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Statins, inflammation and deep vein thrombosis: a systematic review

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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.

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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

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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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Authors and Affiliations

  1. Department of Surgery, Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories, School of Medicine, University of Michigan, A570A MSRB II, 1150 W. Medical Center Dr., Dock #6, Ann Arbor, MI, 48109, USA

    April L. Rodriguez, Brandon M. Wojcik, Shirley K. Wrobleski, Daniel D. Myers Jr., Thomas W. Wakefield & Jose A. Diaz

  2. Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI, USA

    Daniel D. Myers Jr.

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  1. April L. Rodriguez
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  2. Brandon M. Wojcik
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Correspondence to Jose A. Diaz.

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Rodriguez, A.L., Wojcik, B.M., Wrobleski, S.K. et al. Statins, inflammation and deep vein thrombosis: a systematic review. J Thromb Thrombolysis 33, 371–382 (2012). https://doi.org/10.1007/s11239-012-0687-9

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