PMID- 26497848 OWN - NLM STAT- MEDLINE DCOM- 20161014 LR - 20220330 IS - 1879-0844 (Electronic) IS - 1388-9842 (Linking) VI - 18 IP - 1 DP - 2016 Jan TI - Growth differentiation factor 15 in heart failure with preserved vs. reduced ejection fraction. PG - 81-8 LID - 10.1002/ejhf.431 [doi] AB - AIM: Growth differentiation factor 15 (GDF15) is a cytokine highly expressed in states of inflammatory stress. We aimed to study the clinical correlates and prognostic significance of plasma GDF15 in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction(HFrEF), compared with N-terminal pro-brain natriuretic peptide (NT-proBNP), an indicator of haemodynamic wall stress. METHODS: Plasma GDF15 and NT-proBNP were prospectively measured in 916 consecutive patients with HFrEF (EF <50%; n = 730) and HFpEF (EF >/=50%; n = 186), and measured again at 6 months in 488 patients. Patients were followed up for a composite outcome of death or first HF rehospitalization. RESULTS: Median GDF15baseline values were similarly elevated in HFpEF [2862 (1812 represent the 25th percentile and 4176 represent the 75th percentile) ng/L] and HFrEF [2517 (1555, 4030) ng/L] (P = 0.184), whereas NT-proBNP was significantly lower in HFpEF than HFrEF (1119 ng/L vs. 2335 ng/L, P < 0.001). Independent correlates of GDF15baseline were age, systolic blood pressure, New York Heart Association (NYHA) class, diabetes, atrial fibrillation, sodium, haemoglobin, creatinine, diuretic therapy, high sensitivity troponin T (hsTnT) and NT-proBNP (all P < 0.05). During a median follow-up of 23 months, there were 379 events (307 HFrEF, 72 HFpEF). GDF15 remained a significant independent predictor for composite outcome even after adjusting for important clinical predictors including hsTnT and NT-proBNP (adjusted hazard ratio 1.76 per 1 Ln U, 95% confidence interval 1.39-2.21; P < 0.001), regardless of HF group (Pinteraction = 0.275). GDF15baseline provided incremental prognostic value when added to clinical predictors, hsTnT and NT-proBNP (area under receiver operating characteristic curve increased from 0.720 to 0.740, P < 0.019), with a net reclassification improvement of 0.183 (P = 0.004). Patients with >/=20% GDF156months increase had higher risk for composite outcome (adjusted hazard ratio 1.68, 95% confidence interval 1.15-2.45; P = 0.007) compared with those with GDF156months within +/- 20% of baseline. CONCLUSIONS: The similarly elevated levels and independent prognostic utility of GDF15 in HFrEF and HFpEF suggest that beyond haemodynamic stress (NT-proBNP), inflammatory injury (GDF15) may play an important role in both HF syndromes. CI - (c) 2015 The Authors European Journal of Heart Failure (c) 2015 European Society of Cardiology. FAU - Chan, Michelle M Y AU - Chan MM AD - SingHealth Internal Medicine Residency Program, Singapore Health Services, Singapore. FAU - Santhanakrishnan, Rajalakshmi AU - Santhanakrishnan R AD - Department of Medicine, Section of Cardiovascular Medicine, Boston University, Boston, MA, USA. FAU - Chong, Jenny P C AU - Chong JP AD - Cardiovascular Research Institute, National University of Singapore, Singapore. FAU - Chen, Zhaojin AU - Chen Z AD - Investigational Medicine Unit, National University Health System Singapore, Singapore. FAU - Tai, Bee Choo AU - Tai BC AD - Saw Swee Hock School of Public Health, National University of Singapore, Singapore. FAU - Liew, Oi Wah AU - Liew OW AD - Cardiovascular Research Institute, National University of Singapore, Singapore. FAU - Ng, Tze Pin AU - Ng TP AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore. FAU - Ling, Lieng H AU - Ling LH AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore. FAU - Sim, David AU - Sim D AD - National Heart Centre Singapore, Singapore. FAU - Leong, Kui Toh G AU - Leong KT AD - Changi General Hospital, Singapore. FAU - Yeo, Poh Shuan Daniel AU - Yeo PS AD - Tan Tock Seng Hospital and Apex Heart Clinic, Gleneagles Hospital, Singapore. FAU - Ong, Hean-Yee AU - Ong HY AD - Khoo Teck Puat Hospital, Singapore. FAU - Jaufeerally, Fazlur AU - Jaufeerally F AD - Singapore General Hospital and Duke-NUS Graduate Medical School, Singapore. FAU - Wong, Raymond Ching-Chiew AU - Wong RC AD - National University Heart Centre Singapore, Singapore. FAU - Chai, Ping AU - Chai P AD - National University Heart Centre Singapore, Singapore. FAU - Low, Adrian F AU - Low AF AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore. FAU - Richards, Arthur M AU - Richards AM AD - Cardiovascular Research Institute, National University of Singapore, Singapore. AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore. FAU - Lam, Carolyn S P AU - Lam CS AD - Cardiovascular Research Institute, National University of Singapore, Singapore. AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore. AD - Christchurch Heart Institute, University of Otago, Christchurch, New Zealand. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151025 PL - England TA - Eur J Heart Fail JT - European journal of heart failure JID - 100887595 RN - 0 (Biomarkers) RN - 0 (Growth Differentiation Factor 15) RN - 0 (Peptide Fragments) RN - 0 (pro-brain natriuretic peptide (1-76)) RN - 114471-18-0 (Natriuretic Peptide, Brain) SB - IM MH - Aged MH - Biomarkers/blood MH - Female MH - Growth Differentiation Factor 15/*blood MH - *Heart Failure/blood/diagnosis/epidemiology/physiopathology MH - Humans MH - Inflammation/blood MH - Male MH - Middle Aged MH - Natriuretic Peptide, Brain/blood MH - Patient Readmission/statistics & numerical data MH - Peptide Fragments/blood MH - Prognosis MH - Proportional Hazards Models MH - ROC Curve MH - Singapore/epidemiology MH - *Stroke Volume MH - Survival Analysis OTO - NOTNLM OT - Growth differentiation factor 15 OT - Heart failure with preserved ejection fraction OT - Natriuretic peptides OT - Prognosis EDAT- 2015/10/27 06:00 MHDA- 2016/10/16 06:00 CRDT- 2015/10/27 06:00 PHST- 2015/05/19 00:00 [received] PHST- 2015/08/23 00:00 [revised] PHST- 2015/09/14 00:00 [accepted] PHST- 2015/10/27 06:00 [entrez] PHST- 2015/10/27 06:00 [pubmed] PHST- 2016/10/16 06:00 [medline] AID - 10.1002/ejhf.431 [doi] PST - ppublish SO - Eur J Heart Fail. 2016 Jan;18(1):81-8. doi: 10.1002/ejhf.431. Epub 2015 Oct 25.