1. Date of download: 6/29/2016 Copyright © The American College of Cardiology. All rights reserved. From: A Test in Context: High-Sensitivity C-Reactive Protein J Am Coll Cardiol. 2016;67(6):712-723. doi:10.1016/j.jacc.2015.11.037 Predictive Usefulness of hsCRP in Primary Prevention The relationship of hsCRP levels in healthy subjects to future risks of coronary heart disease and vascular deaths (top). The magnitude of cardiovascular risk associated with a 1-standard deviation (SD) change in hsCRP is at least as great as that associated with a similar change in systolic blood pressure, total cholesterol, or non–HDL-C (bottom). Data from Kaptoge et al. (6). BP = blood pressure; CI = confidence interval; hsCRP = high-sensitivity C-reactive protein; HDL-C = high-density lipoprotein cholesterol. Figure Legend:

2. Date of download: 6/29/2016 Copyright © The American College of Cardiology. All rights reserved. From: A Test in Context: High-Sensitivity C-Reactive Protein J Am Coll Cardiol. 2016;67(6):712-723. doi:10.1016/j.jacc.2015.11.037 Magnitude of Risk Associated With hsCRP Is Comparable With and Independent of LDL-C (A) Increasing quintiles of both hsCRP and LDL-C predict vascular risk. (B) The highest-risk patients in a primary prevention setting are those with both increased hsCRP and increased LDL-C. Data from Ridker et al. (7). CVD = cardiovascular disease; hsCRP = high- sensitivity C-reactive protein; LDL = low-density lipoprotein; LDL-C = low-density lipoprotein cholesterol. Figure Legend:

3. Date of download: 6/29/2016 Copyright © The American College of Cardiology. All rights reserved. From: A Test in Context: High-Sensitivity C-Reactive Protein J Am Coll Cardiol. 2016;67(6):712-723. doi:10.1016/j.jacc.2015.11.037 The JUPITER Trial Primary results of the JUPITER trial, demonstrating the efficacy of statin therapy in reducing first major cardiovascular events among patients with low levels of LDL-C, but increased levels of high-sensitivity C-reactive protein. Data from Ridker et al. (19). CI = confidence interval; JUPITER = Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; RR = relative risk. Figure Legend:

4. Date of download: 6/29/2016 Copyright © The American College of Cardiology. All rights reserved. From: A Test in Context: High-Sensitivity C-Reactive Protein J Am Coll Cardiol. 2016;67(6):712-723. doi:10.1016/j.jacc.2015.11.037 Clinical Interpretation of hsCRP for Cardiovascular Risk Prediction The relationship of inflammation to cardiovascular risk is linear across a wide range of hsCRP values. Blue bars represent crude relative risks; red bars represent relative risks adjusted for traditional Framingham risk factors. Data from Ridker et al. (65). CV = cardiovascular; hsCRP = high-sensitivity C-reactive protein. Figure Legend:

5. Date of download: 6/29/2016 Copyright © The American College of Cardiology. All rights reserved. From: A Test in Context: High-Sensitivity C-Reactive Protein J Am Coll Cardiol. 2016;67(6):712-723. doi:10.1016/j.jacc.2015.11.037 Overestimation and Underestimation of Risk in a Comparison of Global Risk Scores Performed in a Contemporary, Prospective, Multiethnic Population Of scores tested, the Reynolds Risk Score (RRS) showed the greatest ability to discriminate between cases and controls and was the best calibrated with regard to matching predicted and observed event rates. Data from DeFilippis et al. (49). ACC = American College of Cardiology; AHA = American Heart Association; ASCVD = atherosclerotic cardiovascular disease; ATPIII = Adult Treatment Panel III; CHD = coronary heart disease; CVD = cardiovascular disease; FRS = Framingham Risk Score. Figure Legend:

6. Date of download: 6/29/2016 Copyright © The American College of Cardiology. All rights reserved. From: A Test in Context: High-Sensitivity C-Reactive Protein J Am Coll Cardiol. 2016;67(6):712-723. doi:10.1016/j.jacc.2015.11.037 Completed and Ongoing Trials of LDL Reduction and Inflammation Inhibition Trials of statins or statins plus ezetimibe are proved to lower vascular event rates and these agents reduce both LDL-C and hsCRP (top). Outcome trials of PCSK9 inhibitors, which reduce LDL-C with no anti-inflammatory effects, are ongoing (middle), as are trials of the anti-inflammatory agents methotrexate and canakinumab, which reduce hsCRP, but have no effect on LDL-C (bottom). CRP = C-reactive protein; LDL = low-density lipoprotein; MTX = methotrexate; PCSK9 = proprotein convertase subtilisin/kexin type 9; other abbreviations as in Figure 2. Figure Legend: