Serum phosphate and long-term outcome among patients with stable heart failure.

BACKGROUND: Elevated serum phosphate levels are associated with excess risk for cardiovascular mortality in patients with and without chronic kidney disease and with increased risk for incident heart failure. We determined the association of serum phosphate concentrations with disease severity and long-term outcome in patients with overt heart failure. METHODS AND RESULTS: Clinical and laboratory parameters of 974 ambulatory heart failure patients were evaluated. Prevalence of elevated phosphate levels (>4.5 mg/dL) was 5.8% in men and 6.0% in women. Phosphate was significantly correlated with disease severity as assessed by New York Heart Association class, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide (P < .01, respectively). Multivariate sex-stratified Cox regression analysis adjusted for various clinically relevant covariates revealed baseline phosphate to be independently associated with death from any cause or heart transplantation (HR 1.26 [95% CI 1.04-1.52]; P < .001). This relation was maintained in patients with and without chronic kidney disease. After categorization based on quartiles of phosphate levels, a graded, independent relation between phosphate and outcome was observed (P for trend <.001). CONCLUSIONS: We found a graded, independent relation between serum phosphate and adverse outcome in patients with stable heart failure. Also, serum phosphate was related to disease severity. These findings further highlight the clinical importance of serum phosphate in cardiovascular disease.

Glutamate decarboxylase 67 is expressed in hippocampal mossy fibers of temporal lobe epilepsy patients.

Recently, expression of glutamate decarboxylase-67 (GAD67), a key enzyme of GABA synthesis, was detected in the otherwise glutamatergic mossy fibers of the rat hippocampus. Synthesis of the enzyme was markedly enhanced after experimentally induced status epilepticus. Here, we investigated the expression of GAD67 protein and mRNA in 44 hippocampal specimens from patients with mesial temporal lobe epilepsy (TLE) using double immunofluorescence histochemistry, immunoblotting, and in situ hybridization. Both in specimens with (n = 37) and without (n = 7) hippocampal sclerosis, GAD67 was highly coexpressed with dynorphin in terminal areas of mossy fibers, including the dentate hilus and the stratum lucidum of sector CA3. In the cases with Ammon's horn sclerosis, also the inner molecular layer of the dentate gyrus contained strong staining for GAD67 immunoreactivity, indicating labeling of mossy fiber terminals that specifically sprout into this area. Double immunofluorescence revealed the colocalization of GAD67 immunoreactivity with the mossy fiber marker dynorphin. The extent of colabeling correlated with the number of seizures experienced by the patients. Furthermore, GAD67 mRNA was found in granule cells of the dentate gyrus. Levels, both of GAD67 mRNA and of GAD67 immunoreactivity were similar in sclerotic and nonsclerotic specimens and appeared to be increased compared to post mortem controls. Provided that the strong expression of GAD67 results in synthesis of GABA in hippocampal mossy fibers this may represent a self-protecting mechanism in TLE. In addition GAD67 expression also may result in conversion of excessive intracellular glutamate to nontoxic GABA within mossy fiber terminals.