title: Urinary Proteome and Systolic Blood Pressure as Predictors of 5-Year Cardiovascular and Cardiac Outcomes in a General Population.
abstract: In a previous cross-sectional study, we identified a multidimensional urinary classifier (HF1), which was associated with left ventricular dysfunction. We investigated whether HF1 predicts cardiovascular end points over and beyond traditional risk factors. In 791 randomly recruited Flemish (mean age, 51.2 years; 50.6% women), we quantified HF1 by capillary electrophoresis coupled with mass spectrometry. In addition, we measured cardiovascular risk factors. HF1 averaged -0.97 U (range, -3.26 to 2.60). Over 6.1 years (median), 35 participants died and 63, 45, and 22 experienced fatal or nonfatal cardiovascular, cardiac, or coronary events, respectively. The incidence of fatal combined with nonfatal cardiovascular and cardiac end points, standardized for sex and age, increased across thirds of the HF1 distribution (P≤0.014), whereas trends for all-cause mortality and coronary events were nonsignificant (P≥0.10). The multivariable-adjusted hazard ratios (+1-SD) were 1.30 (95% confidence interval, 1.03-1.65; P=0.029) and 1.39 (1.06-1.84; P=0.018) for cardiovascular and cardiac events in relation to HF1. For systolic pressure, the corresponding estimates were 0.97 (0.74-1.28; P=0.85) and 0.93 (0.67-1.29; P=0.66), respectively. The HF1 upper thresholds optimized by maximizing Younden's index were -0.50 and -0.36 U for cardiovascular and cardiac end points, respectively. Prognostic accuracy significantly (P≤0.006) improved by adding HF1 to Cox models already including the other baseline predictors. Sensitivity analyses, from which we excluded 71 participants with previous cardiovascular disease, were confirmatory. In conclusion, over a 6-year period, the urinary proteome, but not systolic pressure, predicted cardiovascular and cardiac disease.
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Thijs
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Thibault
authors.initials: T
authors.lastname: Petit
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Gu
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Lotte
authors.initials: L
authors.lastname: Jacobs
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Yang
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Koeck
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Petra
authors.initials: P
authors.lastname: Zürbig
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Voigt
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kuznetsova
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.).
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.affiliation: From the Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology (Z.-Y.Z., L.T., T.P., Y.-M.G., L.J., W.-Y.Y., Y.-P.L., Y.J., T. Kuznetsova, J.A.S.), Centre for Molecular and Vascular Biology (P.V.), and Research Unit Cardiology (J.-U.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium; Mosaiques Diagnostic and Therapeutics GmbH, Hannover, Germany (T. Koeck, P.Z., H.M.); BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (H.M.); and R&D VitaK Group, Maastricht University, Maastricht, The Netherlands (J.A.S.). jan.staessen@med.kuleuven.be ja.staessen@maastrichtuniversity.nl.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Staessen
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001530:Belgium / Q000453:epidemiology; D001794:Blood Pressure; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000453:epidemiology; D019075:Electrophoresis, Capillary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology; D015994:Incidence; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009026:Mortality; D010455:Peptides / Q000652:urine*; D011379:Prognosis; D016016:Proportional Hazards Models; D020543:Proteome; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013599:Systole; D016482:Urinalysis / Q000379:methods
chemical_list: D000959:Antihypertensive Agents; D010455:Peptides; D020543:Proteome; D002784:Cholesterol
keywords: biomarker; cardiovascular disease; morbidity; mortality; proteomics