Impact of diabetes on the predictive value of heart failure biomarkers.
Patients with diabetes mellitus (DM) have an increased risk of developing heart failure (HF). Further, DM is associated with poor prognosis in patients with HF. Our aim was to determine whether DM has any impact on the predictive value of a multi-biomarker panel in patients with HF.



We included 1069 consecutive ambulatory HF patients in the study: age 66.2 ± 12.8 years, 33.5 ± 13.3 left ventricular ejection fraction, 36% diabetic patients. We measured serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), ST2, galectin-3, high-sensitivity C reactive protein (hs-CRP), cystatin-C, soluble transferrin receptor (sTfR), and neprilysin and followed patients for 4.9 ± 2.8 years. Primary endpoints were all-cause and cardiovascular death.



During follow-up, 534 patients died; 283 died of cardiovascular causes. Diabetic subjects had higher mortality (57.7 vs. 45.6%, p < 0.001). NTproBNP (p = 0.07), hs-TnT (p < 0.001), galectin-3 (p < 0.001), and cystatin-C (p = 0.001) concentrations were higher in diabetic patients, whereas sTfR levels were lower (p = 0.005). There were no interactions between DM and NTproBNP, hs-TnT, galectin-3, hs-CRP, cystatin-C, sTfR, and neprilysin relative to risk prediction for all-cause or cardiovascular death. By contrast, ST2 significantly interacted with DM for all-cause (p = 0.02) and cardiovascular (p = 0.03) death. In diabetic patients, HRs for ST2 were 1.27 (95% CI 1.16-1.40, p < 0.001) and 1.23 (95% CI 1.09-1.39, p = 0.001) for all-cause and cardiovascular death, respectively. In nondiabetic patients, HRs for ST2 were 1.53 (95% CI 1.35-1.73, p < 0.001) and 1.64 (95% CI 1.31-2.05, p < 0.001) for all-cause and cardiovascular death, respectively. The multivariable Cox regression analysis showed that hs-TnT and ST2 were the only markers that were independently associated with both all-cause and cardiovascular mortality in patients with HF and diabetes. Moreover, in these patients, the combination of these two markers significantly increased discrimination as assessed by the area under the curve.



Biomarkers used in the general population to predict the clinical course of heart failure are also useful in patients with diabetes. In these patients, among all the biomarkers analysed only hs-TnT and ST2 were independently associated with both all-cause and cardiovascular mortality.
Heart Failure Clinic, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain.|Department of Endocrinology and Nutrition, CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Badalona, Spain.
Nuria
0000-0001-5844-2221
N
Alonso
Heart Failure Clinic, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain.|Department of Medicine, Universitat Autonoma de Barcelona, Badalona, Spain.
Josep
J
Lupón
Department of Biochemistry, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Jaume
J
Barallat
Heart Failure Clinic, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain.
Marta
M
de Antonio
Heart Failure Clinic, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain.
Mar
M
Domingo
Heart Failure Clinic, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain.|Department of Medicine, Universitat Autonoma de Barcelona, Badalona, Spain.
Elisabet
E
Zamora
Heart Failure Clinic, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain.
Pedro
P
Moliner
Department of Biochemistry, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
Amparo
A
Galán
Heart Failure Clinic, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain.
Javier
J
Santesmases
Department of Biochemistry, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Cruz
C
Pastor
Department of Endocrinology and Nutrition, CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Badalona, Spain. didacmauricio@gmail.com.|Department of Medicine, UAB, Endocrinology and Nutrition Service, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s/n, 08916, Badalona, Spain. didacmauricio@gmail.com.
Dídac
D
Mauricio
Heart Failure Clinic, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain. abayesgenis@gmail.com.|Department of Medicine, Universitat Autonoma de Barcelona, Badalona, Spain. abayesgenis@gmail.com.|Department of Medicine, UAB, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s/n, 08916, Badalona, Spain. abayesgenis@gmail.com.
Antoni
A
Bayes-Genis
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002423:Cause of Death; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume; D013997:Time Factors; D020107:Troponin T / Q000097:blood*; D015854:Up-Regulation; D016277:Ventricular Function, Left
D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D020107:Troponin T
Biomarkers; Diabetes mellitus; Heart failure; Prognostic; ST2