title: Von Willebrand factor improves risk prediction in addition to N-terminal pro-B-type natriuretic peptide in patients referred to coronary angiography and signs and symptoms of heart failure and preserved ejection fraction.
abstract: BACKGROUND
  Heart failure with preserved ejection fraction (HFpEF) represents a growing health burden associated with substantial mortality and morbidity. Consequently, risk prediction is of highest importance. Endothelial dysfunction has been recently shown to play an important role in the complex pathophysiology of HFpEF. We therefore aimed to assess von Willebrand factor (vWF), a marker of endothelial damage, as potential biomarker for risk assessment in patients with HFpEF.
  
  
  RESULTS
  Concentrations of vWF were assessed in 457 patients with HFpEF enrolled as part of the LUdwigshafen Risk and Cardiovascular Health (LURIC) study. All-cause mortality was observed in 40% of patients during a median follow-up time of 9.7 years. vWF significantly predicted mortality with a hazard ratio (HR) per increase of 1 SD of 1.45 (95% confidence interval, 1.26-1.68; P<0.001) and remained a significant predictor after adjustment for age, sex, body mass index, N-terminal pro-B-type natriuretic peptide (NT-proBNP), renal function, and frequent HFpEF-related comorbidities (adjusted HR per 1 SD, 1.22; 95% confidence interval, 1.05-1.42; P=0.001). Most notably, vWF showed additional prognostic value beyond that achievable with NT-proBNP indicated by improvements in C-Statistic (vWF×NT-proBNP: 0.65 versus NT-proBNP: 0.63; P for comparison, 0.004) and category-free net reclassification index (37.6%; P<0.001).
  
  
  CONCLUSIONS
  vWF is an independent predictor of long-term outcome in patients with HFpEF, which is in line with endothelial dysfunction as potential mediator in the pathophysiology of HFpEF. In particular, combined assessment of vWF and NT-proBNP improved risk prediction in this vulnerable group of patients.
authors.affiliation: From the Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology) (M.E.K., T.B.G., G.D., W.M.) and Mannheim Institute of Public Health, Social and Preventive Medicine (T.B.G.), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (L.K., G.G., P.S., A.N.); Clinical Institute of Medical and Chemical Laboratory Diagnostics (H.S., W.M.), Department of Internal Medicine, Division of Cardiology (A.T.), and Department of Internal Medicine, Division of Endocrinology and Metabolism (S.P.), Medical University of Graz, Graz, Austria; Department of Angiology, Inselspital, Bern, Switzerland (G.S.); Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria (A.T.); and Synlab Center of Laboratory Diagnostics, Heidelberg, Germany (W.M.).
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.affiliation: From the Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology) (M.E.K., T.B.G., G.D., W.M.) and Mannheim Institute of Public Health, Social and Preventive Medicine (T.B.G.), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (L.K., G.G., P.S., A.N.); Clinical Institute of Medical and Chemical Laboratory Diagnostics (H.S., W.M.), Department of Internal Medicine, Division of Cardiology (A.T.), and Department of Internal Medicine, Division of Endocrinology and Metabolism (S.P.), Medical University of Graz, Graz, Austria; Department of Angiology, Inselspital, Bern, Switzerland (G.S.); Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria (A.T.); and Synlab Center of Laboratory Diagnostics, Heidelberg, Germany (W.M.).
authors.forename: Lorenz
authors.initials: L
authors.lastname: Koller
authors.affiliation: From the Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology) (M.E.K., T.B.G., G.D., W.M.) and Mannheim Institute of Public Health, Social and Preventive Medicine (T.B.G.), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (L.K., G.G., P.S., A.N.); Clinical Institute of Medical and Chemical Laboratory Diagnostics (H.S., W.M.), Department of Internal Medicine, Division of Cardiology (A.T.), and Department of Internal Medicine, Division of Endocrinology and Metabolism (S.P.), Medical University of Graz, Graz, Austria; Department of Angiology, Inselspital, Bern, Switzerland (G.S.); Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria (A.T.); and Synlab Center of Laboratory Diagnostics, Heidelberg, Germany (W.M.).
authors.forename: Georg
authors.initials: G
authors.lastname: Goliasch
authors.affiliation: From the Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology) (M.E.K., T.B.G., G.D., W.M.) and Mannheim Institute of Public Health, Social and Preventive Medicine (T.B.G.), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (L.K., G.G., P.S., A.N.); Clinical Institute of Medical and Chemical Laboratory Diagnostics (H.S., W.M.), Department of Internal Medicine, Division of Cardiology (A.T.), and Department of Internal Medicine, Division of Endocrinology and Metabolism (S.P.), Medical University of Graz, Graz, Austria; Department of Angiology, Inselspital, Bern, Switzerland (G.S.); Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria (A.T.); and Synlab Center of Laboratory Diagnostics, Heidelberg, Germany (W.M.).
authors.forename: Patrick
authors.initials: P
authors.lastname: Sulzgruber
authors.affiliation: From the Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology) (M.E.K., T.B.G., G.D., W.M.) and Mannheim Institute of Public Health, Social and Preventive Medicine (T.B.G.), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (L.K., G.G., P.S., A.N.); Clinical Institute of Medical and Chemical Laboratory Diagnostics (H.S., W.M.), Department of Internal Medicine, Division of Cardiology (A.T.), and Department of Internal Medicine, Division of Endocrinology and Metabolism (S.P.), Medical University of Graz, Graz, Austria; Department of Angiology, Inselspital, Bern, Switzerland (G.S.); Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria (A.T.); and Synlab Center of Laboratory Diagnostics, Heidelberg, Germany (W.M.).
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.affiliation: From the Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology) (M.E.K., T.B.G., G.D., W.M.) and Mannheim Institute of Public Health, Social and Preventive Medicine (T.B.G.), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (L.K., G.G., P.S., A.N.); Clinical Institute of Medical and Chemical Laboratory Diagnostics (H.S., W.M.), Department of Internal Medicine, Division of Cardiology (A.T.), and Department of Internal Medicine, Division of Endocrinology and Metabolism (S.P.), Medical University of Graz, Graz, Austria; Department of Angiology, Inselspital, Bern, Switzerland (G.S.); Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria (A.T.); and Synlab Center of Laboratory Diagnostics, Heidelberg, Germany (W.M.).
authors.forename: Günther
authors.initials: G
authors.lastname: Silbernagel
authors.affiliation: From the Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology) (M.E.K., T.B.G., G.D., W.M.) and Mannheim Institute of Public Health, Social and Preventive Medicine (T.B.G.), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (L.K., G.G., P.S., A.N.); Clinical Institute of Medical and Chemical Laboratory Diagnostics (H.S., W.M.), Department of Internal Medicine, Division of Cardiology (A.T.), and Department of Internal Medicine, Division of Endocrinology and Metabolism (S.P.), Medical University of Graz, Graz, Austria; Department of Angiology, Inselspital, Bern, Switzerland (G.S.); Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria (A.T.); and Synlab Center of Laboratory Diagnostics, Heidelberg, Germany (W.M.).
authors.forename: Tanja B
authors.initials: TB
authors.lastname: Grammer
authors.affiliation: From the Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology) (M.E.K., T.B.G., G.D., W.M.) and Mannheim Institute of Public Health, Social and Preventive Medicine (T.B.G.), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (L.K., G.G., P.S., A.N.); Clinical Institute of Medical and Chemical Laboratory Diagnostics (H.S., W.M.), Department of Internal Medicine, Division of Cardiology (A.T.), and Department of Internal Medicine, Division of Endocrinology and Metabolism (S.P.), Medical University of Graz, Graz, Austria; Department of Angiology, Inselspital, Bern, Switzerland (G.S.); Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria (A.T.); and Synlab Center of Laboratory Diagnostics, Heidelberg, Germany (W.M.).
authors.forename: Graciela
authors.initials: G
authors.lastname: Delgado
authors.affiliation: From the Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology) (M.E.K., T.B.G., G.D., W.M.) and Mannheim Institute of Public Health, Social and Preventive Medicine (T.B.G.), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (L.K., G.G., P.S., A.N.); Clinical Institute of Medical and Chemical Laboratory Diagnostics (H.S., W.M.), Department of Internal Medicine, Division of Cardiology (A.T.), and Department of Internal Medicine, Division of Endocrinology and Metabolism (S.P.), Medical University of Graz, Graz, Austria; Department of Angiology, Inselspital, Bern, Switzerland (G.S.); Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria (A.T.); and Synlab Center of Laboratory Diagnostics, Heidelberg, Germany (W.M.).
authors.forename: Andreas
authors.initials: A
authors.lastname: Tomaschitz
authors.affiliation: From the Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology) (M.E.K., T.B.G., G.D., W.M.) and Mannheim Institute of Public Health, Social and Preventive Medicine (T.B.G.), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (L.K., G.G., P.S., A.N.); Clinical Institute of Medical and Chemical Laboratory Diagnostics (H.S., W.M.), Department of Internal Medicine, Division of Cardiology (A.T.), and Department of Internal Medicine, Division of Endocrinology and Metabolism (S.P.), Medical University of Graz, Graz, Austria; Department of Angiology, Inselspital, Bern, Switzerland (G.S.); Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria (A.T.); and Synlab Center of Laboratory Diagnostics, Heidelberg, Germany (W.M.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.affiliation: From the Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology) (M.E.K., T.B.G., G.D., W.M.) and Mannheim Institute of Public Health, Social and Preventive Medicine (T.B.G.), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (L.K., G.G., P.S., A.N.); Clinical Institute of Medical and Chemical Laboratory Diagnostics (H.S., W.M.), Department of Internal Medicine, Division of Cardiology (A.T.), and Department of Internal Medicine, Division of Endocrinology and Metabolism (S.P.), Medical University of Graz, Graz, Austria; Department of Angiology, Inselspital, Bern, Switzerland (G.S.); Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria (A.T.); and Synlab Center of Laboratory Diagnostics, Heidelberg, Germany (W.M.).
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: From the Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, and Rheumatology) (M.E.K., T.B.G., G.D., W.M.) and Mannheim Institute of Public Health, Social and Preventive Medicine (T.B.G.), Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany; Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria (L.K., G.G., P.S., A.N.); Clinical Institute of Medical and Chemical Laboratory Diagnostics (H.S., W.M.), Department of Internal Medicine, Division of Cardiology (A.T.), and Department of Internal Medicine, Division of Endocrinology and Metabolism (S.P.), Medical University of Graz, Graz, Austria; Department of Angiology, Inselspital, Bern, Switzerland (G.S.); Specialist Clinic for Rehabilitation, PV Bad Aussee, Bad Aussee, Austria (A.T.); and Synlab Center of Laboratory Diagnostics, Heidelberg, Germany (W.M.). alexander.niessner@meduniwien.ac.at.
authors.forename: Alexander
authors.initials: A
authors.lastname: Niessner
mesh_terms: D000368:Aged; D001317:Austria / Q000453:epidemiology; D002423:Cause of Death / Q000639:trends; D016001:Confidence Intervals; D017023:Coronary Angiography / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D013318:Stroke Volume / Q000502:physiology*; D015996:Survival Rate / Q000639:trends; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D014841:von Willebrand Factor; D020097:Natriuretic Peptide, Brain
keywords: diastolic heart failure; prognosis; von Willebrand factor