Combining biomarkers and imaging for short-term assessment of cardiovascular disease risk in apparently healthy adults

Maria Odette Gore; Colby R. Ayers; Amit Khera; Christopher R. Defilippi; Thomas J. Wang; Stephen L. Seliger; Vijay Nambi; Elizabeth Selvin; Jarett D. Berry; W. Gregory Hundley; Matthew Budoff; Philip Greenland; Mark H. Drazner; Christie M. Ballantyne; Benjamin D. Levine; James A. de Lemos

doi:10.1161/JAHA.119.015410

Combining biomarkers and imaging for short-term assessment of cardiovascular disease risk in apparently healthy adults

Maria Odette Gore^*, Colby R. Ayers, Amit Khera, Christopher R. Defilippi, Thomas J. Wang, Stephen L. Seliger, Vijay Nambi, Elizabeth Selvin, Jarett D. Berry, W. Gregory Hundley, Matthew Budoff, Philip Greenland, Mark H. Drazner, Christie M. Ballantyne, Benjamin D. Levine, James A. de Lemos

^*Corresponding author for this work

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

BACKGROUND: Current strategies for cardiovascular disease (CVD) risk assessment focus on 10-year or longer timeframes. Shorter-term CVD risk is also clinically relevant, particularly for high-risk occupations, but is under-investigated. METHODS AND RESULTS: We pooled data from participants in the ARIC (Atherosclerosis Risk in Communities study), MESA (Multi-Ethnic Study of Atherosclerosis), and DHS (Dallas Heart Study), free from CVD at baseline (N=16 581). Measurements included N-terminal pro-B-type natriuretic peptide (>100 pg/mL prospectively defined as abnormal); high-sensitivity cardiac troponin T (abnormal >5 ng/L); high-sensitivity C-reactive protein (abnormal >3 mg/L); left ventricular hypertrophy by ECG (abnormal if present); carotid intima-media thickness, and plaque (abnormal >75th percentile for age and sex or presence of plaque); and coronary artery calcium (abnormal >10 Agatston U). Each abnormal test result except left ventricular hypertrophy by ECG was independently associated with increased 3-year risk of global CVD (myocardial infarction, stroke, coronary revascularization, incident heart failure, or atrial fibrillation), even after adjustment for traditional CVD risk factors and the other test results. When a simple integer score counting the number of abnormal tests was used, 3-year multivariable-adjusted global CVD risk was increased among participants with integer scores of 1, 2, 3, and 4, by ≈2-, 3-, 4.5-and 8-fold, respectively, when compared with those with a score of 0. Qualitatively similar results were obtained for atherosclerotic CVD (fatal or non-fatal myocardial infarction or stroke). CONCLUSIONS: A strategy incorporating multiple biomarkers and atherosclerosis imaging improved assessment of 3-year global and atherosclerotic CVD risk compared with a standard approach using traditional risk factors.

Original language	English (US)
Article number	e015410
Journal	Journal of the American Heart Association
Volume	9
Issue number	15
DOIs	https://doi.org/10.1161/JAHA.119.015410
State	Published - Aug 4 2020

Funding

Siemens Healthcare, Roche Diagnostics, and Metabolomics. Dr Seliger received grant support from Roche Diagnostics and Siemens Healthineers. Dr de Lemos received grant support from Abbott Diagnostics and Roche Diagnostics, and consulting income from Roche Diagnostics, Abbott Diagnostics, Ortho Clinical Diagnostics, Quidel Cardiovascular, Amgen, Regeneron, Janssen, and Novo Nordisk. Drs deFilippi, Seliger and de Lemos have been named as co-inventors on a patent issued to University of Maryland (US Patent Application Number: 15/309,754) entitled “Methods for Assessing Differential Risk for Developing Heart Failure”. Dr Nambi is an investigator on a provisional patent (patent no. 61721475) entitled “Biomarkers to Improve Prediction of Heart Failure Risk” filed by Roche and Baylor College of Medicine and is site principal investigator for a study sponsored by Merck. Dr Berry received research funding from Abbott. Dr Ballantyne received research funding and is a consultant for Abbott and Roche, and is named on provisional patent no. 61721475 entitled “Biomarkers to Improve Prediction of Heart Failure Risk” filed by Baylor College of Medicine and Roche. The remaining authors have no disclosures to report. This study was supported by National Space Biomedical Research Institute research grant CA03801 (to de Lemos). Gore was supported by a career development grant (K23-HL131939) from the National Heart, Lung, and Blood Institute (NHLBI), by a University of Colorado School of Medicine Fund to Retain Clinical Scientists research award from the Doris Duke Charitable Foundation, and by a Pilot Study Research Grant for Junior Investigators from Denver Health and Hospital Authority. The MESA study was supported by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from NHLBI, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences). The DHS was supported by a grant from the Donald W. Reynolds Foundation and by a grant from the National Center for Advancing Translational Sciences (UL1TR001105). The ARIC study was supported by contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I from NHLBI. Selvin was supported by grant R01-DK089174 from the National Institute of Diabetes and Digestive and Kidney Diseases. Budoff was supported by grant R01-HL071739 from NHLBI. Drazner was supported by the James M. Wooten Chair in Cardiology from UT Southwestern Medical Center. Ballantyne was supported by grant R01-HL134320 from NHLBI. Levine was supported by grants P01-HL137630 from NHLBI and 14SFRN20510023 from the American Heart Association.

Keywords

Carotid intima-media thickness
Coronary artery calcium
High-sensitivity C-reactive protein
High-sensitivity cardiac troponin T
N-terminal pro B-type natriuretic peptide
Plaque

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1161/JAHA.119.015410

Cite this

Gore, M. O., Ayers, C. R., Khera, A., Defilippi, C. R., Wang, T. J., Seliger, S. L., Nambi, V., Selvin, E., Berry, J. D., Hundley, W. G., Budoff, M., Greenland, P., Drazner, M. H., Ballantyne, C. M., Levine, B. D., & de Lemos, J. A. (2020). Combining biomarkers and imaging for short-term assessment of cardiovascular disease risk in apparently healthy adults. Journal of the American Heart Association, 9(15), Article e015410. https://doi.org/10.1161/JAHA.119.015410

@article{d7282e3beb3c43128c4a7e60ff0e33f3,

title = "Combining biomarkers and imaging for short-term assessment of cardiovascular disease risk in apparently healthy adults",

abstract = "BACKGROUND: Current strategies for cardiovascular disease (CVD) risk assessment focus on 10-year or longer timeframes. Shorter-term CVD risk is also clinically relevant, particularly for high-risk occupations, but is under-investigated. METHODS AND RESULTS: We pooled data from participants in the ARIC (Atherosclerosis Risk in Communities study), MESA (Multi-Ethnic Study of Atherosclerosis), and DHS (Dallas Heart Study), free from CVD at baseline (N=16 581). Measurements included N-terminal pro-B-type natriuretic peptide (>100 pg/mL prospectively defined as abnormal); high-sensitivity cardiac troponin T (abnormal >5 ng/L); high-sensitivity C-reactive protein (abnormal >3 mg/L); left ventricular hypertrophy by ECG (abnormal if present); carotid intima-media thickness, and plaque (abnormal >75th percentile for age and sex or presence of plaque); and coronary artery calcium (abnormal >10 Agatston U). Each abnormal test result except left ventricular hypertrophy by ECG was independently associated with increased 3-year risk of global CVD (myocardial infarction, stroke, coronary revascularization, incident heart failure, or atrial fibrillation), even after adjustment for traditional CVD risk factors and the other test results. When a simple integer score counting the number of abnormal tests was used, 3-year multivariable-adjusted global CVD risk was increased among participants with integer scores of 1, 2, 3, and 4, by ≈2-, 3-, 4.5-and 8-fold, respectively, when compared with those with a score of 0. Qualitatively similar results were obtained for atherosclerotic CVD (fatal or non-fatal myocardial infarction or stroke). CONCLUSIONS: A strategy incorporating multiple biomarkers and atherosclerosis imaging improved assessment of 3-year global and atherosclerotic CVD risk compared with a standard approach using traditional risk factors.",

keywords = "Carotid intima-media thickness, Coronary artery calcium, High-sensitivity C-reactive protein, High-sensitivity cardiac troponin T, N-terminal pro B-type natriuretic peptide, Plaque",

author = "Gore, {Maria Odette} and Ayers, {Colby R.} and Amit Khera and Defilippi, {Christopher R.} and Wang, {Thomas J.} and Seliger, {Stephen L.} and Vijay Nambi and Elizabeth Selvin and Berry, {Jarett D.} and Hundley, {W. Gregory} and Matthew Budoff and Philip Greenland and Drazner, {Mark H.} and Ballantyne, {Christie M.} and Levine, {Benjamin D.} and {de Lemos}, {James A.}",

note = "Funding Information: Siemens Healthcare, Roche Diagnostics, and Metabolomics. Dr Seliger received grant support from Roche Diagnostics and Siemens Healthineers. Dr de Lemos received grant support from Abbott Diagnostics and Roche Diagnostics, and consulting income from Roche Diagnostics, Abbott Diagnostics, Ortho Clinical Diagnostics, Quidel Cardiovascular, Amgen, Regeneron, Janssen, and Novo Nordisk. Drs deFilippi, Seliger and de Lemos have been named as co-inventors on a patent issued to University of Maryland (US Patent Application Number: 15/309,754) entitled “Methods for Assessing Differential Risk for Developing Heart Failure”. Dr Nambi is an investigator on a provisional patent (patent no. 61721475) entitled “Biomarkers to Improve Prediction of Heart Failure Risk” filed by Roche and Baylor College of Medicine and is site principal investigator for a study sponsored by Merck. Dr Berry received research funding from Abbott. Dr Ballantyne received research funding and is a consultant for Abbott and Roche, and is named on provisional patent no. 61721475 entitled “Biomarkers to Improve Prediction of Heart Failure Risk” filed by Baylor College of Medicine and Roche. The remaining authors have no disclosures to report. Funding Information: This study was supported by National Space Biomedical Research Institute research grant CA03801 (to de Lemos). Gore was supported by a career development grant (K23-HL131939) from the National Heart, Lung, and Blood Institute (NHLBI), by a University of Colorado School of Medicine Fund to Retain Clinical Scientists research award from the Doris Duke Charitable Foundation, and by a Pilot Study Research Grant for Junior Investigators from Denver Health and Hospital Authority. The MESA study was supported by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from NHLBI, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences). The DHS was supported by a grant from the Donald W. Reynolds Foundation and by a grant from the National Center for Advancing Translational Sciences (UL1TR001105). The ARIC study was supported by contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I from NHLBI. Selvin was supported by grant R01-DK089174 from the National Institute of Diabetes and Digestive and Kidney Diseases. Budoff was supported by grant R01-HL071739 from NHLBI. Drazner was supported by the James M. Wooten Chair in Cardiology from UT Southwestern Medical Center. Ballantyne was supported by grant R01-HL134320 from NHLBI. Levine was supported by grants P01-HL137630 from NHLBI and 14SFRN20510023 from the American Heart Association. Publisher Copyright: {\textcopyright} 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.",

year = "2020",

month = aug,

day = "4",

doi = "10.1161/JAHA.119.015410",

language = "English (US)",

volume = "9",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "American Heart Association Inc.",

number = "15",

}

Gore, MO, Ayers, CR, Khera, A, Defilippi, CR, Wang, TJ, Seliger, SL, Nambi, V, Selvin, E, Berry, JD, Hundley, WG, Budoff, M, Greenland, P, Drazner, MH, Ballantyne, CM, Levine, BD & de Lemos, JA 2020, 'Combining biomarkers and imaging for short-term assessment of cardiovascular disease risk in apparently healthy adults', Journal of the American Heart Association, vol. 9, no. 15, e015410. https://doi.org/10.1161/JAHA.119.015410

TY - JOUR

T1 - Combining biomarkers and imaging for short-term assessment of cardiovascular disease risk in apparently healthy adults

AU - Gore, Maria Odette

AU - Ayers, Colby R.

AU - Khera, Amit

AU - Defilippi, Christopher R.

AU - Wang, Thomas J.

AU - Seliger, Stephen L.

AU - Nambi, Vijay

AU - Selvin, Elizabeth

AU - Berry, Jarett D.

AU - Hundley, W. Gregory

AU - Budoff, Matthew

AU - Greenland, Philip

AU - Drazner, Mark H.

AU - Ballantyne, Christie M.

AU - Levine, Benjamin D.

AU - de Lemos, James A.

N1 - Funding Information: Siemens Healthcare, Roche Diagnostics, and Metabolomics. Dr Seliger received grant support from Roche Diagnostics and Siemens Healthineers. Dr de Lemos received grant support from Abbott Diagnostics and Roche Diagnostics, and consulting income from Roche Diagnostics, Abbott Diagnostics, Ortho Clinical Diagnostics, Quidel Cardiovascular, Amgen, Regeneron, Janssen, and Novo Nordisk. Drs deFilippi, Seliger and de Lemos have been named as co-inventors on a patent issued to University of Maryland (US Patent Application Number: 15/309,754) entitled “Methods for Assessing Differential Risk for Developing Heart Failure”. Dr Nambi is an investigator on a provisional patent (patent no. 61721475) entitled “Biomarkers to Improve Prediction of Heart Failure Risk” filed by Roche and Baylor College of Medicine and is site principal investigator for a study sponsored by Merck. Dr Berry received research funding from Abbott. Dr Ballantyne received research funding and is a consultant for Abbott and Roche, and is named on provisional patent no. 61721475 entitled “Biomarkers to Improve Prediction of Heart Failure Risk” filed by Baylor College of Medicine and Roche. The remaining authors have no disclosures to report. Funding Information: This study was supported by National Space Biomedical Research Institute research grant CA03801 (to de Lemos). Gore was supported by a career development grant (K23-HL131939) from the National Heart, Lung, and Blood Institute (NHLBI), by a University of Colorado School of Medicine Fund to Retain Clinical Scientists research award from the Doris Duke Charitable Foundation, and by a Pilot Study Research Grant for Junior Investigators from Denver Health and Hospital Authority. The MESA study was supported by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from NHLBI, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences). The DHS was supported by a grant from the Donald W. Reynolds Foundation and by a grant from the National Center for Advancing Translational Sciences (UL1TR001105). The ARIC study was supported by contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I from NHLBI. Selvin was supported by grant R01-DK089174 from the National Institute of Diabetes and Digestive and Kidney Diseases. Budoff was supported by grant R01-HL071739 from NHLBI. Drazner was supported by the James M. Wooten Chair in Cardiology from UT Southwestern Medical Center. Ballantyne was supported by grant R01-HL134320 from NHLBI. Levine was supported by grants P01-HL137630 from NHLBI and 14SFRN20510023 from the American Heart Association. Publisher Copyright: © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

PY - 2020/8/4

Y1 - 2020/8/4

N2 - BACKGROUND: Current strategies for cardiovascular disease (CVD) risk assessment focus on 10-year or longer timeframes. Shorter-term CVD risk is also clinically relevant, particularly for high-risk occupations, but is under-investigated. METHODS AND RESULTS: We pooled data from participants in the ARIC (Atherosclerosis Risk in Communities study), MESA (Multi-Ethnic Study of Atherosclerosis), and DHS (Dallas Heart Study), free from CVD at baseline (N=16 581). Measurements included N-terminal pro-B-type natriuretic peptide (>100 pg/mL prospectively defined as abnormal); high-sensitivity cardiac troponin T (abnormal >5 ng/L); high-sensitivity C-reactive protein (abnormal >3 mg/L); left ventricular hypertrophy by ECG (abnormal if present); carotid intima-media thickness, and plaque (abnormal >75th percentile for age and sex or presence of plaque); and coronary artery calcium (abnormal >10 Agatston U). Each abnormal test result except left ventricular hypertrophy by ECG was independently associated with increased 3-year risk of global CVD (myocardial infarction, stroke, coronary revascularization, incident heart failure, or atrial fibrillation), even after adjustment for traditional CVD risk factors and the other test results. When a simple integer score counting the number of abnormal tests was used, 3-year multivariable-adjusted global CVD risk was increased among participants with integer scores of 1, 2, 3, and 4, by ≈2-, 3-, 4.5-and 8-fold, respectively, when compared with those with a score of 0. Qualitatively similar results were obtained for atherosclerotic CVD (fatal or non-fatal myocardial infarction or stroke). CONCLUSIONS: A strategy incorporating multiple biomarkers and atherosclerosis imaging improved assessment of 3-year global and atherosclerotic CVD risk compared with a standard approach using traditional risk factors.

AB - BACKGROUND: Current strategies for cardiovascular disease (CVD) risk assessment focus on 10-year or longer timeframes. Shorter-term CVD risk is also clinically relevant, particularly for high-risk occupations, but is under-investigated. METHODS AND RESULTS: We pooled data from participants in the ARIC (Atherosclerosis Risk in Communities study), MESA (Multi-Ethnic Study of Atherosclerosis), and DHS (Dallas Heart Study), free from CVD at baseline (N=16 581). Measurements included N-terminal pro-B-type natriuretic peptide (>100 pg/mL prospectively defined as abnormal); high-sensitivity cardiac troponin T (abnormal >5 ng/L); high-sensitivity C-reactive protein (abnormal >3 mg/L); left ventricular hypertrophy by ECG (abnormal if present); carotid intima-media thickness, and plaque (abnormal >75th percentile for age and sex or presence of plaque); and coronary artery calcium (abnormal >10 Agatston U). Each abnormal test result except left ventricular hypertrophy by ECG was independently associated with increased 3-year risk of global CVD (myocardial infarction, stroke, coronary revascularization, incident heart failure, or atrial fibrillation), even after adjustment for traditional CVD risk factors and the other test results. When a simple integer score counting the number of abnormal tests was used, 3-year multivariable-adjusted global CVD risk was increased among participants with integer scores of 1, 2, 3, and 4, by ≈2-, 3-, 4.5-and 8-fold, respectively, when compared with those with a score of 0. Qualitatively similar results were obtained for atherosclerotic CVD (fatal or non-fatal myocardial infarction or stroke). CONCLUSIONS: A strategy incorporating multiple biomarkers and atherosclerosis imaging improved assessment of 3-year global and atherosclerotic CVD risk compared with a standard approach using traditional risk factors.

KW - Carotid intima-media thickness

KW - Coronary artery calcium

KW - High-sensitivity C-reactive protein

KW - High-sensitivity cardiac troponin T

KW - N-terminal pro B-type natriuretic peptide

KW - Plaque

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Combining biomarkers and imaging for short-term assessment of cardiovascular disease risk in apparently healthy adults

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Keywords

ASJC Scopus subject areas

UN SDGs

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