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Thromb Haemost 2022; 122(10): 1804-1813
DOI: 10.1055/a-1827-7896
Atherosclerosis and Ischaemic Disease

High-Density Lipoprotein Particle Subclasses in Statin-Treated Patients with Peripheral Artery Disease Predict Long-Term Survival

Bernhard Zierfuss 
1   Division of Angiology, Department of Medicine 2, Medical University of Vienna, Vienna, Austria
,
Clemens Höbaus 
1   Division of Angiology, Department of Medicine 2, Medical University of Vienna, Vienna, Austria
,
Carsten T. Herz
2   Division of Nephrology and Dialysis, Department of Medicine 3, Medical University of Vienna, Vienna, Austria
,
Renate Koppensteiner
1   Division of Angiology, Department of Medicine 2, Medical University of Vienna, Vienna, Austria
,
Herbert Stangl
3   Center for Pathobiochemistry and Genetics, Institute for Medical Chemistry, Medical University of Vienna, Vienna, Austria
,
Gerit-Holger Schernthaner
1   Division of Angiology, Department of Medicine 2, Medical University of Vienna, Vienna, Austria
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Abstract

Low-density lipoprotein-cholesterol reduction showed a strong reduction of cardiovascular (CV) event rates in CV disease. However, the residual risk of future CV events remains high, which especially extends to peripheral arterial disease (PAD). Nuclear magnetic resonance (NMR) spectroscopy offers a novel method for analysis of the lipoprotein spectrum. This study investigates lipoprotein subclasses using NMR spectroscopy and assesses implications for long-term survival in PAD. NMR spectroscopy was performed by Nightingale Inc., in 319 patients with stable PAD and well-controlled CV risk factors. Patients were followed-up for 10 years. During that period, 123 patients (38.5%) died, of those 68 (21.3%) were defined as CV deaths. Outcome data were analyzed by the Kaplan–Meier method and multivariable Cox-regression for lipoprotein particles. Small and medium high-density lipoprotein-particles (S-HDL-P and M-HDL-P) showed a significant inverse association with all-cause mortality in Cox-regression analyses after multivariable adjustment (S-HDL-P, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.57–0.88; M-HDL-P, HR: 0.72, 95% CI: 0.58–0.90) for each increase of one standard deviation. In contrast, cholesterol-rich X-large HDL-particles (XL-HDL-P) showed a positive association with all-cause mortality (HR: 1.51, 95% CI: 1.20–1.89). Only the association between XL-HDL-P and CV death sustained multivariable adjustment (HR: 1.49, 95% CI: 1.10–2.02), whereas associations for S-HDL-P and M-HDL-P were attenuated (HR: 0.76, 95% CI: 0.57–1.01; HR: 0.80, 95% CI: 0.60–1.06). This study shows a novel association for a beneficial role of S-HDL-P and M-HDL-P but a negative association with higher cholesterol-rich XL-HDL-P for long-term outcome in well-treated patients with PAD. Thus, these results provide evidence that NMR-measured HDL particles identify patients at high CV residual risk beyond adequate lipid-lowering therapy.

Keywords

peripheral artery disease - lipoproteins - NMR spectroscopy - mortality

Author Contributions

B.Z. conducted the literature research, study design, performed the statistical analyses, interpreted the results, and drafted the manuscript. C.H. interpreted the results and revised the manuscript. C.T.H. performed the statistical analyses and interpreted the results. R.K. revised the manuscript. H.S. interpreted the results and revised the manuscript. G.H.S. oversaw and supervised the entire project and designed the VMC study. All authors read and approved the final manuscript.


Supplementary Material



Publication History

Received: 06 December 2021

Accepted: 15 April 2022

Accepted Manuscript online:
18 April 2022

Article published online:
18 June 2022

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