Soluble CD40 Ligand
In the 1980s, postmortem studies confirmed that erosions or ruptures in atherosclerotic fibrous caps lead to platelet activation—the main pathophysiologic contributor in ACS.59 This fundamental actuality suggests that biomarkers of platelet activation may provide supplemental information in patients who present with chest pain of cardiac origin. Another acute inflammatory marker, soluble CD40 ligand, is a marker of active platelet stimulation.60 Increased serum levels of soluble CD40 ligand have been correlated to increased risk for cardiovascular events in apparently healthy women.61
Soluble CD40 ligand, expressed within seconds of platelet activation, is also commonly found on various leukocytes, endothelial cells, and smooth-muscle cells.60 This may provide insight into cardiovascular disease progression and plaque deterioration that precedes the events of ACS.
Therapeutic antiplatelet medications are now the mainstay in the treatment and prevention of cardiovascular complications associated with ischemic thrombus formation.11 Platelet biomarkers are likely to play an essential supplemental role in the diagnosis of ACS.
Pregnancy-Associated Plasma Protein A
Additional risk-stratifying biomarkers include those that may determine whether a patient has plaques that are acutely vulnerable to rupture. Pregnancy-associated plasma protein A (PAPP-A), first detected in the 1970s in the circulation of pregnant women, is now widely used in first-trimester screening for fetal trisomy.62
Since then, it has been found that PAPP-A, which is theorized to be produced by vascular smooth-muscle cells, is extensively expressed in unstable coronary artery plaques, while minimally expressed in stable plaques.63 Since a significant proportion of patients who present with symptoms of ACS have normal cTn levels, PAPP-A may help identify patients who are at increased risk for subsequent short-term cardiovascular complications resulting from occult disease.64 This relatively new marker may also prove useful for screening in the office setting, identifying outpatients who are at high cardiovascular risk. Further studies are needed to define the release kinetics of PAPP-A, guiding clinicians in its implementation and clinical use.
CONCLUSION
When used in conjunction with the history and physical exam, cardiac biomarkers can provide a simple, noninvasive means to further the clinician’s exploration into a suspected underlying cardiovascular process. As advances continue in the understanding of the pathogenesis of heart disease, new interpretations of existing markers and discovery of novel markers may allow for specific therapeutic interventions to improve patient outcomes.
It is important to note that the list of biomarkers described here is by no means complete, and there is continued interest in finding more specific and sensitive markers of heart disease. Numerous cardiovascular organizations are now suggesting a shift toward a multi-marker strategy to determine the best etiology in the patient who presents with decompensating cardiovascular disease. A change in cardiac enzyme panels may be inevitable in the near future. Practicing PAs and NPs, particularly those who care for patients at risk for CVD, should remain up-to-date and proficient in interpreting those results to help determine the best course of action for each patient.
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