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Mitochondrial dysfunction induced by statin contributes to endothelial dysfunction in patients with coronary artery

Yuk-Ling Dai1, Ting-Hin Luk, Chung-Wah Siu

  • 1Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Rm 1928, Block K, Pokfulam, Hong Kong.

Cardiovascular Toxicology
|April 13, 2010
PubMed

Insights

High statin doses may cause mitochondrial dysfunction (MD) in coronary artery disease (CAD) patients, leading to endothelial dysfunction. This mitochondrial dysfunction (MD) impairs beneficial effects of statin therapy in cardiovascular disease (CVD) patients.

Area of Science:

  • Cardiovascular Medicine
  • Mitochondrial Biology
  • Pharmacology

Background:

  • Coronary artery disease (CAD) patients on statin therapy remain at risk for cardiovascular events.
  • Mitochondrial dysfunction (MD) may contribute to endothelial dysfunction, limiting statin efficacy.
  • Investigating the link between statin use, MD, and endothelial function is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the effect of mitochondrial dysfunction (MD) on endothelial function in patients with coronary artery disease (CAD) on long-term statin therapy.
  • To determine the association between statin dosage, MD, and endothelial function (flow-mediated dilation, FMD).

Main Methods:

  • Assessed brachial artery flow-mediated dilation (FMD) using high-resolution ultrasonography in 119 CAD patients on statins.
  • Measured blood lactate, pyruvate, glucose, and lipid levels to define and assess MD.
  • Utilized multivariate analysis to identify independent predictors of MD and its impact on FMD.

Main Results:

  • Mitochondrial dysfunction (MD), defined by lactate/pyruvate ratio, was observed in 36% of patients.
  • Patients with MD had significantly lower FMD (2.69% vs. 4.33%) and received higher statin doses.
  • Statin dosage was independently associated with MD (OR: 1.03, P=0.03), and MD predicted a 1.36% decrease in FMD (P=0.01).

Conclusions:

  • A significant proportion of CAD patients on statins develop mitochondrial dysfunction (MD).
  • High-dose statin therapy is associated with increased risk of MD.
  • MD contributes to endothelial dysfunction, potentially limiting the cardiovascular benefits of statins.

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