Effects of intravenous furosemide plus small-volume hypertonic saline solutions on markers of heart failure.

AIMS: We sought to compare the effects of furosemide + hypertonic saline solution (HSS) treatment in patients with acute decompensated heart failure in comparison with furosemide alone and the response in a compensated state after an acute saline load with regard to serum levels of heart failure biomarkers. METHODS AND RESULTS: We enrolled 141 patients with acute decompensated heart failure with reduced ejection fraction admitted to our Internal Medicine ward from March 2017 to November 2019. A total of 73 patients were randomized to treatment with i.v. high-dose furosemide plus HSS, whereas 68 patients were randomized to i.v. high-dose furosemide alone. Patients treated with furosemide plus HSS compared with controls treated with furosemide alone showed a comparable degree of reduction in the serum levels of interleukin (IL)-6, soluble suppression of tumorigenicity 2 (sST2), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the 'between-group' analysis. Nevertheless, patients treated with high-dose furosemide + HSS showed significantly higher absolute delta values of IL-6 (2.3 ± 1.2 vs. 1.7 ± 0.9, P < 0.0005, and 2.0 ± 0.8 vs. 1.85 ± 1.1, P = 0.034), sST2 (41.2 ± 8.6 vs. 27.9 ± 7.6, P < 0.0005, and 37.1 ± 6.6 vs. 28.4 ± 6.7, P < 0.0005), high-sensitivity troponin T (0.03 ± 0.02 vs. 0.02 ± 0.01, P = 0.001, and 0.03 ± 0.02 vs. 0.02 ± 0.01, P = 0.009), NT-proBNP (7237 ± 7931 vs. 3244 ± 4159, P < 0.005, and 5381 ± 4829 vs. 4466 ± 4332, P = 0.004), and galectin-3 (15.7 ± 3.2 ng/mL vs. 11.68 ± 1.9 ng/mL, P < 0.0005, and 16.7 ± 3.9 ng/mL vs. 11.8 ± 2.4 ng/mL, P < 0.0005) than patients treated with furosemide alone. After acute saline load, patients treated with i.v. furosemide + HSS in comparison with subjects treated with furosemide alone showed a significantly lower increase in the serum concentrations of IL-6 (-0.26 ± 0.42 pg/mL vs. -1.43 ± 0.86 pg/mL, P < 0.0005), high-sensitivity troponin T (0 vs. -0.02 ± 0.02 ng/mL, P < 0.0005), sST2 (-8.5 ± 5.9 ng/mL vs. -14.6 ± 6.2 ng/mL, P < 0.0005), galectin-3 (-2.1 ± 1.5 ng/mL vs. -7.1 ± 3.6 ng/mL, P < 0.0005), and NT-proBNP (77 ± 1373 vs. -1706 ± 2259 pg/mL, P < 0.0005). CONCLUSIONS: Our findings concerning a comparable degree of reduction in the serum levels of three cardinal biomarkers indicate that a reduction in serum heart failure markers is not linked to the higher degree of congestion relief with a more rapid achievement of a clinical compensation state. This issue may have possible benefits on clinical practice concerning its therapeutic effects over and beyond the simple amelioration of clinical congestion signs and symptoms. Nevertheless, our findings of higher delta values after treatment with i.v. furosemide plus HSS indicate a possible higher efficacy by means of modulation of the stretching and fibrosis mechanisms.

Metabolic and Vascular Effect of the Mediterranean Diet.

Several studies indicated how dietary patterns that were obtained from nutritional cluster analysis can predict disease risk or mortality. Low-grade chronic inflammation represents a background pathogenetic mechanism linking metabolic risk factors to increased risk of chronic degenerative diseases. A Mediterranean diet (MeDi) style has been reported as associated with a lower degree of inflammation biomarkers and with a protective role on cardiovascular and cerebrovascular events. There is heterogeneity in defining the MedDiet, and it can, owing to its complexity, be considered as an exposome with thousands of nutrients and phytochemicals. Recently, it has been reported a novel positive association between baseline plasma ceramide concentrations and cardiovascular events and how adherence to a Mediterranean Diet-style may influence the potential negative relationship between elevated plasma ceramide concentrations and cardiovascular diseases (CVD). Several randomized controlled trials (RCTs) showed the positive effects of the MeDi diet style on several cardiovascular risk factors, such as body mass index, waist circumference, blood lipids, blood pressure, inflammatory markers and adhesion molecules, and diabetes and how these advantages of the MeDi are maintained in comparison of a low-fat diet. Some studies reported a positive effect of adherence to a Mediterranean Diet and heart failure incidence, whereas some recent studies, such as the PREDIMED study, showed that the incidence of major cardiovascular events was lower among those assigned to MeDi supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet. New studies are needed to better understand the molecular mechanisms, whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases, but also discussing other related diseases. We review MedDiet composition and assessment as well as the latest advances in the genomic, epigenomic (DNA methylation, histone modifications, microRNAs, and other emerging regulators), transcriptomic (selected genes and whole transcriptome), and metabolomic and metagenomic aspects of the MedDiet effects (as a whole and for its most typical food components). We also present a review of the clinical effects of this dietary style underlying the biochemical and molecular effects of the Mediterranean diet. Our purpose is to review the main features of the Mediterranean diet in particular its benefits on human health, underling the anti-inflammatory, anti-oxidant and anti-atherosclerotic effects to which new knowledge about epigenetic and gut-microbiota relationship is recently added.