Altered HDL proteome predicts incident CVD in chronic kidney disease patients

Area of Science:

• Cardiovascular Medicine
• Nephrology
• Proteomics

Background:

• Patients with chronic kidney disease (CKD) face a significantly elevated risk of cardiovascular disease (CVD).
• Traditional lipid markers, such as high-density lipoprotein cholesterol (HDL-C), inadequately explain this heightened CVD risk in CKD.
• The role of specific high-density lipoprotein (HDL) proteins in predicting incident CVD events within the CKD population remains largely uncharacterized.

Purpose of the Study:

• To investigate the association between the levels of 31 HDL proteins and the occurrence of new CVD events in patients with CKD.
• To determine if HDL protein composition, rather than HDL-C levels, serves as a better predictor of CVD risk in CKD.

Main Methods:

• A prospective case-control study involving 92 CKD patients (46 with incident CVD, 46 matched controls).
• Targeted proteomics was employed to quantify 31 distinct HDL proteins.
• Matched logistic regression analysis was utilized to assess the association between HDL proteins and incident CVD, adjusting for clinical confounders, lipids, C-reactive protein, and proteinuria.

Main Results:

• No significant association was found between HDL-C levels and incident CVD after full adjustment.
• Inverse associations were observed between incident CVD and the HDL proteins paraoxonase/arylesterase 1 (PON1), paraoxonase/arylesterase 3 (PON3), and lecithin-cholesterol acyltransferase (LCAT).
• Apolipoprotein A-IV was also associated with incident CVD, but this association diminished upon adjustment for inflammation and proteinuria.

Conclusions:

• HDL protein levels, specifically PON1, PON3, LCAT, and apolipoprotein A-IV, are inversely associated with incident CVD events in CKD patients.
• The protein cargo of HDL, rather than HDL-C concentration, may function as a crucial marker and potential mediator of elevated CVD risk in individuals with CKD.