The cardiometabolic care gap laboratories can help identify earlier

Data generated within the clinical laboratory stands to reshape long-term patient care strategies. One opportunity is identifying heart failure risk in patients with diabetes.

Heart failure and diabetes mellitus are among the most prevalent and interconnected chronic conditions worldwide. As cardiometabolic disease is increasingly recognized as a multi-organ continuum, it has become clear that glycemic control alone does not fully capture cardiovascular risk in patients with diabetes. Individuals with diabetes face a substantially increased risk of developing heart failure, often years before symptoms emerge and frequently in the absence of overt coronary artery disease.^1,2

Increasing evidence shows that cardiometabolic disease is not a series of siloed conditions, but rather an interconnected spectrum. Insulin resistance and obesity serve as root contributors, triggering cascades affecting the heart, kidney, liver, and vascular system. These interconnected pathways make individuals with diabetes far more susceptible to early cardiac stress and eventual heart failure, even before symptoms arise. 

Cardiac biomarkers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin (hs-cTn), offer laboratorians objective tools to support earlier detection of myocardial stress and injury, improve risk stratification, and facilitate more proactive cardiometabolic care.^1-3

The expanding and earlier burden of heart failure

Heart failure remains a major public health challenge, affecting more than 64 million people globally and accounting for substantial morbidity, mortality, and healthcare utilization.⁴ Contemporary definitions of heart failure have evolved to reflect earlier disease recognition. In addition to symptoms and structural or functional cardiac abnormalities, abnormal cardiac biomarkers are now recognized as integral components of heart failure diagnosis and classification.^1,5

This shift acknowledges that myocardial stress and injury often precede overt clinical manifestations. For patients with diabetes who may develop cardiac dysfunction through metabolic and microvascular mechanisms, biomarker-based assessment offers a means to identify risk earlier in the disease course.²

Diabetes and the cardiometabolic continuum

Diabetes confers a two- to five-fold increased risk of heart failure.² This elevated risk is driven not only by traditional cardiovascular pathways, but also by insulin resistance, chronic inflammation, endothelial dysfunction, and altered myocardial metabolism.^3,6 Diabetes frequently coexists with obesity and chronic kidney disease, conditions that further amplify cardiac stress and accelerate progression toward heart failure. Poorly controlled blood glucose accelerates vascular damage, which contributes to complications such as atherosclerosis, heart failure, and kidney disease. Hemoglobin A1c (A1C), a key biomarker that reflects average blood glucose over approximately three months, is essential in the cardiometabolic continuum as even modest elevations are associated with increased cardiovascular risk. Maintaining A1C within target ranges helps slow disease progression, reduce complications, and improve long-term cardiometabolic outcomes.

These overlapping mechanisms underscore the importance of moving beyond glucose-centric assessment toward integrated cardiometabolic risk evaluation.

Heart failure risk in patients with diabetes extends beyond glycemic control and reflects a complex cardiometabolic continuum.

Natriuretic peptides: Biology that informs interpretation

Natriuretic peptides, including BNP and NT-proBNP, are synthesized and released by cardiomyocytes in response to increased myocardial wall stress.⁷ Acting as counter-regulatory hormones, they promote vasodilation, natriuresis, and attenuation of maladaptive cardiac remodeling through cyclic GMP-mediated pathways.

NT-proBNP is released in equimolar amounts with BNP but has a longer circulating half-life due to differences in clearance mechanisms. Understanding this biology, along with the presence of multiple circulating peptide fragments detected by clinical assays, supports appropriate interpretation across acute and chronic care settings.^7,8

Importantly, natriuretic peptides are intended to support, not replace, clinical judgment. Appropriate use requires understanding of peptide biology, differential diagnosis, and clinical context.^8,9

Diagnosis and exclusion of heart failure

Natriuretic peptides are embedded in international heart failure guidelines as diagnostic aids.^1,5 Low concentrations provide a strong negative predictive value, effectively excluding heart failure in patients presenting with dyspnea or nonspecific symptoms, while elevated values support further cardiovascular evaluation.⁵

Risk stratification and prognosis

Beyond diagnosis, NT-proBNP and BNP provide independent prognostic information. Elevated concentrations are associated with increased risk of heart failure hospitalization and cardiovascular mortality, even in patients without previously diagnosed heart failure.^1,10 Serial measurements further enhance prognostic value by identifying patients whose risk trajectory is worsening over time.¹⁰

Interpreting biomarkers in diabetes and comorbid conditions

Interpretation of natriuretic peptides requires careful attention to comorbidities common in diabetes. Elevated values may reflect myocardial stress related to atrial fibrillation, pulmonary hypertension, renal dysfunction, or systemic illness, and should not be interpreted in isolation.^7,8

Conversely, obesity is associated with lower circulating natriuretic peptide concentrations due to suppressed peptide production and altered hemodynamics.¹¹ In this context, values that appear modest may still represent abnormal cardiac stress, highlighting the importance of laboratorian–clinician collaboration.

High-sensitivity troponin and subclinical myocardial injury

High-sensitivity cardiac troponin assays detect low-grade myocardial injury below thresholds for acute coronary syndromes. In patients with diabetes, such subclinical injury is common and reflects microvascular disease and metabolic stress.³ Elevated hs-cTn concentrations, even within the reference range, are independently associated with incident heart failure and adverse cardiovascular outcomes.¹⁰

When interpreted alongside natriuretic peptides, hs-cTn provides complementary insight into myocardial injury and hemodynamic stress, enabling a more comprehensive assessment of cardiometabolic risk.^3,10

Toward prevention: Identifying stage B heart failure

An emerging application of cardiac biomarkers is the identification of stage B heart failure, defined by structural heart disease or abnormal cardiac biomarkers in the absence of clinical symptoms.^1,5 Asymptomatic individuals with elevated NT-proBNP face a significantly higher risk of progressing to overt heart failure.¹⁰

Consensus guidelines increasingly support biomarker testing in high-risk populations, including patients with diabetes, to identify early heart falure risk and prompt timely clinical evaluation.^1,2 This biomarker-guided approach aligns with contemporary strategies aimed at shifting heart failure care from reactive diagnosis to proactive prevention.

The end game: Using lab data to affect change

Labs offer objective biomarker insights to detect signs of cardiometabolic risk earlier. Taking it one step further, asserting data-driven insights can shape longer-term care strategies in partnership with clinicians to ensure clinical data is fully understood and applied.¹² Rather than operating in isolation, laboratory teams are called to embrace close collaboration with clinicians, contribute to education and training, and continually deepen their understanding of clinical needs so that diagnostic testing can more effectively support patient care.

If there’s one silver lining to intensifying pressure to achieve better patient outcomes, it is that physicians now widely welcome this type of collaboration.¹³ By advancing earlier detection and supporting coordinated, patient-centered care, these biomarkers highlight how laboratory medicine can help drive meaningful progress against the leading cause of death in the United States.

References

1. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145:e895–e1032. doi:10.1161/CIR.0000000000001063. 
2. American Diabetes Association. Cardiovascular disease and risk management: Standards of care in diabetes—2025. Diabetes Care. 2025;48(Suppl 1):S190–S230. doi:10.2337/dc25-S010.
3. deFilippi CR, de Lemos JA, Christenson RH, et al. Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults. JAMA. 2010;304(22):2494–2502. doi:10.1001/jama.2010.1708. 
4. Ambrosy AP, Fonarow GC, Butler J, et al. The global health and economic burden of hospitalizations for heart failure: Lessons learned from hospitalized heart failure registries. J Am Coll Cardiol. 2014;63(12):1123-1133. doi:10.1016/j.jacc.2013.11.053.
5. Bozkurt B, Coats AJ, Tsutsui H, et al. Universal definition and classification of heart failure: A report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure. J Card Fail. 2021;27(4):387-413. doi:10.1016/j.cardfail.2021.01.022. 
6. Bajaj NS, Gupta K, Gharpure N, et al. Effect of immunomodulation on cardiac remodelling and outcomes in heart failure: A quantitative synthesis of the literature. ESC Heart Fail. 2020;7(3):1319-1330. doi:10.1002/ehf2.12681.
7. Januzzi JL Jr, Chen-Tournoux AA, Moe G. Amino-terminal pro-B-type natriuretic peptide testing for the diagnosis or exclusion of heart failure in patients with acute symptoms. Am J Cardiol. 2008;101(3A):29-38. doi:10.1016/j.amjcard.2007.11.017. 
8. Januzzi JL Jr. Natriuretic peptides in heart failure: biology, diagnosis, prognosis, and prevention. Educational webinar presentation. Presented 2025.
9. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137-e161. doi:10.1161/CIR.0000000000000509. 
10. McKie PM, Burnett JC Jr. NT-proBNP: The gold standard biomarker in heart failure. J Am Coll Cardiol. 2016;68(22):2437-2439. doi:10.1016/j.jacc.2016.10.001. 
11. Wang TJ, Larson MG, Levy D, et al. Impact of obesity on plasma natriuretic peptide levels. Circulation. 2004;109(5):594-600. doi:10.1161/01.CIR.0000112582.
12. Wells D. The Atellica IM High-Sensitivity Troponin I assay expands capabilities in cardiac care. SelectScience. February 4, 2025. Accessed February 3, 2026. https://www.selectscience.net/article/the-atellica-im-high-sensitivity-troponin-i-assay-expands-capabilities-in-cardiac-care.
13. Siemens survey highlights critical role of medical lab staff, influences on doctors’ orders. MLO Online. August 4, 2025. Accessed February 3, 2026. https://www.mlo-online.com/management/news/55307375/siemens-survey-highlights-critical-role-of-medical-lab-staff-influences-on-doctors-orders.