Diabetes and Occult Coronary Diabetes and Occult Coronary Artery DiseaseArtery Disease

Mun K. Hong, MD, FACC, FSCAIMun K. Hong, MD, FACC, FSCAIDirector, Cardiac Catheterization Laboratory & Director, Cardiac Catheterization Laboratory &

Interventional CardiologyInterventional CardiologySt. LukeSt. Luke’’ss--Roosevelt Hospital CenterRoosevelt Hospital Center

New York, New YorkNew York, New York

Severe 3Severe 3--vessel CAD in a Diabetic Patient and vessel CAD in a Diabetic Patient and DyspneaDyspnea attributed to COPDattributed to COPD

Diabetes and CAD:Diabetes and CAD:A Terrible CombinationA Terrible Combination

Frequently silent ischemia (Diabetes Care Frequently silent ischemia (Diabetes Care 2004;27:19542004;27:1954--61)61)

Atypical symptoms = Atypical symptoms = dyspneadyspnea, fatigue, or , fatigue, or ““GIGI””symptoms rather than typical angina (Ann Intern Med symptoms rather than typical angina (Ann Intern Med 1988;108:1701988;108:170--175)175)

Initial manifestation could be multiInitial manifestation could be multi--vessel CAD or vessel CAD or ““endend--stagestage”” (Am J (Am J CardiolCardiol 2000;86:8972000;86:897--902)902)

Diabetes and CAD:Diabetes and CAD:A Terrible CombinationA Terrible Combination

Poor coronary collateral development (Circulation Poor coronary collateral development (Circulation 1999;99:22391999;99:2239--2242)2242)

High risk with both angioplasty and CABG versus High risk with both angioplasty and CABG versus nonnon--diabetic patients (Am J diabetic patients (Am J CardiolCardiol 1994;74:3341994;74:334--339; 339; Circulation 1996;94:1818Circulation 1996;94:1818--1825)1825)

Likely Explanation:Likely Explanation:

We are NOT We are NOT detecting the occult detecting the occult

CAD in diabetic CAD in diabetic patients!patients!

Prolonged Latent Period of Prolonged Latent Period of Undiagnosed DMUndiagnosed DM

Prevalence of retinopathy used to estimate the latent Prevalence of retinopathy used to estimate the latent period of undiagnosed DM and its implication.period of undiagnosed DM and its implication.

““Onset of NIDDM occurs at least 4Onset of NIDDM occurs at least 4--7 years before 7 years before clinical diagnosis.clinical diagnosis.””

““Because other data indicate that diabetes may be Because other data indicate that diabetes may be present for 5 years before retinopathy becomes present for 5 years before retinopathy becomes evident, onset of NIDDM may occur evident, onset of NIDDM may occur 99--12 years12 years before before its clinical diagnosis.its clinical diagnosis.””

Harris MI, et al. Diabetes Care 1992;15:815Harris MI, et al. Diabetes Care 1992;15:815--819819

Adverse Effects of HyperglycemiaAdverse Effects of Hyperglycemia

InflammationInflammation

Endothelial dysfunctionEndothelial dysfunction

Activated platelet activityActivated platelet activity

Deranged nitric oxide metabolismDeranged nitric oxide metabolism

Am J Am J CardiolCardiol 2006;98:8422006;98:842--856856

DibeticsDibetics have diffuse atherosclerosis have diffuse atherosclerosis with large plaque burden.with large plaque burden.

IVUS evaluation of plaque burden in REVERSAL StudyIVUS evaluation of plaque burden in REVERSAL Study

In multivariate analysis, diabetes, male gender, and a history oIn multivariate analysis, diabetes, male gender, and a history of f a prior interventional procedure were strong predictors of a prior interventional procedure were strong predictors of increased increased atheromaatheroma volume.volume.

Although diabetics had increased disease burden by IVUS Although diabetics had increased disease burden by IVUS measures compared with nonmeasures compared with non--diabetics, angiographic diabetics, angiographic stenosisstenosisseverity was not different.severity was not different.

Most likely a major cause of difficulty with detection and Most likely a major cause of difficulty with detection and revascularizationrevascularization

JACC 2006;47:1967JACC 2006;47:1967--7575

Relevant QuestionsRelevant Questions

Will aggressive screening identify those Will aggressive screening identify those diabetic patients with occult CAD?diabetic patients with occult CAD?

WILL IDENTIFICATION AND WILL IDENTIFICATION AND REVASCULARIZATION OF DIABETIC REVASCULARIZATION OF DIABETIC PATIENTS WITH OCCULT CAD IMPROVE PATIENTS WITH OCCULT CAD IMPROVE SURVIVAL?SURVIVAL?

DIAD StudyDIAD Study

DDetection of etection of IIschemia in schemia in AAsymptomatic symptomatic DDiabeticsiabetics

1,123 patients with type 2 diabetes, aged 501,123 patients with type 2 diabetes, aged 50--75 years, with no 75 years, with no known or suspected coronary artery diseaseknown or suspected coronary artery disease

Randomly assigned to either stress testing and 5Randomly assigned to either stress testing and 5--year clinical year clinical followfollow--up or to followup or to follow--up onlyup only

CAD/silent ischemia assessed by adenosine technitiumCAD/silent ischemia assessed by adenosine technitium--99m 99m sestamibisestamibi singlesingle--photon emissionphoton emission--computed tomography computed tomography myocardial perfusion imagingmyocardial perfusion imaging

Diabetes Care 2004;27:1954Diabetes Care 2004;27:1954--19611961

DIAD Study ResultsDIAD Study Results60% had two or more ADA screening risk factors.60% had two or more ADA screening risk factors.

Only 50% were capable of performing lowOnly 50% were capable of performing low--level exercise in level exercise in conjunction with adenosine infusion.conjunction with adenosine infusion.

22% had silent ischemia with 6% having moderate to large 22% had silent ischemia with 6% having moderate to large perfusion defectperfusion defect..

In multivariate logistic regression, the lowest quartile of hearIn multivariate logistic regression, the lowest quartile of heart t rate ratios during the rate ratios during the ValsalvaValsalva maneuver (cardiac autonomic maneuver (cardiac autonomic dysfunction), male sex, and diabetes duration were independent dysfunction), male sex, and diabetes duration were independent predictors of moderate or large perfusion abnormalities.predictors of moderate or large perfusion abnormalities.

Diabetes Care 2004;27:1954Diabetes Care 2004;27:1954--19611961

CAVEAT: CAVEAT: ““Balanced IschemiaBalanced Ischemia””

Prevalence of CAD Prevalence of CAD ((60%60% in both groups!)in both groups!)

010

20

30

4050

60

70

80

Group A Group B

1-vessel2-vessel3-vessel

((≥≥2 risk factors)2 risk factors) ((≤≤1 risk factor)1 risk factor)

JACC 2006;47:65JACC 2006;47:65--7171

Prevalence of Prevalence of ““DiffuseDiffuse”” CADCAD

0

10

20

30

40

50

60

Group A Group B

diffuse diseaseocclusion

((≥≥2 risk factors)2 risk factors) ((≤≤1 risk factor)1 risk factor)

54.9%54.9%

31.2%31.2%

18.8%18.8% 3.5%3.5%

JACC 2006;47:65JACC 2006;47:65--7171

Complete RevascularizationComplete Revascularization

0

20

40

60

80

100

Group A Group B

NSRRevasc

((≥≥2 risk factors)2 risk factors) ((≤≤1 risk factor)1 risk factor)

41.6%41.6%

73.3%73.3%

11%11%

97.2%97.2%

NSR = Anatomy not suitable for revascularizationNSR = Anatomy not suitable for revascularizationJACC 2006;47:65JACC 2006;47:65--7171

Resolved IssueResolved Issue

Will aggressive screening identify those diabetic Will aggressive screening identify those diabetic patients with occult CAD? patients with occult CAD? YES!YES!The earlier the screening, the greater the The earlier the screening, the greater the likelihood for detection of less complex likelihood for detection of less complex coronary artery disease more amenable to coronary artery disease more amenable to revascularization.revascularization.

Improved Survival in Asymptomatic Diabetic Patients Improved Survival in Asymptomatic Diabetic Patients with Highwith High--Risk SPECT Imaging Treated with CABGRisk SPECT Imaging Treated with CABG

826 asymptomatic diabetics without known CAD, who had 826 asymptomatic diabetics without known CAD, who had abnormal SPECTabnormal SPECT

Revascularization was independently associated with improved Revascularization was independently associated with improved survival in patients with highsurvival in patients with high--risk scans, with 5risk scans, with 5--year survival year survival after CABG of 85%, after PCI of 72%, and with medical after CABG of 85%, after PCI of 72%, and with medical therapy of 67% (p=0.02).therapy of 67% (p=0.02).

There was no survival advantage by treatment for patients with There was no survival advantage by treatment for patients with less severe SPECT abnormalities.less severe SPECT abnormalities.

Circulation 2005;112(Suppl I):ICirculation 2005;112(Suppl I):I--311311--II--316316

Candidates for SPECT ScreeningCandidates for SPECT Screening

Among 1,427 asymptomatic diabetic patients without Among 1,427 asymptomatic diabetic patients without knonwknonwCAD, an abnormal stress SPECT imaging scan was present in CAD, an abnormal stress SPECT imaging scan was present in 58% and a high58% and a high--risk scan in 18%.risk scan in 18%.

Multivariate analysis demonstrated Q waves on EKG and Multivariate analysis demonstrated Q waves on EKG and peripheral arterial disease as the most significant predictors operipheral arterial disease as the most significant predictors of f highhigh--risk SPECT imaging result.risk SPECT imaging result.

Annual mortality rates by SPECT imaging scans were highAnnual mortality rates by SPECT imaging scans were high--risk risk 5.9%, intermediate5.9%, intermediate--risk 5%, and lowrisk 5%, and low--risk 3.6% (p<0.001).risk 3.6% (p<0.001).

JACC 2005;45:43JACC 2005;45:43--99

Importance of CoronaryImportance of Coronary Artery Calcification Artery Calcification and Plasma and Plasma OsteoprotegerinOsteoprotegerin LevelLevel

Plasma Plasma OsteoprotegerinOsteoprotegerin LevelsLevels

In asymptomatic patients with NIDDM, only In asymptomatic patients with NIDDM, only osteoprotegerinosteoprotegerin(rather than high sensitivity(rather than high sensitivity--CRP or interleukinCRP or interleukin--6 levels), 6 levels), predicted both predicted both subclinicalsubclinical coronary artery disease and shortcoronary artery disease and short--term cardiovascular events.term cardiovascular events.

Could this biomarker be a simple test to identify highCould this biomarker be a simple test to identify high--risk type risk type 2 diabetic patients with asymptomatic CAD?2 diabetic patients with asymptomatic CAD?

JACC 2006;47:1850JACC 2006;47:1850--77

JACC 2006;47:1850JACC 2006;47:1850--18571857

MultiMulti--Slice CT for ScreeningSlice CT for Screening

Important QuestionsImportant Questions

Will aggressive screening identify those diabetic Will aggressive screening identify those diabetic patients with occult CAD? patients with occult CAD? YES!YES!

Will revascularization regardless of the Will revascularization regardless of the symptom status in these diabetic patients symptom status in these diabetic patients improve survival? improve survival? Probably.Probably.

ConclusionsConclusions

Routine screening of diabetic patients regardless of symptom Routine screening of diabetic patients regardless of symptom status should uncover a large percentage of patients with occultstatus should uncover a large percentage of patients with occultCAD.CAD.

Both aggressive risk factor modification and revascularization Both aggressive risk factor modification and revascularization should improve the poor prognosis in diabetic population.should improve the poor prognosis in diabetic population.

It remains to be determined whether It remains to be determined whether percutaneouspercutaneous intervention intervention could rival the benefits of bypass surgery.could rival the benefits of bypass surgery.

New nonNew non--invasive imaging modalities and novel biomarkers invasive imaging modalities and novel biomarkers may further aid in the early detection of occult CAD in may further aid in the early detection of occult CAD in diabetics.diabetics.