Heart Failure in Type 2 Diabetes: Improving the Risk Model

Heart Failure in AF
Heart Failure in AF
N-terminal pro-B-type natriuretic peptide showed the strongest association with heart failure in patients with type 2 diabetes.

In patients with type 2 diabetes (T2D), N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicted the incidence or progression of heart failure beyond conventional risk factors, according to data published in Diabetes Care.

Researchers conducted a nested case-cohort study in a group of participants from the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; ClinicalTrials.gov identifier: NCT00145925) clinical trial to examine the association between cardiac stress biomarkers and inflammatory markers and heart failure in patients with T2D.  A total of 3098 participants were included in this analysis.

The primary outcome was incidence or progression of heart failure (death or hospitalization due to heart failure or worsening New York Heart Association Functional classification).

After adjustment for age, sex, randomized blood-pressure lowering and glucose-lowering interventions, and clinical risk factors, the risk for heart failure increased significantly with higher levels of all biomarkers (all P for trend <.01). However, the hazard ratio (HR) per 1-standard deviation increase was highest for NT-proBNP (HR 3.06; 95% CI, 2.37-3.96) compared with high-sensitivity cardiac troponin T (hs-cTnT; HR 1.50; 95% CI, 1.27-1.77), interleukin-6 (IL-6; HR 1.48; 95% CI, 1.27-1.72), and high-sensitive C-reactive protein (hs-CRP; HR 1.32; 95% CI, 1.12-1.55).

Adding NT-proBNP to a conventional risk factor model improved 5-year risk-predictive performance (C statistic: 0.8162-0.8800; continuous net reclassification improvement: 73.1%; categorical net reclassification improvement: 24.2%).

Moreover, associations with heart failure became nonsignificant for hs-CRP and hs-cTnT after further adjustment for the other biomarkers. NT-proBNP demonstrated the strongest association with heart failure in all adjustments (HR 2.77; 95% CI, 2.12-3.63).

“[We]e found that IL-6, hs-CRP, hs-cTnT, and NT-proBNP were independent predictors of the incidence of heart failure in patients with [T2D]. However, only the addition of NT-proBNP materially improved the predictive performance for heart failure beyond that from conventional clinical risk factors,” the researchers concluded.

Disclosures: Several researchers report financial relationships with pharmaceutical companies including Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Janssen-Cilag, Merck Sharp & Dohme, Medtronic, Novartis, Sanofi, Servier Laboratories, and Takeda, among others.


Ohkuma T, Jun M, Woodward M, et al; on behalf of the ADVANCE Collaborative Group. Cardiac stress and inflammatory markers as predictors of heart failure in patients with type 2 diabetes: the ADVANCE trial [published online July 6, 2017]. Diabetes Care. doi:10.2337/dc17-0509