Screening for asymptomatic cad in diabetes

DID YOU KNOW?
 Diabetes currently affects 246 million people worldwide and is
expected to affect 380 million by 2025.
 In 2007, the five countries with the largest numbers of people
with diabetes are India (40.9 million), China (39.8
million), the United States (19.2 million), Russia (9.6 million)
and Germany (7.4 million).
 By 2025, the largest increases in diabetes prevalence will take
place in developing countries.
Diabetes Atlas, third edition, International Diabetes Federation, 2007.
Diabetes and Cardiovascular Disease: Time to Act, International Diabetes Federation, 2001.
World Health Organization Diabetes Unit

CARDIOVASCULAR DISEASE (CVD) IN
INDIVIDUALS WITH DIABETES
 CVD is the major cause of morbidity, mortality for those with
diabetes
 Common conditions coexisting with type 2 diabetes
(e.g., hypertension, dyslipidemia) are clear risk factors for CVD
 Diabetes itself confers independent risk
 Benefits observed when individual cardiovascular risk factors are
controlled to prevent/slow CVD in people with diabetes
ADA. VI. Prevention, Management of Complications. Diabetes Care 2012;35(suppl 1):S28.

CARDIOVASCULAR DISEASE (CVD) IN
INDIVIDUALS WITH DIABETES
 Diabetes reflected by the four-fold greater incidence of CAD.
 Early detection of CAD in patients with diabetes may be of
paramount importance and could improve outcome.
 However, a complicating issue is the silent progression of CAD in
patients with diabetes. The disease is frequently already in an
advanced state when it becomes clinically manifest.
 In addition, recent studies have indicated that conventional
coronary risk factors are of limited value for detection of CAD in
asymptomatic type 2 diabetes patients.
 These observations have raised the question of whether or not
asymptomatic patients with diabetes should be screened for
CAD.
Report by A Joanne D Schuijf et al; Screening for Coronary Artery Disease in Asymptomatic Diabetic Patients; Cardiac Markers,
TOUCH BRIEFINGS 2007

TYPE 1 DIABETES AND CORONARY ARTERY
DISEASE
 The excess coronary artery calcification (CAC) in type 1
diabetes seen in studies from Denver and London.
 Major concern - Calcium reflects atherosclerosis or medial
wall calcification (i.e., Mockenberg‟s sclerosis) commonly
seen in type 1 diabetes.
 Overall, the risk of having any CAC appears to be increased
by 50%.
TREVOR J. ORCHARD et al; Type 1 Diabetes and Coronary Artery Disease; DIABETES CARE, VOLUME 29, NUMBER
11, NOVEMBER 2006

DISEASE
 Sex-specific analyses suggested - Nephropathy strong CAD risk
factor in men, whereas waist-to-hip ratio and hypertension
predominated in women.
 Mechanisms account for premature cardiac death in CAD
 Subclinical but Advanced coronary atherosclerosis,
 Abnormalities in Coronary vasomotor capacity,
 Changes in Systolic and Diastolic function, and
 Lastly, Life-threatening Arrhythmia
 HDL cholesterol inversely predicts CHD mortality in type 1
diabetes, as in the general population, HDL cholesterol levels are
generally 10 mg/dl higher in type 1 diabetes
 Probably reflecting enhanced lipoprotein lipase and reduced hepatic
lipase activity due to systemic insulin administration and altered HDL
metabolism.
TREVOR J. ORCHARD et al; Type 1 Diabetes and Coronary Artery Disease; DIABETES CARE, VOLUME 29, NUMBER
11, NOVEMBER 2006

DISEASE
 Longstanding (>5 years since diagnosis) type 2 DM regarded
as a MI equivalent
 Because the long-term cardiovascular mortality is similar in diabetic
patients without prior myocardial infarction and non-diabetic patients
with pre-existing myocardial infarction
 Three major studies of tight glycemic control in type 2 DM
produced conflicting results on its impact on macro-vascular
complications and
 One suggested that very tight control (hemoglobin A1c<6.0%)
may in fact be detrimental to those with pre-existing
cardiovascular disease and long duration of DM.
Jamshid Shirani & Vasken Dilsizian; Screening Asymptomatic Patients With Type 2 Diabetes Mellitus for Coronary
Artery Disease: Does It Improve Patient Outcome? Curr Cardiol Rep (2010) 12:140–146

RISK OF CAD EVENTS IN ASYMPTOMATIC
DIABETIC PATIENTS
 In diabetic patients without known CAD, large epidemiologic
studies have demonstrated a high incidence of myocardial
infarction (11% to 16%), death (8% to 15%), and need for
revascularization (41%) over follow-up periods ranging from 3
to 10 years.
 In the United Kingdom Prospective Diabetes Study, 12% of
subjects with newly diagnosed type 2 diabetes developed
CAD (ie, fatal or nonfatal myocardial infarction, or angina with
abnormal electrocardiogram [ECG] at rest or after treadmill
test) within 10 year.
Lawrence H. Young, Powell Jose, BS, and Deborah Chyun; Diagnosis of CAD in Patients with Diabetes: Who to
Evaluate; Current Diabetes Reports 2003, 3:19–27

SCREENING FOR ASYMPTOMATIC
MYOCARDIAL ISCHEMIA
 The current ADA (American Diabetic Association)
recommendations include a yearly ECG as part of
standard clinical practice to evaluate older patients
for the presence of CAD.
 ADA has suggested that physicians should consider
screening with specialized testing in diabetic
patients with more than two additional cardiac risk
factors
 Microalbuminuria, Vascular disease, or Cardiac
autonomic neuropathy.
 Treadmill exercise ECG is perhaps the least
expensive and most widely used screening
approach.
 In recent studies, the prevalence of myocardial
ischemia, as assessed through exercise ECG, in
asymptomatic diabetic patients has ranged widely
from 9% to 31%.

MYOCARDIAL ISCHEMIA
 Exercise ECG results are not interpretable in
patients with underlying LBBB, ventricular paced
rhythms, or left ventricular hypertrophy with
marked ST-Twave abnormalities.
 Myocardial perfusion imaging or
echocardiography, which yield important
physiologic information about the cardiac
response to stress.
 These techniques increase the sensitivity and
specificity of exercise testing, and are often
used along with pharmacologic stress
(eg, adenosine or dobutamine infusions) to
provide diagnostic information in patients who
are unable to exercise

MYOCARDIAL ISCHEMIA
 Myocardial perfusion imaging used in screening studies for
those patients who are unable to exercise or
 As a follow-up evaluation in those who have had a positive
exercise ECG rather than in the overall population with
diabetes.
 In one study of patients unable to exercise, and thus thallium
perfusion imaging was performed with dipyridamole, the
prevalence of myocardial perfusion abnormalities was 19%.
 Recent results from this study indicate that approximately 26%
of patients have abnormal stress technetium-sestamibi single
photon emission computed tomography (SPECT) imaging.

MYOCARDIAL ISCHEMIA
 In asymptomatic patients with diabetes, there have been a
number of studies that have examined the link between
baseline SMI and subsequent CHD events.
 The weight of evidence now indicates that SMI is related to
subsequent CHD events in „high-risk‟ asymptomatic patients
with diabetes, and therefore two clinical questions become
important.
 Firstly, what is the predictive value for a positive or negative test
for SMI in relation to subsequent CHD events?
 Secondly, what are the relative and absolute CHD risks
associated with SMI?
Martin K Rutter* and Richard W Nesto; The changing costs and benefits of screening for asymptomatic coronary heart disease in
patients with diabetes; NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM JANUARY 2007 VOL 3 NO 1

MYOCARDIAL ISCHEMIA
 These are difficult questions to answer because of the limited
available data, and variation in patient CHD risk, testing
methodology and duration of follow-up.
 Annualized event rates associated with positive and negativen
tests for SMI (Silent Myocardial Ischemia) vary from 2.6% to
35.0%, and from 0% to 9%, respectively; and CHD risk ratios
for SMI also show great variability.
 Given the large variability in these estimates it is evident that
more research is required.

WHICH SCREENING TEST?
 Because there are no large studies to assist the clinician with
the choice between stress echocardiography and myocardial
perfusion imaging, in clinical practice that decision should be
made based on the local expertise.

DIABETIC PATIENTS AT RISK FOR
ASYMPTOMATIC ISCHEMIA
 The prevalence of asymptomatic ischemia in patients
with diabetes depends greatly on the specific population
examined.
 Individuals with type 2 diabetes who may have a higher risk
for CAD because of their older age and multiple associated
cardiac risk factors.
 Type 1 diabetic patients are those with renal insufficiency who
are at very high risk for CAD

 Because widespread screening of diabetic patients for CAD is
not feasible, there is great interest in identifying patients who
are at high enough risk to warrant screening with specialized
cardiac testing.
 The clinical characteristics identified as predictors of abnormal
noninvasive screening tests and abnormal angiography in
asymptomatic diabetic patients include
 ST-T wave abnormalities at rest; macro- or microalbuminuria; male
gender, hypertension, insulin use; retinopathy; smoking; lipoprotein
abnormalities; age; peripheral vascular disease; and family history of
CAD

SILENT MYOCARDIAL ISCHEMIA AND
ANGIOGRAPHIC CHD
 Studies of the prevalence of angiographic CHD in
asymptomatic patients with diabetes show a wide
variation in prevalence and severity.
 Which can be explained by differences in patient selection
and testing methodology.
 Coronary angiography was recommended if any one of
the non invasive tests was positive for SMI.

FIGURE 1 VALUE OF NONINVASIVE TESTING FOR MYOCARDIAL ISCHEMIA IN
DETECTING ANGIOGRAPHIC CHD IN UNSELECTED ASYMPTOMATIC SUBJECTS
WITH DIABETES
Rutter MK and Nesto RW (2007) The changing costs and benefits of screening for asymptomatic coronary heart
disease in patients with diabetes
Nat Clin Pract Endocrinol Metab 3: 26–35 doi:10.1038/ncpendmet0352

 Autonomic neuropathy (AN) is relatively common in
diabetes, contribute to their lack of anginal symptoms.
 The relationship between AN and asymptomatic ischemia has
been examined in few studies to date,
 In one small study of unselected patients from a diabetes
clinic, asymptomatic ischemia was more frequently detected in those
with AN (38%) as compared to those without AN (5%).
 Milan Study, there was a trend toward AN being more prevalent in
diabetic men who had asymptomatic ischemia on exercise perfusion
imaging, although similar findings did not appear to be present in
diabetic women
 Thus, whether there is a clear association of AN neuropathy
with asymptomatic ischemia remains uncertain and requires
further evaluation.

LONG-TERM PROGNOSIS ASSOCIATED WITH
ASYMPTOMATIC MYOCARDIAL ISCHEMIA
 There is little information available to address the degree to
which inducible ischemia predicts CAD events in totally
asymptomatic patients with diabetes
 In a recent small series of asymptomatic patients with either
type 1 or type 2 diabetes,
 Those with perfusion imaging tended to have an increased incidence
of major cardiac events (eg, death, nonfatal myocardial infarction, or
revascularization) over 3 to 7 years of follow-up.
 Patients with both perfusion abnormalities and AN appeared
to be at highest risk.
 Further studies need to be done to confirm above associations
and to identify a patient population at substantial risk for CAD
events.

IMPLICATIONS FOR SCREENING
 There is ongoing controversy as to whether patients with
diabetes should be screened with cardiac testing for the
presence of asymptomatic CAD or silent ischemia.
 Proponents for screening highlight the relatively high
incidence of inducible ischemia in asymptomatic type 2
patients and propose that early detection will ensure the use
of therapies that may reduce the incidence of myocardial
infarction or cardiac death.
 However, once a diagnosis of CAD is established, both the
patient and health care provider have stronger motivation to
pursue intensive therapy, sometimes including β-blockers to
prevent ischemia.

IMPLICATIONS FOR SCREENING
 Critics of generalized screening programs counter with
concerns that screening tests are not entirely accurate
and have yet to conclusively identify those patients at
high risk for cardiovascular events.
 The argument has been made that screening may in
fact only place diabetic patients at increased risk by
prompting unnecessary angiography and
revascularization procedures.

CURRENT LIMITATIONS OF
SCREENING
Physical and psychological costs
 The high false-positive rate of existing non invasive tests is a
major concern, especially in low-risk patients, and is caused
by factors that include left ventricular hypertrophy, resting
electrocardiogram abnormalities and observer error.
 This high false-positive rate exposes patients unnecessarily to
the risks of angiography
 The incidence of important complications from coronary
angiography is between 0.5% and 1.8% in the general population

CURRENT LIMITATIONS OF
SCREENING
 The detrimental psychological effects - People given false-
positive results have increased anxiety levels that do not
rapidly return to normal after further testing confirms the
absence of disease.
 Another detrimental psychological effect of screening is the
„certificate of health‟ effect in which patients who screen
negative (the majority) for CHD may in fact be less likely to
adhere to healthy lifestyle behaviors

FINANCIAL AND RESOURCE IMPLICATIONS
 In developing countries Financial concerns are
important as far as output is concerned
 There are considerable resource implications and
financial costs of CHD screening.
 These have yet to be adequately assessed by any
study.

POTENTIAL BENEFITS OF EARLIER
DIAGNOSIS
 There have been two small studies suggesting prognostic
benefits from revascularization in asymptomatic patients with
diabetes found to have CHD through screening.
 Anti-ischemia therapy could also benefit these patients.
 Although there is no hard evidence in these patients, data from
studies in the general population make this an attractive
hypothesis.
 An early diagnosis of CHD could improve compliance and
outcome with lifestyle and medical therapy, and knowledge of the
presence of CHD might reduce the time to presentation to
hospital, in the event of an acute myocardial infarction.

POTENTIAL BENEFITS OF EARLIER
DIAGNOSIS
 It was shown that intensive blood sugar control in type 1 DM
can have long-lasting beneficial effects through “metabolic
memory” and that 10 years after the initiation of such therapy
cardiovascular complications can be reduced by 57%.
 Unfortunately, such information is presently less convincing for
type 2 DM despite the fact that it represents more than 90% of
all cases of diabetes.
Jamshid Shirani & Vasken Dilsizian; Screening Asymptomatic Patients With Type 2 Diabetes Mellitus for Coronary Artery Disease:
Does It Improve Patient Outcome? Curr Cardiol Rep (2010) 12:140–146

SCREENING DOES NOT
REDUCE CARDIAC EVENTS
 Screening for asymptomatic coronary artery disease in
patients with type 2 diabetes fails to significantly reduce future
cardiac events, according to the results of a new study [1].
 In light of the findings, the researchers conclude that routine
screening for inducible ischemia in asymptomatic patients with
diabetes mellitus should not be advocated.
 Because what you end up finding is relatively mild, and screening
did not make a difference.
 Also, the event rate we observed is very low, so the cost of
screening to prevent myocardial infarction would be very high.
It isn't cost-effective."
Young LH, Wackers FJ, Chyun DA, et al. Cardiac outcomes after screening for asymptomatic coronary
artery disease in patients with type 2 diabetes. JAMA 2009; 301: 1547-1555.

SCREENING DOES NOT
REDUCE CARDIAC EVENTS
 The DIAD trial first to prospectively address the issue of
systematic screening for inducible ischemia in an
unselected, unbiased, asymptomatic patient population with
type 2 diabetes mellitus.
 At five years, 70% and 80% of patients were receiving primary-
prevention care, and although we can't prove it, it is very likely
that this aggressive treatment had something to do with the very
low cardiac event rate observed in this study.
 The recently published Action to Control Cardiovascular Risk
in Diabetes (ACCORD) also reported low event rates, 1.4%
per year, which makes DIAD consistent with that trial.
Michael O'Riordan; Screening for Asymptomatic CAD in Diabetic Patients Does Not Reduce Cardiac Events;
http://www.medscape.com/viewarticle/591148

RECOMMENDATIONS:
CORONARY HEART DISEASE SCREENING
Acording to ADA (American Diabetes Association)
…
 Screening for CAD is reviewed in a recently updated
consensus statement
 However, recent studies concluded that using this approach
fails to identify which patients with type 2 diabetes will have
silent ischemia on screening tests
 Recommendations:
 In asymptomatic patients, routine screening for CAD is
not recommended, as it does not improve outcomes as
long as CVD risk factors are treated (A)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2012;35(suppl 1):S32.

CONCLUSION
 Over the past 20 years, the greatest advance in CHD therapy in
diabetes has been in disease prevention and not in screening.
 Recent research suggests the possibility that there are significant
numbers of high-risk asymptomatic patients with diabetes and
undiagnosed CHD who could in fact benefit from anti-ischemia
therapy and revascularization.
 However, with the recent advances in medical therapy, and the
uncertain benefits of screening, the AHA has strongly
discouraged this practice, except in limited clinical situations,
such as before major surgery

Screening for asymptomatic cad in diabetes

Screening for asymptomatic cad in diabetes

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Screening for asymptomatic cad in diabetes