Sclerostin and Vascular Pathophysiology Catalano, Antonino; Bellone, Federica; Morabito, Nunziata ...
International journal of molecular sciences,
07/2020, Letnik:
21, Številka:
13
Journal Article
Recenzirano
Odprti dostop
There is cumulating evidence for a contribution of Wnt signaling pathways in multiple processes involved in atherosclerosis and vascular aging. Wnt signaling plays a role in endothelial dysfunction, ...in the proliferation and migration of vascular smooth muscle cells (VSMCs) and intimal thickening. Moreover, it interferes with inflammation processes, monocyte adhesion and migration, as well as with foam cell formation and vascular calcification progression. Sclerostin is a negative regulator of the canonical Wnt signaling pathway and, accordingly, the consequence of increased sclerostin availability can be disruption of the Wnt signalling cascade. Sclerostin is becoming a marker for clinical and subclinical vascular diseases and several lines of evidence illustrate its role in the pathophysiology of the vascular system. Sclerostin levels increase with aging and persist higher in some diseases (e.g., diabetes, chronic kidney disease) that are known to precipitate atherosclerosis and enhance cardiovascular risk. Current knowledge on the association between sclerostin and vascular diseases is summarized in this review.
Prevalence of sarcopenia is substantial in most geriatrics settings, but estimates vary greatly across studies because of difference in population characteristics, diagnostic criteria, and methods ...used to assess muscle mass, muscle strength, and physical performance. We investigated the feasibility of the European Working Group on Sarcopenia in Older People (EWGSOP) algorithm assessment in hospitalized older adults and analyzed prevalence and clinical correlates of sarcopenia.
Cross-sectional analysis of 655 participants enrolled in a multicenter observational study of older adults admitted to 12 acute hospital wards in Italy. Sarcopenia was assessed as low skeletal mass index (kg/m2) plus either low handgrip strength or low walking speed (EWGSOP criteria). Skeletal muscle mass was estimated using bioimpedance analysis.
Of the 655 patients (age 81.0 ± 6.8 years; women 51.9%) enrolled in the study, 275 (40.2%) were not able to perform the 4-m walking test because of medical problems. The overall prevalence of sarcopenia on hospital admission was 34.7% (95% confidence interval 28-37) and it steeply increased with aging (p < .001). In multivariable analysis, patients with sarcopenia on hospital admission were older and were more likely to be male and to have congestive heart failure, cerebrovascular disease, and severe basic activities of daily living disability. The prevalence of sarcopenia was inversely correlated with body mass index.
Based on EWGSOP criteria, prevalence of sarcopenia is extremely high among older adults on admission to acute hospital wards. Older age, male gender, congestive heart failure, cerebrovascular disease, severe activities of daily living disability, and body mass index were the clinical variables significantly associated with the presence of sarcopenia.
Background
New evidence is emerging on the importance of lean body mass during periods of illness and recovery. The preservation of lean body mass during such periods of intense stress impacts both ...patient and treatment outcomes. However, data concerning the incidence of sarcopenia among older people during hospitalization are scarce. The objective of this study was to evaluate the development of sarcopenia in a sample of hospitalized older subjects.
Methods
We used data of 394 participants from the multicentre Italian Study conducted by the Gruppo Lavoro Italiano Sarcopenia—Trattamento e Nutrizione (GLISTEN) in 12 Acute Care Wards (Internal Medicine and Geriatrics) of University Hospitals across Italy. This study was designed to determine the prevalence of sarcopenia at hospital admission and the change in muscle mass and strength during hospitalization. Sarcopenia was defined as low skeletal mass index (kg/m2) along with either low handgrip strength or slow walking speed European Working Groups on Sarcopenia in Older People (EWGSOP) criteria. Estimation of skeletal muscle mass was performed by bioelectrical impedance analysis (BIA).
Results
The mean age of the 394 enrolled patients (including 211 females who accounted for 53% of the sample) was 79.6 ± 6.4 years. Among those without sarcopenia at hospital admission, 14.7% of the study sample met the EWGSOP sarcopenia diagnostic criteria at discharge. The incidence of sarcopenia during hospitalization was significantly associated with the number of days spent in bed but was not correlated with the total length of hospital stay. In particular, patients who developed sarcopenia spent an average of 5.1 days in bed compared with 3.2 days for those with no sarcopenia at discharge (P = 0.02). Patients with sarcopenia showed a significantly lower body mass index compared with non‐sarcopenic peers (25.0 ± 3.8 kg/m2 vs. 27.6 ± 4.9 kg/m2, respectively; P < 0.001). Similarly, the skeletal mass index at admission was significantly lower among patients who developed sarcopenia during hospital stay.
Conclusions
Incident sarcopenia during hospital stay is relatively common and is associated with nutritional status and the number of days of bed rest.
Older people have paid a huge toll in terms of mortality during the coronavirus disease-19 (COVID-19) pandemic. Frailty may have contributed to the vulnerability of older people to more severe ...clinical presentation. We aimed at reviewing available evidence about frailty and COVID-19. We searched PUBMED, Web of Science, and EMBASE from 1 December 2019 to 29 May 2020. Study selection and data extraction were performed by three independent reviewers. Qualitative synthesis was conducted and quantitative data extracted when available. Forty papers were included: 13 editorials, 15 recommendations/guidelines, 3 reviews, 1 clinical trial, 6 observational studies, 2 case reports. Editorials and reviews underlined the potential clinical relevance of assessing frailty among older patients with COVID-19. However, frailty was only investigated in regards to its association with overall mortality, hospital contagion, intensive care unit admission rates, and disease phenotypes in the few observational studies retrieved. Specific interventions in relation to frailty or its impact on COVID-19 treatments have not been evaluated yet. Even with such limited evidence, clinical recommendations on the use of frailty tools have been proposed to support decision making about escalation plan. Ongoing initiatives are expected to improve knowledge of COVID-19 interaction with frailty and to promote patient-centered approaches.
We aimed at summarizing current evidence about mechanisms for potentially harmful effects of Proton Pump Inhibitors (PPIs).
A Pubmed search was performed, and 207 studies concerning the relationship ...between use of PPIs and cardiovascular diseases, kidney impairment, nutritional disorders, fractures, infections, functional decline, and mortality were selected and reviewed.
PPIs may cause potentially harmful effects by several mechanisms, including endothelial dysfunction, hypomagnesemia, drug interactions, reduced absorption of selected nutrients, increased gastric microbiota and small intestine bacterial overgrowth, reduced immune response, tubular-interstitial inflammation, increased bone turnover, accumulation of amyloid in the brain. Clinical and epidemiologic evidence is not consistent in regard to some negative outcomes during PPI treatment. Data from randomized clinical trials seem to deny most of them, but they are usually designed to investigate efficacy of drugs in ideal conditions and are not powered enough to detect adverse events. Besides being at special risk of experiencing negative outcomes during long-term treatment with PPIs, older and complex patients treated with polypharmacy regimens are persistently excluded from randomized clinical trials. Thus, large observational studies involving real-world patients should be considered as an important informative source about potential risks related to PPIs.
Current evidence suggests that use of PPIs may be associated with negative outcomes by eliciting several different pathophysiologic mechanisms. While short-term PPIs could be considered effective and safe in adult patients with acid-related disorders, their long-term and often inappropriate use in patients carrying vulnerability to adverse events and/or high risk of drug-interactions should be avoided.
Frailty is a broadly investigated geriatric condition, which is characterized by an increased vulnerability to stressors. It represents an extremely relevant public health issue, increasingly ...conceptualized in a multidimensional perspective. The concept of cognitive reserve (CR), as originally conceptualized by Stern, has been developed in the past decades as a potential factor able to determine individual differences in cognitive vulnerability and trajectories occurring with aging. Our purpose was to provide a comprehensive review of the literature exploring the relationship between CR dimensions, selected according to the Stern model, and frailty status. A review of the literature on the association between potential CR dimensions and frailty was carried out through PubMed, Web of Knowledge and Scopus. CR expressed in terms of education, occupation, premorbid intelligence quotient and leisure time activities was associated with frailty in both cross‐sectional and longitudinal observations. The majority of reviewed evidence suggests a potential protective role of CR factors against the onset and the worsening of frailty among older adults. To the best of our knowledge, this is the first attempt to provide a comprehensive overview regarding the association between CR dimensions and frailty. Education, occupation, premorbid intelligence quotient and leisure time activities are able to interact with the general concept of frailty, rather than simply affecting the cognitive trajectory towards dementia. The lack of a unique and operationalized approach to the assessment of CR, as well as the wide heterogeneity of frailty evaluation tools and criteria, denote some methodological critical issues that need to be overcome. Geriatr Gerontol Int 2020; 20: 1005–1023..
Psychological features have been bidirectionally associated with osteoporosis, but it is still unclear whether patient's anxiety fluctuations during the anti-osteoporotic treatment can have an impact ...on bone mineral density (BMD) variation. The aim of this study was to investigate the interrelations between psychological distress features, such as anxiety, depression, health-related QoL (HRQoL) and bone health in women receiving anti-osteoporotic treatment.
192 post-menopausal osteoporotic women were treated with alendronate or risedronate according to the standard procedure. The levels of anxiety, depression, and perceived HRQoL, along with BMD, were assessed at baseline and at a 2-year follow-up.
At the end of the study, the patients showed a statistically significant increase of both psychic and somatic anxiety (p<0.0001) and exhibited a worsening of depressive symptoms (p<0.0001), whereas HRQoL showed no change. BMD improved and no incident fractures occurred. BMD variation (ΔBMD) at lumbar spine was significantly associated with anxiety levels (r=0.23, p=0.021). Multiple regression analysis showed that both patients' worsening anxiety levels (β = -0.1283, SE=0.06142, p=0.04) and their treatment adherence (β=0.09, SE=0.02, p=0.0006) were independently associated with ΔBMD.
The findings of the current follow-up study suggest that BMD in post-menopausal women undergoing anti-osteoporotic treatment was predicted by treatment adherence and anxiety change over time.
Vitamin D modulates bisphosphonate (BP) efficacy, but its contribution to bone mineral density (BMD) after BP discontinuation is not known. To address this topic, we performed a retrospective ...analysis of postmenopausal women exposed to alendronate (ALN) to treat osteoporosis who regularly continued the supplementation of cholecalciferol or calcifediol at recommended doses. In the ninety-six recruited women (age 61.1 ± 6.9 years), ALN was administered for 31.2 ± 20.6 months and then discontinued for 33.3 ± 18.9 months. The modification of 25(OH)D serum levels over time was associated with a change of alkaline phosphatase (r = −0.22, p = 0.018) and C-terminal collagen type 1 telopeptide (r = −0.3, p = 0.06). Women in the tertile of the highest increase in 25(OH)D level showed a 5.7% BMD gain at lumbar spine, that was twice as great in comparison with participants with a lower 25(OH)D variation. At a multiple regression analysis, BMD change was associated with time since menopause (ß = 2.28, SE 0.44, p < 0.0001), FRAX score for major fracture (ß = −0.65, SE 0.29, p = 0.03), drug holiday duration (ß = −2.17, SE 0.27, p < 0.0001) and change of 25(OH)D levels (ß = 0.15, SE 0.03, p = 0.0007). After ALN discontinuation, improving the vitamin D status boosts the ALN tail effect on BMD.
There is growing interest in the relationship between chronic kidney disease (CKD) and fragility fracture risk. Bone mineral density (BMD) is a major determinant of bone strength, although its role ...as a predictor of fracture in advanced CKD and hemodialysis is still under debate. We aimed to further investigate surrogates of bone quality and their associations with muscle strength and fracture risk in hemodialysis. Multiple clinical risk factors for fracture and an estimated 10-year probability of fracture, BMD at lumbar spine and femur, trabecular bone score (TBS), X-ray vertebral morphometry, phalangeal bone quantitative ultrasonography (QUS), tibial pulse-echo ultrasonography (PEUS), and handgrip strength were evaluated in a setting of hemodialysis patients in treatment with acetate-free biofiltration (AFB) or bicarbonate hemodialysis. The bone ultrasound measurements, both at phalangeal and tibial sites, were significantly associated with lumbar and femoral DXA values. Handgrip strength was significantly associated with the 10-year probability of fracture (
r
= −0.57,
p
< 0.001 for major fractures and
r
= −0.53,
p
< 0.001 for hip fracture, respectively), with femur neck, total femur, and L1–L4 BMD values (
r
= 0.47,
p
= 0.04;
r
= 0.48,
p
= 0.02;
r
= 0.58,
p
= 0.007, respectively), with TBS at the lumbar spine (
r
= 0.71,
p
< 0.001) and with the phalangeal QUS measure of AD-SoS (
r
= 0.369,
p
= 0.023). In the hemodialysis group, 10 participants (24.3%) reported at least one morphometric vertebral fracture (Vfx); conversely, only six participants (15%) showed Vfx in the control group. In the hemodialysis group, participants with Vfx compared with participants without Vfx reported significantly different TBS, bone transmission time (BTT), cortical thickness, and handgrip strength (
p
< 0.05). At multiple regression analysis, by identifying as dependent variable the 10-year fracture risk for major fracture, after correcting for age, BMI, time since dialysis, AD-SoS, cortical bone thickness, and handgrip strength, only BTT (
β
= −15.21, SE = 5.91,
p
= 0.02) and TBS (
β
= −54.69, SE = 21.88,
p
= 0.02) turned out as independently associated with fracture risk. In conclusion, hemodialysis patients showed a higher fracture risk and lower surrogate indices of bone strength as TBS and QUS parameters. In this cohort of patients, handgrip strength measurements appeared to be a useful instrument to identify high-fracture-risk subjects.
Aim
The association between anticholinergic burden and mortality is controversial. We aimed to investigate whether the anticholinergic cognitive burden (ACB) score predicts 1‐year mortality in older ...patients discharged from acute care hospitals.
Methods
Our series consisted of 807 hospitalized patients aged ≥65 years. Patients were followed up for 12 months after discharge. All‐cause mortality was the outcome of the study. The ACB score at discharge (0, 1, ≥2) and increasing ACB score from admission to discharge (no increase, +1, +2 or more) were calculated and used as exposure variables. Cox proportional hazards models adjusted for potential confounders were used for the analysis. Interactions between the ACB score and cognitive impairment or history of falls were also investigated.
Results
During the follow‐up period, 177 out of 807 participants (21.9%) died. After adjusting for potential confounders, a discharge ACB score of ≥2 (HR 1.69, 95% CI 1.09–2.65) was significantly associated with the outcome, whereas the association between increasing ACB score of +2 or more and mortality was weaker (HR 1.30, 95% CI 0.95–1.92). The interaction between the ACB score at discharge or increasing ACB score and cognitive impairment was statistically significant (P = 0.003 and P = 0.004, respectively), whereas that between the ACB score and falls was not.
Conclusions
The ACB score at discharge and, to a lesser extent, an increasing ACB score during hospital stay are associated with an increased risk of 1‐year mortality in older patients discharged from hospital. Such an association is stronger among patients with cognitive impairment. Geriatr Gerontol Int 2018; 18: 705–713
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