An Assessment of Incremental Coronary Risk Prediction Using C-Reactive Protein and Other Novel Risk Markers

TLDR

Interest has grown in whether novel blood markers such as C‑reactive protein can improve coronary heart disease risk prediction beyond traditional factors. Using case‑cohort analyses of 15,792 ARIC participants, the study evaluated 19 novel markers—including inflammatory, endothelial, fibrin, fibrinolytic, B‑vitamin, and infectious‑agent antibodies—by measuring changes in the area under the ROC curve relative to a baseline model of traditional risk factors. The baseline model achieved an AUC of ~0.8, and C‑reactive protein and most other markers added negligible improvement (AUC increase ≤0.003), with only lipoprotein‑associated phospholipase A2, vitamin B6, interleukin‑6, and soluble thrombomodulin raising the AUC by 0.006–0.011, leading the authors to conclude routine measurement of these markers is unwarranted while emphasizing the continued importance of major modifiable risk factors.

Abstract

<h3>Background</h3> There has been interest in recent years in whether additional, and in particular novel, risk factors or blood markers, such as C-reactive protein, can enhance existing coronary heart disease (CHD) prediction models. <h3>Methods</h3> Using a series of case-cohort studies, the prospective Atherosclerosis Risk in Communities (ARIC) Study assessed the association of 19 novel risk markers with incident CHD in 15 792 adults followed up since 1987-1989. Novel markers included measures of inflammation, endothelial function, fibrin formation, fibrinolysis, B vitamins, and antibodies to infectious agents. Change in the area under the receiver operating characteristic curve (AUC) was used to assess the additional contribution of novel risk markers to CHD prediction beyond that of traditional risk factors. <h3>Results</h3> The basic risk factor model, which included traditional risk factors (age, race, sex, total and high-density lipoprotein cholesterol levels, systolic blood pressure, antihypertensive medication use, smoking status, and diabetes), predicted CHD well, as evidenced by an AUC of approximately 0.8. The C-reactive protein level did not add significantly to the AUC (increase in AUC of 0.003), and neither did most other novel risk factors. Of the 19 markers studied, lipoprotein-associated phospholipase A₂, vitamin B₆, interleukin 6, and soluble thrombomodulin added the most to the AUC (range, 0.006-0.011). <h3>Conclusions</h3> Our findings suggest that routine measurement of these novel markers is not warranted for risk assessment. On the other hand, our findings reinforce the utility of major, modifiable risk factor assessment to identify individuals at risk for CHD for preventive action.