PATIENTS AND METHODS: Blood samples were collected and cardiac magnetic resonance imaging was performed prior to
doxorubicin initiation and at 6 and 24 months. Thirteen
biomarkers (
arginine-
nitric oxide metabolites,
paraoxonase-1 [PON-1] activity, and
myeloperoxidase) were measured. Dimensionality reduction using principal component analysis was used to define
biomarker clusters. Linear mixed-effects models determined the changes in
biomarkers over time according to treatment group. Mediation analysis determined if
biomarker clusters explained the lack of effect of
atorvastatin on LVEF.
RESULTS: Among 202 participants with available
biomarkers, median age was 53 years; 86.6% had
breast cancer; median LVEF was 62%. Cluster 1 levels, reflecting
arginine methylation metabolites, were lower over time with
atorvastatin, although this was not statistically significant (p=0.081); cluster 2 levels, reflecting PON-1 activity, were significantly lower with
atorvastatin (p=0.024). There were no significant changes in other
biomarker clusters (p>0.05).
Biomarker clusters did not mediate an effect of
atorvastatin on LVEF (p>0.05) Conclusions:
Atorvastatin demonstrated very modest effects on oxidative/nitrosative stress
biomarkers in this low cardiovascular risk population. Our findings provide potential mechanistic insight into the lack of effect of
atorvastatin on LVEF in the PREVENT trial.