Supplementary Online Content

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1 Supplementary Online Content Malik S, Zhao Y, Budoff M, et al. Coronary artery calcium score for long-term risk classification in individuals with type 2 diabetes and metabolic syndrome from the Multi-Ethnic Study of Atherosclerosis. JAMA Cardiol. Published online November 8, doi: /jamacardio etable 1. Secondary Analysis for Association of Coronary Heart Disease and Atherosclerotic Cardiovascular Disease With Coronary Artery Calcium in Those With Mellitus etable 2. Area Under the Curve With 95% CI for Predicting Coronary Heart Disease and Atherosclerotic Cardiovascular Disease and Comparison Between Models With and Without Coronary Artery Calcium Measures etable 3. Net Reclassification Improvement for Coronary Heart Disease and Atherosclerotic Cardiovascular Disease Among Those With Mellitus, Metabolic syndrome, or Neither Condition efigure 1. Coronary Heart Disease and Atherosclerotic Cardiovascular Disease Incidence per 1000 Person-Year According to Coronary Artery Calcium Score Categories and Duration (A), Insulin Use (B), Hemoglobin A 1c (C), Framingham Risk Score or Pooled Cohort Equation (D), or Metabolic Syndrome (E) in Those With Mellitus efigure 2. Kaplan-Meier Analyses Showing Event-Free Survival for Coronary Heart Disease (A) and Atherosclerotic Cardiovascular Disease (B) According to Coronary Artery Calcium (CAC) Score in Those With Mellitus (DM), According to Insulin Use efigure 3. Kaplan-Meier Analyses Showing Event-Free Survival for Coronary Heart Disease (A) and Atherosclerotic Cardiovascular Disease (B) According to Coronary Artery Calcium (CAC) Score in Those With Mellitus (DM), According to Hemoglobin A 1c efigure 4. Risk Stratification Capacity (3 Categories) of the Model With and Without Coronary Artery Calcium for Coronary Heart Disease and Atherosclerotic Cardiovascular Disease in Mellitus (A), Metabolic Syndrome (B), and Neither Metabolic Syndrome nor Mellitus (C) efigure 5. Risk Stratification Capacity (2 Categories) of the Model With and Without Coronary Artery Calcium for Coronary Heart Disease and Atherosclerotic Cardiovascular Disease in Mellitus (A), Metabolic Syndrome (B), and Neither Metabolic Syndrome nor Mellitus (C) This supplementary material has been provided by the authors to give readers additional information about their work.

2 etable 1. Secondary Analysis for Association of Coronary Heart Disease and Atherosclerotic Cardiovascular Disease With Coronary Artery Calcium in Those With Mellitus CHD ASCVD HR 95% CI HR 95% CI Model A CAC =0 1 reference 1 Reference (adjusted for FRS/PCE, CAC = ethnicity/race, SES, DM CAC = * * duration and interaction of CAC = ** ** DM duration*cac, n=575) P value for interaction Model B CAC =0 1 reference 1 Reference (adjusted for FRS/PCE, CAC = * ethinicity/race, SES, DM CAC = **** **** duration and interaction of CAC = **** **** insulin use*cac, n=881) P value for interaction Model C (adjusted for CAC =0 1 reference 1 Reference FRS/PCE, ethnicity/ race CAC = and SES in those with both CAC = ** ** DM and MetS, n=690) CAC = **** **** Model D (adjusted for CAC =0 1 reference 1 Reference FRS/PCE, ethnicity/ race CAC = and SES in those with DM CAC = * but no MetS) CAC = * ** * p<0.05, ** p<0.01, *** p<0.001, **** p< Abbreviation: ASCVD=atherosclerotic cardiovascular disease, CAC=coronary artery calcium, CHD=coronary heart disease, DM=diabetes mellitus, FRS=Framingham risk score, MetS=metabolic syndrome, PCE=pooled cohort equation, SES=socioeconomic status.

3 etable 2. Area Under the Curve With 95% CI for Predicting Coronary Heart Disease and Atherosclerotic Cardiovascular Disease and Comparison Between Models With and Without Coronary Artery Calcium Measures CHD ASCVD MetS without No MetS or diabetes MetS without No MetS or diabetes Model ( ) 0.66( ) 0.71( ) 0.60( ) 0.70( ) 0.73( ) Model ( )** 0.72( )** 0.77( )*** 0.67( )** 0.72( ) 0.76( )** Model ( )** 0.73( )** 0.77( )*** 0.67( )** 0.72( ) Model1: FRS (or PCE for ASCVD) + Ethnicity/race + SES; Model 2: FRS (or PCE for ASCVD) + Ethnicity/race + SES + lncac; Model 3: FRS (or PCE for ASCVD) + Ethnicity/race + SES + CAC category; We compared Model 2 with Model 1 and Model 3 with Model 1 and reported p value; * p<0.05, ** p<0.01, *** p<0.001, **** p< Abbreviation: ASCVD=atherosclerotic cardiovascular disease, CAC=coronary artery calcium, CHD=coronary heart disease, DM=diabetes mellitus, FRS=Framingham risk score, MetS=metabolic syndrome, PCE=pooled cohort equation, SES=socioeconomic status.

4 etable 3. Net Reclassification Improvement for Coronary Heart Disease and Atherosclerotic Cardiovascular Disease Among Those With Mellitus, Metabolic syndrome, or Neither Condition Model1 vs. Model2 CHD MetS without No MetS or diabetes 0.00( ) 0.22( )*** 0.34( )**** 0.23( ( ) -0.09( )**** 0.08)***** 0.23( ( )** 0.25( )*** 0.35)**** 0.56( ( )**** 0.65( )**** 0.81)**** ASCVD MetS without No MetS or diabetes -0.06( ) 0.14( )*** 0.23( ( )**** 0.03)**** 0.17( ( )* 0.25)**** 0.45( ( )**** 0.68)**** NRI for events (95%CI) -0.13( )**** NRI for non- 0.31(0.27- events(95%ci) 0.35)**** 3-category NRI 0.18(0.11- (95%CI) 0.25)**** Category-free 0.47(0.29- NRI 0.65)**** Absolute IDI 0.034**** 0.024**** 0.023**** 0.029**** 0.017**** 0.010* Relative IDI Model1 vs. NRI for events (95%CI) -0.01( ) 0.23( )*** 0.26( )**** -0.13( )**** -0.07( )* 0.14 ( )**** Model3 NRI for nonevents(95%ci) 0.21( )**** 0.01( ) -0.06( )**** 0.28( )**** 0.21( )**** ( )**** 3-category NRI 0.19( )** 0.23( )**** 0.20( ( ( ( )** (95%CI) 0.30)*** 0.23)**** 0.22)*** Category-free NRI 0.48( )**** 0.61( )**** 0.59( )**** 0.38( )**** 0.38( )**** 0.48( )**** Absolute IDI 0.029**** 0.027**** 0.020**** 0.028**** 0.017**** 0.010** Relative IDI Model1: FRS (or PCE for ASCVD) + Ethnicity/race + SES; Model 2: FRS (or PCE for ASCVD) + Ethnicity/race + SES + lncac; Model 3: FRS (or PCE for ASCVD) + Ethnicity/race + SES + CAC category; * p<0.05, ** p<0.01, *** p<0.001, **** p< Cutpoint of risk were 5% and 7.5% for CHD and ASCVD events. Abbreviation: ASCVD=atherosclerotic cardiovascular disease, CAC=coronary artery calcium, CHD=coronary heart disease, DM=diabetes mellitus, FRS=Framingham risk score, IDI= integrative discrimination index,mets=metabolic syndrome, NRI=net reclassification improvement, PCE=pooled cohort equation, SES=socioeconomic status.

5 efigure 1. Coronary Heart Disease and Atherosclerotic Cardiovascular Disease Incidence per 1000 Person-Year According to Coronary Artery Calcium Score Categories and Duration (A), Insulin Use (B), Hemoglobin A 1c (C), Framingham Risk Score or Pooled Cohort Equation (D), or Metabolic Syndrome (E) in Those With Mellitus

6 efigure 2. Kaplan-Meier Analyses Showing Event-Free Survival for Coronary Heart Disease (A) and Atherosclerotic Cardiovascular Disease (B) According to Coronary Artery Calcium (CAC) Score in Those With Mellitus (DM), According to Insulin Use

7 efigure 3. Kaplan-Meier Analyses Showing Event-Free Survival for Coronary Heart Disease (A) and Atherosclerotic Cardiovascular Disease (B) According to Coronary Artery Calcium (CAC) Score in Those With Mellitus (DM), According to Hemoglobin A 1c

8 efigure 4. Risk Stratification Capacity (3 Categories) of the Model With and Without Coronary Artery Calcium for Coronary Heart Disease and Atherosclerotic Cardiovascular Disease in Mellitus (A), Metabolic Syndrome (B), and Neither Metabolic Syndrome nor Mellitus (C)

9 efigure 5. Risk Stratification Capacity (2 Categories) of the Model With and Without Coronary Artery Calcium for Coronary Heart Disease and Atherosclerotic Cardiovascular Disease in Mellitus (A), Metabolic Syndrome (B), and Neither Metabolic Syndrome nor Mellitus (C)