The association between frailty and MRI features of cerebral small vessel disease

Abstract: Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype

Impact of Plasma Kynurenine Level on Functional Capacity and Outcome in Heart Failure - Results From Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).

BACKGROUND Kynurenine is a circulating metabolite from the essential amino acid tryptophan. Accelerated degradation of kynurenine in skeletal muscle has been reported to provide an anti-inflammatory effect. The aim of this study was to investigate the association between blood kynurenine and muscle mass/function in patients with heart failure (HF), in whom diseased muscle mass/function plays a pathophysiological role.Methods and Results:Plasma kynurenine was assessed in 249 patients with HF (67±11 years, 21% women) and in 45 controls from the SICA-HF study. Kynurenine was higher in 173 HF patients with reduced ejection fraction (EF) and in 76 patients with preserved EF than controls (3.5±1.5, 3.4±1.3, and 2.4±1.1 μmol/L, P<0.001). In HF patients, kynurenine had an inverse association with handgrip strength (r=-0.26, P<0.01), peak oxygen consumption (r=-0.29, P<0.01), 6-min walk distance (r=-0.23, P<0.01), and had a positive association with kidney and liver function parameters. No correlation was observed between kynurenine and lean mass. On multivariable linear regression analysis, a significant association was noted between kynurenine and peak oxygen consumption even after adjustment for age, gender, BMI, and hemoglobin (β=-0.23, P<0.001). Patients with higher kynurenine were at higher risk of death (adjusted HR, 1.46 per 1 μmol/L, P<0.01). CONCLUSIONS In stable HF patients, plasma kynurenine was inversely correlated with muscle strength and functional capacity as well as with liver and kidney function

Relaxin-2 Does Not Ameliorate Nephropathy in an Experimental Model of Type-1 Diabetes

Background/Aims: In diabetic nephropathy (DN), the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC), there is no specific remedy available. Relaxin-2 (Rlx) - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide - is a candidate drug for both. Methods: Low-dose (32 µg/kg/day) and high-dose (320 µg/kg/day) Rlx were tested against vehicle (n = 20 each) and non-diabetic controls (n = 14) for 12 weeks in a model of type-1 diabetes induced in endothelial nitric oxide synthase knock-out (eNOS-KO) mice by intraperitoneal injection of streptozotocin. Results: Diabetic animals showed normal plasma creatinine, markedly increased albuminuria and urinary malonyldialdehyde, elevated relative kidney weight, glomerulosclerosis, and increased glomerular size, but no relevant interstitial fibrosis. Neither dose of Rlx affected these changes although the drug was active and targeted plasma levels were achieved. Of note, we found no activation of the renal TGF-β pathway in this model. In the hearts of diabetic animals, no fibrotic alterations indicative of DC could be determined which precluded testing of the initial hypothesis. Conclusions: We investigated a model showing early DN without overt tubulo-interstitial fibrosis and activation of the TGF-β-Smad-2/3 pathway. In this model, Rlx proved ineffective; however, the same may not apply to other models and types of diabetes