혈관기능측정법

성균관의대삼성서울병원

박승우

Importance of Subclinical

Atherosclerosis• CHD events often occur with no clinical

history and often normal risk factors (e.g.,

total cholesterol is a poor predictor)

• Most heart attacks result from coronary

lesions of less than 50% stenosis, often

undetectable by traditional methods (exercise

test, angiogram)

• Need to identify disease early enough to

intervene to prevent clinical events

Ideal Surrogate Measures of

Atherosclerosis

• Use as intermediate endpoints rather than waiting until hard endpoints occur

• May have implications for identifying and tracking earlier, subclinical disease

• Compared to clinical event studies, studies of surrogate endpoints are lower cost, require fewer subjects, less-follow-up

• Use to follow progression of disease and effects of medical intervention

Characteristics of a Good Test

• Identify high and low risk groups more accurately--low false (+) and and false (-)

• Reproducible measures

• Better identification of high risk individuals (improved discrimination)

• Predict outcomes

• Safe for subjects

• Cost-effective

• Educate the public

Diagnostic Modalities for Vasculopathy

• Carotid Duplex ultrasonography: Image and

velocity

• Ankle-Brachial Index (ABI) for assessment of

peripheral vascular disease

• Echocardiographic left ventricular mass /

hypertrophy, systolic (incl. Ejection fraction) and

diastolic function

• Pulse wave velocity / arterial compliance for

assessing large artery stiffness

• Brachial artery reactivity testing

Other Measures Associated

with Cardiovascular Risk

• CT (EBT or multislice detectors):

coronary calcium score or volume

• Magnetic resonance imaging of carotid

plaques: vessel wall area

• CTA or MRA

• Intravascular ultrasound

• Conventional Angiography

Vascular Imaging

Carotid B-Mode

Ultrasonography• Measurement of intimal medial thickness

• Non-invasive, inexpensive, no radiation

• Well-established as an indicator of

cardiovascular risk from epidemiologic

studies

• Published clinical trials on utility of carotid

IMT as measure of progression of

atherosclerosis and effects of therapy

Cardiovascular Health Study: combined IMT

thickness predicts total MI and stroke

O’Leary et al. New Engl J Med 1999; 340:14-22

Regression of Carotid IMT

• ACAPS showed lovastatin therapy in those

aged 40-79 with elevated LDL-C to be

associated with regression in maximal IMT

(Furberg et al., Circ 1994; 90: 1679-87)

• KAPS showed in men 45-65 a 45% lower rate

of progression in those treated with

pravastatin (Salonen et al., Circ 1995; 92:

1758-64).

Carotid Doppler

Gray-Scale and Doppler US Criteria for

Diagnosis of ICA Stenosis

Radiology 2003;229:340-346

Ankle Brachial Index (ABI)

• Simple and inexpensive

• Measurment of systolic BP (by Doppler

probe) in the brachial, posterior tibial, and

dorsalis pedis arteries

• The highest of the four measurements in

the ankles and feet ÷ the higher of the two

brachial measurements

ABI by Doppler Analysis

Arterial Stiffness

Three processes to increase arterial stiffness

– Structural breakdown of elastin fibers

• occurs primarily in the aorta

• age driven (cum. millions of cardiac cycles)

– Damage to endothelial function

• occurs primarily in the smooth muscle conduit arteries

• disease driven (e.g., Type II diabetes,

hypercholesterolemia, atherosclerosis)

– Increase in mean arterial pressure

• occurs systemically throughout the arterial system.

Measurement of Arterial Stiffness

• Pulse Wave Velocity

• Carotid-Femoral PWV: - mainly aorta, but some smooth muscle.

• Carotid-Radial PWV: - limited aortic, mainly smooth muscle

• Augmentation Index

• Central aortic augmentation index(Aix) is:

- a systemic measure, integrated appropriately

- it is the clinically-relevant arterial stiffness measure

• Peripheral AIx

• Mean Pressure Changes

Flow Mediated Vasodilation

• The endothelium regulates vascular tone through release of vasodilators and vasoconstrictors.

• Brachial artery flow-mediated vasodilation (FMD) is assessed by high-frequency ultrasound assessment of changes in brachial artery diameter after 5-minute blood pressure cuff arterial occlusion.

• Endothelial dysfunction demonstrated as reduced FMD, and associated with coronary risk factors.

• Brachial artery FMD correlates with coronary artery FMD.

• Brachial or coronary artery flow mediated vasodilation (FMD) predict long-term cardiovascular events.

• Clinical applicability not well-established, but measures frequently used to measure endothelial function.

• FMD decreases after age 40 in men and 50 in women, reduced at SBP>100 mmHg, LDL > 75 mg/dl, and in diabetics

• Cholesterol reduction rapidly improves FMD

Flow Mediated Vasodilation

Brachial Artery Images Pre-Post

Pressure Cuff Occlusion

Initial Follow-up

-50

-40

-30

-20

-10

0

10

20

30

Initial Follow-up

Placebo group Lovastatin group

Dilatation

Constriction

Effects of Lipid-Lowering Therapy on

Endothelial Function in CHD Patients

Change in

diameter

(%)

Treasure CB et al. N Engl J Med. 1995;332:481-487.

Coronary Artery Calcium

• Coronary calcium invariably indicates the presence of atherosclerosis, but atherosclerotic lesions do not always contain calcium (1-3).

• Calcium deposition may occur early in life, as early as the second decade, and in lesions that are not advanced (4-5).

1) Wexler et al., Circ 1996; 94: 1175-92, 2) Blankenhorn and Stern, Am J Roentgenol 1959;

81: 772-7, 3) Blankenhorn and Stern, Am J Med Sci 1961; 42: 1-49, 4) Stary, Eur Heart J

1990; 11(suppl E): 3-19, 5) Stary, Arteriosclerosis 1989; 9 (suppl I): 19-32.

Coronary Calcium Evaluation:

EBT and Multidetector Scanners• Non-invasive, moderate cost, convenient

• Detects location and quantity (score, mass, volume) of coronary calcium, estimating “burden of atherosclerosis”

• Highly sensitive for angiographic disease, specificity variable depending on standard

• Reproducibility good (best at higher scores) but similar in EBT vs. multidetector scanners

• Artifact “noise” greater in EBT scanners

Significant Coronary Artery

Calcium (Score >400)

Estimated Annual CHD Death or MI Rates

Recommendations for

Noninvasive Screening

• AHA and ACC (Greenland et al., Circ. 2007)

indicated persons at intermediate risk may be

suitable for screening by noninvasive tests,

including ABI and carotid US for those over age

50 years, and coronary calcium screening.

• ATP III has suggested CAC scores above 75th

percentile indications for more aggressive

treatment (e.g., as CHD risk equivalent).

Conclusions

• Surrogate measures of atherosclerosis predict CHD risk and are sensitive to monitoring effects of therapeutic interventions.

• Noninvasive methods to measure subclinical atherosclerosis and its progression provide an opportunity to enhance primary prevention efforts

• Patient compliance to risk-reduction may be enhanced by knowledge of disease (e.g., IMT, CAC)

• Identification of those with the greatest amount of subclinical atherosclerosis may provide a better rationale for aggressive treatment (lipids, HTN).