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Diane Bild, MD, MPHScreening for Subclinical Atherosclerosis as a Strategy for CVD Prevention

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Screening for Subclinical Atherosclerosis as a Strategy for CVD Prevention

AHA Quality and OutcomesMay 21, 2010

Diane Bild, MD, MPHAssociate Director, Prevention and Population Sciences Program

Division of Cardiovascular Sciences

The views expressed are not necessarily those of NHLBI.

Prevent morbidity and mortality due to CVD◦Identify disease before it becomes symptomatic.

◦Prevent disease progression.

The Goals of Subclinical CVD Screening

Footnote: “Screening” is a standardized population or case-finding approach, not an individualized strategy.

It may be costly. It may cause undue psychological

stress. Coronary artery calcium detection

requires CT scanning and radiation, which may induce cancer.

CT scans may uncover other subclinical disease (such as pulmonary nodules) that requires further work-up.

Possible Harms of Subclinical CVD Screening

Hundreds of risk factors Countless analyses from observational studies

Recent progress in modeling risk prediction, particularly with clinical relevance◦ Discrimination◦ Calibration ◦ Reclassification

Prediction

Theoretical pathway from screening to prevention

http://lifebeat.pt/en2.php

Identify high risk

Further diagnosis

Treatment Rx? statins? aspirin? antihypertensives

Long-term adherence

Risk lowered

Atherosclerosis Test

Very Low Risk3

Negative Test• CACS =0• CIMT <50th percentile

LowerRisk

ModerateRisk

Positive Test• CACS ≥1• CIMT 50th percentile or Carotid Plaque

ModeratelyHigh Risk

HighRisk

VeryHigh Risk

No Risk Factors5 + Risk Factors • CACS <100 & <75th%• CIMT <1mm & <75th%

& no Carotid Plaque

• Coronary Artery Calcium Score (CACS)or

• Carotid IMT (CIMT) & Carotid Plaque4

• CACS 100-399 or >75th%• CIMT 1mm or >75th%

or <50% Stenotic Plaque

• CACS >100 & >90th%or CACS 400

• 50% Stenotic Plaque6

IndividualizedIndividualizedIndividualized5-10 years5-10 yearsRe-test Interval

<70 mg/dl<100 mg/dl<70 Optional

<130 mg/dl<100 Optional

<130 mg/dl<160 mg/dlLDL Target

All >75y receive unconditional treatment2

Apparently Healthy Population Men>45y Women>55y1

ExitExit

MyocardialIschemiaTest

NoAngiography

Follow Existing Guidelines

Yes

The 1st S .H .A .P .E . GuidelineTowards the National Screening for Heart Attack Prevention and Education (SHAPE) Program

Step 1

Step 2

Step 3Optional

CRP>4mg

ABI<0.9

1: No history of angina, heart attack, stroke, or peripheral arterial disease.2: Population over age 75y is considered high risk and must receive therapy without testing for atherosclerosis.3: Must not have any of the following: Chol>200 mg/dl, blood pressure >120/80 mmHg, diabetes, smoking, family history, metabolic syndrome.4: Pending the development of standard practice guidelines.5: High cholesterol, high blood pressure, diabetes, smoking, family history, metabolic syndrome.6: For stroke prevention, follow existing guidelines.

How do we decide when screening is valuable?

Wilson JM. J R Coll Gen Pract 1968;16 Suppl 2:48 –57.

How do we decide when screening is valuable?

Wilson JM. J R Coll Gen Pract 1968;16 Suppl 2:48 –57.

Criteria for Evaluation of Novel Markers of Cardiovascular Risk

Hlatky, et al. Circulation 2009; 119:2408-2416.

??

CAC?

U.S. Preventive Services Task ForceGrade

DefinitionSuggestions for Practice

A The USPSTF recommends the service. There is high certainty that the net benefit is substantial.

Offer or provide this service.

B The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.

Offer or provide this service.

C The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is at least moderate certainty that the net benefit is small.

Offer or provide this service only if other considerations support the offering or providing the service in an individual patient.

U.S. Preventive Services Task ForceGrade

DefinitionSuggestions for Practice

D The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.

Discourage the use of this service

I State

ment

The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

Read the clinical considerations section of USPSTF Recommendation Statement. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms.

Condition Explanation Grade

Abdominal aortic aneurysm (2005)

One-time screening for AAA by ultrasonography in men aged 65 to 75 who have ever smoked.

B

No recommendation for or against screening for AAA in men aged 65 to 75 who have never smoked.

C

The USPSTF recommends against routine screening for AAA in women.

D

CV screening recommendations per USPSTF

Condition Explanation Grade

Carotid artery stenosis (2007)

Recommends against screening for asymptomatic carotid artery stenosis in the general adult population.

D

Peripheral artery disease (2005)

The USPSTF recommends against routine screening for peripheral arterial disease.

D

CV screening recommendations per USPSTF, continued

Condition Explanation Grade

Coronary heart disease (2004)

Recommends against routine screening with resting electrocardiography (ECG), exercise treadmill test (ETT), or electron-beam computerized tomography (EBCT) scanning for coronary calcium for either the presence of severe coronary artery stenosis (CAS) or the prediction of coronary heart disease (CHD) events in adults at low risk for CHD events.

D

Insufficient evidence to recommend for or against routine screening with ECG, ETT, or EBCT scanning for coronary calcium for either the presence of severe CAS or the prediction of CHD events in adults at increased risk for CHD events.

I

CV screening recommendations per USPSTF, continued

Condition Explanation Grade

Risk assessment, nontraditional risk factors (2009)

Evidence is insufficient to assess the balance of benefits and harms of using the nontraditional risk factors discussed in this statement to screen asymptomatic men and women with no history of CHD to prevent CHD events

I

CV screening recommendations per USPSTF, continued

The nontraditional risk factors included in this recommendation are high-sensitivity C-reactive protein (hs-CRP), ankle-brachial index (ABI), leukocyte count, fasting blood glucose level, periodontal disease, carotid intima-media thickness (carotid IMT), coronary artery calcification (CAC) score on electron-beam computed tomography (EBCT), homocysteine level, and lipoprotein(a) level.

Condition Explanation Grade

Lipid disorders in adults (2008) - Men

The U.S. Preventive Services Task Force (USPSTF) strongly recommends screening men aged 35 and older for lipid disorders.  

The USPSTF recommends screening men aged 20 to 35 for lipid disorders if they are at increased risk for coronary heart disease.

A

B

Lipid disorders in adults (2008) – Women at increased risk

The USPSTF strongly recommends screening women aged 45 and older for lipid disorders if they are at increased risk for coronary heart disease.  

The USPSTF recommends screening women aged 20 to 45 for lipid disorders if they are at increased risk for coronary heart disease.

A

B

CV screening recommendations per USPSTF, continued

Condition Explanation Grade

Lipid disorders in Adults --Young Men and All Women Not at Increased Risk

The USPSTF makes no recommendation for or against routine screening for lipid disorders in men aged 20 to 35, or in women aged 20 and older who are not at increased risk for coronary heart disease.

C

Blood pressure

The U.S. Preventive Services Task Force (USPSTF) recommends screening for high blood pressure in adults aged 18 and older.

A

CV screening recommendations per USPSTF, continued

Level of evidence A: recommendation based on evidence from multiple randomized trials or meta-analyses

Level of evidence B: recommendation based on evidence from a single randomized trial or nonrandomized studies

Level of evidence C: recommendation based on expert opinion, case studies, or standards of care

The ACC/AHA guidelines grading scheme – Results for CAC

Tricoci, et al. JAMA 2009;301:831-841.

CAC improves CHD risk prediction, calibration, and classification

Polonsky, et al. JAMA 2010;303:1610-16.

Efficacy of cholesterol-lowering treatment:prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins

Source: Cholesterol Treatment Trials Collaborators. Lancet 2005:366:1267–78

“Treatment better”~25% risk reduction

Randomized, placebo-controlled trial of cholestyramine

Lipid Research Clinics Program. JAMA 1984;251:351-64.

Published in 1967 N=143

Randomized placebo-controlled trial of diuretics in severe hypertension

VA Cooperative Study Group on Antihypertensive Agents. JAMA 1967;202:116-21.

We have come only so far . . .

Call for trials of imaging

Douglas, et al. Outcomes Research in Cardiovascular Imaging: Report of a Workshop Sponsored by the National Heart, Lung, and Blood Institute. JACC Cardiovasc Imaging 2009;2:897-907.

Guidelines may need to be changed due to:◦Emergence of new evidence◦Changes in disease prevalence◦Consideration of new risk groups◦Development of new therapies◦Changes in the cost of treatment

Re-evaluating Screening Guidelines

Goals are laudable; some candidate screening markers have promising characteristics.

Harms of screening need to be carefully considered, especially for coronary artery calcium detection.

Few screening targets in cardiovascular disease prevention are deemed beneficial -- most notably, BP and lipids.

Much work has been performed in estimating prediction; little in estimating outcomes.

Any screening guidelines need periodic re-evaluation.

Summary – Subclinical CVD Screening