Effects of 5-day Statin Withdrawal on Endothelial Progenitor Cells and Inflammatory Markers in Type 2 Diabetic Patients
Condition: Type 2 Diabetes Mellitus; Atherosclerosis; Dyslipidemia
MeSH terms: Atherosclerosis; Diabetes Mellitus, Type 2; Dyslipidemias
Study type: Interventional
Phase: Phase 4

Summary: 
      Statins are commonly prescribed to lower cardiovascular risk in primary and secondary
      prevention. Despite their well known efficacy, statin withdrawal is a common event. Even a
      short term statin withdrawal can have dramatic consequences on atherosclerotic plaque
      stability, owing to a rebound in cholesterol levels and inflammation.

      The effects of a short term statin withdrawal on endothelial progenitor cells (EPC) and
      monocyte/macrophage polarization is unknown.

      In this study, the investigators will explore the effects of a 5-day statin withdrawal on EPC
      and monocyte/macrophage polarization, together with other inflammatory biomarkers in type 2
      diabetic patients. The investigators hypothesize that statin withdrawal determines a
      reduction in EPC levels and an inflammatory cell polarization.

      Patients will be randomized to continue their habitual statin regimen or to withdraw statin.
      At baseline and 5 days later, blood samples will be collected for experimental measures.
    

Detailed description: 
      Statins are commonly prescribed to lower cardiovascular risk in primary and secondary
      prevention. Despite their well known efficacy with relatively low NNTs, statin withdrawal is
      a common event for several reasons. Patients often stop statin therapies for long or short
      periods of time. Even a short term statin withdrawal can have dramatic consequences on
      atherosclerotic plaque stability, owing to a rebound in cholesterol levels and inflammation.
      Previous studies have demonstrated worsening of inflammation and endothelial function after a
      short-term statin withdrawal. This may be even more dramatic in patients who are at increased
      risk of cardiovascular disease, such as diabetic patients.

      Endothelial integrity is accomplished through the contribution of circulating endothelial
      progenitor cells (EPC) which repair the damaged endothelial layer and contribute to
      cardiovascular health in general. EPC are stimulated by statins, but there is no data on the
      effect of statin withdrawal on EPCs.

      One important aspect of inflammation is the pro- versus anti-inflammatory polarization of
      circulating monocyte/macrophage (MM) cells. Schematically, MM can exist in 2 different states
      of activation: the classically activated pro-inflammatory cells (M1) and the alternatively
      activated anti-inflammatory cells (M2). The balance between these 2 (M1/M2 ratio) reflects
      the state of MM polarization. The effects of statin withdrawal on MM polarization is unknown.

      In this study, we will explore the effects of a 5-day statin withdrawal on EPC and
      monocyte/macrophage polarization, together with other inflammatory biomarkers (namely high
      sensitive C-reactive protein) in type 2 diabetic patients. We hypothesise that statin
      withdrawal determines a reduction in EPC levels and an inflammatory cell polarization.

      Patients will be randomized to continue their habitual statin regimen or to withdraw statin.
      At baseline and 5 days later, blood samples will be collected for experimental measures (EPC,
      M1, M2 and hsCRP).
    

Intervention name(s): Statin withdrawal
Intervention type(s): Other
Intervention description(s): Patients are instructed to stop taking statin pills for the duration of the study. The rest of therapy will remain unchanged.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Stem cells; Regeneration; Inflammation