Cystatin C, NT-proBNP, and inflammatory markers in acute heart failure: insights into the cardiorenal syndrome.

BACKGROUND: Inflammation is thought to be a mediator in the pathophysiology of the cardiorenal syndrome. We evaluated the interactions between kidney function, cardiac stress, and various inflammatory cytokines in patients with acute heart failure (AHF). The effect on 1-year mortality was also assessed. METHODS AND RESULTS: Plasma levels of cystatin C, NT-proBNP, and inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-α [TNF-α], IL-10) were measured in consecutive patients (n = 465) hospitalized for AHF. After adjustment for demographic characteristics and comorbidities, TNF-α had the strongest relation with renal function (ß = 0.39, P < 0.0001). Elevated TNF-α levels were seen in patients with high cystatin C, irrespective of NT-proBNP. Levels of IL-6 (ß = 0.26, P < 0.0001) and IL-10 (ß = 0.15, P < 0.01), but not TNF-α, were associated with NT-proBNP. Moreover, the most elevated levels of IL-6 were seen in patients with combined high NT-proBNP and high cystatin C. Cox regression analysis found IL-6 above median to be independently predictive of mortality (hazard ratio 1.9; 95% CI 1.2-2.9, P = 0.003). TNF-α was not significantly associated with prognosis in the overall population after adjustment for multiple covariates, but improved risk stratification in the subgroup with low cystatin C and NT-proBNP. CONCLUSION: Levels of TNF-α in AHF are related to kidney function, but not to NT-proBNP. IL-6 seems to be more associated with cardiac stress. Patients with severe dual organ dysfunction have the highest levels of IL-6 and TNF-α. Different relations of inflammatory cytokines to renal function and cardiac stress need to be considered when evaluating heart--kidney interactions.

Cerebrospinal fluid angiotensin-converting enzyme (ACE) correlates with length of illness in schizophrenia.

The aim of the study was to evaluate a possible progression with time of cerebrospinal fluid (CSF) angiotensin-converting enzyme (ACE) levels in treated schizophrenia patients. CSF ACE was determined in duplicate by a sensitive inhibitor-binding assay (IBA) from morning CSF samples of 56 acute and chronic in-patients with schizophrenic psychoses diagnosed according to DSM-IV. CSF ACE correlated significantly with length of schizophrenic psychosis (r=0.39, p=0.003). There was also a positive significant correlation between CSF ACE and duration of current psychotic episode (r=0.39, p=0.003) as well as duration of current hospitalization (r=0.66, p<0.001). These significances were maintained even when patients who were not treated with antipsychotics at the time of sampling were excluded. The correlations also remained significant when controlling for current neuroleptic dose in chlorpromazine equivalents. Serum ACE did not correlate with any clinical variable. No significant correlations between serum or CSF ACE and age, diagnostic subgroup, gender, serum ACE, CSF to serum albumin ratios, or neuroleptic dose in chlorpromazine equivalents were detected. The elevation of CSF ACE seemed to be confined to a subgroup of chronic patients with few positive symptoms. Elevated CSF ACE may reflect an increased solubilization of ACE from cell membranes in the central nervous system or constitute an increased expression of the ACE gene in response to some stimuli. This may be a function of treatment or a result of the deteriorating schizophrenic process.

Accumulation of macrophages in the CSF of schizophrenic patients during acute psychotic episodes.

OBJECTIVE: There have been numerous reports of organic or structural abnormalities in the central nervous system (CNS) of patients with schizophrenia. Given that pathological conditions in the CNS are frequently reflected in the cell profiles of CSF, the authors compared the cytology of CSF from schizophrenic patients with that from a reference population in order to find out trails of elementary pathogenetic events in this serious psychiatric disease. METHOD: CSF samples from 35 patients with acute schizophrenia and 46 comparison subjects were prepared by Millipore filtration. The total and differential counts of CSF mononuclear cells were performed by light microscopy. RESULTS: At the beginning of treatment, the proportion of mononuclear phagocytes/macrophages in the patients' CSF was significantly higher than that in the comparison subjects. During treatment with conventional neuroleptic medication, the cytology returned to normal in several patients. CONCLUSIONS: The high proportion of macrophages in schizophrenia without a significantly higher total cell count may reflect neurodevelopmental disorder, a neurodegenerative process, or subtle CNS immunoactivation with mobilization of microglia.

Higher cerebrospinal fluid angiotensin-converting enzyme levels in neuroleptic-treated than in drug-free patients with schizophrenia.

The aim of this study was to replicate our earlier finding of elevated angiotensin-converting enzyme (ACE) in cerebrospinal fluid (CSF) in schizophrenia and to elucidate the role of neuroleptic treatment in this phenomenon. Drug-free and medicated patients with acute schizophrenic psychoses, as well as healthy controls were recruited. Levels of ACE were measured in CSF and serum from 7 drug-free patients, 36 neuroleptic-treated patients, and 19 healthy control subjects. Although ACE levels in CSF did not differ between patients and controls, the drug-free patients showed significantly lower levels than the neuroleptic-treated patients. Serum ACE did not differ between groups. The elevation of CSF ACE may be more prominent in patients with deficit symptoms than in those with mainly psychotic symptoms. The possible enhancement of CSF ACE production or solubility by neuroleptic treatment is discussed. Elevated ACE levels in CSF may, together with other possible factors, cause polydipsia, stimulate secretion of arginine vasopressin, and even affect neuron growth and differentiation in schizophrenic psychoses.

A longitudinal study of cerebrospinal fluid angiotensin-converting enzyme in neuroleptic-treated schizophrenia.

1. The aim of the study was to replicate our earlier finding of elevated cerebrospinal fluid (CSF) angiotensin-converting enzyme (ACE) in neuroleptic-treated schizophrenia and to elucidate the correlations between CSF ACE, neuroleptic treatment, and psychotic symptoms in a longitudinal study. 2. Levels of ACE were measured in CSF and serum from 9 acutely psychotic schizophrenic patients at two separate points of time; within a few days of admission and at follow-up after 3-4 weeks. CSF ACE was also determined from 9 healthy controls. 3. The schizophrenic patients showed non-significantly higher levels of CSF ACE than the controls. Although a significant clinical improvement was observed and the neuroleptic medication was reduced during the follow-up period, there were no significant differences in serum or CSF ACE between the two observation points in the schizophrenia group.

Abnormal distributions of T-lymphocyte subsets in the cerebrospinal fluid of patients with acute schizophrenia.

We analysed the percentages of CD4+ and CD8+ T lymphocytes in the cerebrospinal fluid (CSF) from 31 acutely ill schizophrenic patients. The psychotic patients had in their CSF clearly altered proportions of CD4+ and/or CD8+ T cells. As compared to the distribution of T cell subsets in the CSF from non-psychotic controls, the schizophrenic patients displayed both abnormally high and abnormally low frequencies of CD4+ and/or CD8+ cells. Changes in the distribution of T cell subsets corresponding to those seen in the CSF were not observed in paired blood samples from schizophrenic patients.