Increased Plasma Concentrations of Soluble ST2 Independently Predict Mortality but not Cardiovascular Events in Stable Coronary Heart Disease Patients: 13-Year Follow-up of the KAROLA Study

Purpose

sST2 (soluble suppression of tumorigenicity 2), a member of the interleukin-1 family, has been suggested to play a role in cardiac remodeling and inflammatory signaling. We assessed the association between sST2 in patients with stable coronary heart disease (CHD) with multiple cardiovascular outcomes and total mortality, simultaneously controlling for a large number of potential confounders.

Methods

Plasma concentrations of sST2 (ELISA, Critical Diagnostics) were measured at baseline in a cohort of 1081 patients. The Cox-proportional hazards model was used to determine the prognostic value of sST2 on a combined cardiovascular disease (CVD) endpoint, on cardiovascular death, and on total mortality after adjustment for covariates.

Results

The median sST2 level was 28.9 ng/mL (IQR 23.8, 35.1) (mean age at baseline 58.9 years, 84.6% male). sST2 concentration was positively correlated with inflammatory markers and emerging risk factors, e.g., cystatin C, N-terminal probrainnatriuretic peptide (NT-proBNP), high-sensitivity (hs)-Troponin T and I, mid-regional pro-atrial natriuretic peptide (MR-proANP), and growth differentiation factor 15 (GDF-15). Results after short- and long-term (4.5 and 12.3 years, respectively) follow-up (FU) displayed no statistically significant association with the combined endpoint of non-fatal and fatal CVD events when the top quartile (Q4) of sST2 concentration was compared to the bottom quartile (Q1). A relationship during long-term FU was seen with CVD mortality even after multivariable adjustments including clinical risk variables (HR 1.65; 95% CI 1.02–2.86), but not in a fully adjusted model whereas, in contrast, it was still highly significant after short-term FU (HR (5.97 (95%CI 1.32–27.06)). In addition, the sST2 concentration was still strongly associated with total mortality in the fully adjusted model including clinical variables and cystatin C based estimated glomerular filtration rate, NT-proBNP, hsCRP and hs-TnI comparing Q4 vs Q1 during long-term FU (HR of 1.48 (95% CI 1.03–2.13)) and short-term FU (HR 3.06 (95% CI 1.29–7.24)).

Conclusions

Elevated levels of sST2 concentration in stable CHD patients may independently predict short- and long-term risk for fatal CVD events and total mortality but not non-fatal CVD events.

     

Linear Endobronchial Ultrasound as the Initial Diagnostic Tool in Patients With Indications of Mediastinal Disease

IntroductionLinear endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has proven useful for sampling mediastinal masses and nodes and staging lung cancer. The aim of this study was to assess the usefulness of this diagnostic tool in patients with indications of mediastinal disease that could not be diagnosed by noninvasive methods or white light bronchoscopy.Patients and MethodsAll patients undergoing linear EBUS-TBNA for the diagnosis of mediastinal masses and/or adenopathy at our endoscopy unit were included in the study. Diagnoses obtained by linear EBUSTBNA or any surgical technique performed after a nondiagnostic EBUS-TBNA were considered as final.ResultsIn the study population of 128 patients with a mean (SD) age of 62.0 (11.2) years, a total of 294 TBNAs were performed on 12 masses and 282 nodes. Satisfactory samples were obtained in 11 cases (91.7%) from masses and in 233 cases (82.6%) from nodes. Linear EBUS-TBNA was diagnostic, obviating the need for mediastinoscopy in 115 patients (diagnostic sensitivity, 89.8%). The technique confirmed the diagnosis in 85 of the 94 patients with cancer (90.4%), in 8 of the 10 patients with tuberculosis (80.0%), and in the 5 with sarcoidosis.ConclusionsLinear EBUS-TBNA is a useful diagnostic tool in patients with mediastinal disease for whom a pathologic diagnosis is not achieved by noninvasive methods or white light bronchoscopy.     

Impact of tacrolimus and mycophenolate mofetil regimen vs. a conventional therapy with steroids on cardiovascular risk in liver transplant patients

The aim of this study was to evaluate the impact of a steroid‐free regimen with tacrolimus and mycophenolate mofetil (modified therapy) vs. a standard regimen of tacrolimus and steroids on the cardiovascular risk score of liver transplant recipients. Patients who received a liver transplant were randomized to a modified therapy (n = 58) or a standard regimen (n = 59). Both groups were balanced at baseline, except for a higher prevalence of diabetes mellitus (DM) (p < 0.01) and a higher serum creatinine concentration (p < 0.05) in the modified therapy group. After 12 months, the prevalence of new‐onset DM, arterial hypertension, hypercholesterolemia, hypertriglyceridemia, and changes in cardiovascular risk factors was similar in both groups. The increase in serum creatinine (mg/dL) compared to baseline at one yr post‐transplantation was numerically lower in the modified therapy group (0.22 ± 0.42) than in the standard regimen group (0.41 ± 0.67) (p = 0.068). Although estimated cardiovascular risk score did not vary significantly compared to baseline in either group, there was a slight reduction in the modified regimen (?0.27 ± 2.87) vs. a mild increase (0.17 ± 2.94) in the standard regimen (p = 0.566). In conclusion, a steroid‐free regimen with tacrolimus and mycophenolate mofetil was associated with a trend toward better preservation of kidney function and reduction of cardiovascular risk score.     

A role for anterior thalamic nuclei in affective cognition: Interaction with environmental conditions

Damage to anterior thalamic nuclei (ATN) is a well‐known cause of diencephalic pathology that produces a range of cognitive deficits reminiscent of a hippocampal syndrome. Anatomical connections of the ATN also extend to cerebral areas that support affective cognition. Enriched environments promote recovery of declarative/relational memory after ATN lesions and are known to downregulate emotional behaviors. Hence, the performance of standard‐housed and enriched ATN rats in a range of behavioral tasks engaging affective cognition was compared. ATN rats exhibited reduced anxiety responses in the elevated plus maze, increased activity and reduced corticosterone responses when exploring an open field, and delayed acquisition of a conditioned contextual fear response. ATN rats also exhibited reduced c‐Fos and phosphorylated cAMP response element‐binding protein (pCREB) immunoreactivity in the hippocampal formation and the amygdala after completion of the contextual fear test. Marked c‐Fos hypoactivity and reduced pCREB levels were also evident in the granular retrosplenial cortex and, to a lesser extent, in the anterior cingulate cortex. Unlike standard‐housed ATN rats, enriched ATN rats expressed virtually no fear of the conditioned context. These results show that the ATN regulate affective cognition and that damage to this region may produce markedly different behavioral effects as a function of environmental housing conditions. © 2013 Wiley Periodicals, Inc.     

Prevalence of inflammatory bowel disease among relatives of patients with ulcerative colitis

The familial occurrence of inflammatory bowel disease (IBD) was investigated among 963 patients with ulcerative colitis (UC) diagnosed in 1955-1979 in Stockholm County. For 76 patients who had a relative with IBD a pedigree was drawn. The diagnoses of the diseased relatives were verified. There was a general prevalence of 7.9% for IBD among relatives. In 80% one relative was affected, in most cases a first-degree relative with UC. Sibship was the commonest relationship. No concordance for UC was found among three pairs of monozygotic twins. The prevalence of UC in first-degree relatives was 15 times higher than in non-relatives. The age of onset was significantly lower among patients with a family history for UC; they also had a higher incidence of total colitis. The prevalence of Crohn's disease in first-degree relatives of patients with UC was almost 3.5 times higher than in non-relatives.     

Existence of L-dopa immunoreactive neurons in the rat preoptic area and anterior hypothalamus

We demonstrate the presence of L-DOPA (L-3,4-dihydroxyphenylalanine)-labelled cell bodies and fibers in the rat preoptic and anterior hypothalamic areas, using a rabbit polyclonal antiserum against conjugated L-DOPA and a glutaraldehyde coupled immunohistochemical technique. In contrast, using a monoclonal anti conjugated dopamine (DA) antibody, no DA labelled neurons were detectable in the preoptic region, whereas a few weakly immunostained DA neurons began to appear in the ventral part of the medial preoptic area. These observations point to the hypothesis that these cells contain mainly L-DOPA neurons in the preoptic and anterior hypothalamic areas. Thus, we suggest that L-DOPA plays a more important role in the hypothalamic functions than has been hitherto assumed.