Table 2.
Articles included in this manuscript that fit the eligibility criteria
| Ref nos. |
±* | Increases** | Decreases** | No change** | Sample size | Comments | Type of study |
|---|---|---|---|---|---|---|---|
| Section 1: Inflammation and DVT | |||||||
| [14] | (+) | MCP-1 | 192 Mice | Found that increased levels of MCP-1 in mice and rats increased thrombus resolution, independent of monocyte recruitment. | Basic science in vivo | ||
| [15] | (+) | sP-selectin | 116 Patients 129 Controls |
Case–control study with 245 patients and controls found increased sP-selectin was associated with VTE. | Case–control study | ||
| [16] | (+) | Thrombus dissolution, neovascularization, thrombus blood flow, PMN’s, fibrosis, absolute femoral venous pressure | Vascular endothelial growth factor | MCP-1, macrophage inflammatory protein-1alpha | 42 Rats | Basic science study utilizing a rodent model of DVT and treating with IV IL-8 daily. Overall found that administration of IL-8, which induced a pro-inflammatory state, enhanced thrombus resolution. | Basic science in vivo |
| [17] | (+) | Percent vein reopening | Vein wall inflammation, microparticle tissue factor activity (MPTFA), sP-selectin | 9 Primates | Basic science study utilizing a primate model of DVT compared outcomes in animals treated with enoxaparin, P-selectin inhibitor (PSI-421), and controls. Found that PSI-421 treated animals’ demonstrated reduced MPTFA and vein wall inflammation in addition to greater vein reopening. | Basic science in vivo | |
| [18] | (+) | D-dimer, sPselectin CRP, Wells score, platelet derived MP | Leukocyte derived MP | 318 Participants | Study included 318 participants, 208 were analyzed. Thirty healthy controls, 62 were positive for DVT via compression ultrasound, 116 presented with leg pain but were DVT negative via duplex scan. Overall found that the combination of Wells score and sP-selectin levels could both confirm and exclude DVT effectively. | Prospective non randomized | |
| [19] | (+) | IL-6, IL-8, CRP | 99 Patients | Elevated inflammatory biomarkers were observed to be the highest on day of admission for DVT and decreased thereafter. | Prospective non randomized | ||
| [20] | (+) | IL-6, CRP | 110 Patients | Elevated baseline IL-6 levels were found to be associated with increased VOR at 3 months, post DVT. | Prospective non randomized | ||
| [21] | (+) | F VIII, vWF, FVII CRP | 19,237 Patients | Prospective study with 19,237 patients over a 7.8 year follow-up. | Cohort study | ||
| [22] | (+) | IL-6, IL-8, MCP-1 | 532 Patients | Biomarkers were found to be elevated in patients with a history of recurrent DVT. | Case–control study | ||
| [23] | (+) | IL-8 | 948 Patients | Case–control study found elevated levels of IL-8 were a risk factor for VTE and levels remained elevated in chronic DVT. | Case–control study | ||
| [24] | (−) | IL-6 | 355 Participants | No association was observed between IL-6 and VTE. Interleukin-6 was measured in 128 patients with DVT, 105 with PE, and 122 healthy controls. |
Case–control study | ||
| [25] | (−) | hs-CRP | 318 Participants | Association was initially seen between hs-CRP levels and VTE, but after adjustment for BMI this association was no longer observed. Levels were measured in 117 patients with DVT, 97 patients with PE, and 104 healthy controls. | Case–control study | ||
| [26] | (+) | TNFa, IL-6, MCP-1, IL-8 | 6 Baboons | Elevated levels of inflammatory markers were observed in a baboon venous thrombosis model. | Basic science in vivo | ||
| [27] | (+) | P-selectin, TNFa | 28 Rats | Inhibition of P-selectin and TNF in a rat venous thrombosis model suggested that the neutralization of these biomarkers could play a role in attenuation of inflammation in venous thrombosis. | Basic science in vivo | ||
| [28] | (+) | CCL2, monocyte recruitment, vein wall intimal thickness, fibrosis | 136 Mice | Basic science study utilizing a mouse model of DVT and treatment with IL-6 Ab, to neutralize IL-6, led to outcomes listed. This suggested IL-6 could serve as a target in order to prevent complications generally seen in PTS. | Basic science in vivo | ||
| Section 2: Statins and Inflammation | |||||||
| [30] | (+) | CRP | 2,884 Participants | Prospective randomized double blinded study and open label study using 40 mg pravastatin, which found decreased CRP at 12 and 24 weeks with pravastatin use. | RCT | ||
| [31] | (+) | CRP | Cell cultures | Basic science study that found statins to reduce CRP production directly in hepatocytes. | Basic science in vitro | ||
| [32] | (+) | HDL, Apo A1. | LDL-C, TC, TG, Apo B, C3c, LDL-Ab, F VII, F I, F II, Ag-tPA bo, PAI-1 ao, thrombin, antithrombin | 67 Participants | Treatment with statins was found to exert a dose-dependent effect in lowering risk of thrombotic events in patients who have suffered a myocardial infarction (ao: after occlusion, bo: before occlusion). | Cross-sectional study | |
| [33] | (+) | MCP-1, IL-6, IL-6R | Cell cultures | Basic science study that found decreased expression of various biomarkers in human aortic endothelial cells stimulated with IL-6, when in the presence of statins. | Basic science in vitro | ||
| [34] | (−) | LDL | ApoB, TNFa R2, IL-6, hsCRP, TNFa, TLR2, TLR4, monocyte stimulation | 20 Participants | RCT that found no effect of statins on plasma inflammatory biomarkers. | RCT | |
| [35] | (+) | Thrombomodulin, eNOS | IL-8, MCP-1, PAI-1, endothelin | Cell cultures | Basic science study that concluded that statins directly change gene expression in endothelial cells. | Basic science in vitro | |
| [29] | (+) | Inflammatory biomarkers: Serum IL-6, IL-8, MCP-1. In vitro study: mRNA expression IL-6, IL-8, MCP-1 |
107 Participants | Inflammatory biomarkers: Decreased serum cytokines were observed in hypercholesterolemic patients treated with simvastatin for 6 months. In vitro study: involving HUVECs and monocytes from healthy volunteers. |
Basic science in vitro | ||
| Section 3: Statins and DVT | |||||||
| [9] | (+) | DVT rate, hs-CRP | 17,802 Participants | RCT found decreased incidence of DVT in patients with elevated CRP and normal LDL levels who were treated with statins. | RCT | ||
| [36] | (+) | DVT rate | 2,427 Participants | Case control, which found a lower risk of venous thrombosis in current statins users. | Case–control study | ||
| [37] | (+) | VTE rate | 740 Participants | Case control that found reduction in occurrence of VTE in patients with a history of solid organ tumor with the use of statins for at least 2 months. | Case–control study | ||
| [38] | (+) | VTE rate | 754 Participants | Case control that found association between VTE and statin use. | Case–control study | ||
| [39] | (+) | Mice (n = 245) and cell cultures | Basic science study in rodents found that NCX6560, an atorvastatin derivative that releases nitric oxide, possessed anti-inflammatory, vasorelaxant and anti-thrombotic properties while maintaining inhibitory effects on cholesterol biosynthesis in vitro and superior in vivo lipid lowering properties. This study compared the effects of this new agent, versus atorvastatin and found that NCX6560 had improved anti-inflammatory, anti-thrombotic, and lipid-lowering properties. | Basic science in vivo | |||
| [40] | (+) | DVT rate | 4,538 Participants | Case control study that found that use of statins were associated with a reduced risk of DVT. When stratified by statin type, pravastatin was found to have a greater benefit than simvastatin. | Case–control study | ||
| [41] | (+) | DVT rate | 125,862 Participants | Retrospective cohort study found a reduction in rate of DVT in statin users. | Cohort study | ||