Disclosures: Berg reports receiving research grant support paid to his institution from AstraZeneca and Pfizer, and consultant fees from AstraZeneca. Please see the study for all other authors’ relevant financial disclosures.
October 11, 2021
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Biomarker-based score predicts heart failure hospitalization risk in type 2 diabetes

Disclosures: Berg reports receiving research grant support paid to his institution from AstraZeneca and Pfizer, and consultant fees from AstraZeneca. Please see the study for all other authors’ relevant financial disclosures.
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A novel risk calculator leveraging two widely available clinical biomarkers can accurately predict heart failure hospitalization for adults with type 2 diabetes at high atherosclerotic cardiovascular disease risk, data show.

Currently, the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Heart Failure in Diabetes is a simple clinical risk score that predicts risk for heart failure (HF) hospitalization in patients with type 2 diabetes using five clinical variables: prior HF, coronary artery disease, atrial fibrillation, estimated glomerular filtration rate and urine albumin-to-creatinine ratio.

Berg is an associate physician in the cardiovascular division at Brigham and Women’s Hospital and an investigator in the TIMI study group.

“Traditional cardiovascular risk tools used in patients with diabetes have focused on predicting risk of atherosclerotic complications such as myocardial infarction or stroke,” David D. Berg, MD, MPH, associate physician in the cardiovascular division at Brigham and Women’s Hospital and an investigator in the TIMI study group, told Healio. “Until recently, we have paid relatively little attention to HF risk in this patient population, even though patients with diabetes who develop HF have a very high risk of dying. Fortunately, we now have effective treatments to prevent heart failure in patients in diabetes, including SGLT2 inhibitors, so recognizing HF risk and discussing this with our patients is more important than ever.”

Berg and colleagues derived a risk score for hospitalization for HF using clinical data and two biomarkers — high-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) data — from 6,106 placebo-treated patients with type 2 diabetes who participated in SAVOR-TIMI 53, a large CV outcomes trial. Log-transformed biomarker concentrations were entered into a multivariable Cox regression model for hospitalization for HF along with the five clinical risk indicators included in TIMI Risk Score for Heart Failure in Diabetes. The risk score model was internally validated using 1,000 bootstrap samples and was externally validated in 7,251 patients from the placebo arm of DECLARE-TIMI 58, which assessed the safety and efficacy of the SGLT2 inhibitor dapagliflozin (Farxiga, AstraZeneca).

The findings were published in Diabetes Care.

Researchers found that the strongest indicators of HF hospitalization risk were NT-proBNP, prior HF and high-sensitivity troponin T (P for each < .001). A risk score using these three variables identified a gradient of HF hospitalization risk (P for trend < .001) in the derivation and validation cohorts, with C-indices of 0.87 (95% CI, 0.84-0.89) and 0.84 (95% CI, 0.81-0.86), respectively.

There was no significant effect of dapagliflozin compared with placebo on HF hospitalization in the low-risk group; however, dapagliflozin significantly reduced HF hospitalization in the intermediate-, high- and very high-risk groups, with HRs of 0.64 (95% CI, 0.43-0.95), 0.63 (95% CI, 0.43-0.94) and 0.72 (95% CI, 0.54-0.96), respectively. Correspondingly, absolute risk reductions also increased across the intermediate-, high- and very high-risk groups by 1% (95% CI, 0-1.9), 3% (95% CI, 0.7-5.3) and 4.4% (95% CI, –0.2 to 8.9), respectively.

The researchers noted the biomarker-based risk score is well-calibrated between cohorts and further refines risk estimates when compared with a clinical variable-only risk score.

“The key-take home messages of the study are that NT-proBNP and high-sensitivity troponin T strongly predict HF risk in patients with diabetes, and that we can estimate a patient’s risk of being hospitalized for HF by measuring these blood biomarkers and using them to calculate a patient’s TIMI Biomarker Score for Heart Failure in Diabetes,” Berg told Healio. “Doing so can inform when it is a priority to treat a patient with an SGLT2 inhibitor.”

For more information:

David D. Berg, MD, MPH, can be reached at dberg1@bwh.harvard.edu; Twitter: @ddbergMD.