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. 2019 Feb 23;20(4):977.
doi: 10.3390/ijms20040977.

Compositional Features of HDL Particles Interact with Albuminuria to Modulate Cardiovascular Disease Risk

James P Corsetti  1 , Stephan J L Bakker  2 , Ronald T Gansevoort  3 , Eke G Gruppen  4   5 , Margery A Connelly  6 , Charles E Sparks  7 , Robin P F Dullaart  8
Affiliations

Compositional Features of HDL Particles Interact with Albuminuria to Modulate Cardiovascular Disease Risk

James P Corsetti et al. Int J Mol Sci. .

Abstract

Lipoproteins containing apolipoprotein B modify associations of elevated urinary albumin excretion (UAE) with cardiovascular disease (CVD). Additionally, it is known that elevated UAE alters high-density lipoprotein functionality. Accordingly, we examined whether HDL features might also modify UAE-associated CVD. Multivariable Cox proportional-hazards modeling was performed on participants of the PREVEND (Prevention of Renal and Vascular Endstage Disease) study at the baseline screening with standard lipid/lipoprotein analyses and, three-to-four years later (second screen), with nuclear magnetic resonance lipoprotein analyses focusing on HDL parameters including HDL particle (HDL-P) and apolipoprotein A-I concentrations. These were used with UAE and derived measures of HDL apoA-I content (apoA-I/HDL-C and apoA-I/HDL-P) in risk models adjusted for gender, age, apoB, diabetes, past CVD history, CRP and GFR. Interaction analysis was also performed. Baseline screening revealed significant associations inverse for HDL-C and apoA-I and direct for apoA-I/HDL-C. The second screening demonstrated associations inverse for HDL-P, large HDL-P, medium HDL-P, HDL size, and apoA-I/HDL-P. Significant interactions with UAE included apoA-I/HDL-C at the baseline screening, and apoA-I/HDL-P and medium HDL-P but not apoA-I/HDL-C at the second screening. We conclude that features of HDL particles including apoA-I/HDL-P, indicative of HDL apoA-I content, and medium HDL-P modify associations of elevated UAE with CVD risk.

Keywords: HDL; HDL subfractions; albuminuria; apolipoprotein A-I; urinary albumin excretion.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of study design.
Figure 2
Figure 2
Hazard ratio for cardiovascular disease risk as a function of urinary albumin excretion (UAE) and mean HDL apoA-I content (ApoA-I/HDL-P) given as the number of apoA-I molecules per HDL particle over all HDL particles: (A) without inclusion of interaction of UAE and apoA-I content; and (B) with inclusion of interaction of UAE and apoA-I content.
Figure 3
Figure 3
Hazard ratio for cardiovascular disease risk as a function of urinary albumin excretion (UAE) and medium-size HDL particle concentration: (A) without inclusion of interaction of UAE and HDL particle concentration; and (B) with inclusion of interaction of UAE and HDL particle concentration.
See this image and copyright information in PMC

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