ReviewThe Utility of Biomarkers in Sorting Out the Complex Patient
Section snippets
The Increasing Prevalence of Complex Patients
It is estimated that currently nearly one fourth of the US population has metabolic syndrome and that over 80 million American adults (1 in 3) have 1 or more types of cardiovascular disease.2 Of these Americans with cardiovascular disease, 38 million are estimated to be over 60 years old. Certainly, advances in modern medicine have allowed patients to live longer, illustrated by the increased survival in patients suffering acute myocardial infarction in the era of angioplasty and stent
The Importance of Differentiating Diseases in the Complex Patient
Simply stated, patients do better when diagnosed and treated, immediately and effectively, for the complications with which they present. Take 2 examples:
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How many asymptomatic diabetic patients presenting with fatigue have died because they were sent home with an undiagnosed myocardial infarction? Indeed, missed diagnosis of acute coronary syndrome occurs in 2%-8% of patients presenting to an emergency department, resulting in dire consequences for both patients and physicians. Patients
New Tools that Help Diagnose Patients With Complex Problems
While expensive tests such as computed tomography and magnetic resonance imaging scans are used more frequently in this era of “defensive” medicine, the Obama administration's health task force made it evident that expensive tests need to be replaced by cheaper but effective means of diagnosis. Hence, the case for using effective biomarkers has never been so important.
The Attributes that Comprise an Ideal Biomarker
Ideal biomarkers are both sensitive and specific to the disease state being examined. They ideally define a disease (not necessarily a disease process), and potentially reflect on the underlying etiology that can be targeted for therapy. Clinical uses of biomarkers include diagnosis, risk stratification, screening, and guiding therapy.
Promising Cardiac, Renal, and Metabolic Biomarkers Important in Diagnosis, Prognosis, and Management of Patients
There are many emerging biomarkers currently under study, as well as a portfolio of established biomarkers that can bring immediate promise to understanding underlying etiologies of the complex patient (Figure 1). Several of these relevant biomarkers are included below with clinical examples.
Natriuretic Peptides
Natriuretic peptides, specifically B-type natriuretic peptide (BNP) and the amino-terminal fragment of proBNP (NT-proBNP), are well-established tools in the diagnosis and prognosis of patients with heart failure. Plasma natriuretic peptides (NPs) are released from the heart in response to volume overload, as well as serving as markers of elevated filling pressures, a finding that in many cases would otherwise be detectable only with invasive testing.9 Therefore, the use of NPs are an important
Newer Diagnostic and Prognostic Markers of Heart Failure
Arrays of biomarkers that will likely prove useful in heart failure are on the horizon. The mid-regional pro-A-type natriuretic peptide assay is a newer addition to the existing panel of hemodynamic stress heart failure markers. Mid-regional pro-A-type natriuretic peptide has been found to have diagnostic value comparable to BNP and NT-proBNP, as shown in Figure 4, and even has been shown to have independent prognostic power.19 Less specific markers also have emerged as possible adjunctive
Diagnosing Pneumonia in Patients With Underlying Heart Failure
A relatively common diagnostic dilemma is a patient with underlying heart failure who presents with acute dyspnea, representing most likely either an acute exacerbation of heart failure or possibly pneumonia. This is especially important because patients with heart failure are actually more prone to lower respiratory tract infections. A biomarker that can effectively identify bacterial infections in these patients would be extremely valuable. Procalcitonin (PCT) has been studied as a marker of
Troponins
Just as BNP levels can be considered the arbiter of CHF, cardiac troponins (troponin I/troponin T) are decisive for myocardial necrosis. Because myocardial necrosis, whether associated with a coronary occlusion or subendocardial ischemia, is prognostic, a true elevation often leads to commencement of a cardiac-specific treatment.
Consider the following case: A woman with a history of diabetes and reflux disease, as well as a left anterior descending stent placed 2 weeks prior now presents to the
The Next Generation “Highly Sensitive” Troponin Assays
Cardiac troponin is the preferred biomarker for the detection of myocardial necrosis based on its high clinical sensitivity and absolute near specificity for myocardial tissue.29 The introduction of novel assays with even higher clinical sensitivity, detecting troponin levels at nanogram quantities, suggests even earlier diagnosis of acute myocardial infarction and identification of patients at substantial risk postinfarction.30 However, very low levels of troponin elevation, especially when
Providing Additional Information to the Supersensitive Troponins
Additional markers that have reasonable specificity for acute coronary syndrome might consequently offer additive value in further elucidating small, and perhaps rising, levels of troponin. Markers of oxidative stress, such as myeloperoxidase (MPO), may serve this important role. MPO may contribute to several phases of atherothrombosis, from the initial insult to the vascular endothelium, to development of the atheroma, to rupture of the vulnerable plaque and its clinical manifestation as acute
Neutrophil Gelatinase-Associated Lipocalin for Acute Kidney Injury
Neutrophil gelatinase-associated lipocalin (NGAL) is one of the earliest and most robustly induced genes and proteins in the kidney after ischemic or nephrotoxic injury. Elevations are detectable within hours of acute kidney injury, whereas corresponding creatinine elevations lag 1 to 3 days behind.32 Studies have already demonstrated its usefulness as a diagnostic biomarker in the complex patient undergoing cardiopulmonary bypass, angiography with contrast administration, and
Conclusion
The increasing prevalence of obesity, cardiovascular disease, diabetes, metabolic syndrome, and chronic kidney disease collectively contributes to an increased prevalence of complex patients. Complex patients are difficult to diagnosis with traditional tools alone, and in this new era of affordable health care, less expensive tools are actively being sought as a way to improve patient care. Cardiac, renal, and metabolic biomarkers play a critical role in diagnosis, prognosis, and treatment
References (37)
- et al.
Natriuretic peptides
J Am Coll Cardiol
(2007) - et al.
Bedside B-Type natriuretic peptide in the emergency diagnosis of heart failure with reduced or preserved ejection fractionResults from the Breathing Not Properly Multinational Study
J Am Coll Cardiol
(2003) - et al.
Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting
J Am Coll Cardiol
(2001) - et al.
Association between renal function and circulating levels of natriuretic peptides (from the Dallas Heart Study)
Am J Cardiol
(2008) - et al.
Comparison of midregional pro-atrial natriuretic peptide with N-terminal pro-B-type natriuretic peptide in predicting survival in patients with chronic heart failure
J Am Coll Cardiol
(2007) - et al.
Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure
J Am Coll Cardiol
(2007) - et al.
Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure
J Am Coll Cardiol
(2006) Serum soluble ST2 as a biochemical marker of acute heart failure: future areas of research
J Am Coll Cardiol
(2008)- et al.
Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure
J Am Coll Cardiol
(2008) - et al.
Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy
Chest
(2007)
Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage
Am J Kidney Dis
Increasing prevalence of the metabolic syndrome among U.S. adults
Diabetes Care
Heart disease and stroke statistics—2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee
Circulation
Identifying and managing post-myocardial infarction patients with left ventricular dysfunctionMedscape Cardiology
Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000
J Am Soc Nephrol
Prevalence of multiple cardiovascular disease risk factors among women in the United States, 1992 and 1995: the Behavioral Risk Factor Surveillance System
J Womens Health
Evaluation of the patient with acute chest pain
N Engl J Med
Rehospitalizations among patients in the Medicare fee-for-service program
N Engl J Med
Cited by (23)
The assessment of acute kidney injury in critically ill patients
2017, European Journal of Internal MedicineCitation Excerpt :Biomarker alone-based strategies are costly and prone to failure because of the clinical heterogeneity displayed by individual patients. A predictive model for a complex disease such as AKI ideally requires a combination of epidemiological, clinical, biological and hereditary factors along with a panel of biomarkers [52]. In the proposed risk score model authors developed and validated a risk score derived from patient's demographics, chronic comorbidities and acute risk factors and demonstrated that it can reliably predict AKI in a critically ill adult population at ICU admission.
Clinical benefits of natriuretic peptides and galectin-3 are maintained in old dyspnoeic patients
2017, Archives of Gerontology and GeriatricsCitation Excerpt :Natriuretic peptides (NPs) are recommended to ascertain the cardiac origin of undifferentiated dyspnoea, but it is still matter of debate, which NP among B-type natriuretic peptide (BNP), its precursor form (proBNP), its amino-terminal fragment (NT-proBNP), and the mid-regional pro-atrial natriuretic peptide (MR-proANP) has the best diagnostic performance, in particular in elderly patients (O'Donoghue & Braunwald, 2010; Trinquart, Ray, Riou, & Teixeira, 2011). In recent years, novel biomarkers in addition to NPs have been shown to hold prognostic value in both acute and chronic HF settings, but their performance in elderly patients is unknown (Fermann et al., 2012; Moriates & Maisel, 2010). Galectin-3 (Gal-3) is a soluble beta galactoside binding lectin secreted by activated macrophages that interacts with extracellular matrix components and participates to mechanisms of tissue inflammation (Januzzi, Pascual-Figal, & Daniels, 2015).
Biomarkers for Heart Failure: An Update for Practitioners of Internal Medicine
2016, American Journal of MedicineCitation Excerpt :Almost all medical practitioners will interact with heart failure patients and should be familiar with their care. Biomarkers have become an integral part of medicine, aiding in the diagnosis and treatment of numerous conditions.2 This review provides a focused update on biomarkers that are and will soon be regularly used in the management of heart failure.
Biomarkers in Acute Lung Injury: Insights into the Pathogenesis of Acute Lung Injury
2011, Critical Care ClinicsLung injury prediction scores: Clinical validation and C-reactive protein involvement in high risk patients
2020, Medicina IntensivaCitation Excerpt :The notion of using a biomarker reflecting the severity and course of alveolocapillary inflammation and increased permeability characterizing the ARDS is enthusiastic. Theoretically, the ideal biomarker would be involved in the disease pathogenesis, easy to measure, rapid results availability, and highly sensitive and specific in predicting the required outcome.29 Many biomarkers related to DAD and its association with distal airway pathologic changes characterizing ARDS might be seen of value30,31 and even, too specific biomarker at the molecular level had been studied.32
Predicting Risk Factors of Acute Kidney Injury in the First 7 Days after Admission: Analysis of a Group of Critically Ill Patients
2022, Cardiovascular Therapeutics
Funding: None.
Conflict of Interest: Christopher Moriates: no conflicts of interest. Alan Maisel: Consultant for Inverness. Research support from BRAHMS, Abbott, Inverness, Roche, Critical Diagnostics. Advisory board for Critical Diagnostics.
Authorship: All authors had access to the data and a role in writing the manuscript.