A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients.
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. Twenty-four 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.
Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery, Weill Medical College of Cornell University, , New York, NY, USA.
Doruk
D
Erkan
Rohan
R
Willis
Vijaya L
VL
Murthy
Gurjot
G
Basra
JoAnn
J
Vega
Patricia
P
Ruiz-Limón
Ana Laura
AL
Carrera
Elizabeth
E
Papalardo
Laura Aline
LA
Martínez-Martínez
Emilio B
EB
González
Silvia S
SS
Pierangeli
D000328:Adult; D016736:Antiphospholipid Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D013925:Thromboplastin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C573420:ICAM1 protein, human; D007211:Indoles; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D000077340:Fluvastatin; D013925:Thromboplastin
Antiphospholipid Antibodies; Antiphospholipid Syndrome; Cytokines; Inflammation; Treatment