1. Presenter Disclosure Information Diane Bild, MD, MPH Screening for Subclinical Atherosclerosis as a Strategy for CVD Prevention FINANCIAL DISCLOSURE: None UNLABELED/UNAPPROVED USES DISCLOSURE: None

2. Diane Bild, MD, MPH Associate Director, Prevention and Population Sciences Program Division of Cardiovascular Sciences The views expressed are not necessarily those of NHLBI.

3.  Prevent morbidity and mortality due to CVD ◦ Identify disease before it becomes symptomatic. ◦ Prevent disease progression. Footnote: “Screening” is a standardized population or case-finding approach, not an individualized strategy.

4.  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.

5.  Hundreds of risk factors  Countless analyses from observational studies  Recent progress in modeling risk prediction, particularly with clinical relevance ◦ Discrimination ◦ Calibration ◦ Reclassification

6. http://lifebeat.pt/en2.php Identify high risk Further diagnosis Treatment Rx ? statins ? aspirin ? antihypertensives Long-term adherence Risk lowered

7. 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.

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

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

11. GradeDefinition Suggestions 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.

12. GradeDefinition Suggestions 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.

13. ConditionExplanationGrade 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

14. ConditionExplanationGrade 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

15. ConditionExplanationGrade 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

16. ConditionExplanationGrade 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 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.

17. ConditionExplanationGrade 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. ABAB 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. ABAB

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

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

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

21. Source: Cholesterol Treatment Trials Collaborators. Lancet 2005:366:1267–78 “Treatment better” ~25% risk reduction

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

23.  Published in 1967  N=143 VA Cooperative Study Group on Antihypertensive Agents. JAMA 1967;202:116-21.

25. 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.

26.  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

27.  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.