Diabetes and heart failure: Understanding the role of cardiac biomarker testing

Laboratories may begin to see an influx of cardiac biomarker tests accompanying HbA1c testing based on updated American Diabetes Association (ADA) guidelines concerning heart failure in people with diabetes. Released late last year, the ADA’s “Standards of Care in Diabetes-2024,”1 marks the first-time use of cardiac biomarkers, namely the measurement of natriuretic peptides, for heart failure risk prediction has been included in the organization’s official guidelines for diabetes care. Specifically, the ADA’s heart failure recommendations advise that clinicians consider testing adults with diabetes by measuring B-type natriuretic peptide [BNP] or N-terminal pro-BNP [NT-proBNP] levels to help prevent stage C, or symptomatic, heart failure.2 

This is not the first time the ADA has recognized the clinical significance of this simple blood test in the management of diabetes. In its consensus report published in Diabetes Care in 2022, the ADA noted, “the addition of relatively inexpensive biomarker testing as part of the standard of care may help refine [heart failure] risk prediction in individuals with diabetes.” Endorsed by the American College of Cardiology, the consensus report also states that “substantial data indicate the ability of these biomarkers to identify those in Stage A or B [heart failure] at highest risk of progressing to symptomatic [heart failure] or death.”3

The value of natriuretic peptides and other cardiac biomarkers, such as high-sensitivity troponin, cannot be overstated when considering their impact on heart failure risk prediction, early diagnosis, clinical decision-making, and as a key in improving patient outcomes (See Figure 1). These biomarkers are the most sensitive tools available today to detect the onset of ventricular wall stress, injury, and remodeling of the heart that accompanies the development of heart failure. 

Finding clinically proven ways to address the high incidence of heart failure in the United States is a major concern from a public health perspective as well. In the U.S., 6.2 million adults are living with heart failure.4 When considering that people with diabetes—a population that numbers more than 37 million5—are at increased risk of heart failure, the number of people with the disease could rise to a staggering level in the coming years. A panel of clinical experts from the Diabetes Technology Society affirms that investing in heart failure monitoring in this population is in the public interest. Referencing the use of cardiac biomarker testing, the panel states, “Biomarker screening for heart failure in people with diabetes is a sensible public health practice because both the disease and the available screening tests meet the criteria of a sound screening program for identifying asymptomatic heart failure.”6


Use of cardiac biomarkers for diagnosis and monitoring

First used to diagnose acute heart failure in the emergency department (ED), the use of cardiac biomarkers—specifically natriuretic peptides—has evolved over the past two decades. Following their application in the ED, lab measurements of natriuretic peptides were used more broadly to diagnose symptomatic heart failure. The employment of cardiac biomarkers eventually expanded to include risk prediction—from the acute phase to new acute episodes—and ultimately to predict long-term risk and risk in specific populations, such as people with diabetes. Today, clinicians use regular natriuretic peptide testing to monitor patients at risk and to regularly evaluate a patient’s trajectory along the course of the disease once the patient is diagnosed with heart failure.

For prognostication and early diagnosis of heart failure in people with diabetes, the ADA’s consensus report states that “measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure.”


Advantages of NT-proBNP in cardiac biomarker testing

While the ADA states that either NT-proBNP or BNP testing can be used to screen for heart failure, there are several analytical advantages of using laboratory-based NT-proBNP assays. For testing ordered in a primary care setting, the extended stability of NT-proBNP compared to BNP is a real advantage when samples must be sent from a clinician’s office to an off-site lab. NT-proBNP has a longer half-life—60 to 120 minutes, as compared to 20 minutes for BNP7— and a lower intrinsic biological variability with approximately 25% as compared to BNP with approximately 40%.8  For laboratories, this enables more flexibility for outreach and add-on testing. Consistent results in the ED and inpatient and outpatient settings allow for more confidence in the management of heart failure. 

Finally, it is important to note that some cardiac biomarkers are affected by angiotensin receptor-neprilysin inhibitor (ARNI), a newer, best-in-class medication that is becoming more frequently prescribed to patients with diagnosed heart failure. In patients taking an ARNI, BNP levels will appear elevated, which could lead to errors in treatment. In contrast, NT-proBNP is not affected by neprilysin. 

With ARNIs going off patent soon, it is expected that more heart failure patients will be prescribed these proven medications. As a result, I believe it is likely that NT-proBNP will become the more widely used cardiac biomarker testing strategy moving forward. 


Cutoff values and what they signal for clinical management

Laboratorians have the notable job of providing results of cardiac biomarker testing to clinicians charged with making decisions about heart failure treatment. Results of laboratory-based cardiac biomarker testing help guide heart failure treatment for people with diabetes. 

According to the ADA consensus report, pre-heart failure, or Stage B, is defined by an NT-proBNP value greater than 125 pg/mL. For BNP, Stage B is defined by a value greater than 50 pg/mL.3 These values indicate early molecular changes of pre-symptomatic structural heart disease and are the recommended cutoffs for outpatient non-acute testing. The rule-out cutoff for NT-proBNP for acute heart failure is <300 pg/mL (high negative predictive value) and the age-stratified rule-in cutoffs, which reflect aging effects on the heart, are <450 pg/mL for adults younger than 50, <900 pg/mL for adults ages 50 to 75, and <1800 pg/mL for adults older than age 75 (good positive predictive value).9 The rule-out cutoff for BNP is <100 pg/ml, while the rule-in cutoff, across all age groups, is >400 pg/mL.8

When cardiac biomarkers are elevated indicating a risk of heart failure, the clinical guidance for adults with type 2 diabetes is to prescribe a sodium-glucose cotransporter 2 (SGLT2) inhibitor for glycemic management. These medications also help reduce the cardiovascular risk associated with diabetes. If the patient is also obese, a glucagon-like peptide 1 (GLP-1) receptor agonist may be prescribed in addition. Optimizing the management of additional risk factors, such as hypertension and dyslipidemia, is also recommended.1,3 


Improving patient outcomes through cardiac biomarker testing

In people with diabetes, early diagnosis of heart failure could enable targeted treatment to prevent progression of disease and other adverse outcomes. If annual cardiac biomarker monitoring is widely adopted when treating people with diabetes, more patients can be appropriately monitored and diagnosed with heart failure earlier in the disease course. This sets the stage for improved treatment, delayed disease progression, and the potential for improved quality of life over a longer period of time for these patients.

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1 American Diabetes Association Professional Practice Committee. Standards of care in diabetes – 2024. Diabetes Care. January 2024. doi:10.2337/dc24-SINT.

2 American Diabetes Association Professional Practice Committee. 10. Cardiovascular disease and risk management: Standards of care in diabetes – 2024. Diabetes Care. January 2024;47(Supplement_1):S179-S218. doi:10.2337/dc24-S010. 

3 Pop-Busui R, Januzzi JL, Bruemmer D, et. al. Heart failure: an underappreciated complication of diabetes. A consensus report of the American Diabetes Association. Diabetes Care. 2022;45(7):1670-1690.

4 Centers for Disease Control and Prevention. Heart failure. cdc.gov. Updated January 5, 2023. Accessed January 25, 2024. https://www.cdc.gov/heartdisease/heart_failure.htm

5 Centers for Disease Control and Prevention. National diabetes statistics report. cdc.gov. Updated November 29, 2023. Accessed January 25, 2024. https://www.cdc.gov/diabetes/data/statistics-report/index.html

6 Yeung AM, Huang J, Pandey A, et. al. Biomarkers for the diagnosis of heart failure in people with diabetes: a consensus report from Diabetes Technology Society. Prog Cardiovasc Dis. 2023;79:65-79. doi: 10.1016/j.pcad.2023.05.002.

7 Gaggin, HK, Januzzi JL, The past, the present, and the future of natriuretic peptides in the diagnosis of heart failure, European Heart Journal Supplements, 2018;20(G)11–20. doi:10.1093/eurheartj/suy024.

8 Tsutsui H, Albert NM, Coats AJS, et al. Natriuretic peptides: role in the diagnosis and management of heart failure: a scientific statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society. Eur J Heart Fail. 2023;25(5):616-631. doi: 10.1002/ejhf.2848. 

9 Januzzi JL Jr, Chen-Tournoux AA, Christenson RH, et al. N-terminal pro–B-type natriuretic peptide in the emergency department. J Am Coll Cardiol. 2018;71(11):1191-1200. doi:10.1016/j.jacc.2018.01.021.