Integrating Imaging and Biomarkers for Optimal CVD Risk Assessment and Management None Disclosures Arthur Agatston Conceptual Approach to CAD Risk Devereux Circulation, 1993 1
Age Obesity Family Hx Diabetes Hypertension Thrombogenic RFs Obesity Diabetes Hypertension LDL CAC Tobacco LDL Family History Tobacco HDL 9p21 Fitness Microbiome HDL 9p21 Fitness Microbiome (Carnitine) Unknown Unknown Impact of coronary artery calcium on coronary heart disease events in individuals at the extremes of traditional risk factor burden: the Multi-Ethnic Study of Atherosclerosis The New Prevention Strategy Known Family History Life Style Pre-Clinical Disease Silverman, MG. European Heart Journal December 23, 2013 Unknown 2
AG, 54 yo WM Police Major +FH CAD Competitive Runner TC=180 TG= 64 HDL=58 LDL=109 CRP=.04 Family History Known Life Style Pre-Clinical Disease Framingham Risk Score Unknown AG, 54 yo WM Police Major +FH CAD Competitive Runner TC=180 TG= 64 HDL=58 LDL=109 CRP=.04 FRS-Low Family History Known Life Style Pre-Clinical Disease AG, 54 yo WM Police Major +FH CAD Competitive Runner TC=180 TG= 64 HDL=58 LDL=109 CRP=.04? Lp(a) Blocked arteries->bypass Surgery Calcium Score>1500 Unknown 3
AG, 54 yo WM Police Major +FH CAD Competitive Runner TC=180 TG= 64 HDL=58 LDL=109 CRP=.04 Family History Known Life Style Clinical Disease AG-High Risk with Zero Risk Factors Risk of Heart Attack Calcium Score Unknown Lp(a),?HDL Dysfunction Number of (RF) Nasir K, Circ Cardiovasc Imaging. 2012; 5:467-473 PS 70 F TC=314,LDL=229 Known PS-The Power of Zero (MESA) Family History Life Style Calcium Score=0 Pre-Clinical Disease Unknown? Martin SA, Circulation. 2014;129:77-86 4
PS 70 yo TC=314,LDL=229 Calcium Score=0, Large LDL Why FH and 0 CAC?? Large LDL Particles CAC in Familial Hypercholesterolemia n=107, 45+/-13, 36% DMW 56M CAC=750 age 44 +++ FH: father MI/CABG at 50, Brother MI age 50 CACS=1,386 1/11/08; CACS=1,000, 90th% 11/8/05 @ Baptist; CACS=750.9 8/31/01 per EBT; M.H. Miname et al. Atherosclerosis 213 (2010) 486 491 CAC: 1/11/08 11/8/05 8/31/01 1,386 1,000 750 5
High LDL, High CAC (MESA) CAC in Familial Hypercholesterolemia n=107, 45+/-13, 36% Martin SA, Circulation. 2014;129:77-86 M.H. Miname et al. Atherosclerosis 213 (2010) 486 491 SS 70 M, DM, BP, BMI 27, TC, +FH,Low HDL, high TG, small LDL Diabetic, High Cholesterol, Multiple How to Treat? + Diabetes 6
Risk of Heart Attack SS-CAC=0 The Power of Zero Calcium Score CAC Score Groups Diabetes & no CAC Is Rx indicated? No MetS/DM (n= 4036 ) MetS without DM (n =1687) DM (n=882 ) CHD Event rate per 1000 Person Year 0 0.7 (0.3-1.4) 1.2 (0.5-2.8) 1.6 (0.5-5.1) 1-99 3.3 (2.1-5.2) 6.1 (3.7-9.9) 9.1 (5.0-16.4) 100-399 6.0 (3.7-9.9) 12.6 (7.9-20.0) 13.4 (7.4-24.2) Number of (RF) Nasir K, Circ Cardiovasc Imaging. 2012; 5:467-473 400+ 12.0 (7.7-18.6) 15.3 (9.1-25.8) 18.3 (10.9-30.9) Malik S, Budoff M, Katz R, Blementhal RJ, Alain Bertoni, Blumenthal RS, Nasirk K, Szklo M, Barr G, Wong ND ( Diabetes Care 2012) AG, 54 yo WM Police Major +FH CAD Competitive Runner TC=180 TG= 64 HDL=58 LDL=109 CRP=.04? Blocked arteries->bypass Surgery Calcium Score>1500 Why?? HDL Dysfunction 7
LDLR Cholesterol Pool HDL Metabolism Liver LDL/VLDL CETP HDL 2 ABCA1 NL Function HDL GGE (80 yo WF with Calcium Score=0) Apo A1 SRB1 HDL 3 ABCA1 Plaque Down Regulated ABCA1 Too Much HDL3 Liver HDL 2 ABCA1 SRB1 HDL 3 ABCA1 8
HDL Size Distribution Spectrum Healthy Un Healthy HDL Dysfunction Treatment BP-69 yo F- +FH No other known risk factors 4/17/00 4/16/01 TCS=1766 Stent Stent TG=142 HDL=120 LDL=100 LDL-S=267 Lp(a)=10 FRS=1%? Rx SRB1 Dysfunctional HDL-2 SRB-1 Model LDLR LDL/VLDL CETP Liver HDL 2 ABCA1 HDL 3 ABCA1 9
HDL GGE in SRB1/CETP Downregulation (HDL2 Bump) BP-69 yo F- +FH No other known risk factors 4/17/00 4/16/01 TCS=1766 Stent Stent TG=142 HDL=120 LDL=100 LDL-S=267 Lp(a)=10 FRS=1%? Rx BP-69 yo HDL 120, Low FRS, + FH BP Family (father 84-CAC 121-33 rd %) HDL GGE -2000 BP-69F CAC~1800 HDL=120 SP-54M CAC=443 HDL=87 JP-47 CAC=596 HDL=113 10
M-T Family-father MI 42 JT-59F-CAC=2,267 HDL=144 JT-59F-CAC=2,267 HDL=144 JM-58M-CAC=494 HDL=88 GM 55M CAC=1,154 HDL=102 JT-59F-CAC=2,267 HDL=144 HDL Bump LDL Bump AG, 54 yo WM Police Major +FH CAD Competitive Runner TC=180 TG= 64 HDL=58 LDL=109 CRP=.04 Calcium Score>1500 11
LW 64 WF-DM1-CAC=3,000 Father MI ~43 LW 64 WF-DM1-CAC=3,000 LW 64 WF-DM1-CAC=3,000 HDL in Type 1 Diabetes Epidemiology of Diabetes Complications Study Costacou, T, J Clin Lipidology 2011; 5:387-394 12
Familial HDL Dysfunction Established Clinical CAD/Carotid Calcium Score > 75 th percentile Family h/o Premature CAD Low Risk Framingham Score Normal BMI Normal Insulin Sensitivity Elevated or Normal HDL/TG < 100 HDL 2 Bump NL LDL PPD/Small LDL Bump 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 13
Calcium Density of Coronary Artery Plaque and Risk of Incident Cardiovascular Events Old Young Youngest Younger MH Criqui, MJ Budoff,JAMA. 2014;311(3):271-278. Steady Athero Progression Arrested Progression due to Rx 100 20 Individual Plaque Score 5 0 100 20 Individual Plaque Score 5 0 14
SJ 70 F 2ppd smoker d/ced age 48 CAC-280 JCC-61: cac=79 belly fat resolved 20 yrs ago Late Onset due to Weight Gain Metabolic Syndrome or Young Patient AF 73 M CAC=274, from low score age 63 MS->DM2 x 10 yrs 100 20 Individual Plaque Score 5 0 15
Young, Thrombogenic Event 100 20 Individual Plaque Score 5 0 Devereux Circulation, 1993 PQ Thank You 16
Most People who Develop Heart Attacks have Normal LDL Values Heart attack with normal LDL Lipid levels in patients hospitalized with coronary artery disease: An analysis of 136,905 hospitalizations in Get With The Guidelines Of 136,905 patients hospitalized with CAD, more than 75% had LDL levels below 130 mg/dl 23% had LDL-C <70 mg/dl 2011 CGHDI Sachdevaet al. AHJ, Vol 157, 111-117 Jan 2009 Framingham-Total Cholesterol to HDL Ratio in those with and without future heart attacks AG-High Risk with Zero Risk Factors Lloyd-Jones DM, Arch Intern Med 2001;161:949-954 Silverman, MG. European Heart Journal December 23, 2013 17