screening for asymptomatic cad in diabetes

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WORLD BURDEN OF 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

http://www.idf.org/home/index.cfm?unode=B10FE172-4C41-49A0-A132-8A5B7565EE50



http://www.cvd.idf.org/

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.



STRESS THALLIUM

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

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