NT–proBNP has additive predictive value for heart failure in diabetic patients
Cardiac Stress and Inflammatory Markers as Predictors of Heart Failure in Patients With Type 2 Diabetes: The ADVANCE Trial
Diabetes increases the risk of heart failure (HF) by more than 50% and has a negative impact on HF prognosis [1,2]. Thus, the prevention and treatment of HF in diabetic patients as well as their HF risk stratification are important, however there are limited data regarding the use of cardiovascular disease-related biomarkers in this setting .
In this study, the association of the markers NT-proBNP, hs-cTnT, hs-CRP and IL-6 with risk of HF was evaluated in type 2 diabetes mellitus (T2DM) patients. Moreover, the additional risk-predictive ability of these markers was assessed, on top of traditional clinical risk factors. For this purpose, a nested case-cohort study was conducted including patients from the ADVANCE study, in which 11,140 T2DM patients at high cardiovascular risk were randomized to an intensive gliclazide modified release-based glucose control regimen or standard guidelines-based therapy and after a 6-week run-in period, to perindopril-indapamide or matching placebo [4-6]. In the end, 3,098 patients were included in the analysis. The study outcome was the incidence or progression of HF (death due to HF, HF hospitalization or worsening of NYHA classification).
- During a median follow-up of 5 years, 237 patients who experienced an HF event had significantly higher levels of IL-6, hs-CRP, hs-cTnT and NT-proBNP.
- HF risk increased significantly with increasing levels of all biomarkers after adjustment for age, gender, randomized blood pressure–lowering, glucose-control interventions and clinical risk factors (all P for trend <0.01).
- The multivariable-adjusted HRs for HF according to the highest fifths compared with the lowest fifths of each biomarker were 2.62 for IL-6 (95% CI: 1.48–4.63), 2.22 for hs-CRP (95% CI: 1.33–3.72), 2.70 for hs-cTnT (95% CI: 1.68–4.34), 12.53 for NT-proBNP (95% CI: 5.41–29.02).
- Higher values of all four biomarkers were significantly associated with a higher risk of HF after adjusting for clinical risk factors (all P<0.001).
- After further adjustment for the other studied biomarkers, the associations were attenuated and became non-significant for hs-CRP and hs-cTnT.
- NT-proBNP showed the strongest association with HF (HR 2.77, 95% CI 2.12–3.63).
- Significant heterogeneity (P=0.004) was observed in the association of patients with (HR 2.28, 95% CI 1.08–4.81) and without (HR 3.52, 95% CI 2.66–4.66) a history of myocardial infarction.
- The addition of NT-proBNP to a model including conventional risk factors greatly improved discrimination and classification of the 5-year HF risk (C statistic: 0.8162-0.8800; P<0.001, integrated discrimination index [IDI] 0.107, P<0.001, continuous net reclassification improvement [NRI] 0.731, P<0.001, categorical NRI 0.242, P<0.001).
- The improvements were not uniformly significant when adding IL-6, hs-CRP or hs-cTnT to the above model.
In T2DM patients at high cardiovascular risk, markers IL-6, hs-CRP, hs-cTnT and NT-proBNP were independent predictors of the incidence of HF, but only the addition of NT-proBNP improved the predictive performance for HF on top of conventional clinical risk factors.