115th Annual Convention of Indiana Osteopathic Association

Diabetes and Cardiovascular Disease

Dr. Bradley Weinberg, FACCCommunity Hospital NetworkIndianapolis, Indiana

May 5, 2012

DIABETES

IS

A CORONARY HEART DISEASE

RISK EQUIVALENT

Cardiovascular disease is the major cause of morbidity and mortality in diabetics

It is the largest contributor to direct and indirect cost

Hypertension, Dyslipidemia and Smoking commonly coexist with Diabetes

Large benefits are seen when these risk factors for Cardiovascular disease are addressed concurrently

PREVENTING HEART DISEASE IN DIABETES

BLOOD PRESSURE CONTROL

A goal SBP <130 is the guideline recommendation. I target a SBP < 140

The goal DBP is less than 80 mm Hg

HOT TRIAL Study design

19,000 pts with diastolic pressures of 100-115

Randomized to target diastolic of < 90 or < 85 or < 80

3,000 patients had diabetes

Initial drug felodipine, then ACE-inhibitor, then beta blocker then diuretic

Achieved diastolics lowered 20.3 mm vs 22.3 mm vs 24.3 mm

ACCORD TRIAL BLOOD PRESSURE ARM

4400 DIABETICS WITH SBP of 130-180

RANDOMIZED TO SYSTOLIC BP<120 mm Hg vs <140 mm Hg

ACCORD Mean SBP at each study visit

ACCORD Outcomes by level of BP control

Blood pressure treatment in Diabetes

Start with an ACE-I or ARB

I like to add Tenoretic. (Atenolol + Chlorthalidone)It is a 4$/mo drug and chlorthalidone has data

Next I will change the ACE-I to Lotrel generic which is Amlodipine + Benazepril or an ARB- Amlodipine combination drug.

Finally if indicated and K and renal function OK, I add spironolactone (a secret weapon!) Most pts are controlled on 2 or 3 pills (5 drugs!)

A Few Practical BP tips

Use home BP monitoring

DASH diet

½ hr of exercise 5 days per week

Treat sleep apnea

For GFR < 30 ml/min, use a loop diuretic in place of thiazides and spironolactone. I like once daily torsemide. It is twice as potent as furosemide.

Monitor electrolytes and renal function.

Preventing Heart Disease in Diabetes

Lipid Management

I target an LDL < 100 mg/dl or a reduction of 30-40% below baseline.

If possible, I choose a one of the two highest doses of either atorvastatin or rosuvastatin.

Avoid 80 mg simvastatin daily

In high risk pts a target of LDL <70 mg/dl is reasonable

Lipid Management in Diabetes

The data supporting targeting triglycerides and HDL are thin.

Triglycerides will often remain high until glycemic control is achieved.

I believe fenofibrate is overused.

My blood pressure and lipid approaches are colored by cost considerations and pill burden issues.

Smoking Cessation in Diabetes

Advise all smokers to quit

Chantix bid taken with meals

Nicotine replacement (without Chantix)

Bupropion

1-800-QUIT-NOW

Freedom from Smoking classes

Preventing Heart Disease in Diabetes

Antiplatelet Agents

Aspirin should be used in those with known vascular disease.

Aspirin 81 mg daily is reasonable in those with multiple additional risk factors or over age 50 in men or over age 60 in women.

Clopidogrel is reasonable in similar patients who cannot take aspirin.

The decision can be balanced by bleeding risks.

Screening for Coronary Disease in Diabetics

In asymptomatic patients, routine screening for coronary artery disease IS NOT recommended as it does not improve outcomes and it adds cost (and potential risks) to care without benefit

Glycemic Goals in non-pregnant Adults

A Cardiologist’s Perspective

Blood Glucose / A1CAnd the Relationship toMacrovascular Complications

A1C = Average Glucose28.7 x A1C – 41.7 = estimated average glucose

A1C Average Glucose

6 126

6.5 140

7 154

7.5 169

8 183

8.5 197

9 212

10 240

11 269

12 298

Targets for GlycemicControl in Most Non-Pregnant Adults

A1C <7.0

Fasting Glucose 70-130

Post-prandial Glucose <180

Type 2 Diabetes UKPDS1% A1C decreases Complications

Amputation MicrovascCataractSurgery

HeartFailure

MyocardialInfarction Stroke

↓ ↓ ↓ ↓ ↓ ↓

43% 37% 19% 16% 14% 12%

Blood Sugar Control and Cardiovascular Disease

ACCORD, ADVANCE and VADT did not show improved cardiovascular outcomes with A1C under 6.5%

Other data suggest post-prandial glucose which is difficult to target may contribute to adverse cardiovascular outcomes

A1C and Cardiovascular Outcomes

So What Now?

A1C and Complications

Data suggest lower A1Cs earlier in the course of diabetes is beneficial

Long term poor control may not benefit from stringent control later, particularly with reference to coronary heart disease.

Optimal A1Cs for patients with known heart disease is unclear but < 7.5 may be adequate and even < 8.0 in older and sicker patients.

COURAGE STUDY 20072287 patients (1999-2004)

• 70% proximal narrowing in 1 or more coronaries• Objective evidence of ischemia or typical angina with an

80%+ narrowing in one or more coronaries• Suitable for PCI (percutaneous coronary intervention) EXCLUSIONSClass IV anginaLVEF < 30%Prior revascularization

PCI + OMT (optimal medical therapy) vs OMT alone

What is Optimal Medical Therapy?

• Aspirin or clopidogrel• LDL < 85, HDL >40, Triglycerides < 150• BP < 130/85• A1C < 7.0• 30 minutes or more of exercise 5 + days per wk• Step II AHA diet• Smoking cessation• BMI <25• ACE-inhibitor or ARB• Long acting metoprolol, amlodipine, and long acting

nitrates titrated to angina

Thus, unstable coronary lesions that lead to myocardial infarction are not necessarily severely stenotic, and severely stenotic lesions are not necessarily unstable. Focal management of even severely stenotic coronary lesions with PCI in our study did not reduce the rate of death and myocardial infarction, presumably because the treated stenoses were not likely to trigger an acute coronary event. Furthermore, our lower-than-projected event rate in the medical-therapy group may be explained by systemic therapy that reduced plaque vulnerability through aggressive intervention for multiple risk factors and evidence-based use of medication

COURAGE Study

What are the implications of the COURAGE study?

• PCI added to medical therapy did not reduce the risk of death, MI or other major cardiovascular events compared to optimal medical therapy alone

• In patients with stable coronary artery disease, OMT and aggressive management of multiple treatment targets without initial revascularization can be safely initiated in the majority of patients with chronic stable angina

COURAGE study

• It is reasonable to reserve revascularization for patients with unacceptable symptoms on optimal medial therapy or judged to be at very high risk based on non-invasive testing.

BARI 2D StudyBypass Angioplasty Revascularization

2 Diabetes Study• What is the optimal treatment for patients

with diabetes and angiographically defined stable ischemic heart disease?

• 2368 type II diabetics with either a positive stress test and a > 50% stenosis in a major coronary artery or a >70% stenosis and typical angina pectoris

BARI 2D Treatment Strategies

• First a cardiologist determined whether CABG or PCI (percutaneous revascularization) would be preferred if revascularization was done.

• Then 2x2 randomization was done.• Optimal medical therapy alone vs Optimal

medical therapy plus revascularization• Insulin sensitization initially vs. initial insulin

provision (sulfonylurea or insulin or both)

BARI 2D RESULTS

BARI 2D RESULTS

BARI 2D RESULTS• Prompt revascularization in patients treated with

intensive medical therapy for diabetes and ischemic heart disease did not reduce the rate of death or major cardiovascular events

• Insulin sensitization and insulin provision had similar event rates

• Among patients for who CABG was deemed appropriate, prompt revascularization reduced the rate of major cardiovascular events compared to medical therapy

• Over 5 years, 42% of patients had to cross-over to revascularization because of symptom progression.

Patients meeting target values at 3 yrs in BARI 2D

• A1C < 7.0% 48%• LDL < 100 mg/dl 83%• BP < 130/80 71%

• All 3 targets 28%

Diabetes and Heart FailureDiabetes increases the risk of CHF independent of coronary artery disease and hypertension

The risk of CHF is 2.5 x higher in men and 5 x higher in women with diabetes.

Among patients hospitalized with heart failure in the US about 42% are diabetic

Independent of BMI and BP, diabetics have higher LV mass, more LVH, stiffer arteries and worse systolic function than non-diabetics.

Diabetes and Heart Failure

Diabetics commonly have diastolic dysfunction.

In diabetes increased myocardial fibrosis and collagen is seen.

Autonomic neuropathy may play a role in left ventricular dysfunction with impaired vagal tone and abnormal sympathetic tone.

The vascular bed may have decreased capacitance due to impaired endothelial function.

Diabetes and Heart Failure

Diabetics with heart failure have poorer survival then non-diabetics with heart failure.

Age, low LVEF and diabetes are the strongest predictors of the development of worsening heart failure among patients with coronary disease.

Thiazolidinediones (TZDs) and Heart Failure

TZDs cause fluid retention and increase the risk of CHF

They activate PPAR gamma receptors in the kidney (like aldosterone) and increase renal sodium retention.

This is resistant to loop diuretics but may respond to aldosterone antagonists like spironolactone and eplerenone

Weight gain and edema occur more often with concomitant TZDs and insulin therapy

AHA and ADA guidelines on TZD use

In patients with NYHA class III or IV CHF, TZDs should not be used.

If patients with risks for CHF such as Cr > 2, longstanding DM, age over 70, history of CHF, prior MI, significant valvular heart disease, LVH, hypertension, or edema or weight gain with TZDs, only low doses should be used and the patient followed carefully for heart failure.

If edema or weight gain occur on TZDs, the patient should be assessed for heart failure.

METFORMIN USE

Hemodynamically unstable patients or those with liver disease, significant renal insufficiency or sepsis are at increased risk of potentially fatal lactic acidosis with metformin.

However with stable heart failure with a creatinine less than 1.5 it is relatively safe.

In fact in the European Society of Cardiology’s heart failure guidelines it is recommended as a first line agent in overweight diabetic patients with a GFR over 30 ml/min

Prevention is the Best Medicine

Dyslipidemia

Hypertension

Hyperinsulinemia/insulin resistance

Hemostatic abnormalities

Hyperglycemia

AGE proteins

Oxidative stress

Endothelial Dysfunction

Inflammation

Possible Mechanisms for Increased Atherosclerosis in Type II Diabetes Mellitus

National Diabetes Education Program (NDEP)

Control Your Diabetes for Life The ABCs

A A1C (blood glucose) less than 7 percent

B Blood pressure less than 130/80

C Cholesterol – LDL less than 100 mg/dl

Free educational material 1-800-438-5383 Or visit www.ndep.nih.gov

THANK YOU!