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High-Density Lipoprotein Particle Subclasses in Statin-Treated Patients with Peripheral Artery Disease Predict
Bernhard Zierfuss1, Clemens Höbaus1, Carsten T Herz2
1Division of Angiology, Department of Medicine 2, Medical University of Vienna, Vienna, Austria.
Insights
Small and medium HDL particles are linked to better survival in peripheral artery disease (PAD) patients. Conversely, large HDL particles indicate higher cardiovascular risk, even with optimal treatment.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Medical Diagnostics
Background:
- Despite low-density lipoprotein-cholesterol reduction, cardiovascular (CV) event rates remain high in patients with peripheral arterial disease (PAD).
- Residual CV risk necessitates novel biomarkers for risk stratification in PAD.
- Nuclear magnetic resonance (NMR) spectroscopy enables detailed lipoprotein analysis.
Purpose of the Study:
- To investigate the association between lipoprotein subclasses measured by NMR spectroscopy and long-term survival in patients with stable PAD.
- To assess the prognostic value of different high-density lipoprotein (HDL) particle subclasses in predicting mortality in PAD.
Main Methods:
- NMR spectroscopy was used to analyze lipoprotein subclasses in 319 patients with stable PAD.
- Patients were followed for 10 years, with data on all-cause and CV mortality collected.
- Multivariable Cox-regression models were employed to assess the association between HDL subclasses and mortality outcomes.
Main Results:
- Small and medium HDL particles (S-HDL-P, M-HDL-P) showed a significant inverse association with all-cause mortality.
- Large HDL particles (XL-HDL-P) were positively associated with all-cause mortality.
- XL-HDL-P association with CV death remained significant after adjustment, while S-HDL-P and M-HDL-P associations were attenuated.
Conclusions:
- NMR-measured HDL particle subclasses provide novel prognostic information for long-term outcomes in PAD patients.
- S-HDL-P and M-HDL-P may have a protective role, whereas XL-HDL-P indicates increased CV risk.
- These findings suggest that HDL subclasses can identify patients with high residual CV risk beyond standard lipid-lowering therapy.
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.
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