Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults

Jorge Kizer, David Benkeser, Alice M. Arnold, Joachim H. Ix, Kenneth J. Mukamal, Luc Djousse, Russell P. Tracy, David S. Siscovick, Bruce M. Psaty, Susan J. Zieman

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Advanced glycation/glycoxidation endproducts (AGEs) accumulate in settings of increased oxidative stress - such as diabetes, chronic kidney disease and aging - where they promote vascular stiffness and atherogenesis, but the prospective association between AGEs and cardiovascular events in elders has not been previously examined. Methods: To test the hypothesis that circulating levels of Ne{open}-carboxymethyl-lysine (CML), a major AGE, increase the risk of incident coronary heart disease and stroke in older adults, we measured serum CML by immunoassay in 2111 individuals free of prevalent cardiovascular disease participating in a population-based study of U.S. adults ages 65 and older. Results: During median follow-up of 9.1 years, 625 cardiovascular events occurred. CML was positively associated with incident cardiovascular events after adjustment for age, sex, race, systolic blood pressure, anti-hypertensive treatment, diabetes, smoking status, triglycerides, albumin, and self-reported health status (hazard ratio [HR] per SD [0.99 pmol/l] increase = 1.11, 95% confidence interval [CI] = 1.03-1.19). This association was not materially attenuated by additional adjustment for C-reactive protein, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio. Findings were similar for the component endpoints of coronary heart disease and stroke. Conclusions: In this large older cohort, CML was associated with an increased risk of cardiovascular events independent of a wide array of potential confounders and mediators. Although the moderate association limits CML's value for risk prediction, these community-based findings provide support for clinical trials to test AGE-lowering therapies for cardiovascular prevention in this population.

Original languageEnglish (US)
Pages (from-to)116-121
Number of pages6
JournalAtherosclerosis
Volume235
Issue number1
DOIs
StatePublished - 2014

Fingerprint

Coronary Disease
Stroke
Incidence
Albumins
Blood Pressure
Vascular Stiffness
Glomerular Filtration Rate
Chronic Renal Insufficiency
Immunoassay
C-Reactive Protein
Antihypertensive Agents
Population
Health Status
Creatinine
Atherosclerosis
Triglycerides
Oxidative Stress
Cardiovascular Diseases
Smoking
Clinical Trials

Keywords

  • Advanced glycation endproducts
  • Aging
  • Carboxymethyl-lysine
  • Coronary heart disease
  • Older adults
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults. / Kizer, Jorge; Benkeser, David; Arnold, Alice M.; Ix, Joachim H.; Mukamal, Kenneth J.; Djousse, Luc; Tracy, Russell P.; Siscovick, David S.; Psaty, Bruce M.; Zieman, Susan J.

In: Atherosclerosis, Vol. 235, No. 1, 2014, p. 116-121.

Research output: Contribution to journalArticle

Kizer, J, Benkeser, D, Arnold, AM, Ix, JH, Mukamal, KJ, Djousse, L, Tracy, RP, Siscovick, DS, Psaty, BM & Zieman, SJ 2014, 'Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults', Atherosclerosis, vol. 235, no. 1, pp. 116-121. https://doi.org/10.1016/j.atherosclerosis.2014.04.013
Kizer, Jorge ; Benkeser, David ; Arnold, Alice M. ; Ix, Joachim H. ; Mukamal, Kenneth J. ; Djousse, Luc ; Tracy, Russell P. ; Siscovick, David S. ; Psaty, Bruce M. ; Zieman, Susan J. / Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults. In: Atherosclerosis. 2014 ; Vol. 235, No. 1. pp. 116-121.
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abstract = "Background: Advanced glycation/glycoxidation endproducts (AGEs) accumulate in settings of increased oxidative stress - such as diabetes, chronic kidney disease and aging - where they promote vascular stiffness and atherogenesis, but the prospective association between AGEs and cardiovascular events in elders has not been previously examined. Methods: To test the hypothesis that circulating levels of Ne{open}-carboxymethyl-lysine (CML), a major AGE, increase the risk of incident coronary heart disease and stroke in older adults, we measured serum CML by immunoassay in 2111 individuals free of prevalent cardiovascular disease participating in a population-based study of U.S. adults ages 65 and older. Results: During median follow-up of 9.1 years, 625 cardiovascular events occurred. CML was positively associated with incident cardiovascular events after adjustment for age, sex, race, systolic blood pressure, anti-hypertensive treatment, diabetes, smoking status, triglycerides, albumin, and self-reported health status (hazard ratio [HR] per SD [0.99 pmol/l] increase = 1.11, 95{\%} confidence interval [CI] = 1.03-1.19). This association was not materially attenuated by additional adjustment for C-reactive protein, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio. Findings were similar for the component endpoints of coronary heart disease and stroke. Conclusions: In this large older cohort, CML was associated with an increased risk of cardiovascular events independent of a wide array of potential confounders and mediators. Although the moderate association limits CML's value for risk prediction, these community-based findings provide support for clinical trials to test AGE-lowering therapies for cardiovascular prevention in this population.",
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T1 - Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults

AU - Kizer, Jorge

AU - Benkeser, David

AU - Arnold, Alice M.

AU - Ix, Joachim H.

AU - Mukamal, Kenneth J.

AU - Djousse, Luc

AU - Tracy, Russell P.

AU - Siscovick, David S.

AU - Psaty, Bruce M.

AU - Zieman, Susan J.

PY - 2014

Y1 - 2014

N2 - Background: Advanced glycation/glycoxidation endproducts (AGEs) accumulate in settings of increased oxidative stress - such as diabetes, chronic kidney disease and aging - where they promote vascular stiffness and atherogenesis, but the prospective association between AGEs and cardiovascular events in elders has not been previously examined. Methods: To test the hypothesis that circulating levels of Ne{open}-carboxymethyl-lysine (CML), a major AGE, increase the risk of incident coronary heart disease and stroke in older adults, we measured serum CML by immunoassay in 2111 individuals free of prevalent cardiovascular disease participating in a population-based study of U.S. adults ages 65 and older. Results: During median follow-up of 9.1 years, 625 cardiovascular events occurred. CML was positively associated with incident cardiovascular events after adjustment for age, sex, race, systolic blood pressure, anti-hypertensive treatment, diabetes, smoking status, triglycerides, albumin, and self-reported health status (hazard ratio [HR] per SD [0.99 pmol/l] increase = 1.11, 95% confidence interval [CI] = 1.03-1.19). This association was not materially attenuated by additional adjustment for C-reactive protein, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio. Findings were similar for the component endpoints of coronary heart disease and stroke. Conclusions: In this large older cohort, CML was associated with an increased risk of cardiovascular events independent of a wide array of potential confounders and mediators. Although the moderate association limits CML's value for risk prediction, these community-based findings provide support for clinical trials to test AGE-lowering therapies for cardiovascular prevention in this population.

AB - Background: Advanced glycation/glycoxidation endproducts (AGEs) accumulate in settings of increased oxidative stress - such as diabetes, chronic kidney disease and aging - where they promote vascular stiffness and atherogenesis, but the prospective association between AGEs and cardiovascular events in elders has not been previously examined. Methods: To test the hypothesis that circulating levels of Ne{open}-carboxymethyl-lysine (CML), a major AGE, increase the risk of incident coronary heart disease and stroke in older adults, we measured serum CML by immunoassay in 2111 individuals free of prevalent cardiovascular disease participating in a population-based study of U.S. adults ages 65 and older. Results: During median follow-up of 9.1 years, 625 cardiovascular events occurred. CML was positively associated with incident cardiovascular events after adjustment for age, sex, race, systolic blood pressure, anti-hypertensive treatment, diabetes, smoking status, triglycerides, albumin, and self-reported health status (hazard ratio [HR] per SD [0.99 pmol/l] increase = 1.11, 95% confidence interval [CI] = 1.03-1.19). This association was not materially attenuated by additional adjustment for C-reactive protein, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio. Findings were similar for the component endpoints of coronary heart disease and stroke. Conclusions: In this large older cohort, CML was associated with an increased risk of cardiovascular events independent of a wide array of potential confounders and mediators. Although the moderate association limits CML's value for risk prediction, these community-based findings provide support for clinical trials to test AGE-lowering therapies for cardiovascular prevention in this population.

KW - Advanced glycation endproducts

KW - Aging

KW - Carboxymethyl-lysine

KW - Coronary heart disease

KW - Older adults

KW - Stroke

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