Atherosclerosis, pumpsandpipesmdhc

Pumps & Pipes 1 Christie M. Ballantyne, M.D. Center for Cardiovascular Disease Prevention Methodist DeBakey Heart Center Baylor College of Medicine Houston, Texas Atherosclerosis

Key Clinical Issues

What causes the development of atherosclerosis?

Why do some atherosclerotic plaques develop a thrombus leading to vessel occlusion and clinical symptoms (MI, stroke)

How do we identify early atherosclerosis which does not limit flow and does not cause symptoms?

How do we stop or reverse atherosclerosis?

How do we monitor whether therapy is successful?

How do you know if you are at risk for a heart attack?

Case

A 58-year-old former CEO, recently retired, concerned about his risk for heart disease because of a family history of heart disease. He exercises on a regular basis; diet and weight have fluctuated over the years with his stress and workload. His only medical problem is high blood pressure, which is controlled with medication.

Case

Physical examination: Blood pressure 142/80 Height 6'2", Weight 210 lb

Labs: Total cholesterol 233

Triglycerides 100

HDL cholesterol 36

LDL cholesterol 177

What is his risk for coronary heart disease?

Major Risk Factors That Modify LDL-C Goals

Cigarette smoking

Hypertension:  140/90 mm Hg or on antihypertensive medication

Low HDL-C: <40 mg/dL *

Family Hx of premature CHD: male first-degree relative <55 years, female first-degree relative <65 years

Age: men  45 years, women  55 years

*High HDL-C (  60 mg/dL) is a negative risk factor and decreases by 1 the total number of risk factors

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.

Assessing CHD Risk in Men Note: Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly Caucasian population in Massachusetts, USA. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA . 2001;285:2486-2497. Step 2: Total Cholesterol Point Total 10-Year Risk Point Total 10-Year Risk <0 <1% 11 8% 0 1% 12 10% 1 1% 13 12% 2 1% 14 16% 3 1% 15 20% 4 1% 16 25% 5 2%  17  30% 6 2% 7 3% 8 4% 9 5% 10 6% Step 7: CHD Risk ATP III Framingham Risk Scoring TC Points at Points at Points at Points at Points at (mg/dL) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 <160 0 0 0 0 0 160-199 4 3 2 1 0 200-239 7 5 3 1 0 240-279 9 6 4 2 1  280 11 8 5 3 1 Step 1: Age Years Points 20-34 -9 35-39 -4 40-44 0 45-49 3 50-54 6 55-59 8 60-64 10 65-69 11 70-74 12 75-79 13 HDL-C (mg/dL) Points  60 -1 50-59 0 40-49 1 <40 2 Step 3: HDL-Cholesterol Systolic BP Points Points (mm Hg) if Untreated if Treated <120 0 0 120-129 0 1 130-139 1 2 140-159 1 2  160 2 3 Step 4: Systolic Blood Pressure Step 5: Smoking Status Points at Points at Points at Points at Points at Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 Nonsmoker 0 0 0 0 0 Smoker 8 5 3 1 1 Age Total cholesterol HDL-cholesterol Systolic blood pressure Smoking status Point total Step 6: Adding Up the Points

What is his Framingham Risk Score?

Age

Total cholesterol

HDL cholesterol

Systolic blood pressure

Smoking

Total:

8

3

2

2

0

15

Points Risk of CHD event (MI or death): 20%

High risk for CHD event: >20% over 10 years

Intermediate risk: 10 – 20%

Low risk: <10%

Current Approaches to "Risk Assessment" (Predicting Heart Attack and Stroke)

Count risk factors

Equations to quantitate absolute 10-year risk or lifetime risk

What causes a heart attack?

Endothelial Dysfunction in Atherosclerosis Ross R. N Engl J Med 1999; 340:115–126.

Fatty-Streak Formation in Atherosclerosis Ross R. N Engl J Med 1999; 340:115–126.

Formation of an Advanced, Complicated Lesion in Atherosclerosis Ross R. N Engl J Med 1999; 340:115–126.

Unstable Fibrous Plaques in Atherosclerosis Ross R. N Engl J Med 1999; 340:115–126.

Are there other tests to identify better who might have a heart attack or stroke?

New Tests for Risk Assessment

Blood tests related to inflammation

High-sensitivity C-reactive protein (CRP)

Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 )

LDL LUMEN MEDIA INTIMA The Role of Lp-PLA 2 in CVD Lp-PLA2

Adhesion Molecules LUMEN MEDIA INTIMA Lp-PLA2 The Role of Lp-PLA 2 in CVD Oxidized LDL Cytokines Lyso-PC + OxFA LDL

LUMEN MEDIA INTIMA Lyso-PC + OxFA Lp-PLA2 Adhesion Molecules Cytokines Plaque Formation Foam Cell Monocytes Macrophage The Role of Lp-PLA 2 in CVD Oxidized LDL LDL

Association of Lp-PLA 2 and CRP with Incident Ischemic Stroke 5.52 CRP, mg/L Lp-PLA 2 ,  g/L Ischemic Stroke Hazard Ratio 95% CI 3.13 –41.41, p<0.001 (>3) (1 –3 ) (<1) (  422) (310 –422 ) (<310) 6.02 2.85 4.27 4.36 Ballantyne CM et al. Arch Intern Med 2005;165:2479-2484.