Are there differences in acute phase inflammation markers regarding the type of heart failure?

This study aimed to determine if there are differences in inflammatory markers in the acute phase between systolic heart failure and heart failure with preserved systolic function. One hundred and thirty-one patients with acute heart failure were recruited consecutively. At admission, plasma fibrinogen, C-reactive protein, sialic acid, von Willebrand factor, vascular endothelial growth factor, interleukin-6 and NTproBNP were all evaluated. If the ejection fraction was 45% or over patients were included in the HF-PSF group; the remaining patients were included in the SHF group. The HF-PSF patients were older (72±10 vs 63±12 years, P<0.001), presented a higher rate of atrial fibrillation (56.1 vs 21.3%, P<0.001), and had a lower rate of hemoglobin (12.2±2 vs 13.3±2.1 g/dL, P<0.01). No significant differences were observed in the inflammation markers analyzed among SHF and HF-PSF groups. In the acute phase of heart failure there is a marked elevation of inflammatory markers but there are no differences in the inflammatory markers analyzed between the two different types of heart failure

NT-proBNP predicts cardiovascular death in the general population independent of left ventricular mass and function: Insights from a large population-based study with long-term follow-up.

AIMS: B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) predict cardiovascular endpoints in patients and all-cause death in the general population. This was assigned to their association with clinical cardiac remodelling defined as changes in size, shape and function of the heart. The aim of this study was to evaluate whether NT-proBNP and BNP were associated with cardiovascular and overall death independent of clinical cardiac remodelling measured by echocardiography as left ventricular hypertrophy (LVH), diastolic dysfunction and left ventricular ejection fraction (EF). METHODS AND RESULTS: In a general population-based cohort study from Germany (KORA-S3) with subjects&#39; baseline age ranging from 25 to 74 years, cardiac morphology and function were assessed as left ventricular mass (LVM), diastolic dysfunction and EF by echocardiography and circulating NT-proBNP and BNP were measured at baseline. In 1,223 subjects with mortality follow-up information, we examined the association of baseline NT-proBNP and BNP with cardiovascular mortality (number of deaths = 52, median follow-up time = 12.9years) using Cox regression without and with adjustment for cardiovascular risk factors, LVM, diastolic dysfunction and EF. The risk of cardiovascular mortality increased with higher NT-proBNP levels measured at baseline (hazard ratio HR = 1.67 per unit increment in logNT-proBNP, p = 2.78*10-4, adjusted for age and sex). This increased risk persisted after adjustment for cardiovascular risk factors, LVM, diastolic dysfunction and EF (HR = 1.73; p = 0.047). When excluding subjects with relevant LVH (LVM to body surface area &gt; 149g/m2 in men / 122g/m2 in women), the NT-proBNP association with mortality was still significant (n = 1,138; number of deaths = 35; HR = 1.48; p = 0.04). We found similar results for BNP. CONCLUSION: Our data confirms NT-proBNP and BNP as predictor of cardiovascular mortality in a large general population-based study with long-term follow-up. Our study extends previously published population-based studies to younger and potentially healthier individuals without relevant LVH, diastolic dysfunction or LVD

Head-to-head comparison of BNP and IL-6 as markers of clinical and experimental heart failure: Superiority of BNP.

Activation of BNP and IL-6 are hallmarks of left ventricular (LV) dysfunction and congestive heart failure (CHF). To assess the relative activation of BNP and IL-6 in clinical and experimental heart failure, we performed a human study in which plasma N-terminal proBNP (NT-proBNP) and IL-6 were measured in a large group of patients in the chronic phase after myocardial infarction (MI) and an animal study in which LV gene expression of BNP and IL-6 was assessed in rapid ventricular pacing-induced heart failure. In the human study, NT-proBNP and IL-6 were measured by non-extracted, enzyme-linked immunoassay in 845 subjects (n=468 outpatients after MI, MONICA MI register Augsburg; and 377 siblings without MI, control). NT-proBNP (295+/-23pg/mL vs. CTRL 84+/-8, P&lt;0.05) and IL-6 (2.7+/-0.1pg/mL vs. CTRL 2.1+/-0.1, P&lt;0.05) were both elevated in subjects with MI. These increases were particularly pronounced in the presence of concomitant CHF (both P&lt;0.01 vs. CTRL) and LV dysfunction (EF&lt;45%, both P&lt;0.05 vs. CTRL). However, NT-proBNP was significantly correlated with several cardiac structural and functional parameters (EF, LVMI, history of MI, CHF symptoms; all P&lt;0.05) upon regression analysis whereas IL-6 was only correlated with history of MI (P&lt;0.001). Accordingly, MI subjects with symptomatic LV dysfunction were detected by NT-proBNP with a greater sensitivity, specificity, and ROC-area (85%, 88%, and 0.87, respectively) as compared to IL-6 (69%, 53%, and 0.67, respectively). In the animal study, IL-6 and BNP expression were both significantly elevated in CHF (both P&lt;0.05) but with a much greater absolute activation of BNP. In addition, BNP mRNA expression displayed a stronger inverse correlation with LV function (r=-0.74; P&lt;0.001) than IL-6 (r=-0.53; P=0.001) and was a markedly more sensitive and specific molecular marker of LV dysfunction (sensitivity 91%, specificity 100%, ROC-area 0.94) than IL-6 (sensitivity 74%, specificity 83%, ROC-area 0.87). Our animal study provides evidence that IL-6 expression is activated in heart failure but to a significantly lesser degree than that of BNP. Both the stronger expression of BNP and the better correlation with LV function provide the molecular basis for a diagnostic superiority of NT-proBNP in clinical LV dysfunction and heart failure

Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc