An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: the atherosclerosis risk in communities study

Arch Intern Med. 2006 Jul 10;166(13):1368-73. doi: 10.1001/archinte.166.13.1368.


Background: 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.

Methods: 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.

Results: 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 A(2), vitamin B(6), interleukin 6, and soluble thrombomodulin added the most to the AUC (range, 0.006-0.011).

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Age Factors
  • Aged
  • Antihypertensive Agents / therapeutic use
  • Biomarkers / blood
  • Blood Pressure
  • C-Reactive Protein / analysis*
  • Cholesterol / blood
  • Coronary Disease / blood*
  • Coronary Disease / epidemiology*
  • Diabetes Mellitus / epidemiology
  • Female
  • Humans
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Phospholipases A / blood
  • Prospective Studies
  • ROC Curve
  • Risk Assessment / methods*
  • Risk Factors
  • Sex Factors
  • Smoking / epidemiology
  • Thrombomodulin / blood
  • United States / epidemiology
  • Vitamin B 6 / blood


  • Antihypertensive Agents
  • Biomarkers
  • Interleukin-6
  • Thrombomodulin
  • Vitamin B 6
  • C-Reactive Protein
  • Cholesterol
  • Phospholipases A
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase