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Low-density lipoprotein aggregation predicts adverse cardiovascular events in peripheral artery disease

Sean P Heffron1, Maija K Ruuth2, Yuhe Xia3

  • 1NYU Grossman School of Medicine, Leon H. Charney Division of Cardiology, United States; NYU Grossman School of Medicine, NYU Center for the Prevention of Cardiovascular Disease, United States.

Atherosclerosis
|December 11, 2020
PubMed
Abstract

Insights

Rapid LDL aggregation significantly increases major adverse cardiovascular events (MACE) risk in peripheral artery disease (PAD) patients after lower extremity revascularization (LER). This finding improves cardiovascular risk prediction.

Area of Science:

  • Cardiovascular Medicine
  • Atherosclerosis Research
  • Lipid Metabolism

Background:

  • Peripheral artery disease (PAD) is a manifestation of atherosclerosis linked to high cardiovascular event risk.
  • LDL aggregation is implicated in atherosclerotic plaque progression and instability.
  • The association between LDL aggregation and MACE in PAD patients undergoing lower extremity revascularization (LER) requires investigation.

Purpose of the Study:

  • To determine if LDL aggregation is associated with major adverse cardiovascular events (MACE) in patients with PAD undergoing LER.
  • To assess the utility of LDL aggregation as a risk stratification tool in PAD patients.

Main Methods:

  • Prospective study of 239 PAD patients undergoing LER, followed for one year for MACE.
  • Baseline blood samples analyzed for LDL aggregation using dynamic light scattering after sphingomyelinase exposure.
  • Comparison with 19 age, sex, and LDL-C-matched control subjects without cardiovascular disease.

Main Results:

  • PAD patients exhibited significantly earlier maximal LDL aggregation compared to controls.
  • The highest tertile of LDL aggregation (fastest aggregation) was associated with significantly higher MACE rates (25% vs. 10.1-12.5%).
  • After multivariable adjustment, rapid LDL aggregation (1st tertile) showed a 4.57-fold increased MACE risk (p=0.004).
  • Incorporating LDL aggregation improved the Framingham risk calculator's predictive ability for coronary heart disease events (c-index from 0.57 to 0.63).

Conclusions:

  • Rapid LDL aggregation is a significant predictor of MACE in PAD patients post-LER, even with controlled LDL-cholesterol.
  • LDL aggregation measurement enhances risk stratification accuracy for atherosclerotic cardiovascular disease.
  • Further research into this assay for risk stratification in atherosclerotic CVD patients is warranted.
Keywords:
Low-density lipoproteinMajor adverse cardiovascular eventsPeripheral artery diseaseRisk

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