A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients

Doruk Erkan, Rohan Willis, Vijaya Murthy, Gurjot Basra, Joann Vega, Patricia Ruiz-Limón, Ana Laura Carrera, Elizabeth Papalardo, Laura Aline Martínez-Martínez, Emilio Gonzalez, Silvia S. Pierangeli

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Abstract

Objective To determine if proinflammatory and prothrombotic biomarkers are differentially upregulated in persistently antiphospholipid antibody (aPL)-positive patients, and to examine the effects of fluvastatin on these biomarkers. Methods: Four groups of patients (age 18-65) were recruited: (a) primary antiphospholipid syndrome; (b) systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS) (SLE/APS); (c) persistent aPL positivity without SLE or APS (Primary aPL); and (d) persistent aPL positivity with SLE but no APS (SLE/ aPL). The frequency-matched control group, used for baseline data comparison, was identified from a databank of healthy persons. Patients received fluvastatin 40 mg daily for 3 months. At 3 months, patients stopped the study medication and they were followed for another 3 months. Blood samples for 12 proinflammatory and prothrombotic biomarkers were collected monthly for 6 months. Results: Based on the comparison of the baseline samples of 41 aPL-positive patients with 30 healthy controls, 9/12 (75%) biomarkers (interleukin (IL)-6, IL1β, vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α, interferon (IFN)-α, inducible protein-10 (IP10), soluble CD40 ligand (sCD40L), soluble tissue factor (sTF) and intracellular cellular adhesion molecule (ICAM)-1) were significantly elevated. Twentyfour patients completed the study; fluvastatin significantly and reversibly reduced the levels of 6/12 (50%) biomarkers (IL1β, VEGF, TNFα, IP10, sCD40L and sTF). Conclusions: Our prospective mechanistic study demonstrates that proinflammatory and prothrombotic biomarkers, which are differentially upregulated in persistently aPL-positive patients, can be reversibly reduced by fluvastatin. Thus, statin-induced modulation of the aPL effects on target cells can be a valuable future approach in the management of aPL-positive patients.

Original languageEnglish (US)
Pages (from-to)1176-1180
Number of pages5
JournalAnnals of the Rheumatic Diseases
Volume73
Issue number6
DOIs
StatePublished - 2014

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fluvastatin
Antiphospholipid Antibodies
Biomarkers
Labels
Antiphospholipid Syndrome
Systemic Lupus Erythematosus
CD40 Ligand
Thromboplastin
Vascular Endothelial Growth Factor A
Tumor Necrosis Factor-alpha
Chemokine CXCL10
Hydroxymethylglutaryl-CoA Reductase Inhibitors

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients. / Erkan, Doruk; Willis, Rohan; Murthy, Vijaya; Basra, Gurjot; Vega, Joann; Ruiz-Limón, Patricia; Carrera, Ana Laura; Papalardo, Elizabeth; Martínez-Martínez, Laura Aline; Gonzalez, Emilio; Pierangeli, Silvia S.

In: Annals of the Rheumatic Diseases, Vol. 73, No. 6, 2014, p. 1176-1180.

Research output: Contribution to journalArticle

Erkan, D, Willis, R, Murthy, V, Basra, G, Vega, J, Ruiz-Limón, P, Carrera, AL, Papalardo, E, Martínez-Martínez, LA, Gonzalez, E & Pierangeli, SS 2014, 'A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients', Annals of the Rheumatic Diseases, vol. 73, no. 6, pp. 1176-1180. https://doi.org/10.1136/annrheumdis-2013-203622
Erkan, Doruk ; Willis, Rohan ; Murthy, Vijaya ; Basra, Gurjot ; Vega, Joann ; Ruiz-Limón, Patricia ; Carrera, Ana Laura ; Papalardo, Elizabeth ; Martínez-Martínez, Laura Aline ; Gonzalez, Emilio ; Pierangeli, Silvia S. / A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients. In: Annals of the Rheumatic Diseases. 2014 ; Vol. 73, No. 6. pp. 1176-1180.
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abstract = "Objective To determine if proinflammatory and prothrombotic biomarkers are differentially upregulated in persistently antiphospholipid antibody (aPL)-positive patients, and to examine the effects of fluvastatin on these biomarkers. Methods: Four groups of patients (age 18-65) were recruited: (a) primary antiphospholipid syndrome; (b) systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS) (SLE/APS); (c) persistent aPL positivity without SLE or APS (Primary aPL); and (d) persistent aPL positivity with SLE but no APS (SLE/ aPL). The frequency-matched control group, used for baseline data comparison, was identified from a databank of healthy persons. Patients received fluvastatin 40 mg daily for 3 months. At 3 months, patients stopped the study medication and they were followed for another 3 months. Blood samples for 12 proinflammatory and prothrombotic biomarkers were collected monthly for 6 months. Results: Based on the comparison of the baseline samples of 41 aPL-positive patients with 30 healthy controls, 9/12 (75{\%}) biomarkers (interleukin (IL)-6, IL1β, vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α, interferon (IFN)-α, inducible protein-10 (IP10), soluble CD40 ligand (sCD40L), soluble tissue factor (sTF) and intracellular cellular adhesion molecule (ICAM)-1) were significantly elevated. Twentyfour patients completed the study; fluvastatin significantly and reversibly reduced the levels of 6/12 (50{\%}) biomarkers (IL1β, VEGF, TNFα, IP10, sCD40L and sTF). Conclusions: Our prospective mechanistic study demonstrates that proinflammatory and prothrombotic biomarkers, which are differentially upregulated in persistently aPL-positive patients, can be reversibly reduced by fluvastatin. Thus, statin-induced modulation of the aPL effects on target cells can be a valuable future approach in the management of aPL-positive patients.",
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T1 - A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients

AU - Erkan, Doruk

AU - Willis, Rohan

AU - Murthy, Vijaya

AU - Basra, Gurjot

AU - Vega, Joann

AU - Ruiz-Limón, Patricia

AU - Carrera, Ana Laura

AU - Papalardo, Elizabeth

AU - Martínez-Martínez, Laura Aline

AU - Gonzalez, Emilio

AU - Pierangeli, Silvia S.

PY - 2014

Y1 - 2014

N2 - Objective To determine if proinflammatory and prothrombotic biomarkers are differentially upregulated in persistently antiphospholipid antibody (aPL)-positive patients, and to examine the effects of fluvastatin on these biomarkers. Methods: Four groups of patients (age 18-65) were recruited: (a) primary antiphospholipid syndrome; (b) systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS) (SLE/APS); (c) persistent aPL positivity without SLE or APS (Primary aPL); and (d) persistent aPL positivity with SLE but no APS (SLE/ aPL). The frequency-matched control group, used for baseline data comparison, was identified from a databank of healthy persons. Patients received fluvastatin 40 mg daily for 3 months. At 3 months, patients stopped the study medication and they were followed for another 3 months. Blood samples for 12 proinflammatory and prothrombotic biomarkers were collected monthly for 6 months. Results: Based on the comparison of the baseline samples of 41 aPL-positive patients with 30 healthy controls, 9/12 (75%) biomarkers (interleukin (IL)-6, IL1β, vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α, interferon (IFN)-α, inducible protein-10 (IP10), soluble CD40 ligand (sCD40L), soluble tissue factor (sTF) and intracellular cellular adhesion molecule (ICAM)-1) were significantly elevated. Twentyfour patients completed the study; fluvastatin significantly and reversibly reduced the levels of 6/12 (50%) biomarkers (IL1β, VEGF, TNFα, IP10, sCD40L and sTF). Conclusions: Our prospective mechanistic study demonstrates that proinflammatory and prothrombotic biomarkers, which are differentially upregulated in persistently aPL-positive patients, can be reversibly reduced by fluvastatin. Thus, statin-induced modulation of the aPL effects on target cells can be a valuable future approach in the management of aPL-positive patients.

AB - Objective To determine if proinflammatory and prothrombotic biomarkers are differentially upregulated in persistently antiphospholipid antibody (aPL)-positive patients, and to examine the effects of fluvastatin on these biomarkers. Methods: Four groups of patients (age 18-65) were recruited: (a) primary antiphospholipid syndrome; (b) systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS) (SLE/APS); (c) persistent aPL positivity without SLE or APS (Primary aPL); and (d) persistent aPL positivity with SLE but no APS (SLE/ aPL). The frequency-matched control group, used for baseline data comparison, was identified from a databank of healthy persons. Patients received fluvastatin 40 mg daily for 3 months. At 3 months, patients stopped the study medication and they were followed for another 3 months. Blood samples for 12 proinflammatory and prothrombotic biomarkers were collected monthly for 6 months. Results: Based on the comparison of the baseline samples of 41 aPL-positive patients with 30 healthy controls, 9/12 (75%) biomarkers (interleukin (IL)-6, IL1β, vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α, interferon (IFN)-α, inducible protein-10 (IP10), soluble CD40 ligand (sCD40L), soluble tissue factor (sTF) and intracellular cellular adhesion molecule (ICAM)-1) were significantly elevated. Twentyfour patients completed the study; fluvastatin significantly and reversibly reduced the levels of 6/12 (50%) biomarkers (IL1β, VEGF, TNFα, IP10, sCD40L and sTF). Conclusions: Our prospective mechanistic study demonstrates that proinflammatory and prothrombotic biomarkers, which are differentially upregulated in persistently aPL-positive patients, can be reversibly reduced by fluvastatin. Thus, statin-induced modulation of the aPL effects on target cells can be a valuable future approach in the management of aPL-positive patients.

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