New Paradigms in Predicting CVD Risk Imaging as an Integrator of Lifetime Risk Exposure Michael J. Blaha MD MPH Presented by: Michael J. Blaha September 24, 2014 1 Talk Outline Risk factors vs. Disease scores Imaging paradigm the coronary artery calcium score (CAC) Imaging vs. risk factors vs. serum markers The importance of absence of disease in modern medicine Imaging Biologic Aging September 24, 2014 2 1
Section 1 RISK FACTORS VS. DISEASE SCORES September 24, 2014 3 Traditional 10-Year Risk Model RISK Risk Factor Exposure?? Outcomes?? ATHEROSCLEROSIS 0 10 20 30 40 50 60 70 80 90 AGE 2
Environment Continuum of Atherosclerosis Propagation Prior to a CHD Event Genetics Risk Factors Obesity Hypertension Dyslipidemia Diabetes Biomarkers Inflammation Subclinical Atherosclerosis Coronary Calcification Overt CAD CHD Event Death MI ACS Revasc. hscrp Ischemia Continuum of Atherosclerosis Propagation Prior to a CHD Event Genetics Environment Funnel Risk Factors Biomarkers Subclinical Atherosclerosis Overt CAD 3
Subclinical Disease Detection Model RISK Integrates Risk Exposure!! 0 10 20 30 40 50 60 70 80 90 AGE Risk Factor vs. Disease Score RISK FACTOR Measures increased risk for developing disease Separates risk elements Reduction in risk factor should reduce disease Usually mild risk predictive value Cancer analogy high hormone levels in breast cancer DISEASE SCORE Measures the disease itself Integrates risk exposure Disease score may not measure treatment effect Usually a powerful predictor of risk Cancer analogy detection of suspicious nodule on mammography 4
Section II THE CORONARY ARTERY CALCIUM SCORE September 24, 2014 9 Relationship of Calcification to Coronary Atherosclerosis 20% Rumberger, Circulation 1995 September 24, 2014 10 5
September 24, 2014 11 ~1 msv 6
Calculation of Agatston Score Agatston Score = CAC area x maximal density factor HU x-factor (peak w/in lesion) 130-199 1 200-299 2 300-399 3 >400 4 Area = 15 mm 2, Peak CT = 450 Score = 15 x 4 = 60 Area = 8 mm 2, Peak CT = 290 Score = 8 x 2 = 16 Agatston AS et al. JACC 1990;15:827-32 Images: Rumberger JA Mayo Clin Proc 1999;74:243-52 ST. FRANCIS HEART STUDY Prospective population based study of 5,585 asymptomatic individuals Predominantly low-intermediate risk men and women Follow up=4.3 years CHD events=119 26.2 (12.6-53.7) OR Ref 1.9 (0.8-4.2) 10.2 (4.8-21.6) Arad et al. J Am Coll Cardiol.. 2005; 46:158 165. 7
Risk of All-Cause Mortality in Framingham Risk Categories 0.14 0.12 CAC score 0.1 0.08 0.06 0.04 <10 11-100 101-400 401-1000 >1000 0.02 0 Low Risk n=1,302 Intermediate Risk n=5,876 High Risk n=3,194 Shaw L, Raggi P et al Radiology 2003 8
Are you really as old as your Arteries? MESA 25.31 30 25 17.74 18.93 24.41 20 15 10 3.44 6.88 9.93 7.88 CAC=0 CAC 1-10 CAC>100 5 0 0.97 1.73 2.52 2.08 45-54 years 55-64 years 65-75 years 75-84 years Tota Maharaj R, Blaha MJ, Nasir L, et al. European Heart Journal. 2012. 9
All Cause Mortality (per 1000 person years) Risk factors: smoking, dyslipidemia, diabetes, hypertension, family history of premature CHD Nasir K, et al. Circ Cardiovasc Imaging. 2012; 5:467-473. A Diabetes A CHD Risk Equivalent or Risk Non-Equivalent? Implications for Aspirin Therapy in Primary Prevention From MESA From MESA B Aspirin might be Considered Intermediate Risk Diabetes Group CAC Score Group % of Population Mortality rate per 1,000 personyears 95% CI for rate CAC = 0 29% 2.3 0.7 7.1 CAC 1-100 38% 6.2 3.4 11.6 CAC > 100 33% 20.4 14.0 29.7 From Silverman, et al. 10
Multi-Ethnic Study of Atherosclerosis: MESA CAC predicting CHD events in MESA Detrano, et al. NEJM 2008;358:1336 CAC Scores and CV Risk in Low Risk Women by FRS: The Multi-Ethnic Study of Atherosclerosis (MESA) NIH sponsored prospective study 6,814 Asymptomatic pts 2,684 asymptomatic women 45-79 yo, 3.75 yr f/u 90% low risk FRS CAC scores 0 >0 1-99 100-299 >300 68% 32% 22% 6% 5% HR > 0 vs 0 >300 Absolute events CHD 6.5 7% (3.75 yrs) CVD 5.2 9% (3.75 yrs) Lakoski S, Blumenthal RS. Archives of Internal Medicine. 2007;167:2437-42 11
Section III RISK PREDICTION IMAGING VS. THE REST September 24, 2014 23 It used to be that we would have to compare these alternatives across studies September 24, 2014 24 12
Introduction to the 4 key studies September 24, 2014 25 EISNER September 24, 2014 26 13
ROTTERDAM September 24, 2014 27 MESA From: Comparison of Novel Risk Markers for Improvement in Cardiovascular Risk Assessment in Intermediate- Risk Individuals JAMA. 2012;308(8):788-795. doi:10.1001/jama.2012.9624 September 24, 2014 28 14
MESA From: Comparison of Novel Risk Markers for Improvement in Cardiovascular Risk Assessment in Intermediate- Risk Individuals JAMA. 2012;308(8):788-795. doi:10.1001/jama.2012.9624 September 24, 2014 29 Heinz-Nixdorf Recall Study September 24, 2014 30 15
Heinz-Nixdorf Recall Study September 24, 2014 31 Section IV THE IMPORTANCE OF ABSENCE OF DISEASE IN MODERN MEDICINE September 24, 2014 32 16
CAC = 0 September 24, 2014 34 17
Percent of U.S. Adults Who Would Be Eligible for Statin Therapy for Primary Prevention, According to Set of Guidelines and Age Group. Pencina MJ et al. N Engl J Med 2014. DOI: 10.1056/NEJMoa1315665 September 24, 2014 36 18
Results of Risk Calculator September 24, 2014 37 Results of Risk Calculator in 2 Years September 24, 2014 38 19
JAMA Case: Coronary Artery Calcium Guided Statin Use % of population CHD event rate (per 1000 patientyears) 5-year NNT with 35% event reduction CAC=0 50% 1.8 282 CAC 1-100 37% 7.2 74 CAC >100 13% 12.4 46 JAMA Case: Coronary Artery Calcium Guided Statin Use % of population CHD event rate (per 1000 patientyears) 5-year NNT with 35% event reduction CAC=0 50% 1.8 282 CAC 1-100 37% 7.2 74 CAC >100 13% 12.4 46 Statistics for a man in his 6 th decade of life with elevated cholesterol, normal blood pressure, and Framingham risk score placing him at intermediate risk for a hard CHD event within 10 years. A highly conservative 35% CHD event reduction with statins is assumed. Data source: Multi-Ethnic Study of Atherosclerosis (MESA), mean 7.1 year follow-up. 20
41 What is the Warranty of CAC=0? Warranty Period of CAC=0 in Years 15% (NNS~6) 20% (NNS=5) 25% (NNS=4) Males Females Males Females Males Females All 3.1 3.6 3.5 4.9 4.6 6.4 Low Risk 5.4 5.8 6.4 6.9 7.3 7.9 Intermediate Risk 3.2 3.3 4.3 4.3 4.8 6.0 High Risk 2.9 2.9 3.1 3.2 3.2 3.5 September 24, 2014 42 21
Section V IMAGING BIOLOGIC AGING September 24, 2014 43 CAC and Non-CVD Events 25 20 15 10 5 0 Absolute Event Rates by CAC Group CAC=0 CAC 1-400 CAC >400 * p<0.001 **p<0.05 CAC = 0 (ref) 1.0 1.0 1.0 1.0 1.0 1.0 1.0 CAC >400 1.87 2.31 2.41 3.59 0.95 2.26 3.31 Adjusted HR (1.43, (1.62, (1.64, (2.07, (0.44, (1.15, (1.17, (95% CI) 2.43) 3.29) 3.54) 6.22) 2.07) 4.45) 9.36) 22
Extra-Coronary Calcification September 24, 2014 45 Closing Thoughts Risk factors can neither identify premature CAD nor preferred status The era of risk factors should end We should not look upstream (genes, etc) to improve risk prediction, we should be looking downstream Risk integrators September 24, 2014 46 23
Reduced all-cause mortality Reduced myocardial infarction Reduced MI case fatality rate Marked survival at highest levels of fitness Risk don t improve the FIT Score September 24, 2014 47 THANK YOU! September 24, 2014 48 24