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Chronic PCSK9 inhibitor therapy leads to sustained improvements in endothelial function, arterial stiffness, and

J Schremmer1, L Busch1, S Baasen1

  • 1Department of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, Heinrich-Heine University, Duesseldorf, Germany.

Microvascular Research
|March 4, 2023
PubMed

Insights

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) improve endothelial, arterial, and microvascular function in high-risk patients. These vascular benefits persist long-term and are independent of LDL-C reduction.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Vascular Biology

Background:

  • Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively lower LDL-C and reduce cardiovascular events.
  • Short-term studies suggest PCSK9i may offer vascular benefits beyond lipid reduction.
  • The long-term persistence and microcirculatory effects of PCSK9i on vascular function remain unclear.

Purpose of the Study:

  • To investigate the sustained effects of PCSK9 inhibitor therapy on vascular parameters.
  • To determine if PCSK9i's vascular benefits are independent of its lipid-lowering effects.
  • To assess the impact of PCSK9i on endothelial function, arterial stiffness, and microcirculation.

Main Methods:

  • Prospective trial involving 32 high-cardiovascular-risk patients receiving PCSK9i therapy.
  • Vascular parameters assessed at baseline and after 6 months of treatment.
  • Measurements included flow-mediated dilation (FMD), pulse wave velocity (PWV), augmentation index (AIx), and peripheral tissue oxygenation (StO2).

Main Results:

  • PCSK9i therapy significantly improved FMD (+19%), reduced PWV (-12% in males), and decreased AIx (-16%).
  • Peripheral tissue oxygenation (StO2) significantly increased (+7%) after 6 months.
  • No significant changes in blood pressure were observed, and LDL-C reduction did not correlate with vascular parameter changes.

Conclusions:

  • Chronic PCSK9i therapy leads to sustained improvements in endothelial function.
  • PCSK9i therapy also improves arterial stiffness and microvascular function.
  • These vascular benefits are independent of the drug's lipid-lowering effects.
Abstract

Keywords:
Arterial stiffnessEndothelial functionLipid lowering therapyMicrocirculationPCSK9 inhibitorPleiotropic effectsVery high cardiovascular risk

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