Add-on therapy of EPA reduces oxidative stress and inhibits the progression of aortic stiffness in patients with coronary artery disease and statin therapy: a randomized controlled study.

AIM: We examined the anti-oxidant mechanisms of combined therapy of eicosapentaenoic acid (EPA) plus statin on the progression of atherosclerosis. METHODS: Patients receiving statin therapy for dyslipidemia and with coronary artery disease (CAD) were assigned randomly in an open-label manner to the EPA (1,800 mg/day) -plus-statin group (n= 25; combined-therapy group) or to the statin-only group (n= 25), and followed for 48 weeks. At baseline and 48 weeks after enrollment, oxidative stress, brachial-ankle pulse wave velocity (baPWV) and stiffness parameter ß-index of the carotid were measured. RESULTS: The lipid profile remained unchanged throughout the study. Although the median value of baPWV increased more in the statin-only group than in the combined-therapy group, this difference was not significant (p= 0.29); however, a decrease in baPWV was associated with combined-therapy treatment by multiple regression analysis adjusted for age and mean blood pressure (p= 0.04). In addition, the ß-index of the carotid was lower in the combined-therapy group than in the statin-only group (p= 0.02). Furthermore, although the difference in the reduction of the urinary concentration of 8-isoprostane between the two groups did not reach statistical significance, this concentration was significantly lower in the combined-therapy group with higher baseline levels (≥ 183 pg/mL · Cr) of urinary 8-isoprostane (p= 0.004). CONCLUSIONS: EPA may reduce oxidative stress and inhibit the progression of arterial stiffness more efficiently than statin-only therapy in patients with dyslipidemia and CAD.

Apoptosis and oncosis in the early progression of left ventricular dysfunction in the cardiomyopathic hamster.

The genetic defect in the cardiomyopathic (CM) hamster is a mutation in the glycoprotein-sarcoglycan (a component of the dystrophin-glycoprotein complex). Apoptosis has been identified in skeletal muscle of dystrophin-deficient mice, and therefore the role of myocardial apoptosis in relation to oncosis in causing myocardial necrosis was assessed at the onset of left ventricular (LV) dysfunction in CM hamsters. LV size and function were evaluated in normal and CM hamsters (CHF147 line) by echocardiography at 1, 2, 3, and 5 months (mo) of age. The decrease of LV fractional shortening was found to be most marked (45%) between 1 and 2 mo of age. Apop totic nuclei were identified at each time point using in situ end-labeling of DNA strand breaks (TUNEL), together with immunolabeling of myocytes; DNA fragmentation (laddering) and nuclear morphology were also assessed. Myocyte oncotic necrosis was assessed at 2 mo by Evans blue dye (EBD), wheat germ agglutinin, hematoxylin/eosin staining, and electron microscopy. Apoptotic nuclei were not detected in age-matched normal hamsters. In the CM hamsters apoptotic myocyte nuclei comprised an average of 0.041% of myocyte nuclei between 1 and 5 mo, an increase at 2 mo (to 0.076%) was not significant, and DNA laddering was not detected. The number of myocyte nuclei per unit area decreased by 32% between 1 and 2 mo, and in 2 mo old CM hamsters myocardial staining with EBD was positive in 9.82% of the myocardial cross sectional areas examined, most of which was consistent with sarcolemmal rupture and oncosis with inflammatory cell infiltration. It is concluded that myocyte oncosis provides the major mechanism for the decreased number of myocyte nuclei and the early decrease of cardiac function between 1 and 2 mo of age in the CM hamster, with only a small contribution of myocyte apoptosis.