Highlights
- •85 metabolites were associated with cardiovascular disease (CVD).
- •84 metabolites were associated with coronary artery calcium score (CACS).
- •After risk factor adjustment CVD was associated with HDL-related metabolites.
- •CACS was associated with glucose and triglycerides in larger LDL particles.
- •Metabolites other than LDL cholesterol may contribute to CVD in chronic kidney disease (CKD).
Abstract
Background and aims
The relationship between chronic kidney disease (CKD) and cardiovascular events is
well-established. Clinically recognised risk factors of cardiovascular disease cannot
fully explain this association. The objective of the present cross-sectional study
was to investigate associations between serum metabolites and prevalent cardiovascular
disease, as well as subclinical cardiovascular disease measured as coronary artery
calcium score (CACS) in patients with CKD.
Methods
More than 200 preselected metabolites were quantified using nuclear magnetic resonance
spectroscopy in 725 patients and 174 controls from the Copenhagen CKD Cohort. CACS
was determined by computed tomography.
Results
Mean age of patients was 57.8 years, and 444 (61.3%) were men. Most of patients had
hypercholesterolemia, and 133 (18.3%) had type 2 diabetes. Overall, 85 metabolites
were significantly associated with prevalent cardiovascular disease in a model adjusted
for eGFR, age, and sex, as well as Bonferroni correction for multiple testing (p < 0.001). After further adjusting for diabetes, BMI, smoking, and cholesterol-lowering
medication, the significance was lost for all but six metabolites (concentration of
ApoA-1, cholesterol in total HDL and HDL2, total lipids and phospholipids in large
HDL particles, and the ratio of phospholipids to total lipids in smaller VLDL particles).
Of the 85 metabolites associated with prevalent cardiovascular disease, 71 were also
associated with CACS in a similar pattern. Yet, in the model adjusted for all seven
cardiovascular risk factors, only serum glucose levels and the ratio of triglycerides
to total lipids in larger LDL particles remained significant.
Conclusions
In patients with CKD, associations with prevalent cardiovascular disease were mainly
found for HDL-related metabolites, while CACS was associated with glucose levels and
increased triglycerides to total lipids ratio in LDL particles.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: March 21, 2022
Accepted:
March 16,
2022
Received in revised form:
March 4,
2022
Received:
November 5,
2021
Identification
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© 2022 Elsevier B.V. All rights reserved.
