Monitoring CAC and IMT: A useful clinical tool?

Cardiology ServiceWalter Reed Army Medical

CenterWalter Reed Army Health Care

System

NO CONFLICTS TO DISCLOSE

Allen J. Taylor MDCOL, Medical Corps

Professor of Medicine, USUHS

Chief of Cardiology

How do we monitor successful control of cardiovascular risk?

•Attainment of risk factor targets

•BP, LDL-C, HDL-C

•Use of specific medication classes

•Compliance with therapeutic lifestyle changes

•Tobacco, physical activity and diet

•Inference: Control of risk factors equates to control of the target disease… Atherosclerosis

Is the answer within a “global risk” assessment?

•Multi-variable risk indices are generally not validated for demonstrating the control of cardiovascular risk

•Due to

•Concept of exposure duration

•Measurement error

•High lifetime risk even in the setting of low near term risk

Lloyd-Jones. AJC 2004;94:20-24

Is monitoring atherosclerosis the answer?

•Serial angiographic study in 335 pts, mean age 51, f/u 44 months

Waters et al. Circulation 1993;87:1067-1075

•QCA progression

•>15% increase in diameter stenosis

•42%

•50% increase in adjusted risk for cardiac death/MI

P < .001

Coronary Atherosclerosis ProgressionA marker of increased risk for events

•CLAS: secondary prevention, men, colestipol + niacin vs. placebo

Azen et al. Circulation 1996;93:34-41

•CAD progression

•Common (49%)

•Associated with significantly higher risk for future events

1

1.7

2.3

0

0.5

1

1.5

2

2.5

Regression

Stabilized

Progression

P = .03

IVUS progression predicts clinical events

•Essen University: Serial IVUS study of the left main coronary artery in 56 pts undergoing left coronary PCI

Erbel and colleagues. Circulation 2004;110:1579

•Change in plaque area related to clinical risk factors

•Most events occurred in those with the greatest progression

•P+M 25% vs. 6%

IMT Progression RateA marker of increased risk for

events•CLAS: secondary prevention, men, colestipol/niacin vs. placebo

Hodis. Ann Intern Med 1998;128:262

P < .001

1

1.6

2.3

2.8

0

0.5

1

1.5

2

2.5

3

RR for MI/Death

<.011 mm/y

.011-.017 mm/y

.018-.033 mm/y

>.033 mm/y

• Rate of progression is associated with significantly higher risk for future events

• Predictive power superior to coronary artery progression

Therapeutics shown to slow progression of CIMT

•Lifestyle interventions- exercise

•Lipid modifying agents-

•Binding resins, niacin, STATINS, new agents

•Anti-hypertensives

•CCB’s, blockers, ACEI

•Anti-diabetic agents

•Metformin, TZD’s

•Hormonal therapy: HRT

Could IMT be used to monitor a patients atherosclerosis

extent?•Tension between expected IMT progression vs. test reproducibility

•Annual CIMT progression: .01-.015 mm/y

•Reproducibility

•± .02-.04 mm

•Most reproducible in common carotid > bulb/internal carotid

•Extended time-horizon should improve ability to discriminate signal from noise

Methods to Improve CIMT Reproducibility

•Common carotid vs. other segments

•Collect/analyze images in duplicate

•Consistent technology, sonographers and readers

•High frequency imaging

•Standardization of methods needed

Higher Frequency Imaging

7 MHz: 19958 MHz: 199910 MHz: 199913 MHz: 2005

• Common carotid artery advantageous: obtainable in virtually all

• Far wall measurements

• Minimum 7MHz probes

• Minimum 10 mm length of IMT from well-visualized segment

CAC score progression

Raggi et al. ATVB. 2004;24(7):1272-7

progression in individuals with events

•Open issues:

•Calculation?

•%/year

•Volume

•Determinants uncertain

•Groups overlapRaggi et al. AJC. 2003;92:827

Statin/CAC Paradox: BELLES

Raggi et al. Circulation 2005;112:563

•LDL control vs. CAC progression over 12 months

•RCT, n = 615

•Atorva 80 vs. prava 40

•LDL 92 vs. 129

•No difference in CVS

•~15%/yr

Statin/CAC Paradox: St. Francis

Arad et al. J Am Coll Cardiol 2005;46:166 –72

•Atorva vs. placebo

•RCT, n = 1005

•With CAC>80th percentile

•4 year CAC progression

•No difference despite strong trend for event reduction

•CAC progression:

•Slightly greater in those with events

•44% vs. 33%

•Unrelated to events

ATVB 2005;25:592

•In vitro study of statins on AVMF and osteoblasts

“Statins inhibit calcification in AVMFs by inhibiting the cholesterol biosynthetic pathway, independent ofprotein prenylation, but paradoxically stimulate bone cell calcification. “

Conclusions

•Individuals with atherosclerosis progression is associated with heightened risk for cardiovascular events

•Invasive and noninvasive assessments

•CIMT: Accurate detection of risk will require that the IMT measurement be reproducible enough and time horizon be long enough to accurately discriminate true progression

•Progression of CAC >15% per year has been associated with increased risk of CHD events

•Overlap, determinants, and statin paradox complicate this assessment

•More study needed