CVD Workshop

SDPI CVD Risk Reduction Project

Meeting #5

Denver, Colorado

Case Study

• 62 year old woman presents for her scheduled intake visit for your CVD project

• She has been overweight most of her adult life and has a BMI of ~32

• PMHx: HTN, diet controlled diabetes

• Medication: HCTZ 25 mg Q day

Case Study

• SHx: Walks to the bus every day and occasionally walks with friend on the weekend

• She smoked ½ pack/day until 2 years ago

• FHx: Her sister is overweight, and take metformin for diabetes, her father died from a heart attack, her mother has diabetes

Case Study: Physical Exam

• Vitals: Height: 64” Weight: 188 lb BP 140/90 Waist Circumference: 39”

• Exam: HEENT WNL, Lungs clear, Heart RRR S1/S2 no murmur, GI obese abdomen, Foot exam: monofilament normal in both feet, pulse and skin normal, no pedal edema, nails mild fungal changes

Case Study: Initial Laboratory

• FBS: 165 mg/dl, • A1c 8.1%• TC: 220 mg/dl• TG: 240 mg/dl• HDL-C: 38 mg/dl• LDL-C: 134 mg/dl• Creatinine: 0.6 mg/dl• Urine M/C Ratio: 35

Cardiovascular Risk Assessment:

Modifiable Major Risk Factors

• Hypertension• Hypercholesterolemia• Smoking • Microalbuminurea• Hyperglycemia

Contributing Causes• Obesity, fat distribution• Lack of physical

exercise

• Genetic factors• Age• Disease duration

Garber, AJ American Family Practice December 15 2000

AnyAnydiabetes-diabetes-related related

endpointendpoint

Diabetes-Diabetes-related related deathdeath

Micro-Micro-vascularvascular

endpointsendpoints

-12%-12%((PP<.0001)<.0001)

-10%-10%((PP=.34)=.34)

-25%-25%((PP<.01)<.01)

StrokeStroke

-25%-25%((PP<.005)<.005)

-32%-32%((PP=.019)=.019)

-44%-44%((PP=.013)=.013)

-37%-37%((PP=.009)=.009)

Micro-Micro-vascularvascular

endpointsendpoints

AnyAnydiabetes-diabetes-related related

endpointendpoint

Diabetes-Diabetes-related related deathdeath

UK Prospective Diabetes Study Group 38. BMJ. 1998;317:703-713.UK Prospective Diabetes Study Group 33. Lancet. 1998;352:837-853.

Glucose ControlBP Control

(144/82 vs 154/87 mm Hg)

00

-10-10

-50-50

-20-20

-30-30

-40-40

United Kingdom Prospective DiabetesStudy (UKPDS): Results

STENO-2 Study:Multifactorial Intervention and CVD in Patients with Type 2 Diabetes

• Denmark Study: NEJM 1/30/2003

• 160 patients with type 2 diabetes

• 8 year study with mean age 55 years

• Two study groups: intensive therapy and conventional therapy

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

STENO-2 Study:Multifactorial Intervention and CVD in Patients with Type 2 Diabetes

• Intensive Group: stepwise implementation of behavior modification and pharmacologic therapy targeting:– Hyperglycemia– Hypertension– Dyslipidemia– Microalbuminurea

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

• End point:– Death from cardiovascular causes– Nonfatal myocardial infarction– Stroke– Coronary or peripheral artery

revascularization– Amputation as a result of ischemia

STENO-2 Study:Multifactorial Intervention and CVD in Patients with Type 2 Diabetes

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

STENO-2 Study:Multifactorial Intervention and CVD in Patients with Type 2 Diabetes

Macrovascular Complications

• Conventional Group: 44% of patient had a primary end point event

• Intensive Group: 24% of patients had a primary end point event

Primary composite endpoint:

Death from CV causes, nonfatal MI, CABG, PCI, nonfatal stroke, amputation, or surgery for peripheral atherosclerotic artery disease.

Adapted from Gaede P, et al. N Eng J Med. 2003;348:383-393.

Primary composite endpoint: conventional therapy (44%) and intensive therapy (24%).*Death from CV causes, nonfatal MI, CABG, PCI, nonfatal stroke, amputation, or surgery for peripheral atherosclerotic

artery disease.†Behavior modification and pharmacologic therapy.

Adapted from Gaede P, et al. N Eng J Med. 2003;348:383-393.

Pri

mar

y C

om

po

site

En

dp

oin

t* (

%)

Months of Follow-Up

60

40

20

12 24 36 48 60 72 84 96

Conventional Therapy

Intensive Therapy†

20% Absolute Risk Reduction

N=160; follow-up=7.8 years

Aggressive treatment of†:– Microalbuminuria with ACEIs, ARBs, or combination– Hypertension– Hyperglycemia– Dyslipidemia– Secondary prevention of CVD

Intensive Multiple Risk Factor Management Patients with Type 2 Diabetes and

Macroalbuminuria

CVD Risk

Reduction

Hyperglycemia

Hypertension Control

Lipid Control

Daily AspirinLifestyle ChangesWeight loss, healthy foods,Increased activity

Smoking Cessation

Hypertension

““Failure to titrate or combine medications, Failure to titrate or combine medications, despite knowing the patient is not at goal despite knowing the patient is not at goal BP, represents clinical inertia and must BP, represents clinical inertia and must be overcome.”be overcome.”

Chobanian A, et al. JAMA. 2003;289:2560-2572.

JNC 7

Treatment of Hypertension in DiabetesDiagnosis of Hypertension

BP>130/80 mm Hg

Non-Pharmacologic Therapies

Drug TherapiesACE based regimes preferred

Multi-drug therapy often needed

Target BP<130/85

ACE & ARBSLimits nephropathy and

Lower CVD risk

Thiazide -Blocker* Blocker Ca++CB

Step-wise progression to controlling Blood pressure

Average Number of Antihypertensive Agents Needed Per Patient to Achieve Target BP

UKPDS DBP<85

ABCD DBP<75

VDRD MAP<92

HOT DBP<80

AASK MAP<92

1 2 3 4

Number of Antihypertensive AgentsTrail Target BP mm Hg

SUMMARYTreatment of Hypertension in Diabetes• Blood pressure goal in diabetes = 130/85

– Level of blood pressure more important that type of therapy

– Reduces rates of both micro and macrovascular disease

• ACE based therapies: 1st Line Choice– Reduces CVD complication and offers reno-

protection

• Multi-drug therapy often needed• Aggressive treat essential, if CVD and renal

disease present ideal goal: 125/80 (?)Arch Intern Med, Vol160, Sep 11, 2000, 2447-2452

Hypercholesterol

Prevalence of Dyslipidemia in Type 2 Diabetes

• Most common pattern is elevated triglycerides and low HDL

• TC & LDL concentration is often the same as non-diabetic individuals

• However, LDL particles are smaller, denser and more atherogenic

Goals for Control• LDL < 100• HDL> 45* in men, HDL> 55 in women

• Lipid panel annually• Consider direct LDL if TG >250 or if

specimen is non-fasting• All patients with LDL > 100 need

medical, dietary and lifestyle intervention

Considerations in Therapy

• Diet and exercise are key• Hyperglycemia itself will lead to increased TG:

try to improve sugars first• Metformin will decrease LDL• Glitazones will decrease TG, increase HDL• Check TFTs in initial work-up• Metamucil, increased dietary fiber

Microalbuminuria and CVD in Diabetes

Microalbuminuria and Diabetes

• Independent risk factor for development of cardiovascular disease

• Predictor of cardiovascular mortality in the diabetic population

• Part of the cardiometabolic syndrome

Microalbuminuria and Diabetes

• Test for urine protein yearly

• If negative, screen for microalbuminurea

• Dipstick + microalbuminurea should be confirmed on a separate specimen

• A/C ratio: 30mg/gm

• Treat with ACE-inhibitor, regardless of BP

Smoking Cessation

Smoking Cessation

• Smoking doubles the risk of CVD in patients with diabetes

• Attenuates the benefit of gained from modifying other risks

• Synergistic with TC, possibly through enhanced oxidation of LDL

• MRFIT: independent and ing risk of CVD based on #cigarettes/day

Smoking Cessation: Standards of Care

• Assessment of smoking status and history

• Counseling on smoking prevention and cessation

• Referral to program for delivery of smoking cessation

Aspirin Therapy

Aspirin Therapy in Diabetes

“Aspirin - the poor man’s statin”

• Reduces risk of MI by ~ 15-60%

• Treat all high risk patients with diabetes over the age of 35

• Use 81 – 325mg/day

The Lancet

Procoagulant State

• Platelets are overly sensitive to platelet aggregating agents

• High levels of Thromboxane, a potent vasoconstrictor

• Decreased fibrinolytic activity• Increased levels of Plasminogen Activitor

Inhibitor-1• Clot lysis cannot precede normally

Goals for treatmentPrimary Prevention:

• Strongly consider ASA in patients > 30 with diabetes and high risk for CVD– FHx CVD, smoking, HTN, obese,

albuminurea, dyslipidemia

Secondary Prevention:

• ASA for patients with know CVD: MI, stroke, PVD, claudication, angina

DOSE: 162mg to 325mg

Conclusion:

Aggressive modification of all identified CVD risks factor is essential to reduce the macrovascular complications of diabetes