Effects of rosuvastatin on myeloperoxidase levels in patients with chronic heart failure: a randomized placebo-controlled study.
BACKGROUND
Studies indicate that myeloperoxidase (MPO) is associated with disease progression and severity in heart failure (HF), while it may provide a mechanistic link between inflammation and adverse cardiac remodeling. The mechanisms that regulate MPO are unclear, while it is unknown whether specific treatments such as HMG-CoA reductase inhibitors and xanthine oxidase inhibitors may modify MPO. Therefore in the present study we examined the effects of rosuvastatin and allopurinol on MPO levels in patients HF.


METHODS
Sixty clinically stable patients with systolic HF were randomized to receive rosuvastatin 10mg/day, allopurinol 300mg/day or placebo and followed up for 1 month. Plasma levels of MPO and serum levels of soluble CD40 ligand, interleukin-6, and oxidized LDL were determined using ELISA. All measurements were made before and after 1-month treatment.


RESULTS
Rosuvastatin significantly reduced plasma levels of MPO (p=0.003), which remained unchanged in the other groups. Furthermore, the change of MPO levels in the rosuvastatin-treated group was significantly different compared with the other groups (p<0.05). Rosuvastatin administration also led to a significant decrease in oxidized LDL (p=0.009), while the other inflammatory markers remained unchanged in all groups. In the total population, a significant correlation was observed between the baseline levels of MPO and hsCRP (r=0.275, p=0.027), fibrinogen (r=0.278, p=0.025), and sCD40L (r=0.288, p=0.021).


CONCLUSIONS
Short-term treatment with rosuvastatin regulates inflammatory process in patients with heart failure by significantly reducing plasma levels of MPO. This finding reveals a novel pleiotropic effect of statins in patients with heart failure, and provides further insights into the pathophysiological mechanisms of MPO in heart failure.
Andreou
Ioannis
I
A' Cardiology Department, Hippokration Hospital, Athens University Medical School, 11528 Athens, Greece.
Tousoulis
Dimitris
D
Miliou
Antigoni
A
Tentolouris
Costas
C
Zisimos
Kostas
K
Gounari
Panagiota
P
Siasos
Gerasimos
G
Papageorgiou
Nikos
N
Papadimitriou
Christos A
CA
Dimopoulos
Meletios-Athanasios
MA
Stefanadis
Christodoulos
C
D000368:Aged; D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002908:Chronic Disease; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology* / Q000627:therapeutic use; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D009195:Peroxidase / Q000097:blood*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D014280:Triglycerides; D000493:Allopurinol; D000068718:Rosuvastatin Calcium; D002784:Cholesterol; D009195:Peroxidase