IL-6 AND FGF-23 AS EARLY BIOMARKERS OF LEFT VENTRICULAR HYPERTROPHY AND HEART FAILURE RISK IN DIABETES MELLITUS
Abstract
Objective: Diabetes mellitus (DM) is associated with increased cardiovascular mortality. The aim of this study was to identify early biomarkers of cardiovascular risk in DM patients, focusing on left ventricular hypertrophy (LVH) and heart failure (HF) risk. Design and method: The study included 255 DM patients aged 34 to 75 years and 65 controls without DM. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of VEGF-A, FGF-23, RANTES, TNF-alpha, MIG, CRP/hsCRP, IL-6, podocin, KIM-1, homocysteine, serum creatinine, GFR and albumin/creatinine ratio (A/C). An echocardiographic investigation was performed to study structural and geometric heart parameters. LVH was diagnosed when the left ventricular myocardial mass index (LVMI) exceeded 115 g/m2 in men and 95 g/m2 in women. DM patients were stratified by LVH (LVH+, n=103; LVH-, n=152). LVH+ patients were further stratified by HF risk using guideline thresholds (BNP >35 pg/mL and/or NT-proBNP >125 ng/mL): HF+, n=72; HF-, n=31. Results: Compared with controls, DM patients had higher BNP, NT-proBNP, LV mass and LVMI (p<0.005). LVH+ DM patients showed higher VEGF-A, FGF-23, RANTES, TNF-alpha, MIG, and IL-6 than controls (p<0.005). The LVH- subgroup did not differ from controls in FGF-23, RANTES, TNF-alpha, BNP or NT-proBNP (p>0.05). Within LVH+ patients, in comparison with the HF- group, HF+ subjects had higher VEGF-A (p=0.004), FGF-23 (3.22 [1.09; 9.55] vs 0.52 [0.27; 1.08] pmol/L; p<0.0001), RANTES (p<0.0001), MIG (p<0.0001), IL-6 (7.96 [2.85; 12.65] vs 1.9 [1.6; 3.12] mg/mL; p<0.0001), BNP (p<0.0001) and NT-proBNP (p<0.0001). LVMI correlated with FGF-23 (r=0.544) and MIG (r=0.499) (p<0.001). In multivariable regression, LVMI remained associated with FGF-23 (b=1.48; p=0.04) and MIG (b=0.01; p=0.02), whereas NT-proBNP was associated with IL-6 (b=17.00; p<0.001) and A/C (b=3.51; p=0.01). IL-6 predicted LVH (AUC=0.768; cut-off>0.9 mg/ml; Se 73%, Sp 68%). For HF risk, FGF-23 (AUC=0.758; cut-off >0.9 pmol/L; Se 73.0%, Sp 68.2%) and IL=6 (AUC=0.749; cut-off >2.13 mg/ml; Se 68.2%, Sp 67.4%) were predictive markers. Conclusions: IL-6 and FGF-23 are associated with LV remodeling and HF risk in DM, showing acceptable discrimination for early risk stratification.