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Updated: May 16, 2025
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
High density lipoprotein particle size and function associate with new cardiovascular events in patients with chronic
Anna V Mathew1, Yun Han1, Vetalise C Konje1
1Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Insights
Patients with advanced Chronic Kidney Disease (CKD) and high cardiovascular burden have increased risk of new cardiovascular events. Larger High-density lipoprotein (HDL) particle size is a key predictor of these events, independent of cholesterol efflux capacity.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Lipid Metabolism
Background:
- Chronic Kidney Disease (CKD) significantly increases cardiovascular disease (CVD) mortality.
- The specific lipoprotein profiles predicting new cardiovascular (CV) events in CKD patients with existing cardiovascular burden remain unclear.
Purpose of the Study:
- To investigate the association between specific High-density lipoprotein (HDL) profiles and new CV events in patients with moderate CKD and high cardiovascular burden.
- To characterize the role of HDL size, particle concentration, cholesterol content, and cholesterol efflux capacity (CEC) in predicting CV events.
Main Methods:
- Nuclear magnetic resonance (NMR) spectroscopy was used to profile HDL distribution in 325 CKD patients over 2.5 years.
- Cox regression models, adjusted for clinical factors, were employed to assess the predictive value of HDL parameters for CV events.
- Standardized assays quantified HDL's cholesterol efflux capacity (CEC) and oxidation levels.
Main Results:
- Patients experiencing new CV events showed increased HDL particle size, higher numbers of large HDL particles, and greater CEC.
- Increased HDL particle size (HR=2.56), large HDL particle numbers (HR=1.41), HDL-cholesterol levels (HR=1.03), and CEC (HR=1.46) were significantly associated with CV events.
- Higher HDL particle size predicted new CV events independently of CEC and HDL cholesterol levels.
Conclusions:
- Altered High-density lipoprotein (HDL) metabolism is strongly associated with new cardiovascular events in patients with established CKD and CVD.
- Increased HDL particle size is a significant independent predictor of CV events in this high-risk population.
- These findings can aid in risk stratification and potentially reduce mortality and morbidity in CKD patients with cardiovascular burden.
Abstract:
Chronic Kidney Disease (CKD) is a risk factor for cardiovascular disease (CVD), and patients with CKD have markedly higher CVD mortality compared to healthy controls. However, the relationship between specific lipoprotein profiles and new CV events in patients with advanced CKD and cardiovascular burden is unknown. We profiled the distribution of High density lipoprotein (HDL) size, particle concentration, and cholesterol and triglyceride content of the baseline plasma of 325 subjects with moderate CKD followed for 2.5 years using nuclear magnetic resonance (NMR) spectroscopy. We used Cox regression models controlled for various clinical factors to characterize the role of specific HDL profiles in predicting CV events in this high-risk population. The cholesterol uptake capacity of HDL from peripheral tissues- cholesterol efflux capacity (CEC) and HDL oxidation were also quantified using standardized assays. Patients with new CV events demonstrated increased HDL size, large HDL particle numbers, and CEC. Increased HDL particle size [HR = 2.56, p = 0.002], large HDL particle numbers [HR = 1.41, p = 0.001], HDL-cholesterol levels [HR = 1.03, p = 0.008], and CEC [HR = 1.46, p = 0.03] associated with CV events. Our study demonstrates that higher HDL particle size associated with new CV events in the CKD population with a high cardiovascular burden independent of CEC and HDL cholesterol. Collectively, the data strongly associate altered lipoprotein metabolism, particularly HDL metabolism, and new CV events in patients with established CKD and CVD, allowing us to risk stratify and potentially reduce mortality and morbidity in this high-risk population.
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