Natriuretic Peptide‐Based Screening to Identify Stage B Heart Failure in People With Type 1 Diabetes (2024)

A recent consensus report from the American Diabetes Association endorsed annual screening with natriuretic peptides (NPs) to identify people with diabetes and stage B heart failure (HF) that could benefit from targeted interventions that prevent transition to symptomatic HF.¹ Along these lines, Cunningham etal recently examined a large US health care database and reported that nearly half of the outpatients with type 2 diabetes who underwent either BNP (B‐type natriuretic peptide) or NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) testing met the American Diabetes Association consensus report‐endorsed NP‐based thresholds (ie, BNP ≥50 pg/mL or NT‐proBNP ≥125 pg/mL) for stage B HF.² To our knowledge, there are no comparable data demonstrating how many outpatients with type 1 diabetes (T1D) in the United States meet these recommended NP screening thresholds. To this end, we investigated the Premier Healthcare Database to determine the prevalence and distribution of BNP and NT‐proBNP testing in people with T1D. The Premier Healthcare Database is a large, US hospital‐based, service‐level, all‐payer database that includes >1030 health care institutions with >93 million outpatient encounters annually.³ People with T1D but without HF and without atrial fibrillation were identified using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD‐10‐CM) codes entered during any outpatient encounter that occurred between January 1, 2021 and December 31, 2022. We replicated the methodology of Cunningham etal² by including only people with at least 1 serum creatinine result and by including only the first value when multiple BNP or NT‐proBNP values were obtained for an individual. The University of Virginia Institutional Review Board granted an exemption for this study given that the requirement for informed consent was waived and that all data were deidentified and are HIPAA‐compliant. All statistical analyses were performed with SAS version 9.4 (SAS Institute, Cary, NC). The data that support the findings of this study are available from Premier Inc., but restrictions apply to the availability of these data, which were used under license for the current study and therefore are not publicly available. Data are, however, available from the authors upon reasonable request and with permission of Premier Inc.

We identified 40 084 unique outpatients with T1D that met the aforementioned criteria. Of these, 2631 (6.6%) had NP testing: 1664 (4.2%) with BNP and 967 (2.4%) with NT‐proBNP (Figure). Among those with NP testing, 56.8% were women, 71.9% were White, 20.5% were Black, 6.7% were of other or unknown race, and 0.9% were Asian. Median ages for those who underwent BNP and NT‐proBNP testing were 50 years (interquartile range [IQR], 36–63 years) and 50 years (IQR, 37–62 years), respectively. Median BNP value was 40 pg/mL (IQR, 22–96.4 pg/mL), and 691 values (41.5%) exceeded the American Diabetes Association consensus report threshold of 50 pg/mL. Emerging evidence led the Diabetes Technology Society to recently recommend adoption of a BNP screening threshold of ≥35 pg/mL to align with the Universal Definition and Classification of HF.⁴ In the present study, 1017 values (61.1%) exceeded this threshold. The median NT‐proBNP value was 97 pg/mL (IQR, 38.0–300.0 pg/mL), and 423 values (43.7%) exceeded the guideline‐based threshold of 125 pg/mL. BNP and NT‐proBNP levels were significantly greater in older patients and those with serum creatinine ≥1.50 mg/dL, whereas levels did not differ by sex or race according to univariate logistic regression analyses. We then conducted a sensitivity analysis excluding people with serum creatinine ≥1.50 mg/dL, and found that a similar proportion (2196 values, 5.5%) had NP results available. BNP (median: 40 pg/mL; 57.4% exceeded 35 pg/mL, and 35.4% exceeded 50 pg/mL) and NT‐proBNP (median: 81 pg/mL; 38.1% exceeded 125 pg/mL) values were marginally lower than the primary analysis, but slightly more than half (1101 values, 50.1%) of this cohort still met the criteria for stage B HF.

Our study identified 2 important results that warrant discussion. First, more than half of the people with T1D included in the primary analysis met the Universal Definition and Classification of HF criteria for stage B HF. This result aligns with the Thousand & 1 Study, which enrolled 960 people with T1D (but without heart disease and with left ventricular ejection fraction ≥45%) in Denmark, and reported that 55% had a baseline NT‐proBNP ≥150 pg/mL.⁵ This finding highlights the urgent need to identify medical therapies beyond glycemic control that can reduce incident HF in people with T1D, given that appropriate glycemic control (ie, hemoglobin A1c <7%) has only been shown to reduce, but not completely normalize, progression from preclinical (stage B) to clinical (stages C and D) HF in people with diabetes.⁶ Second, NP screening of people with T1D is an underused practice within the United States given that <7% of the population in the current study had an NP value collected in 2021 or 2022.

In regard to limitations, we recognize that possible underreporting of laboratory testing could subsequently underestimate the proportion of people who underwent NP testing. Like Cunningham etal,² we attempted to address this by only including people with available serum creatinine data given that these people could have easily undergone NP testing, and that their data were known to have been transmitted to the Premier Healthcare Database. We also recognize that defining T1D by ICD‐10‐CM codes is an inherent limitation of this article. Finally, we acknowledge that clinical documentation from specific outpatient encounters was not available; thus, it was impossible to determine whether some of the testing performed was motivated by clinical suspicion of HF. Moreover, the data set analyzed in this study did not include body weight or body mass index for individual patients. Body mass index is a relevant factor in the context of cardiovascular health in individuals with T1D; thus, its inclusion in subsequent analyses represents an avenue for potential investigation.

In summary, this study is the first to quantify HF screening by NP distributions in a real‐world T1D cohort. Future directions for investigation could include evaluating how many patients subsequently underwent echocardiography and were referrd to cardiology in response to abnormal NP screening results.

Sources of Funding

W.B.H. was supported by a career development award from the American Heart Association (grant number: 941481) and a strategic research agreement with the Juvenile Diabetes Research Foundation United States of America (3‐SRA‐2023‐1236‐M‐B).

Disclosures

None.

Acknowledgments

W.B.H. researched the data, contributed to the discussion, and wrote the first draft of the article. J.T.P. researched the data and reviewed and edited the article. Both authors approved the final version of the article. J.T.P. is the guarantor of the work and, as such, had full access to all data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis.

Notes

This article was sent to Sakima A. Smith, MD, MPH, Associate Editor, for review by expert referees, editorial decision, and final disposition.

For Sources of Funding and Disclosures, see page 3.

References