Other Novel Markers

It is possible that other biomarkers, such as soluble CD40L (sCD40L), metalloprotein-ases, MPO, and possibly a marker of ischemia, will be added to or replace the three biomarkers (troponin, BNP, and CRP) that have been most extensively studied to date. Those biomarkers that capture novel information or reflect processes other than necrosis and hemodynamic stress are likely to be most useful; in particular, any candidates that prove to offer greater specificity for inflammation in the vasculature than CRP are likely to be extremely valuable.

cTnl hs-CRP

Fig. 9. Adjusted hazard rate ratio (HR) for risk of death or MI at 10 mo among case subjects (n = 195) and control subjects (n = 195) enrolled in Oral Glycoprotein Ilb/IIIa Inhibition with Orbofiban in Patients with Unstable Coronary Syndromes-TIMI 26 Trial stratified by sCD40L, cTnI, and hsCRP. (Data are from ref. 39.)

cTnl hs-CRP

Fig. 9. Adjusted hazard rate ratio (HR) for risk of death or MI at 10 mo among case subjects (n = 195) and control subjects (n = 195) enrolled in Oral Glycoprotein Ilb/IIIa Inhibition with Orbofiban in Patients with Unstable Coronary Syndromes-TIMI 26 Trial stratified by sCD40L, cTnI, and hsCRP. (Data are from ref. 39.)

sCD40L appears to reflect both inflammatory processes underlying plaque disruption and platelet activation, two critical contributors to atherothrombosis (see Chapter 18). Applied in conjunction with either CRP or cardiac troponin, sCD40L provides incremental information with respect to the risk of death or recurrent ischemic events in patients with ACS (Fig. 9) (39). MPO is an enzyme released during leukocyte degranulation and posited to play an adverse role in atherothrombosis via activation of metalloproteinases and, possibly, consumption of the endogenous vasodilator nitric oxide. The concentration of MPO is increased in some patients with unstable angina and appears to confer prognostic information in patients with ACS that is additive to both cardiac troponin and sCD40L (Fig. 10), and attenuates the predictive value of CRP when considered concurrently (40).

If the prognostic importance of these markers is validated in additional data sets, and analytic benchmarks (e.g., sample types, analytic conditions, optimal cut points, biological variation) can be met, multimarker strategies incorporating these markers will have a strong potential for clinical application. In addition, proteomic and genomic strategies for novel marker discovery (see Chapters 33 and 34) are likely to extend the list of candidate markers.

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