Urinary proteomic biomarkers to predict cardiovascular events

C.E. Brown; Nina Mccarthy; A.D. Hughes; P. Sever; A. Stalmach; W. Mullen; A.F. Dominiczak; N. Sattar; H. Mischak; S. Thom; J. Mayet; A.V. Stanton; C. Delles

doi:10.1002/prca.201400195

Urinary proteomic biomarkers to predict cardiovascular events

C.E. Brown, Nina Mccarthy, A.D. Hughes, P. Sever, A. Stalmach, W. Mullen, A.F. Dominiczak, N. Sattar, H. Mischak, S. Thom, J. Mayet, A.V. Stanton, C. Delles

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Abstract

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Purpose: We have previously demonstrated associations between the urinary proteome profile and coronary artery disease (CAD) in cross-sectional studies. Here, we evaluate the potential of a urinary proteomic panel as a predictor of CAD in the hypertensive atherosclerotic cardiovascular disease (HACVD) substudy population of the Anglo-Scandinavian Cardiac Outcomes Trial study. Experimental design: Thirty-seven cases with primary CAD endpoint were matched for sex and age to controls who had not reached a CAD endpoint during the study. Spot urine samples were analyzed using CE coupled to Micro-TOF MS. A previously developed 238-marker CE-MS model for diagnosis of CAD (CAD238) was assessed for its predictive potential. Results: Sixty urine samples (32 cases; 28 controls; 88% male, mean age 64 ± 5 years) were analyzed. There was a trend toward healthier values in controls for the CAD model classifier (-0.432 ± 0.326 versus -0.587 ± 0.297, p = 0.170), and the CAD model showed statistical significance on Kaplan-Meier survival analysis p = 0.021. We found 190 individual markers out of 1501 urinary peptides that separated cases and controls (AUC >0.6). Of these, 25 peptides were also components of CAD238. Conclusion and clinical relevance: A urinary proteome panel originally developed in a cross-sectional study predicts CAD endpoints independent of age and sex in a well-controlled prospective study.

Original language	English
Pages (from-to)	610-617
Journal	Proteomics - Clinical Applications
Volume	9
Issue number	5-6
DOIs	https://doi.org/10.1002/prca.201400195
Publication status	Published - 2015

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title = "Urinary proteomic biomarkers to predict cardiovascular events",

abstract = "{\textcopyright} 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Purpose: We have previously demonstrated associations between the urinary proteome profile and coronary artery disease (CAD) in cross-sectional studies. Here, we evaluate the potential of a urinary proteomic panel as a predictor of CAD in the hypertensive atherosclerotic cardiovascular disease (HACVD) substudy population of the Anglo-Scandinavian Cardiac Outcomes Trial study. Experimental design: Thirty-seven cases with primary CAD endpoint were matched for sex and age to controls who had not reached a CAD endpoint during the study. Spot urine samples were analyzed using CE coupled to Micro-TOF MS. A previously developed 238-marker CE-MS model for diagnosis of CAD (CAD238) was assessed for its predictive potential. Results: Sixty urine samples (32 cases; 28 controls; 88% male, mean age 64 ± 5 years) were analyzed. There was a trend toward healthier values in controls for the CAD model classifier (-0.432 ± 0.326 versus -0.587 ± 0.297, p = 0.170), and the CAD model showed statistical significance on Kaplan-Meier survival analysis p = 0.021. We found 190 individual markers out of 1501 urinary peptides that separated cases and controls (AUC >0.6). Of these, 25 peptides were also components of CAD238. Conclusion and clinical relevance: A urinary proteome panel originally developed in a cross-sectional study predicts CAD endpoints independent of age and sex in a well-controlled prospective study.",

author = "C.E. Brown and Nina Mccarthy and A.D. Hughes and P. Sever and A. Stalmach and W. Mullen and A.F. Dominiczak and N. Sattar and H. Mischak and S. Thom and J. Mayet and A.V. Stanton and C. Delles",

year = "2015",

doi = "10.1002/prca.201400195",

language = "English",

volume = "9",

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journal = "Proteomics - Clinical Applications",

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TY - JOUR

T1 - Urinary proteomic biomarkers to predict cardiovascular events

AU - Brown, C.E.

AU - Mccarthy, Nina

AU - Hughes, A.D.

AU - Sever, P.

AU - Stalmach, A.

AU - Mullen, W.

AU - Dominiczak, A.F.

AU - Sattar, N.

AU - Mischak, H.

AU - Thom, S.

AU - Mayet, J.

AU - Stanton, A.V.

AU - Delles, C.

PY - 2015

Y1 - 2015

N2 - © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Purpose: We have previously demonstrated associations between the urinary proteome profile and coronary artery disease (CAD) in cross-sectional studies. Here, we evaluate the potential of a urinary proteomic panel as a predictor of CAD in the hypertensive atherosclerotic cardiovascular disease (HACVD) substudy population of the Anglo-Scandinavian Cardiac Outcomes Trial study. Experimental design: Thirty-seven cases with primary CAD endpoint were matched for sex and age to controls who had not reached a CAD endpoint during the study. Spot urine samples were analyzed using CE coupled to Micro-TOF MS. A previously developed 238-marker CE-MS model for diagnosis of CAD (CAD238) was assessed for its predictive potential. Results: Sixty urine samples (32 cases; 28 controls; 88% male, mean age 64 ± 5 years) were analyzed. There was a trend toward healthier values in controls for the CAD model classifier (-0.432 ± 0.326 versus -0.587 ± 0.297, p = 0.170), and the CAD model showed statistical significance on Kaplan-Meier survival analysis p = 0.021. We found 190 individual markers out of 1501 urinary peptides that separated cases and controls (AUC >0.6). Of these, 25 peptides were also components of CAD238. Conclusion and clinical relevance: A urinary proteome panel originally developed in a cross-sectional study predicts CAD endpoints independent of age and sex in a well-controlled prospective study.

AB - © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Purpose: We have previously demonstrated associations between the urinary proteome profile and coronary artery disease (CAD) in cross-sectional studies. Here, we evaluate the potential of a urinary proteomic panel as a predictor of CAD in the hypertensive atherosclerotic cardiovascular disease (HACVD) substudy population of the Anglo-Scandinavian Cardiac Outcomes Trial study. Experimental design: Thirty-seven cases with primary CAD endpoint were matched for sex and age to controls who had not reached a CAD endpoint during the study. Spot urine samples were analyzed using CE coupled to Micro-TOF MS. A previously developed 238-marker CE-MS model for diagnosis of CAD (CAD238) was assessed for its predictive potential. Results: Sixty urine samples (32 cases; 28 controls; 88% male, mean age 64 ± 5 years) were analyzed. There was a trend toward healthier values in controls for the CAD model classifier (-0.432 ± 0.326 versus -0.587 ± 0.297, p = 0.170), and the CAD model showed statistical significance on Kaplan-Meier survival analysis p = 0.021. We found 190 individual markers out of 1501 urinary peptides that separated cases and controls (AUC >0.6). Of these, 25 peptides were also components of CAD238. Conclusion and clinical relevance: A urinary proteome panel originally developed in a cross-sectional study predicts CAD endpoints independent of age and sex in a well-controlled prospective study.

U2 - 10.1002/prca.201400195

DO - 10.1002/prca.201400195

M3 - Article

SN - 1862-8346

VL - 9

SP - 610

EP - 617

JO - Proteomics - Clinical Applications

JF - Proteomics - Clinical Applications

IS - 5-6

ER -

Urinary proteomic biomarkers to predict cardiovascular events

Abstract

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