Plasma advanced glycation end products are associated with incident cardiovascular events in individuals with type 2 diabetes: a case-cohort study with a median follow-up of 10 years (EPIC-NL).
Experimental data suggest a role for advanced glycation end products (AGEs) in cardiovascular disease (CVD), particularly in type 2 diabetes (T2DM). However, epidemiological evidence of an association between high plasma AGEs and increased cardiovascular risk remains inconclusive. Therefore, in a case-cohort study comprising 134 cardiovascular case subjects and a random subcohort of 218 individuals (including 65 cardiovascular case subjects), all with T2DM and nested in the European Prospective Investigation into Cancer and Nutrition in the Netherlands (EPIC-NL) study, plasma levels of protein-bound Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, and pentosidine were measured with liquid chromatography. AGEs were loge-transformed, combined in a z-score, and the association with incident cardiovascular events was analyzed with Cox proportional hazard regression, adapted for case-cohort design (Prentice method). After multivariable adjustment (sex, age, cohort status, diabetes duration, total cholesterol to HDL-cholesterol ratio, smoking, systolic blood pressure, BMI, blood pressure-, cholesterol- and glucose-lowering treatment, prior cardiovascular events, and triglycerides), higher plasma AGE z-scores were associated with higher risk of incident cardiovascular events in individuals without prior cardiovascular events (hazard ratio 1.31 [95% CI: 1.06-1.61]). A similar trend was observed in individuals with prior cardiovascular events (1.37 [0.63-2.98]). In conclusion, high plasma AGEs were associated with incident cardiovascular events in individuals with T2DM. These results underline the potential importance of AGEs in development of CVD.
CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
Nordin M J
NM
Hanssen
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
Joline W J
JW
Beulens
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
Susan
S
van Dieren
CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
Jean L J M
JL
Scheijen
The National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Daphne L
DL
van der A
The National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Annemieke M W
AM
Spijkerman
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
Yvonne T
YT
van der Schouw
CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
Coen D A
CD
Stehouwer
CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands c.schalkwijk@maastrichtuniversity.nl.
Casper G
CG
Schalkwijk
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000378:metabolism*; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D014280:Triglycerides; D002784:Cholesterol