Journal of Thrombosis and Thrombolysis

, Volume 33, Issue 4, pp 371–382 | Cite as

Statins, inflammation and deep vein thrombosis: a systematic review

  • April L. Rodriguez
  • Brandon M. Wojcik
  • Shirley K. Wrobleski
  • Daniel D. MyersJr.
  • Thomas W. Wakefield
  • Jose A. Diaz
Article

Abstract

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism. The 2009 JUPITER trial showed a significant decrease in DVT in non-hyperlipidemic patients, with elevated C-reactive protein (CRP) levels, treated with rosuvastatin. The effects of statins on thrombosis are unclear, prompting this literature review. A literature search was performed (1950 to February 2011) with MEDLINE, EMBASE, and PUBMED databases including the following keywords: “statins”, “hydroxymethylglutaryl-CoA reductase inhibitors”, “VTE”, “PE”, “DVT”, and either “anti-coagulation” or “inflammation”. Editorials, reviews, case reports, meta-analysis and duplicates were excluded. Inflammatory biomarkers of DVT, include interleukin (IL)-6, CRP, IL-8, and monocyte chemotactic protein 1 (MCP-1). Statin therapy reduces IL-6 expression of CRP and MCP-1, usually elevated in VTE. Reduction of IL-6 induced MCP-1 has been linked to vein wall fibrosis, promoting post thrombotic syndrome (PTS) and recurrent DVT in patients. Also, our review suggests that the anti-thrombotic effects are likely exhibited through the anti-inflammatory properties of statins. This work supports that statin therapy has the ability to decrease the incidence and recurrence of VTE and the potential to decrease PTS. This is mainly due to the anti-inflammatory effects of statins and may explain why normolipidemic patients, with elevated CRP, appear to have the greatest reduction in VTE. Given their low risk of bleeding, statins have the potential to serve as a safe adjunctive pharmacological therapy to current treatments in select patients with VTE, however further investigations into this concept are needed and essential.

Keywords

Biomarker Deep vein thrombosis Inflammation Anti-coagulation Statins Venous thromboembolism 

Abbreviations

VTE

Venous thromboembolism

DVT

Deep vein thrombosis

PE

Pulmonary embolism

PTS

Post-thrombotic syndrome

RCT

Randomized controlled trial

CRP

C-reactive protein

LDL-C

Low density lipoprotein cholesterol

HMG-CoA reductase

Hydroxymethylglutaryl-CoA reductase

PAI-1

Plasminogen activator inhibitor-1

tPA

Tissue plasminogen activator

IL

Interleukin

MCP-1

Monocyte chemotactic protein 1

TNFα

Tumor necrosis factor alpha

sP-selectin

Soluble P-selectin

hs-CRP

High sensitivity C-reactive protein

eNOS

Endothelial nitric oxide synthase

HUVEC

Human umbilical vein endothelial cells

Notes

Acknowledgments

This work supported in part by NIH 1PO1HL089407. The authors also would like to acknowledge and extend their gratitude to the Michigan Institute for Clinical & Health Research (MCRiT) program, all the members of the Jobst Vascular Surgery Laboratory at the University of Michigan for their time, training, encouragement and continued support.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • April L. Rodriguez
    • 1
  • Brandon M. Wojcik
    • 1
  • Shirley K. Wrobleski
    • 1
  • Daniel D. MyersJr.
    • 1
    • 2
  • Thomas W. Wakefield
    • 1
  • Jose A. Diaz
    • 1
  1. 1.Department of Surgery, Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories, School of MedicineUniversity of MichiganAnn ArborUSA
  2. 2.Unit for Laboratory Animal MedicineUniversity of MichiganAnn ArborUSA

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