The Science: CHD The Science: CHD and Diabetes as Co-and Diabetes as Co-

morbiditiesmorbiditiesKathy Reims, MDKathy Reims, MD

Center for Strategic Center for Strategic InnovationInnovation

8/27/078/27/07

Objectives:Objectives:

What is the rationale to think about What is the rationale to think about diabetes and coronary heart disease diabetes and coronary heart disease (CHD) together?(CHD) together? Patient perspective Patient perspective PathophysiologyPathophysiology TreatmentTreatment

How can you leverage the systems that How can you leverage the systems that you already have in place to include you already have in place to include CHD? CHD?

What measures might you consider? What measures might you consider?

Patient-centric, not Patient-centric, not Disease-centricDisease-centric

What are the CHD risk What are the CHD risk Factors? Factors?

GenderGender AgeAge RaceRace

SmokingSmoking BP controlBP control Lipid managementLipid management Physical activityPhysical activity Weight Weight DiabetesDiabetes Renal Insufficiency Renal Insufficiency

Much overlap in Much overlap in what causes the what causes the complications in complications in

diabetes and diabetes and Cardiovascular Cardiovascular Disease (CVD) Disease (CVD) We know the correlations, not We know the correlations, not

always the scientific basisalways the scientific basis

Incidence of Myocardial Incidence of Myocardial Infarction in Infarction in

Type 2 DiabetesType 2 Diabetes

Haffner SM et al. N Engl J Med 1998;339:229-234.

50

40

30

20

10

0No Prior MI Prior MI

No diabetes (n=1373)Type 2 Diabetes

(n=1059)

7-y

ear

Incid

en

ce (

%)

Disconnected! Disconnected!

68% of diabetes patients do not 68% of diabetes patients do not consider CVD to be a serious diabetes-consider CVD to be a serious diabetes-related complication, and they are related complication, and they are much more aware of complications much more aware of complications such as blindness (65%) or amputation such as blindness (65%) or amputation (36%) than heart disease (17%), heart (36%) than heart disease (17%), heart attack (14%), or stroke (5%). attack (14%), or stroke (5%).

88% of providers had discussed 88% of providers had discussed diabetes related CVD riskdiabetes related CVD risk

What is it about diabetes What is it about diabetes that increases CVD risk? that increases CVD risk?

Metabolic milieu? Metabolic milieu? Inflammation?Inflammation? Pro-thrombotic state? Pro-thrombotic state? Insulin resistance?Insulin resistance?

C-Reactive ProteinC-Reactive Protein C-reactive protein (CRP) - one of the acute phase C-reactive protein (CRP) - one of the acute phase

proteins that increase during systemic inflammationproteins that increase during systemic inflammation High levels of CRP consistently predict new coronary High levels of CRP consistently predict new coronary

events. Newer high sensitivity (hs-CRP) now used to events. Newer high sensitivity (hs-CRP) now used to better predict CVD risk. better predict CVD risk.

Higher CRP levels also are associated with lower Higher CRP levels also are associated with lower survival rate survival rate

Higher levels of CRP may increase the risk that an artery Higher levels of CRP may increase the risk that an artery will re-close after it’s been opened by balloon will re-close after it’s been opened by balloon angioplasty.  angioplasty. 

High levels of CRP predict prognosis and recurrent High levels of CRP predict prognosis and recurrent events in patients with stroke and peripheral arterial events in patients with stroke and peripheral arterial disease. disease.

What about What about Metabolic Metabolic Syndrome?Syndrome?

Newer findings with Newer findings with nonfasting triglyceride nonfasting triglyceride

valuesvalues Women's Health Study demonstrated that Women's Health Study demonstrated that

nonfasting triglycerides were better nonfasting triglycerides were better independent predictors of cardiovascular independent predictors of cardiovascular events over 11 years than were fasting events over 11 years than were fasting triglycerides.triglycerides.

Same finding recent study of about 14,000 Same finding recent study of about 14,000 men and women in Copenhagen, Denmark men and women in Copenhagen, Denmark

Fat-load (or fat-tolerance) tests have been Fat-load (or fat-tolerance) tests have been found to be abnormal, with higher found to be abnormal, with higher postprandial triglyceride levels, in people with postprandial triglyceride levels, in people with CVD when compared with control subjects.CVD when compared with control subjects.

Best predictor of high nonfasting TG levels is Best predictor of high nonfasting TG levels is the fasting level. the fasting level.

Prothrombotic stateProthrombotic state

Associated with insulin resistanceAssociated with insulin resistance Increased fibrinogen levels,Increased fibrinogen levels, Increased plasminogen activator Increased plasminogen activator

inhibitor-1,inhibitor-1, Various platelet abnormalities Various platelet abnormalities

What does all this mean? What does all this mean?

Much overlap between what is going Much overlap between what is going on metabolically with diabetics and on metabolically with diabetics and with those with CHD.with those with CHD.

Interventions that mitigate CHD risk Interventions that mitigate CHD risk are of paramount importance in are of paramount importance in diabeticsdiabetics

Due to the pathophysiological Due to the pathophysiological overlap, interventions are similar. overlap, interventions are similar.

AHA/ACC Secondary AHA/ACC Secondary Prevention Guidelines Prevention Guidelines

2006: Smoking2006: Smoking Smoking status each visitSmoking status each visit Advise tobacco users to quitAdvise tobacco users to quit Use behavioral and pharmacological Use behavioral and pharmacological

strategy to support cessationstrategy to support cessation Avoid exposure to second hand Avoid exposure to second hand

smokesmokeSmith SC, et.al. AHA/ACC guidelines for secondary prevention for patients with Smith SC, et.al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease:2006 update. Circulation. 2006; coronary and other atherosclerotic vascular disease:2006 update. Circulation. 2006; 113:2363-2372113:2363-2372

Control Blood PressureControl Blood Pressure

Diabetics, CVD, Framingham risk Diabetics, CVD, Framingham risk score >10% or kidney disease – score >10% or kidney disease – 130/80130/80

Otherwise 140/90Otherwise 140/90 LifestyleLifestyle ACE/ARB + thiazides as neededACE/ARB + thiazides as needed

UKPDS Group. UKPDS 38. BMJ. 1998;317:703–713.

Benefits of 144/82 vs 154/87

Ris

k R

ed

uc

tio

n (

%)

Any Diabetes-related

End Point

Diabetes-relatedDeath Retinopathy Stroke

HeartFailure

-24

-32 -34

-44

-56

-70

-20

0

-10

-50

-60

-30

-40

UKPDS: Blood Pressure Control Study in UKPDS: Blood Pressure Control Study in Type 2 DiabetesType 2 Diabetes

Effect of Intensive BP Lowering on Effect of Intensive BP Lowering on Micro- and Macrovascular Complications Micro- and Macrovascular Complications

RiskRiskMyocardialInfarction

-21

RenalFailure

-42

-47

Vision Deterioration

Manage LipidsManage Lipids

LDL-C goal <100LDL-C goal <100 ““reasonable” to treat to <70reasonable” to treat to <70 StatinsStatins

HPS: Conclusions for people with HPS: Conclusions for people with diabetesdiabetes

Lowering LDL cholesterol by 1 mmol/L (40 mg/dL) reduces Lowering LDL cholesterol by 1 mmol/L (40 mg/dL) reduces the risk of major vascular events by about one-quarter the risk of major vascular events by about one-quarter during 5 years of treatmentduring 5 years of treatment

Similar proportional reductions in risk among people with Similar proportional reductions in risk among people with or without diabetes or without diabetes ― ― irrespective of age, sex, vascular irrespective of age, sex, vascular disease or lipid levelsdisease or lipid levels

Continued statin treatment prevents not only first but also Continued statin treatment prevents not only first but also subsequent major vascular events subsequent major vascular events

Exercise PrescriptionExercise Prescription

30 minutes, 7 days/week moderate 30 minutes, 7 days/week moderate intensity activityintensity activity

Supplement with increased lifestyle Supplement with increased lifestyle activities – gardening, houseworkactivities – gardening, housework

Medically supervised programs prnMedically supervised programs prn

Weight ManagementWeight Management

BMI 18.5 to 24.9 kg/mBMI 18.5 to 24.9 kg/m22

Waist circumference:Waist circumference: Men <40 inchesMen <40 inches Women <35 inchesWomen <35 inches

10% decrease from baseline 10% decrease from baseline

Diabetes ManagementDiabetes Management

HbA1c < 7.0%HbA1c < 7.0% Manage other risk factors Manage other risk factors

aggressivelyaggressively

Antiplatelet Antiplatelet Agents/AnticoagulantsAgents/Anticoagulants

81 mg81 mg Additional clopidgrel guidelines for Additional clopidgrel guidelines for

ACS and s/p stentACS and s/p stent Warfarin guidelines for a. fib. and LV Warfarin guidelines for a. fib. and LV

thrombusthrombus

ACE/ARBACE/ARB

LV function < 40%, hypertension, LV function < 40%, hypertension, diabetes, CKDdiabetes, CKD

Consider for all other patientsConsider for all other patients ARBs for those intolerant of ACEARBs for those intolerant of ACE ARBs + ACE systolic-dysfunction ARBs + ACE systolic-dysfunction

heart failureheart failure

ß-blockersß-blockers

S/P MIS/P MI ACSACS LV dysfunction with or without LV dysfunction with or without

symptoms of heart failure symptoms of heart failure

Statins for PrimaryStatins for Primaryor Secondary Prevention:or Secondary Prevention:

Heart Protection Study (HPS)Heart Protection Study (HPS)

Entry Criteria

Placebo (n=10,267) Simvastatin 40 mg (n=10,269)

Primary end point: All-cause and CV mortality

• Increased risk of CV death due to prior disease (MI, CHD, occlusive disease of noncoronary arteries, or RX’ed HTN)

• Age 40-80 y• TC >135 mg/dL• Statins not clearly indicated or contraindicated

Lancet 2002, 360:7

Steno-2 Study: Multi-risk-factor Intervention Steno-2 Study: Multi-risk-factor Intervention ApproachApproach

160 patients with type 2 diabetes randomized to 160 patients with type 2 diabetes randomized to conventional or intensive treatmentconventional or intensive treatment• • Intensive treatment: stepwise implementation of Intensive treatment: stepwise implementation of

behavior modification and pharmacologic therapy behavior modification and pharmacologic therapy targeting hyperglycemia, hypertension,targeting hyperglycemia, hypertension,

dyslipidemia and microalbuminuriadyslipidemia and microalbuminuria

• • Secondary prevention of cardiovascular disease Secondary prevention of cardiovascular disease with aspirinwith aspirin

Steno-2 StudySteno-2 Study

Gaede P et al. N Engl J Med. 2003;348:383-393.

160 Type 2 DM Subjects With Microalbuminuria

0

10

20

30

40

50

60

70

80

HbA1C <6.5%

TC<175 mg/dL

TG <150 mg/dL

SBP <130 mm Hg

DBP <80 mm Hg

Intensive Rx

Conventional Rx

Per

cen

t

*

*

*

*

*= stat.signif.

Steno-2 Study: Reduction in CV Steno-2 Study: Reduction in CV and Microvascular Diseaseand Microvascular Disease

Reductions After 7.8 Years of Intensive vs Conventional Rx

-64

-62

-60

-58

-56

-54

-52

-50

-48

CV Disease Nephropathy Retinopathy Autonomic Dysfunction

Gaede P et al. N Engl J Med. 2003;348:383-393.

Steno-2 Study ConclusionsSteno-2 Study Conclusions

• Multifactorial intervention, including patient

education and motivation in diabetes management,

may reduce risks of both cardiovascular and

microvascular events by up to 50%.

How do you leverage How do you leverage current systems?current systems?

Use baseline dataUse baseline data Pick those areas you think most Pick those areas you think most

important to change; PDSAsimportant to change; PDSAs Encourage all members of the care team Encourage all members of the care team

to participate to improve outcomesto participate to improve outcomes Re-enforce the message and the Re-enforce the message and the

importance of lifestyle issues – self-importance of lifestyle issues – self-managementmanagement

Measure over time Measure over time

Selected measures: Selected measures:

AQA AQA http://www.aqaalliance.org/http://www.aqaalliance.org/ NQF NQF http://www.qualityforum.org/http://www.qualityforum.org/ NCQA (HEDIS) NCQA (HEDIS) http://web.ncqa.org/http://web.ncqa.org/ HDC HDC

http://www.healthdisparities.nethttp://www.healthdisparities.net PQRI PQRI

http://www.cms.hhs.gov/apps/ama/lihttp://www.cms.hhs.gov/apps/ama/license.asp?file=/PQRI/downloads/Mecense.asp?file=/PQRI/downloads/Measure_Specifications_061807.pdfasure_Specifications_061807.pdf

Time for Time for DialogueDialogue