Prognostic Impact of Diabetes and Prediabetes on Survival Outcomes in Patients With Chronic Heart Failure: A Post-Hoc Analysis of the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) Trial

The independent prognostic impact of diabetes mellitus (DM) and prediabetes mellitus (pre-DM) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre-DM on survival outcomes in the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) trial

Hippocampal cerebral blood flow depends on systemic endothelial function in individuals with mild cognitive impairment : the Train the Brain-Mind the vessel study

Background: Dementia has been recently viewed as a predominantly vascular disorder. Indeed, reduced brain NO availability causes increased β-amyloid deposition by several mechanisms, including hypoperfusion. Purpose: To investigate whether a relationship exists between cerebral blood flow in the hippocampal and parahippocampal regions (crucial areas for memory and processing of non-verbal / spatial information) and systemic endothelial function in individuals with mild cognitive impairment (MCI), a subclinical condition predisposing to dementia. Methods: Cerebral blood flow in the hippocampus and parahippocampus (CBF-hipp and CBF-parahipp) were evaluated by magnetic resonance imaging (arterial spin labeling, GE HDxt 1.5 T Signa Neuro-optimized System). Systemic endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery. Results: Complete data about CBF and FMD at enrollment were available for 66 individuals with MCI and 32 without (non-MCI). The two groups were matched for age (75±5 vs 74±5 years respectively, p=0.22), sex (men 45,5% vs 50%, p=0.18) and mean BP (96±10 vs 97±9 mmHg, p=0.41). FMD was significantly lower in MCI than in non-MCI (2.93±2.18 vs 3.74±2.03%, p=0.02); CBF-hipp (64.3±9.43 vs 69.5±7.03 ml/100 gr/min), p=0.002) and CBF-parahipp (66.3±8.02 vs 70.0±8.12 ml/100 gr/min, p=0.002) were significantly lower in MCI as well. Among MCI, FMD was significantly correlated with CBF-parahipp (r=0.26, p=0.03) and CBF-hipp (r=0.32, p=0.009). In a multiple regression model, including age, sex, mean BP, BMI, brachial artery diameter as confounders, FMD remained an independent determinant of CBF-parahipp (beta=0.93, r2=0.063, p=0.04). A similar finding was obtained with CBF-hipp (beta=1.31, r2=0.089, p=0.01). Nor CBF-parahipp (r=-0.13, p=0.48) neither CBF-hipp (r=0.05, p=0.80) were correlated with FMD in non-MCI group. Conclusions: An independent association between hippocampal and parahippocampal CBF and systemic endothelial function is present in individuals with MCI. Acknowledgement/Funding: The study was funded by a grant from Fondazione Cassa di Risparmio di Pis

Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65-89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects

A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease

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Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

Involvement of Abscisic Acid in Regulating Water Status in Phaseolus vulgaris L. during Chilling

During the first hours of chilling, bean (Phaseolus vulgaris L., cv Mondragone) seedlings suffer severe water stress and wilt without any significant increase in leaf abscisic acid (ABA) content (P. Vernieri, A. Pardossi, F. Tognoni [1991] Aust J Plant Physiol 18: 25-35). Plants regain turgor after 30 to 40 h. We hypothesized that inability to rapidly synthesize ABA at low temperatures contributes to chilling-induced water stress and that turgor recovery after 30 to 40 h is mediated by changes in endogenous ABA content. Entire bean seedlings were subjected to long-term (up to 6 d) chilling (3°C, 0.2-0.4 kPa vapor pressure deficit, 100 μmol·m(−2)·s(−1) photosynthetic photon flux density, continuous fluorescent light). During the first 24 h, stomata remained open, and plants rapidly wilted as leaf transpiration exceeded root water absorption. During this phase, ABA did not accumulate in leaves or in roots. After 24 h, ABA content increased in both tissues, leaf diffusion resistance increased, and plants rehydrated and regained turgor. No osmotic adjustment was associated with turgor recovery. Following turgor recovery, stomata remained closed, and ABA levels in both roots and leaves were elevated compared with controls. The application of ABA (0.1 mm) to the root system of the plants throughout exposure to 3°C prevented the chilling-induced water stress. Excised leaves fed 0.1 mm ABA via the transpiration stream had greater leaf diffusion resistance at 20 and 3°C compared with non-ABA fed controls, but the amount of ABA needed to elicit a given degree of stomatal closure was higher at 3°C compared with 20°C. These findings suggest that endogenous ABA may play a role in ameliorating plant water status during chilling