Plasma Levels of Advanced Glycation Endproducts and Risk of Cardiovascular Events: Findings From 2 Prospective Cohorts
Year: 2022
Type: article
Study design: Observational Study
Abstract: 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.
Institutions: San Francisco VA Medical Center, University of California, San Francisco, San Francisco VA Health Care System, University of Washington, Beth Israel Deaconess Medical Center, Harvard University, Brigham and Women's Hospital, New York Academy of Medicine, University of Vermont, University of Vermont Medical Center, Dartmouth College, Dartmouth Health, University of California San Diego
Language: English
Subfield: Clinical Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,700
Awards: G1023702118, G125972088, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, CORONARY HEART DISEASE AND STROKE, Wake Forest Clinical and Translational Science Award, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, Determinants and Cardiovascular Consequences of Diabetes in Older Adults, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G270907595, G2800149121, G3220743633, G3256118428, G34347772, CHS research resources for the cardiovascular health of older adults, Non-esterified Fatty Acids and Cardiometabolic Disease in Older Adults, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, Advanced Glycation Endproducts and Cardio-Renal Disease, G423252844, G5108002584, G5479317095, CHS Events Follow-up Study, Institute for Clinical and Translational Research, CHS-Transition Phase, Clinical and Translational Science Award, G905887895
OpenAlex ID: W4288535429