Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS).

BACKGROUND: Japan EPA Lipid Intervention Study (JELIS) was a large-scale clinical trial examining the effects of eicosapentaenoic acid (EPA) on coronary artery disease (CAD) in hypercholesterolemic patients. Herein, we focused on risk factors other than low-density lipoprotein cholesterol (LDL-C) to investigate the effects of EPA on CAD among JELIS primary prevention cases. METHODS: Hypercholesterolemic patients on statin therapy but without evidence of CAD (n=14,981) were randomly assigned to an EPA group (n=7503) or a control group (n=7478). The relationships between incident CAD, the number of CAD risk factors (hypercholesterolemia; obesity; high triglyceride (TG) or low high-density lipoprotein cholesterol (HDL-C); diabetes; and hypertension) and EPA treatment were investigated. RESULTS: For the control and EPA groups combined, a higher number of risk factors was directly associated with an increased incidence of CAD. Incidence was lower for the EPA group than for the control group regardless of the numbers of risk factors. Compared to patients with normal serum TG and HDL-C levels, those with abnormal levels (TG >or=150 mg/dL; HDL-C <40 mg/dL) had significantly higher CAD hazard ratio (HR: 1.71; 95% CI: 1.11-2.64; P=0.014). In this higher risk group, EPA treatment suppressed the risk of CAD by 53% (HR: 0.47; 95% CI: 0.23-0.98; P=0.043). CONCLUSIONS: Multiple risk factors besides cholesterol are associated with markedly increased incidence of CAD. High TG with low HDL-C represents a particularly potent risk factor. EPA was effective in reducing the incidence of CAD events for patients with this dyslipidemic pattern, suggesting that EPA may be especially beneficial in patients who with abnormal TG and HDL-C levels.

Oral taurine supplementation prevents fructose-induced hypertension in rats.

Taurine is known to have antihypertensive and lipid-lowering effects in some experimental models and patients. On the other hand, intracellular free calcium and magnesium play important roles in regulating the tonus of blood vessels and insulin sensitivity. We examined the effect of oral taurine supplementation on blood pressure, serum metabolic parameters, and platelet cytosolic free calcium ([Ca(2+)](i)) and magnesium ([Mg(2+)](i)) concentration in fructose-fed Sprague-Dawley rats. Systolic blood pressure and platelet [Ca(2+)](i) were significantly higher in rats fed a 60% fructose diet. Oral taurine supplementation (1% in drinking water) completely prevented the elevation of blood pressure and an increase in platelet [Ca(2+)](i), but exacerbated hyperinsulinemia, hypertriglyceridemia, and a decrease in platelet [Mg(2+)](i). In conclusion, taurine may ameliorate fructose-induced hypertension in rats by preventing an increase in intracellular free calcium concentration. The blood pressure-lowering effect of taurine appeared to be independent from its effect on glucose and lipid metabolism in this model.

Identification of functional block line in atrial flutter using three-dimensional intracardiac echocardiography.

The crista terminalis (CT) is reportedly a critical barrier for maintaining typical atrial flutter (AFL), but recent observations have suggested the presence of posteromedial functional block, as well as crista conduction. Therefore, this study was designed to identify the correlation between the posterior boundary of AFL and anatomical architecture in the human right atrium (RA) using 3-dimensional (D) intracardiac echocardiography (ICE). In 11 patients with AFL (typical 9, reverse typical 2), mapping with a 10-pole (n=5) or 32-pole (n=6) catheter was performed during AFL. ICE was used to determine the catheter's position relative to the intra-atrial structures. In all patients, double potentials were recorded at the posteromedial RA and the catheter positions were recognized as posterior to the CT by 3-D ICE. Double potentials were not recorded on the CT, and the activation sequence revealed a craniocaudal direction in the 9 patients with typical AFL and caudocranial direction in the 2 patients with reverse typical AFL. These findings demonstrate that the posterior boundary of the AFL circuit is in the sinus venosa region posterior to the CT, which may provide an important insight into the mechanism of maintaining AFL.

Decreased expression of arginase II in the kidneys of Dahl salt-sensitive rats.

Arginase catalyzes the hydrolysis of arginine to urea and ornithine. Urea is not only an important solute for concentrating urine but also inhibits Na-K-2Cl cotransport. To elucidate the roles of arginase in the development of salt-sensitive hypertension, we examined arginase activity and expression in the kidney and other organs of Dahl/Rapp salt-sensitive (SS) and salt-resistant (SR) rats before and after 4 weeks' administration of a 4% NaCl or control diet. At 4 weeks of age, arginase activity in the kidney was lower in SS rats than in SR rats. Kidney arginase activity was lower in SS rats than in SR rats at 8 weeks of age, and salt loading did not alter arginase activity. Arginase II (the dominant isoform in the kidney) mRNA and protein in the kidney of salt-loaded SS rats were also lower than those of salt-loaded SR rats. Arginase activities in the liver and cerebellum did not differ between SS and SR rats. To examine the effect of urea, the product of arginase reaction, on the development of hypertension, SS rats were given a 4% NaCl diet containing 5% kaolin or 5% urea. Six-week urea supplementation attenuated the development of hypertension in SS rats. These findings suggest that decreased arginase expression in the kidney may be at least partially responsible for the salt-sensitive hypertension in SS rats.