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Association of Triglyceride-Glucose Index With Femoral but Not Carotid Atherosclerosis in Chronic Kidney Disease: A
Serafí Cambray1, Manuel Marti-Antonio2, Marcelino Bermúdez-López3
1Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida Fundació Dr. Pifarré (IRBLleida), Lleida, Catalonia, Spain; Department of Basic Medical Sciences, University of Lleida, Lleida, Catalonia, Spain; RICORS 2040, Instituto de Salud Carlos III, Madrid, Comunity of Madrid, Spain.
Insights
The triglyceride-glucose (TyG) index may causally link to atherosclerosis in chronic kidney disease (CKD) patients, particularly in femoral arteries. This finding could improve risk assessment for lower limb atherosclerosis in CKD individuals.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Genetics
Background:
- Cardiovascular events are more frequent in chronic kidney disease (CKD) patients.
- The triglyceride-glucose (TyG) index predicts cardiometabolic risk and cardiovascular events in CKD.
- The association between TyG index and atherosclerotic burden in CKD remains unclear.
Purpose of the Study:
- To investigate the association between the TyG index and atherosclerotic burden in CKD patients.
- To explore a potential causal relationship using Mendelian randomization (MR).
Main Methods:
- Utilized data from the NEFRONA study, including ultrasound assessment of atherosclerotic plaques.
- Employed multivariable linear regression and two-sample Mendelian randomization (MR) analyses.
- Assessed plaque presence in carotid and femoral arteries.
Main Results:
- Higher TyG index levels correlated positively with plaque numbers in both carotid and femoral arteries.
- The association with femoral plaques remained significant after multivariable adjustment.
- MR analysis suggested a potential causal link between higher TyG index and femoral plaque burden.
Conclusions:
- A higher TyG index may have a causal effect on subclinical atherosclerotic burden in the femoral arteries of CKD patients.
- Genetic insights into the TyG index could enhance atherosclerosis risk stratification in CKD patients' lower limbs.
Objective:
Patients with chronic kidney disease (CKD) have a higher risk of cardiovascular events than matched non-CKD individuals. The triglyceride-glucose (TyG) index is a calculated metric used to predict cardiometabolic risk. Although TyG is associated with cardiovascular events in CKD, its relationship with atherosclerotic burden remains unexplored. This study aimed to investigate this association using Mendelian randomization (MR) METHODS: Subjects from the NEFRONA study with ultrasound assessment of atherosclerotic plaque presence in 6 carotid and 4 femoral arterial territories were included. Multivariable linear regression models were used to explore the association between TyG index and atherosclerotic burden. Two-sample MR was employed to assess whether the TyG index has a causal effect on the number of carotid and femoral plaques.
Results:
358 controls, 709 CKD G3, 569 CKD G4-5 and 463 dialysis subjects were included. Higher TyG levels, analyzed as a continuous variable or by quartiles, were positively associated with the number of plaques in both territories. After multivariable adjustment, the association with femoral plaques remained statistically significant both as a linear variable (beta = 0.11; P = .02) and by quartiles (Q3 vs Q1: beta = 0.16; P = .026; Q4 vs Q1: beta = 0.17; P = .026; Tendency analysis: beta = 0.06; P = .02). Several unadjusted MR methods showed an effect of genetic variants associated with higher TyG levels on femoral, but not carotid, atherosclerosis. Multivariable inverse-variance weighted analysis adjusted for multiple variables suggested a causal relationship between higher TyG index and the number of femoral plaques (estimate:0.95; 95% confidence interval: 0.1-1.80, P = .029).
Conclusions:
Our two-sample MR study suggests a causal effect of higher TyG index on subclinical atherosclerotic burden in femoral arteries in CKD. Genetic testing could be used to stratify the risk of lower-limb atherosclerosis in CKD patients.
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