Plasma Levels of Advanced Glycation Endproducts and Risk of Cardiovascular Events: Findings From 2 Prospective Cohorts
Background Advanced glycation endproducts (AGEs) have been linked to cardiovascular disease (CVD) in cohorts with and without diabetes. Data are lacking on prospective associations of various α‐dicarbonyl‐derived AGEs and incident CVD in the general population. We tested the hypothesis that major pl...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-08-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.121.024012 |
| _version_ | 1827985953749204992 |
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| author | Julio A. Lamprea‐Montealegre Alice M. Arnold Robyn L. McCLelland Kenneth J. Mukamal Luc Djousse Mary L. Biggs David S. Siscovick Russell P. Tracy Paul J. Beisswenger Bruce M. Psaty Joachim H. Ix Jorge R. Kizer |
| author_facet | Julio A. Lamprea‐Montealegre Alice M. Arnold Robyn L. McCLelland Kenneth J. Mukamal Luc Djousse Mary L. Biggs David S. Siscovick Russell P. Tracy Paul J. Beisswenger Bruce M. Psaty Joachim H. Ix Jorge R. Kizer |
| author_sort | Julio A. Lamprea‐Montealegre |
| collection | DOAJ |
| description | Background Advanced glycation endproducts (AGEs) have been linked to cardiovascular disease (CVD) in cohorts with and without diabetes. Data are lacking on prospective associations of various α‐dicarbonyl‐derived AGEs and incident CVD in the general population. We tested the hypothesis that major plasma AGEs are associated with new‐onset CVD in 2 population‐based cohorts of differing age and comorbidities. Methods and Results Analyses involved a random subcohort (n=466) from the Cardiovascular Health Study and a case‐cohort sample (n=1631) from the Multi‐Ethnic Study of Atherosclerosis. Five AGEs and 2 oxidative products were measured by liquid chromatography tandem mass spectrometry. Associations with CVD (myocardial infarction and stroke) were evaluated with Cox regression. Participants in the Cardiovascular Health Study were older than the Multi‐Ethnic Study of Atherosclerosis, and had more comorbidities, along with higher levels of all AGEs. During median follow‐up of 11 years, 439 participants in the Multi‐Ethnic Study of Atherosclerosis and 200 in the Cardiovascular Health Study developed CVD. After multivariable adjustment, carboxymethyl‐lysine, 3‐deoxyglucosone hydroimidazolones and a summary variable of all measured AGEs (principal component 1) were significantly associated with incident CVD in the Cardiovascular Health Study (HRs [95% CI]: 1.20 [1.01, 1.42], 1.45 [1.23, 1.72], and 1.29 [1.06, 1.56], respectively), but not the Multi‐Ethnic Study of Atherosclerosis. Oxidative products were not associated with CVD in either cohort. Conclusions We found α‐dicarbonyl‐derived AGEs to be associated with CVD in an older cohort, but not in a healthier middle‐aged/older cohort. Our results suggest that AGEs may exert detrimental cardiovascular effects only under conditions of marked dicarbonyl and oxidative stress. Further investigation of α‐dicarbonyl derivatives could lead to potential new strategies for CVD prevention in high‐risk older populations. |
| first_indexed | 2024-04-09T23:23:04Z |
| format | Article |
| id | doaj.art-885ccc568011426bb09a4f00a37815f9 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-09T23:23:04Z |
| publishDate | 2022-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-885ccc568011426bb09a4f00a37815f92023-03-21T11:37:26ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802022-08-01111510.1161/JAHA.121.024012Plasma Levels of Advanced Glycation Endproducts and Risk of Cardiovascular Events: Findings From 2 Prospective CohortsJulio A. Lamprea‐Montealegre0Alice M. Arnold1Robyn L. McCLelland2Kenneth J. Mukamal3Luc Djousse4Mary L. Biggs5David S. Siscovick6Russell P. Tracy7Paul J. Beisswenger8Bruce M. Psaty9Joachim H. Ix10Jorge R. Kizer11Cardiology Section San Francisco Veterans Affairs Health Care System San Francisco CADepartment of Biostatistics, School of Public Health University of Washington Seattle WADepartment of Biostatistics, School of Public Health University of Washington Seattle WADepartment of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School Boston MADivision of Aging, Department of Medicine Brigham and Women’s Hospital and Harvard Medical School Boston MADepartment of Biostatistics, School of Public Health University of Washington Seattle WAThe New York Academy of Medicine New York NYDepartment of Pathology and Laboratory Medicine University of Vermont College of Medicine Burlington VTDepartment of Medicine Dartmouth Geisel School of Medicine Hanover NHCardiovascular Health Research Unit, Department of Medicine, Epidemiology and Health Services University of Washington Seattle WADivision of Nephrology, Department of Medicine University of California San Diego CACardiology Section San Francisco Veterans Affairs Health Care System San Francisco CABackground Advanced glycation endproducts (AGEs) have been linked to cardiovascular disease (CVD) in cohorts with and without diabetes. Data are lacking on prospective associations of various α‐dicarbonyl‐derived AGEs and incident CVD in the general population. We tested the hypothesis that major plasma AGEs are associated with new‐onset CVD in 2 population‐based cohorts of differing age and comorbidities. Methods and Results Analyses involved a random subcohort (n=466) from the Cardiovascular Health Study and a case‐cohort sample (n=1631) from the Multi‐Ethnic Study of Atherosclerosis. Five AGEs and 2 oxidative products were measured by liquid chromatography tandem mass spectrometry. Associations with CVD (myocardial infarction and stroke) were evaluated with Cox regression. Participants in the Cardiovascular Health Study were older than the Multi‐Ethnic Study of Atherosclerosis, and had more comorbidities, along with higher levels of all AGEs. During median follow‐up of 11 years, 439 participants in the Multi‐Ethnic Study of Atherosclerosis and 200 in the Cardiovascular Health Study developed CVD. After multivariable adjustment, carboxymethyl‐lysine, 3‐deoxyglucosone hydroimidazolones and a summary variable of all measured AGEs (principal component 1) were significantly associated with incident CVD in the Cardiovascular Health Study (HRs [95% CI]: 1.20 [1.01, 1.42], 1.45 [1.23, 1.72], and 1.29 [1.06, 1.56], respectively), but not the Multi‐Ethnic Study of Atherosclerosis. Oxidative products were not associated with CVD in either cohort. Conclusions We found α‐dicarbonyl‐derived AGEs to be associated with CVD in an older cohort, but not in a healthier middle‐aged/older cohort. Our results suggest that AGEs may exert detrimental cardiovascular effects only under conditions of marked dicarbonyl and oxidative stress. Further investigation of α‐dicarbonyl derivatives could lead to potential new strategies for CVD prevention in high‐risk older populations.https://www.ahajournals.org/doi/10.1161/JAHA.121.024012advanced glycation endproductsagingcardiovascular disease |
| spellingShingle | Julio A. Lamprea‐Montealegre Alice M. Arnold Robyn L. McCLelland Kenneth J. Mukamal Luc Djousse Mary L. Biggs David S. Siscovick Russell P. Tracy Paul J. Beisswenger Bruce M. Psaty Joachim H. Ix Jorge R. Kizer Plasma Levels of Advanced Glycation Endproducts and Risk of Cardiovascular Events: Findings From 2 Prospective Cohorts Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease advanced glycation endproducts aging cardiovascular disease |
| title | Plasma Levels of Advanced Glycation Endproducts and Risk of Cardiovascular Events: Findings From 2 Prospective Cohorts |
| title_full | Plasma Levels of Advanced Glycation Endproducts and Risk of Cardiovascular Events: Findings From 2 Prospective Cohorts |
| title_fullStr | Plasma Levels of Advanced Glycation Endproducts and Risk of Cardiovascular Events: Findings From 2 Prospective Cohorts |
| title_full_unstemmed | Plasma Levels of Advanced Glycation Endproducts and Risk of Cardiovascular Events: Findings From 2 Prospective Cohorts |
| title_short | Plasma Levels of Advanced Glycation Endproducts and Risk of Cardiovascular Events: Findings From 2 Prospective Cohorts |
| title_sort | plasma levels of advanced glycation endproducts and risk of cardiovascular events findings from 2 prospective cohorts |
| topic | advanced glycation endproducts aging cardiovascular disease |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.121.024012 |
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