in clinical trials) that denote how a study participant feels, functions, or survives; or in clinical practice, for example in risk stratification, disease prevention, screening, diagnosis, and monitoring. In public health practice, biomarkers serve as a means to track health status and for making recommendations for preventing, mitigating, and treating diseases or conditions at the population level (IOM, 2010). A related concept used in public health is the surrogate endpoint. The Institute of Medicine (IOM) Committee on Qualification of Biomarkers and Surrogate Endpoints in Chronic Disease defined surrogate endpoint as “a biomarker that is intended to substitute for a clinical endpoint. A surrogate endpoint is expected to predict clinical benefit (or harm, or lack of benefit or harm) based on epidemiologic, therapeutic, pathophysiologic, or other scientific evidence” (IOM, 2010, p. 23). This committee further identified blood pressure as “an exemplar surrogate endpoint for cardiovascular mortality and morbidity due to the levels and types of evidence that support its use” (IOM, 2010, p. 39).
Although biomarkers have wide utility in research, clinical practice, and public health, the biological complexity and variation among individuals is important to consider as potential sources of error in assessing the link between biomarkers and health outcomes. Further, and of critical importance, with the exception of blood pressure and HIV-1RNA (IOM, 2010), biomarkers predict clinical outcomes but are not necessarily directly correlated with them. Indeed, there are situations where treatment recommendations based on biomarkers have led to patient harm, once outcome studies were finally performed. For these reasons, the committee reviewed evidence from its literature search on a range of intermediate markers for health outcomes but did not include these studies in its assessment of relevant research in response to the task.
Given the limitations associated with most biomarkers as indicators of risk of adverse health outcome, as discussed in the Dietary Reference Intake (DRI) report (IOM, 2005), the DGAC (HHS and USDA, 2010) report, and the report on biomarkers and surrogate endpoints (IOM, 2010), blood pressure is widely recognized as a strong surrogate indicator for primary cardiovascular disease (CVD) clinical endpoints, such as myocardial infarction (MI) and stroke. The committee considered the strength of the evidence for blood pressure as a surrogate endpoint for risk of CVD and stroke and this evidence underpinned its assessment of new evidence on health outcomes. The committee summarizes new evidence for blood pressure as an indirect indicator of risk of CVD in this chapter, but does not include its assessment of this indicator in its comprehensive evidence review and analysis of sodium intake and direct health outcomes in Chapter 4.