Risk Factors, the New Calcium Score, Rheology and Atherosclerosis Progression Arthur Agatston 2/21/15 The Vulnerable Plaque vs. Plaque Burden CT Angiogram Is There a Role for Coronary Artery Calcium Scoring for Management of Asymptomatic Patients at Risk for Coronary Artery Disease? Who Cares About the Past? Blaha, M. Circ Cardiovasc Imaging. 2014;7:398-408 Why Is Subclinical Disease Superior to Risk Factor Assessment? Family Hx Age Diabetes Integration of Risk Factors including Unknown Factors, Multiple SNPs Obesity Hypertension Subclinical Disease Reflects the Dosage of Risk Factors over time LDL HDL CAC Tobacco Fitness Quantifying Subclinical Disease Reflects the High Risk Patient-the vulnerable plaque does not 9p21 Unknown Microbiome 1
What is the extent of atherosclerosis at the time of coronary events? Coronary Atherosclerosis is a Diffuse, Not a Focal Disease Roberts WC. Am J Cardiol 1988:62; 142-143 Coronaries in Angina Diffuse CAD in Pts Ieth AMI and CABG Roberts WC Circulation 1976: 54(3) 388. Roberts WC. Am J Cardiol 1988:62 (1); 144-147 Glagov S, NEJM 1987;316:1371-5 Glagov S, NEJM 1987;316:1371-5 2
Angiographically unrecognized left main coronary artery disease. Glagov S, NEJM 1987;316:1371-5 Topol E J, and Nissen S E Circulation. 1995;92:2333-2342 Prognostic Value of Presence and Extent of Non-obstructive and Obstructive CAD By CT Angiography Atherosclerosis: what is it and why does it occur? Michael J. Davies Circ Cardiovasc Imaging. 2014;7:282-291. Br Heart J 1993;69(Supplement):S 3-S 11 The Quantitative Nature of the Relationship of the Extent of Coronary Artery Atherosclerosis and Coronary Heart Disease Risk Prevalence of and Risk Factors for Autopsy-Determined Atherosclerosis Among US Service Members, 2001-2011 Degree of Atherosclerosis in Standard Score Units John Gofman. Cardiology Digest February 1969: p.28-38 Weber BJ. JAMA. 2012;308(24):2577-2583 3
The Concept of Duration of Risk Factor Exposure Conventional Approach-Ignores Duration of Risk Factor Exposure Past and Future One Time Measurement In Older Patients Blaha, M. Circ Cardiovasc Imaging. 2014;7:398-408 Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension Lancet 2010; 375: 938 48 Hypertrophy What about the Cumulative Dosage of High Blood Pressure, Hypercholesterolemia and other Risk Factors? 4
Hyperlipidemia in Early Adulthood Increases Long- Term Risk of Coronary Heart Disease Duration of LDL Lowering using Mendelian Randomization Circulation 2015, 114: 1-20 Effect of Long-Term Exposure to Lower LDL Beginning Early in Life on the Risk of CAD A Mendelian Randomization Analysis The emerging data suggest that CHD risk is likely best expressed as a function of cumulative exposure to all risk determinants over a lifetime Ference BA. J Am Coll Cardiol 2012;60:2631 9 Blaha, M. Circ Cardiovasc Imaging. 2014;7:398-408 Is There a Role for Coronary Artery Calcium Scoring for Management of Asymptomatic Patients at Risk for Coronary Artery Disease? Does the Extent of Atherosclerosis or the Rate of Atherosclerosis Predict Future Coronary Events? Percentile vs. Score? Percentile Score vs. Total CAC/Plaque Burden= Prognosis Blaha, M. Circ Cardiovasc Imaging. 2014;7:398-408 Detrano NEJM Volume 358:1336-1345 5
Why Do Coronary Events Occur Almost Exclusively After Extensive Atherosclerosis is Present? The Role of Rheology Rheology and Atherosclerosis The role of shear stress in the pathogenesis of atherosclerosis The role of shear stress in the pathogenesis of atherosclerosis Cunningham, C. Laboratory Investigation (2005) 85, 9 23 Cunningham, C. Laboratory Investigation (2005) 85, 9 23 6
Carotid Flow Effects of Disturbed Flow on Vascular Endothelium Annu. Rev. Biomed. Eng. 1999. 01:299 329 Physiol Rev 91: 327 387, 2011; A shear gradient dependent platelet aggregation mechanism drives thrombus formation Rheology and Thrombosis Nesbitt WS, NATURE MEDICINE VOLUME 2009;15 (6) : 665 A shear gradient dependent platelet aggregation mechanism drives thrombus formation Nesbitt WS, NATURE MEDICINE VOLUME 2009;15 (6) : 665 Nesbitt WS, NATURE MEDICINE VOLUME 2009;15 (6) : 665 7
Disturbed Blood Flow Acutely Induces Activation and Apoptosis of the Human Vascular Endothelium Thus, our findings raise the idea that disturbed blood flow induces EMPs which may further promote endothelial dysfunction at distal sites, resulting in a feed-forward vicious cycle of vascular injury. Jenkins NT, Hypertension. 2013;61:615-621 8
The Future of Coronary Imaging There is a lot more clinical information in CT and CTA Images Natural History of Atherosclerotic Plaque Natural History of the Post Rupture Lesions Fibrous tissue Calcium Old Young 9
Old How do we best quantify this atherosclerosis progression on a CT scan? Young Youngest Younger # of Lesions in Range Steady Athero Progression-55 yo >100 20-100 5-20 0-5 Range Individual Plaque Score <0 # of Lesions in Range Steady Athero Progression 70 yo >100 20-100 5-20 0-5 Range Individual Plaque Score <0 Steady Athero Progression 45 yo Life Long Exposure (Homozygous 9P21) # of Lesions in Range >100 20-100 5-20 0-5 Range Individual Plaque Score <0 10
# of Lesions in Range Arrested Progression due to Rx >100 20-100 5-20 0-5 <0 Individual Plaque Score AF 73 M CAC=274, from low score age 63 MS->DM2 x 10 yrs # of Lesions in Range Late Onset due to Weight Gain Metabolic Syndrome or Young Patient >100 20-100 5-20 0-5 <0 Individual Plaque Score Is There a Role for Coronary Artery Calcium Scoring for Management of Asymptomatic Patients at Risk for Coronary Artery Disease? Blaha, M. Circ Cardiovasc Imaging. 2014;7:398-408 11
Noninvasive Assessment of Gender Differences in Coronary Plaque Composition with Multidetector Computed Tomographic Angiography Noninvasive Assessment of Plaque Characteristics With CTA in Symptomatic Type 2 Diabetic Patients CAC=150 CAC=400 CAC=300 CAC=500 Am J Cardiol 2010;105:453 458 Diabetes Care 30:1113 1119, 2007 Natural Hx of Atherosclerosis Progression Natural Hx of Atherosclerosis Progression Cumulative Atherosclerosis Wt Gain MS RXRX DM2 Familial Dyslipidemia pre/post menopause Metabolic Syndrome-> DM2 Treated Atherosclerosis Slowed Progression Cumulative Atherosclerosis RX RX Untreated Dyslipidemia Treated Atherosclerosis Slowed Progression Aggressively Treated Arrested Progression Menopause 10 20 30 40 50 60 70 80 Age Aggressively Treated Arrested Progression 10 20 30 40 50 60 70 80 Age Atherosclerosis Progression Patterns CAC=150 CAC=300 Thank You 55 yo Female 55 yo Male CAC=400 CAC=500 60 yo non-diabetic with CAD 60 yo diabetic with CAD 12
Monitoring Atherosclerosis Progression 13