Effects of two lipid lowering therapies on immune responses in hyperlipidemic subjects.
OBJECTIVE
To compare the effects of two of the most effective lipid-lowering therapies with similar LDL-cholesterol reduction capacity on the innate and adaptive immune responses through the evaluation of autoantibodies anti-oxidized LDL (anti-oxLDL Abs) and electronegative LDL [LDL(-)] levels.


METHODS
We performed a prospective, randomized, open label study, with parallel arms and blinded endpoints. One hundred and twelve subjects completed the study protocol and received rosuvastatin 40 mg or ezetimibe/simvastatin 10/40 mg for 12 weeks. Lipids, apolipoproteins, LDL(-), and anti-oxLDL Abs (IgG) were assayed at baseline and end of study.


RESULTS
Main clinical and laboratory characteristics were comparable at baseline. Lipid modifications were similar in both treatment arms, however, a significant raise in anti-oxLDL Abs levels was observed in subjects treated with rosuvastatin (p=0.026 vs. baseline), but not in those receiving simvastatin/ezetimibe. (p=0.233 vs. baseline), thus suggesting modulation of adaptive immunity by a potent statin. Titers of LDL(-) were not modified by the treatments.


CONCLUSIONS
Considering atherosclerosis as an immune disease, this study adds new information, showing that under similar LDL-cholesterol reduction, the choice of lipid-lowering therapy can differently modulate adaptive immune responses.
Department of Medicine, Federal University of São Paulo, Sao Paulo, SP, Brazil.
Flavio Tocci
FT
Moreira
Department of Medicine, Federal University of São Paulo, Sao Paulo, SP, Brazil.
Silvia Cristina
SC
Ramos
Complex Fluids Laboratory, Institute of Physics, University of Sao Paulo, Sao Paulo, SP, Brazil.
Andrea Moreira
AM
Monteiro
Department of Medicine, Federal University of São Paulo, Sao Paulo, SP, Brazil.
Tatiana
T
Helfenstein
Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
Magnus
M
Gidlund
Department of Nutrition, School of Public Health, University of Sao Paulo, SP, Brazil.
Nagila Raquel Teixeira
NR
Damasceno
Complex Fluids Laboratory, Institute of Physics, University of Sao Paulo, Sao Paulo, SP, Brazil.
Antonio Martins Figueiredo
AM
Neto
Department of Medicine, Federal University of São Paulo, Sao Paulo, SP, Brazil.
Maria Cristina
MC
Izar
Department of Medicine, Federal University of São Paulo, Sao Paulo, SP, Brazil. Electronic address: fahfonseca@terra.com.br.
Francisco Antonio Helfenstein
FA
Fonseca
D000906:Antibodies / Q000097:blood / Q000378:metabolism*; D001384:Azetidines / Q000494:pharmacology / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D000069438:Ezetimibe; D005464:Fluorobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000276:immunology*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007107:Immune System / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*
D000906:Antibodies; D001384:Azetidines; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D006681:HLA-D Antigens; D000960:Hypolipidemic Agents; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D000069438:Ezetimibe
Dyslipidemia; Electronegative low-density lipoprotein; Ezetimibe; Oxidized LDL; Statins