Reflections on the Evolution of Cardiac Biomarkers

Abstract

I was asked for this special issue to reflect on the area of laboratory tests for identifying cardiac injury. I will include my own experiences in this area, as well as some of others and a bit of personal perspective. I have published elements of this history previously (1–3) and freely admit to drawing on my prior publications. Considerations for a blood protein biomarker to identify the death of any cell involve 3 major factors: sensitivity, which will be affected by the abundance and location of the protein in the cell; the timing of sampling, which is influenced by the mode of entry into blood and the half-life of elimination; and specificity for the cell of interest. A compounding factor in myocardial infarction (MI)2 (acute coronary syndrome) is that the acute event is caused by blockage of blood flow in a coronary artery or arteries that leads to hypoxia and cell death. This blockage delays protein markers from reaching the blood because they cannot readily diffuse into the blood; instead, they reach the blood via the lymphatics, which is somewhat akin to traveling on city streets rather than on an interstate. Today, we have several discovery tools for identifying candidate cell injury biomarkers via gene expression (4) or proteomics (5) in a reasonably straightforward manner. It is noteworthy that cardiac biomarkers evolved without such tools, and appropriate biomarkers were found intuitively and empirically (Table 1), probably because the heart's major function is contraction, which requires energy. The biomarkers used were all involved in energy production or control of contraction. View this table: Table 1. History of use of biochemical markers of myocardial injury. The first practical test used was serum glutamic-oxaloacetic transaminase (SGOT), now called “aspartate aminotransferase” (AST) (6). Practical use of this test in clinical laboratories required the development of robust, temperature-controlled spectrophotometers, such as the Gilford 300N developed by …