Prevalence (%) Prevalence of CAC by Degree of cPB No Carotid Plaque cPB Tertile 1 cPB Tertile 2 cPB Tertile 3 (n=1,316) (n=1,498) (n=1,497) (n=1,497) Supplementary.

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Prevalence (%) Prevalence of CAC by Degree of cPB No Carotid Plaque cPB Tertile 1 cPB Tertile 2 cPB Tertile 3 (n=1,316) (n=1,498) (n=1,497) (n=1,497) Supplementary Figure 1. Prevalence of coronary artery calcium (CAC) groups by level of carotid plaque burden (cPB).

Supplementary Table 1A. Hazard Ratios (95% Confidence Interval) for Primary MACE Endpoint Associated with Coronary Calcification and Carotid Plaque Burden After Adjusting for Risk Factors and Both Imaging Modalities No AtherosclerosisTertile 1Tertile 2Tertile 3p-value (trend) CAC1.0 (ref)1.05 ( )1.38 ( )2.42 ( )0.01 cPB1.0 (ref)0.71 ( )1.26 ( )1.80 ( )0.03 Supplementary Table 1B. Hazard Ratios (95% Confidence Interval) for Secondary MACE Endpoint Associated with Coronary Calcification and Carotid Plaque Burden After Adjusting for Risk Factors and Both Imaging Modalities No AtherosclerosisTertile 1Tertile 2Tertile 3p-value (trend) CAC1.0 (ref)1.28 ( )1.31 ( )2.42 ( )<0.001 cPB1.0 (ref)1.41 ( )1.87 ( )2.25 ( )0.001 CAC – coronary artery calcification; cPB – carotid plaque burden; MACE – major adverse cardiovascular events; Hazard ratios generated from multivariable models adjusted for CAC, cPB, race, age and sex, diabetes mellitus, current smoking, body mass index, systolic blood pressure, anti- hypertensive use, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and use of lipid lowering drugs.

Supplementary Table 2A. Hazard Ratios (95% Confidence Interval) for Primary MACE Endpoint Associated with Coronary Calcification or Carotid Plaque Burden Based on Quartiles of Atherosclerosis No AtherosclerosisQuartile 1Quartile 2Quartile 3Quartile 4p-value (trend) CAC1.0 (ref)0.81 ( )1.22 ( )2.05 ( )3.64 ( )<0.001 cPB1.0 (ref)0.70 ( )1.46 ( )1.45 ( )2.53 ( )0.002 Supplementary Table 2B. Hazard Ratios (95% Confidence Interval) for Secondary MACE Endpoint Associated with Coronary Calcification or Carotid Plaque Burden Based on Quartiles of Atherosclerosis No AtherosclerosisQuartile 1Quartile 2Quartile 3Quartile 4p-value (trend) CAC1.0 (ref)1.23 ( )1.44 ( )1.88 ( )3.38 ( )<0.001 cPB1.0 (ref)1.45 ( )1.79 ( )2.60 ( )2.88 ( )<0.001 CAC – coronary artery calcification; cPB – carotid plaque burden; MACE – major adverse cardiovascular events; Hazard ratios for MACE associated with CAC or cPB quartiles generated from multivariable models adjusted for race, age, sex, diabetes mellitus, current smoking, body mass index, systolic blood pressure, anti-hypertensive use, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and use of lipid lowering drugs.

Supplementary Table 3 Categorical Net Reclassification Tables for Primary MACE Endpoint with CAC (top panel) and cPB (bottom panel) Classification According to the Framingham Risk ScoreReclassification Accounting for CACTotal No. Without EventsLowIntermediateHigh Low, < 10% in 10 yrs Intermediate, 10%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number without events With Events Low, < 10% in 10 yrs Intermediate, 10%-20% in 10 yrs High, ≥ 20% in 10 yrs12811 Total number with events Net Reclassification improvement0.19 Classification According to the Framingham Risk ScoreReclassification Accounting for cPBTotal No. Without EventsLowIntermediateHigh Low, < 10% in 10 yrs Intermediate, 10%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number without events With Events Low, < 10% in 10 yrs Intermediate, 10%-20% in 10 yrs High, ≥ 20% in 10 yrs23611 Total number with events Net Reclassification improvement0.14

Supplementary Table 4 Categorical Net Reclassification Tables for Secondary MACE Endpoint with CAC (top panel) and cPB (bottom panel) Classification According to the Framingham Risk ScoreReclassification Accounting for CACTotal No. Without EventsLowIntermediateHigh Low, < 10% in 10 yrs Intermediate, 10%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number without events With Events Low, < 10% in 10 yrs Intermediate, 10%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number with events Net Reclassification improvement0.16 Classification According to the Framingham Risk ScoreReclassification Accounting for cPBTotal No. Without EventsLowIntermediateHigh Low, < 10% in 10 yrs Intermediate, 10%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number without events With Events Low, < 10% in 10 yrs Intermediate, 10%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number with events Net Reclassification improvement0.13

Net Reclassification Improvement Supplementary Figure 2. Clinical Net Reclassification Improvement for Primary and Secondary MACE Endpoints with coronary artery calcium (CAC) and carotid plaque burden (cPB) in Intermediate Risk Subjects. Primary MACE Endpoint Secondary MACE Endpoint Clinical Net Reclassification with CAC or cPB Using Framingham Risk Score

Supplementary Table 5 Categorical Net Reclassification Tables for Primary MACE Endpoint with CAC (top panel) and cPB (bottom panel) Classification According to the Pooled Cohort Risk EquationsReclassification Accounting for CACTotal No. Without EventsLowIntermediateHigh Low, < 7.5% in 10 yrs Intermediate, 7.5%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number without events With Events Low, < 7.5% in 10 yrs Intermediate, 7.5%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number with events Net Reclassification improvement0.17 Classification According to the Pooled Cohort Risk EquationsReclassification Accounting for cPBTotal No. Without EventsLowIntermediateHigh Low, <7.5% in 10 yrs Intermediate, 7.5%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number without events With Events Low, < 7.5% in 10 yrs Intermediate, 7.5%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number with events Net Reclassification improvement0.14

Supplementary Table 6 Categorical Net Reclassification Tables for Secondary MACE Endpoint with CAC (top panel) and cPB (bottom panel) Classification According to the Pooled Cohort Risk EquationsReclassification Accounting for CACTotal No. Without EventsLowIntermediateHigh Low, < 7.5% in 10 yrs Intermediate, 7.5%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number without events With Events Low, < 7.5% in 10 yrs Intermediate, 7.5%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number with events Net Reclassification improvement0.17 Classification According to the Pooled Cohort Risk EquationsReclassification Accounting for cPBTotal No. Without EventsLowIntermediateHigh Low, < 7.5% in 10 yrs Intermediate, 7.5%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number without events With Events Low, < 7.5% in 10 yrs Intermediate, 7.5%-20% in 10 yrs High, ≥ 20% in 10 yrs Total number with events Net Reclassification improvement0.13

Net Reclassification Improvement Supplementary Figure 3. Clinical Net Reclassification Improvement for Primary and Secondary MACE Endpoints with coronary artery calcium (CAC) and carotid plaque burden (cPB) in Intermediate Risk Subjects. Primary MACE Endpoint Secondary MACE Endpoint Clinical Net Reclassification with CAC or cPB Using Pooled Cohort Risk Equations