J. Tsoporis

301 Abrogation of S100B expression in S100A1 deficient mice improves survival post myocardial infarction

in these low dose groups. Using the medium dose group as the reference group, adjusted hazard ratios (HRs) for all-cause mortality were 1.16 (95% confidence interval [CI] 1.12-1.20) and 0.90 (95% CI 0.86-0.94) for low and high dose ACE inhibitors, respectively. For ARBs, adjusted HRs for mortality were 1.15 (95% CI 1.06-1.24) and 0.93 (95% CI 0.86-1.00) for the low and high dose groups, respectively. High dose ACE inhibitors significantly reduced the combined endpoint of allcause mortality or CHF readmission; HR 1.16 (95% CI 1.121.21) and HR 0.90 (95% CI 0.86-0.95) for low and high doses, respectively. However, medium and high dose ARBs similarly affected the combined endpoint. Sensitivity analyses between dosage groups revealed that high dose ACE inhibitors improved survival more than the medium and low doses combined (HR 0.91 [95% CI 0.85-0.98]), while this distinction between medium and high doses was not as significant in the case of ARB users (HR 0.93 [95% CI 0.870.99]). Nonetheless, all low dose users had worse outcomes in both endpoints, and treatment compliance increased with dosage. CONCLUSION: To our knowledge, this is the first study to perform a population-based analysis of CHF patients 65 years which, unlike clinical trials, reflects real-life clinical practice. We have shown that out of over 43,000 elderly CHF patients, nearly one third were prescribed ACE inhibitors or ARBs at a low dose. ACE inhibitors and ARBs reduced all-cause mortality in a dose-dependent manner, while only high dose ACE inhibitors significantly improved the combined endpoint. Since treatment compliance rates supported higher dose regimens, physicians should attempt to achieve elevated, guidelinerecommended doses of these medications in CHF patients.

Vasopeptidase Inhibition Peri- and Post-MI in Zucker Insulin Resistant Rats: Effect on MI Size, Arrhythmias, Remodeling, Function and Fetal Gene Expression

SummaryMortality peri-myocardial infarction (MI) is increased with insulin resistance. As the vasopeptidase inhibitor (VPI) omapatrilat improves insulin sensitivity, it may be beneficial peri-MI in Zucker Insulin Resistant rats (ZIR). ZIR rats (n = 228) received omapatrilat 10 mg/kg/day, 7 days pre-MI, to 38 days post-MI, or control. Twenty-four protocol (n = 72): a subgroup of rats received the kinin receptor antagonist icatibant. Ambulatory ECG recordings, and MI size were evaluated. Thirty-eight-day protocol (n = 156): left ventricular (LV) remodeling, cardiac hemodynamics, morphology, infarct size, and RT-PCR for GLUT-4 and fetal genes were measured. Omapatrilat improved post-MI survival 24 h (62% vs 38%, P = 0.0007) which was maintained 38 days. There was a kinin-induced reduction of ventricular arrhythmias and there appeared to be a kinin-independent reduction in MI size (23.5 ± 2.4% vs 17.0 ± 2.2%, P = 0.053) for 24-h post-MI. Omapatrilat reduced but did not prevent LV dilatation, dysfunction, and fetal gene expression 38 days post-MI. Omapatrilat did not prevent reduced cardiac GLUT-4 expression. In ZIR rats, mortality post-MI is reduced by omapatrilat, due and a kinin-dependent reduction in ventricular arrhythmias and possibly a kinin-independent reduction in MI size. Ventricular dilatation, dysfunction, and fetal gene expression are variably attenuated but not prevented.