndrome
or is a surrogate of combined risk factors that put the
individual at particular risk.
15
The most current definition incorporates the
International Diabetes Federation (IDF) and American
Heart Association/National Heart, Lung and Blood
Institute (AHA/NHLBI) definitions and requires a
patient tohaveany threeof the followingfiveconditions.
14
• Elevated waist circumference (ethnicity specific
values, e.g. European males > 94 cm [40 in] and
females > 80 cm)
• Triglycerides 1.7 mmol/L or greater 150 mg/dL
• HDL-chol below 1.03 mmol/L [< 40 mg/dL]
• BP > 135/85 mmHg
• Fasting glucose > 5.6 mmol/L [> 100 mg/dL]
EDhas been linked tomultiple selected aspects of the
metabolicsyndrome,includingtype2diabetesmellitus,
7,16
increased fasting blood glucose,
17,18
arteriosclerotic
disease manifestations,
19-21
hypertension,
7,17,22-24
and
obesity.
7,17,18
Moreover, Bal et al
18
noted that the risk
of ED increased in line with the number of factors of
the MetS exhibited by a patient. Several interrelated
mechanisms may explain the observed relationship
between the MetS and ED. One obvious mechanism
could be a low testosterone level, which has been shown
to be associatedwithmoderate and severe ED,
25
possibly
via a mechanism of diminished NO synthesis.
26
This
hypothesis was supported by a report that testosterone
treatment increases cavernosal expression of NO
synthetasemRNAin rats.
27
In thisway, hypogonadismas
amanifestation of theMetS could result in a diminished
NOsynthesis andsubsequent ED. Anothermechanismis
peripheral arterial insufficiencydue to an atherosclerotic
disease. The presence of arterial vasculogenic ED is
associatedwith ischemic heart disease inmen > 40 years
old in several studies.
28
Furthermore, men with ED are
twice as likely to have sustained amyocardial infarction
compared with men without ED, and the risk becomes
more pronounced with increasing age.
28
Increasing
alpha adrenergic activity has been linked to several
established aspects of the MetS, and is an attractive
potentialmechanismthat could explain the link between
theMetS and ED. Evidence supporting thismechanism
has come from a study demonstrating that men with
organic ED have significantly higher sympathetic
activity than thosewithout (p < 0.05).
29
Thismechanism
27
Erectile dysfunction in primary care: a focus on cardiometabolic risk evaluation and stratification for future
cardiovascular events
