Established and emerging plasma biomarkers in the prediction of first atherothrombotic events.

Abstract

In the current Adult Treatment Panel guidelines for cardiovascular risk detection,1 the plasma-based markers recommended for use in global risk assessment or in the definition of the metabolic syndrome are low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. It is widely recognized, however, that more than half of all future vascular events occur in individuals without overt hyperlipidemia. For example, in a recent large-scale analysis of >27 000 healthy American women, 77% of all future events occurred in those with LDL-C levels <4.14 mmol/L (<160 mg/dL) and 45% of all events occurred in those with LDL-C values <3.36 mmol/L (<130 mg/dL).2 Although risk-scoring systems that additionally evaluate traditional risk factors such as smoking, hypertension, and diabetes greatly improve risk prediction, multiple studies demonstrate that 20% to 25% of all future events occur in individuals with only 1 of these factors.3 Moreover, the prevalence of traditional risk factors is almost as high in those without disease as in affected individuals.4 As our understanding of the pathobiology of atherothrombosis has improved, researchers have attempted to evaluate the activities of these biological processes by measuring markers in plasma or urine (ie, biomarkers). Indeed, a series of candidate biomarkers reflecting inflammation, hemostasis, thrombosis, and oxidative stress have been evaluated as potential clinical tools in an effort to improve risk prediction. To be useful in a clinical setting, the biomarker of interest must be shown in multiple prospective studies to predict future cardiovascular events. Retrospective studies are of limited value because they are prone to bias and cannot exclude the possibility that the particular biomarker is elevated as a result of, rather than a cause of, disease. To be used widely, the proposed biomarker should provide independent information on risk or prognosis beyond that available from global assessment algorithms such …