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Updated: Aug 1, 2025
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Low concentrations of medium-sized HDL particles predict incident CVD in chronic kidney disease patients
Baohai Shao1, Farsad Afshinnia2, Anna V Mathew2
1Department of Medicine, UW Medicine Diabetes Institute, University of Washington, Seattle, WA, USA.
Insights
Medium-sized HDL particles may predict cardiovascular disease (CVD) risk in chronic kidney disease (CKD) patients. This finding offers a new potential biomarker for CVD in CKD, beyond traditional risk factors.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Biomarkers
Background:
- Patients with chronic kidney disease (CKD) face a significantly elevated risk of cardiovascular disease (CVD).
- Traditional CVD risk factors do not fully account for the heightened CVD incidence observed in CKD populations.
- While altered HDL proteome is implicated, other HDL metrics' association with CVD in CKD remains unclear.
Purpose of the Study:
- To investigate the association of various high-density lipoprotein (HDL) metrics, including particle size, concentration (HDL-P), and cholesterol efflux capacity (CEC), with incident CVD in patients with CKD.
- To determine if specific HDL subspecies are more predictive of CVD risk than overall HDL measures in this population.
Main Methods:
- Analysis of samples from two independent prospective case-control cohorts: Clinical Phenotyping and Resource Biobank Core (CPROBE) and Chronic Renal Insufficiency Cohort (CRIC).
- Measurement of HDL particle sizes and concentrations (HDL-P) using calibrated ion mobility analysis.
- Assessment of HDL cholesterol efflux capacity (CEC) using cAMP-stimulated J774 macrophages.
- Logistic regression analysis to test associations between HDL metrics and incident CVD, adjusting for clinical confounders and lipid risk factors.
Main Results:
- No significant associations were found for HDL cholesterol (HDL-C) or HDL-CEC with incident CVD in either cohort.
- Total HDL-P showed a negative association with incident CVD only in the CRIC cohort (unadjusted analysis).
- Medium-sized HDL-P was significantly and negatively associated with incident CVD in both the CPROBE and CRIC cohorts after adjustment for confounders (ORs ranging from 0.42 to 0.45).
Conclusions:
- Medium-sized HDL-P emerges as a potential prognostic biomarker for cardiovascular risk in patients with chronic kidney disease.
- Other HDL metrics, including total HDL-P, HDL-C, and HDL-CEC, did not demonstrate significant predictive value for incident CVD in this CKD population.
- These findings highlight the importance of specific HDL subspecies in assessing cardiovascular risk stratification in CKD.
Abstract:
Patients with chronic kidney disease (CKD) are at high risk for CVD. However, traditional CVD risk factors cannot completely explain the increased risk. Altered HDL proteome is linked with incident CVD in CKD patients, but it is unclear whether other HDL metrics are associated with incident CVD in this population. In the current study, we analyzed samples from two independent prospective case-control cohorts of CKD patients, the Clinical Phenotyping and Resource Biobank Core (CPROBE) and the Chronic Renal Insufficiency Cohort (CRIC). We measured HDL particle sizes and concentrations (HDL-P) by calibrated ion mobility analysis and HDL cholesterol efflux capacity (CEC) by cAMP-stimulated J774 macrophages in 92 subjects from the CPROBE cohort (46 CVD and 46 controls) and in 91 subjects from the CRIC cohort (34 CVD and 57 controls). We tested associations of HDL metrics with incident CVD using logistic regression analysis. No significant associations were found for HDL-C or HDL-CEC in either cohort. Total HDL-P was only negatively associated with incident CVD in the CRIC cohort in unadjusted analysis. Among the six sized HDL subspecies, only medium-sized HDL-P was significantly and negatively associated with incident CVD in both cohorts after adjusting for clinical confounders and lipid risk factors with odds ratios (per 1-SD) of 0.45 (0.22-0.93, P = 0.032) and 0.42 (0.20-0.87, P = 0.019) for CPROBE and CRIC cohorts, respectively. Our observations indicate that medium-sized HDL-P-but not other-sized HDL-P or total HDL-P, HDL-C, or HDL-CEC-may be a prognostic cardiovascular risk marker in CKD.
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