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Clinical Research and Public HealthIn-Press PreviewCardiologyInflammation Open Access | 10.1172/JCI204287

Lipoprotein(a)-Associated Proteomic Signature Predicts Cardiovascular Disease in Young Adults

Sascha N. Goonewardena,1 Shanshan Yao,1 Tomasz Jurga,2 Lanyue Zhang,3 Donald Lloyd-Jones,4 Dilna Damodaran,1 Bharat Thyagarajan,5 David R. Jacobs Jr,6 Supriya Shore,1 Eric J. Brandt,1 Clary Clish,7 Kahraman Tanriverdi,8 Jane E. Freedman,8 Chirag J. Patel,9 Mark A. Sarzynski,10 Brian T. Emmer,11 John T. Wilkins,12 Ron Do,13 Vera Bittner,14 Ravi Shah,8 Marios K. Georgakis,3 Robert S. Rosenson,15 and Venkatesh Murthy1

1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

Find articles by Bittner, V. in: PubMed | Google Scholar

1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America

2Department of Pharmacy, VA Ann Arbor Health System, Ann Arbor, United States of America

3Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany

4Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, United States of America

6Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, United States of America

7Broad Institute of MIT and Harvard, Cambridge, United States of America

8Vanderbilt Translational and Clinical Research Center, Cardiovascular Divis, Vanderbilt University Medical Center, Nashville, United States of America

9Department of Biomedical Informatics, Harvard Medical School, Boston, United States of America

10Department of Exercise Science, University of South Carolina, Columbia, United States of America

11Department of Internal Medicine, Division of Hospital Medicine, University of Michigan Medical School, Ann Arbor, United States of America

12Division of Cardiology, Department of Medicine Northwestern, University Feinberg School of Medicine,, Chicago, United States of America

13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America

14Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, United States of America

15Metabolism and Lipids Program, Zena and Michael A. Wiener Cardiovascular In, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, United States of America

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Published April 21, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI204287.
Copyright © 2026, Goonewardena et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 21, 2026 - Version history
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Abstract

BACKGROUND. Elevated lipoprotein(a) [Lp(a)] is associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD). Although Lp(a) is a genetically determined risk factor, the plasma proteomic features associated with Lp(a) and whether they provide information about ASCVD risk beyond Lp(a) concentration are not well characterized.

OBJECTIVE. We sought to identify plasma proteomic features associated with Lp(a) concentration and to evaluate whether an Lp(a)-associated proteomic signature is associated with ASCVD phenotypes in young, healthy adults.

METHODS. In the Coronary Artery Risk Development in Young Adults (CARDIA) study, we measured Year 7 Lp(a) and 184 cardiovascular proteins using the Olink proximity extension assay in 3,920 participants without prior coronary heart disease. Lp(a)-associated proteomic signatures were derived using LASSO regression in a split-sample design and tested for association with coronary artery calcification (CAC), incident CHD, and hs-CRP over 27 years of follow-up. External replication was performed in the UK Biobank (n=37,996).

RESULTS. Lp(a) was associated with CAC (OR 1.23 [1.13-1.34]; p<0.0001) and incident CHD (HR 1.23 [1.07-1.41]; p=0.004). Lp(a) correlated with proteomic features reflecting immune activation, coagulation, and vascular dysfunction. A quantitative Lp(a) proteomic score was independently associated with incident CAC (standardized beta = 0.40, p<0.0001) and hs-CRP (standardized beta = 0.11, p = 0.00015) after adjustment for Lp(a) concentration. In the UK Biobank, a recalibrated Lp(a)-associated proteomic score was associated with CRP, incident CHD, and all-cause mortality.

CONCLUSIONS. In young adults, Lp(a) is associated with distinct proteomic features that independently predict ASCVD phenotypes beyond Lp(a) concentration, generating hypotheses regarding biological pathways linked to Lp(a)-related cardiovascular risk.

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