TY - JOUR
T1 - Low concentrations of medium-sized HDL particles predict incident CVD in chronic kidney disease patients
AU - Shao, Baohai
AU - Afshinnia, Farsad
AU - Mathew, Anna V.
AU - Ronsein, Graziella E.
AU - Thornock, Carissa
AU - Irwin, Angela D.
AU - Kansal, Mayank
AU - Rao, Panduranga S.
AU - Dobre, Mirela
AU - Al-Kindi, Sadeer
AU - Weir, Matthew R.
AU - Go, Alan
AU - He, Jiang
AU - Chen, Jing
AU - Feldman, Harold
AU - Bornfeldt, Karin E.
AU - Pennathur, Subramaniam
N1 - Publisher Copyright:
© 2023 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.
PY - 2023/6
Y1 - 2023/6
N2 - 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 ¼ 0.032) and 0.42 (0.20-0.87, P ¼ 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.
AB - 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 ¼ 0.032) and 0.42 (0.20-0.87, P ¼ 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.
KW - cardiovascular disease
KW - case-control study
KW - cholesterol efflux capacity
KW - CKD
KW - HDL particle concentration
KW - HDL-C levels
KW - high density lipoprotein
KW - incident CVD
KW - ion mobility analysis
KW - medium HDL-P
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U2 - 10.1016/j.jlr.2023.100381
DO - 10.1016/j.jlr.2023.100381
M3 - Article
C2 - 37100172
AN - SCOPUS:85161271382
SN - 0022-2275
VL - 64
JO - Journal of lipid research
JF - Journal of lipid research
IS - 6
M1 - 100381
ER -