Statins Do Not Significantly Affect Oxidative Nitrosative Stress Biomarkers in the PREVENT Randomized Clinical Trial.

PURPOSE: Preventing Anthracycline Cardiovascular Toxicity with Statins (PREVENT; NCT01988571) randomized patients with breast cancer or lymphoma receiving anthracyclines to atorvastatin 40 mg daily or placebo. We evaluated the effects of atorvastatin on oxidative and nitrosative stress biomarkers, and explored whether these biomarkers could explain the lack of effect of atorvastatin on LVEF (left ventricular ejection fraction) in PREVENT. PATIENTS AND METHODS: Blood samples were collected and cardiac MRI was performed before 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 whether 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.

Obstructive Sleep Apnea and Structural/Functional Properties of the Thoracic Ascending Aorta: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Structural and functional properties of the proximal thoracic aorta have important implications in clinical and subclinical cardiovascular disease (CVD). We examined whether obstructive sleep apnea (OSA) is associated with proximal aortic size and aortic stiffness in a multi-ethnic community-based cohort. METHODS: The sample included the Multi-Ethnic Study of Atherosclerosis (MESA) Sleep Ancillary study participants without known CVD who underwent cardiac magnetic resonance imaging. The main exposure variable was OSA severity based on the polysomnography-derived apnea hypopnea index (AHI; normal, AHI <5/h; mild, 5≤ AHI <15/h; moderate to severe, AHI ≥15/h). The study outcomes were ascending aortic diameter (AoD, cm), aortic pulse wave velocity (AoPWV, m/s), and ascending aortic distensibility (AAD, %/mm Hg). Analyses were performed in the overall sample and in sex-specific strata, adjusted for multiple potential confounders. RESULTS: The 708 participants were 55.9% female and on average 68 years old (54-93 years). There was a significant trend (p < 0.0001) of greater mean (SD) AoD across the three OSA groups: normal (n = 87), 3.13 cm (0.35); mild (n = 215), 3.25 (0.34); moderate to severe (n = 406), 3.37 (0.36). In adjusted analysis, participants with moderate to severe OSA had a greater mean AoD compared with the normal group: adjusted mean difference (95% CI), 0.12 cm (0.05, 0.20), p = 0.002. This AoD gradient was observed in women but not in men (p for interaction = 0.02). No differences were found in AoPWV or AAD among the OSA groups. CONCLUSION: In a diverse community-based cohort, moderate to severe OSA (vs. no OSA) was associated with a larger ascending AoD in women.