ACHIEVING BEST PRACTICE
SA JOURNAL OF DIABETES & VASCULAR DISEASE
76
VOLUME 7 NUMBER 2 • JUNE 2010
limited and obeys Bayesian theory, that is, it depends on the pre-
test probability of detecting CAD. Therefore false positive results
are common in patients who do not describe angina and have no
high-risk markers. In such patients confirmation should be sought
with myocardial perfusion imaging or stress echocardiography.
29
Stress echocardiography is especially appealing as impairment
of left ventricular diastolic and then systolic function occurs early in
the ischaemic cascade, before the development of ECG changes.
These can be observed as regional wall motion abnormalities on
echo. Stress echo is well recognised to provide greater diagnostic
accuracy than ETT in the general clinical population.
30
Furthermore
dobutamine stress echocardiography allows for the functional
assessment of patients unable to exercise. Stress echo has been
used effectively in studies to detect silent myocardial ischaemia.
17
Cardiac CT scanning allows the non-invasive visualisation of
the coronary anatomy. Furthermore, calcification severity predicts
the presence of significant anatomic CAD.
31
While associated
with a radiation dose it avoids the other potential complications
associated with percutaneous coronary angiography. It has been
demonstrated that the coronary artery calcium score can identify
high-risk asymptomatic individuals as havingmyocardial ischaemia.
32
In the UK cardiac CT scanning is less widely available than ETT or
stress echo. With wider access and further studies, it may emerge
as a valuable tool in the diagnosis of occult CAD.
Treatment
Risk factor modification
Silent ischaemia, like angina, is a marker of underlying CAD.
Therefore perhaps the most important strategy is aggressive risk
factor modification to stabilise and prevent the progression of
atherosclerosis. The MRFIT trial found that men with elevated
risk factors, who had an abnormal exercise test response, derived
substantial benefit from risk factor reduction.
18
The DIAD-2 study followed a cohort of type 2 diabetes
patients for three years. They showed that the prevalence of silent
myocardial ischaemia decreased over this time period. This was
attributed to the intensification of medical treatment in the form of
statins, aspirin and angiotensin-converting enzyme inhibitors over
that time.
33
In the non-diabetic population it is therefore of importance
to detect silent ischaemia because risk factor modification will
improve prognosis. However, diabetes has been recognised as
a cardiovascular disease risk equivalent. Most diabetic patients
therefore require intensive risk factor modification even in the
absence of silent ischaemia.
34,35
Coronary revascularisation
This begs the question whether the detection of silent ischaemia
in diabetic patients impacts upon their treatment? Unfortunately
even after risk factor modification, the cardiovascular mortality of
diabetic patients remains high: it was 1.54 per 100 person-years at
risk, in the treatment arm of the CARDS trial.
36
This high mortality will, in part, be due to silent, prognostically
important CAD (e.g. left main stem, proximal left anterior
descending or three-vessel disease). If this disease can be detected
and revascularised then the poor prognosis will improve.
37,38
This
represents a powerful argument in favour of investigating high-risk
diabetic patients for silent ischaemia.
In patients with non-prognostically important disease, data on
revascularisation are limited, although several small trials have
suggested a trend towards improved outcomes.
39-41
However,
extrapolation of the results of the courage trial,
42
in patients
with stable angina, would suggest that optimal medical therapy
is as effective as revascularisation in patients with non-prognostic
disease.
The evidence for coronary revascularisation is more clear in the
post-MI setting. The danami trial, which included patients with
symptomatic and asymptomatic ischaemia, compared medical
management with revascularisation in patients with inducible
ischaemia post-MI.
43
The primary end-point (mortality, re-infarction,
unstable angina) occurred less frequently in the invasive group at
one, two and four years of follow-up.
Anti-ischaemic therapy
Beta-blockers have been shown to reduce the adverse outcome
associated with silent ischaemia. This may be due to a reduction of
the ischaemic load and therefore of the adverse effects of recurrent
silent episodes. However, no other anti-anginal agents have shown
a similar effect. The ability of beta blockers to prevent arrhythmia
and cardiac remodelling may also be of importance.
The asist trial evaluated the effect of atenolol 100 mg versus
placebo in patients with silent ischaemia.
44
It confirmed a reduction
in the ischaemic burden on Holter monitoring, prolonged event-
free survival and increased time to first event. In the tibbs trial,
patients who had
>
50% suppression of silent ischaemia, with
bisoprolol, had an improved event-free survival at 1 year.
45
Deciding who to investigate
Given the high incidence of silent ischaemia in diabetic populations,
screening asymptomatic diabetic patients for CAD is an appealing
concept. However, no prospective trial has shown clinical benefit
of such a strategy; the prevalence of prognostically important
disease is unclear; and the financial implications of screening all
these patients are considerable. At present most national and
international guidelines do not recommend routine screening.
Cases are currently picked up on an opportunistic, individual basis.
Deciding when to investigate for silent myocardial ischaemia is
not straightforward. There are, however, several strong predictive
markers as to its presence. These can be used to identify patients
at high risk of silent ischaemia who would benefit from further
investigation. Guidelines from the American Diabetes Association
suggest that ECG changes and atypical cardiac symptoms are of
particular use.
46
We will address these first.
Breathlessness on exertion
Breathlessness on exertion involves a wide differential diagnosis.
However, it may signify angina equivalent and underlyingmyocardial
ischaemia. In this case, breathlessness is due to impaired ventricular
performance which occurs early in the ischaemic cascade (Fig. 1).
Diabetic patients describing breathlessness have been shown to
have a significantly higher likelihood of myocardial ischaemia and a
worse outcome than those who were completely asymptomatic or
suffered from angina.
47
Unfortunately breathlessness is a common symptom in the
diabetic population and often due to other causes such as respiratory
disease and weight gain. Often it will be multifactorial. Great care is
therefore required in trying to exclude other causes.
