ESC Congress 2026 Abstract · Oct 26, 2026
Fourteen-year risk of MACE stratified by NT-proBNP and inflammatory biomarkers in type 2 diabetes
By Bahrami HSZ, Jorgensen PG, Rasmussen LJH et al.
Background: As the global prevalence of type 2 diabetes (T2D) approaches 1 billion individuals, a parallel rise in cardiovascular disease (CVD) is anticipated, underscoring an urgent need for improved risk stratification. Despite recent advances, cardiovascular risk in individuals without CVD remains incompletely captured by contemporary risk factors, prompting interest in novel biomarkers. NT-proBNP and biomarkers of chronic inflammation have each demonstrated robust prognostic value. However, whether their combined assessment provides complementary prognostic information remains unknown. Purpose: To examine whether combined NT-proBNP and inflammatory biomarker elevations are associated with increased risk of major adverse cardiovascular events (MACE). Methods: In a prospective clinical cohort of individuals with T2D without CVD, baseline concentrations of N-terminal pro–B-type natriuretic peptide (NT-proBNP), soluble urokinase plasminogen activator receptor (suPAR), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were measured. The primary endpoint was MACE, defined as a composite of all-cause mortality or incident hospitalization for ischemic heart disease, heart failure, or stroke. Associations were examined using Cox models with biomarkers modeled per doubling of concentration. NT-proBNP was dichotomized at 125 pg/mL and modeled with median-based categories of inflammatory biomarkers to examine joint-biomarker elevations. Analyses were adjusted for albuminuria and SCORE2-Diabetes variables (age, sex, smoking, systolic blood pressure, total and high-density lipoprotein cholesterol, HbA1c, estimated glomerular filtration rate, and age at diabetes diagnosis). Results: Among 589 participants (median age 64 years; 59% men), 367 events occurred during 14 years (interquartile range, 8-13 years) with complete (100%) ascertainment (Figure 1). In adjusted analyses, each doubling of biomarker concentrations was associated with increased risk of MACE: NT-proBNP HR 1.53 (95% confidence interval [CI] 1.34 to 1.74), suPAR HR 2.67 (1.97 to 3.62), IL-6 HR 1.09 (1.00 to 1.19), and hsCRP HR 1.11 (1.00 to 1.24). Single-biomarker concentrations above the predefined cutoffs were likewise associated with increased risk: NT-proBNP HR 1.92 (1.36 to 2.72), suPAR HR 1.73 (1.22 to 2.46), IL-6 HR 1.61 (1.18 to 2.20), and hsCRP HR 1.36 (1.00 to 1.87). Joint elevations of NT-proBNP and an inflammatory biomarker, compared with both non-elevated, identified a distinct high-risk subgroup: NT-proBNP+suPAR HR 3.35 (1.93 to 5.80), NT-proBNP+IL-6 HR 2.90 (1.73 to 4.87), and NT-proBNP+hsCRP HR 2.29 (1.43 to 3.68) (Figure 2). Conclusions: In individuals with T2D without CVD, a combined assessment of NT-proBNP and an inflammatory biomarker is associated with long-term risk of MACE. Integrating these biomarkers into risk stratification in primary prevention of CVD may be warranted.