The Science: CHD and Diabetes as Co-morbidities Kathy Reims, MD Center for Strategic Innovation 8/27/07

Objectives: What is the rationale to think about diabetes and coronary heart disease (CHD) together? What is the rationale to think about diabetes and coronary heart disease (CHD) together? Patient perspective Patient perspective Pathophysiology Pathophysiology Treatment Treatment How can you leverage the systems that you already have in place to include CHD? How can you leverage the systems that you already have in place to include CHD? What measures might you consider? What measures might you consider?

Patient-centric, not Disease-centric

What are the CHD risk Factors? Gender Gender Age Age Race Race Smoking BP control Lipid management Physical activity Weight Diabetes Renal Insufficiency

Much overlap in what causes the complications in diabetes and Cardiovascular Disease (CVD) We know the correlations, not always the scientific basis

Incidence of Myocardial Infarction in Type 2 Diabetes Haffner SM et al. N Engl J Med 1998;339: No Prior MIPrior MI No diabetes (n=1373) Type 2 Diabetes (n=1059) 7-year Incidence (%)

Disconnected! 68% of diabetes patients do not consider CVD to be a serious diabetes-related complication, and they are much more aware of complications such as blindness (65%) or amputation (36%) than heart disease (17%), heart attack (14%), or stroke (5%). 68% of diabetes patients do not consider CVD to be a serious diabetes-related complication, and they are much more aware of complications such as blindness (65%) or amputation (36%) than heart disease (17%), heart attack (14%), or stroke (5%). 88% of providers had discussed diabetes related CVD risk 88% of providers had discussed diabetes related CVD risk

What is it about diabetes that increases CVD risk? Metabolic milieu? Metabolic milieu? Inflammation? Inflammation? Pro-thrombotic state? Pro-thrombotic state? Insulin resistance? Insulin resistance?

C-Reactive Protein C-reactive protein (CRP) - one of the acute phase proteins that increase during systemic inflammation C-reactive protein (CRP) - one of the acute phase proteins that increase during systemic inflammation High levels of CRP consistently predict new coronary events. Newer high sensitivity (hs-CRP) now used to better predict CVD risk. High levels of CRP consistently predict new coronary events. Newer high sensitivity (hs-CRP) now used to better predict CVD risk. Higher CRP levels also are associated with lower survival rate Higher CRP levels also are associated with lower survival rate Higher levels of CRP may increase the risk that an artery will re-close after it’s been opened by balloon angioplasty. Higher levels of CRP may increase the risk that an artery will re-close after it’s been opened by balloon angioplasty. High levels of CRP predict prognosis and recurrent events in patients with stroke and peripheral arterial disease. High levels of CRP predict prognosis and recurrent events in patients with stroke and peripheral arterial disease.

What about Metabolic Syndrome?

Newer findings with nonfasting triglyceride values Women's Health Study demonstrated that nonfasting triglycerides were better independent predictors of cardiovascular events over 11 years than were fasting triglycerides. Women's Health Study demonstrated that nonfasting triglycerides were better independent predictors of cardiovascular events over 11 years than were fasting triglycerides. Same finding recent study of about 14,000 men and women in Copenhagen, Denmark Same finding recent study of about 14,000 men and women in Copenhagen, Denmark Fat-load (or fat-tolerance) tests have been found to be abnormal, with higher postprandial triglyceride levels, in people with CVD when compared with control subjects. Fat-load (or fat-tolerance) tests have been found to be abnormal, with higher postprandial triglyceride levels, in people with CVD when compared with control subjects. Best predictor of high nonfasting TG levels is the fasting level. Best predictor of high nonfasting TG levels is the fasting level.

Prothrombotic state Associated with insulin resistance Associated with insulin resistance Increased fibrinogen levels, Increased fibrinogen levels, Increased plasminogen activator inhibitor-1, Increased plasminogen activator inhibitor-1, Various platelet abnormalities Various platelet abnormalities

What does all this mean? Much overlap between what is going on metabolically with diabetics and with those with CHD. Much overlap between what is going on metabolically with diabetics and with those with CHD. Interventions that mitigate CHD risk are of paramount importance in diabetics Interventions that mitigate CHD risk are of paramount importance in diabetics Due to the pathophysiological overlap, interventions are similar. Due to the pathophysiological overlap, interventions are similar.

AHA/ACC Secondary Prevention Guidelines 2006: Smoking Smoking status each visit Smoking status each visit Advise tobacco users to quit Advise tobacco users to quit Use behavioral and pharmacological strategy to support cessation Use behavioral and pharmacological strategy to support cessation Avoid exposure to second hand smoke Avoid exposure to second hand smoke Smith SC, et.al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease:2006 update. Circulation. 2006; 113:

Control Blood Pressure Diabetics, CVD, Framingham risk score >10% or kidney disease – 130/80 Diabetics, CVD, Framingham risk score >10% or kidney disease – 130/80 Otherwise 140/90 Otherwise 140/90 Lifestyle Lifestyle ACE/ARB + thiazides as needed ACE/ARB + thiazides as needed

UKPDS Group. UKPDS 38. BMJ. 1998;317:703–713. Benefits of 144/82 vs 154/87 Risk Reduction (%) Any Diabetes- related End Point Diabetes- related Death Retinopathy Stroke Heart Failure UKPDS: Blood Pressure Control Study in Type 2 Diabetes Effect of Intensive BP Lowering on Micro- and Macrovascular Complications Risk Myocardial Infarction -21 Renal Failure Vision Deterioration

Manage Lipids LDL-C goal <100 LDL-C goal <100 “reasonable” to treat to <70 “reasonable” to treat to <70 Statins Statins

HPS: Conclusions for people with diabetes Lowering LDL cholesterol by 1 mmol/L (40 mg/dL) reduces the risk of major vascular events by about one-quarter during 5 years of treatment Lowering LDL cholesterol by 1 mmol/L (40 mg/dL) reduces the risk of major vascular events by about one-quarter during 5 years of treatment Similar proportional reductions in risk among people with or without diabetes ― irrespective of age, sex, vascular disease or lipid levels Similar proportional reductions in risk among people with or without diabetes ― irrespective of age, sex, vascular disease or lipid levels Continued statin treatment prevents not only first but also subsequent major vascular events Continued statin treatment prevents not only first but also subsequent major vascular events

Exercise Prescription 30 minutes, 7 days/week moderate intensity activity 30 minutes, 7 days/week moderate intensity activity Supplement with increased lifestyle activities – gardening, housework Supplement with increased lifestyle activities – gardening, housework Medically supervised programs prn Medically supervised programs prn

Weight Management BMI 18.5 to 24.9 kg/m 2 BMI 18.5 to 24.9 kg/m 2 Waist circumference: Waist circumference: Men <40 inches Men <40 inches Women <35 inches Women <35 inches 10% decrease from baseline 10% decrease from baseline

Diabetes Management HbA1c < 7.0% HbA1c < 7.0% Manage other risk factors aggressively Manage other risk factors aggressively

Antiplatelet Agents/Anticoagulants 81 mg 81 mg Additional clopidgrel guidelines for ACS and s/p stent Additional clopidgrel guidelines for ACS and s/p stent Warfarin guidelines for a. fib. and LV thrombus Warfarin guidelines for a. fib. and LV thrombus

ACE/ARB LV function < 40%, hypertension, diabetes, CKD LV function < 40%, hypertension, diabetes, CKD Consider for all other patients Consider for all other patients ARBs for those intolerant of ACE ARBs for those intolerant of ACE ARBs + ACE systolic-dysfunction heart failure ARBs + ACE systolic-dysfunction heart failure

ß-blockers S/P MI S/P MI ACS ACS LV dysfunction with or without symptoms of heart failure LV dysfunction with or without symptoms of heart failure

Statins for Primary or Secondary Prevention: 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 y TC >135 mg/dL Statins not clearly indicated or contraindicated Lancet 2002, 360:7

Steno-2 Study: Multi-risk-factor Intervention Approach 160 patients with type 2 diabetes randomized to conventional or intensive treatment 160 patients with type 2 diabetes randomized to conventional or intensive treatment Intensive treatment: stepwise implementation of behavior modification and pharmacologic therapy targeting hyperglycemia, hypertension, Intensive treatment: stepwise implementation of behavior modification and pharmacologic therapy targeting hyperglycemia, hypertension, dyslipidemia and microalbuminuria dyslipidemia and microalbuminuria Secondary prevention of cardiovascular disease with aspirin Secondary prevention of cardiovascular disease with aspirin

Steno-2 Study Gaede P et al. N Engl J Med. 2003;348: Type 2 DM Subjects With Microalbuminuria HbA 1C <6.5% TC <175 mg/dL TG <150 mg/dL SBP <130 mm Hg DBP <80 mm Hg Intensive Rx Conventional Rx Percent * * * * *= stat.signif.

Steno-2 Study: Reduction in CV and Microvascular Disease Reductions After 7.8 Years of Intensive vs Conventional Rx CV DiseaseNephropathyRetinopathyAutonomic Dysfunction Gaede P et al. N Engl J Med. 2003;348:

Steno-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 current systems? Use baseline data Use baseline data Pick those areas you think most important to change; PDSAs Pick those areas you think most important to change; PDSAs Encourage all members of the care team to participate to improve outcomes Encourage all members of the care team to participate to improve outcomes Re-enforce the message and the importance of lifestyle issues – self-management Re-enforce the message and the importance of lifestyle issues – self-management Measure over time Measure over time

Selected measures: AQA AQA NQF NQF NCQA (HEDIS) NCQA (HEDIS) HDC HDC PQRI ?file=/PQRI/downloads/Measure_Specificatio ns_ pdf PQRI ?file=/PQRI/downloads/Measure_Specificatio ns_ pdf ?file=/PQRI/downloads/Measure_Specificatio ns_ pdf ?file=/PQRI/downloads/Measure_Specificatio ns_ pdf

Time for Dialogue