Effect of adding PCSK9 inhibitors to lipid-lowering interventions on arterial stiffness: A systematic review and meta-analysis

Background Atherosclerosis, a leading cause of mortality, necessitates effective management of hypercholesterolemia, specifically elevated low-density lipoprotein cholesterol (LDL-C). The emergence of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has revolutionised lipid-lowering. PCSK9i demonstrates substantial LDL-C reduction and cardiovascular benefits, particularly in statin-intolerant or nonresponsive individuals. However, the potential pleiotropic effects of PCSK9i, especially on arterial stiffness, remain a subject of investigation. This systematic review and meta-analysis seek to provide a nuanced understanding of the potential pleiotropic effects of PCSK9i, specifically on arterial health. The primary objective was to analyse the influence of PCSK9i on arterial stiffness, extending beyond traditional lipid-lowering metrics and contributing to a more comprehensive approach to cardiovascular risk reduction. Methods A systematic search was conducted across major databases, clinical trial registries and grey literature. Inclusion criteria comprised adults in prospective cohort studies undergoing PCSK9i augmentation in lipid-lowering therapy, with a focus on arterial stiffness measured by pulse wave velocity (PWv). Random-effects meta-analyses, sensitivity analyses and meta-regression models were employed to assess the pooled effect of adding PCSK9i to lipid-lowering interventions on arterial stiffness. Results Five studies (158 participants) met the inclusion criteria, demonstrating a significant reduction in PWv (mean difference: −2.61 m/s [95% CI: −3.70, −1.52]; ES: −1.62 [95% CI: −2.53, −.71]) upon adding PCSK9i to lipid-lowering interventions. Subgroup analysis and meta-regression models suggested potential sex-based and baseline PWv-dependent variations, emphasising patient-specific characteristics. Conclusion The meta-analysis provides robust evidence that adding PCSK9i to lipid-lowering interventions significantly improves arterial stiffness, indicating broader vascular benefits beyond LDL-C reduction

The acute effect of exercise on the endothelial glycocalyx in healthy adults: A systematic review and meta-analysis

Background: In recent years, it has been demonstrated that when the endothelial glycocalyx, composed of proteoglycans, glycosaminoglycans and glycoproteins, is altered or modified, this property is lost, playing a fundamental role in cardiovascular pathologies. Cardiovascular risk factors can destroy the endothelial glycocalyx layer. Exercise has a positive effect on cardiovascular risk factors, but little is known about its direct effect on the integrity of the endothelial layer. Methods: The Cochrane Library, PubMed, Web of Science and Scopus databases were searched from their inception to June 30, 2022. The DerSimonian and Laird method was used to compute pooled effectsize estimates and their respective 95% confidence intervals for the acute effect of exercise (within 24h) on the endothelial glycocalyx and its components in healthy adults. Results: Ten studies were included in the meta-analysis, with a total of 252 healthy subjects. The types of exercise included were resistance training, interval training, resistance training and maximal incremental exercise, with a duration range of 30–60min. Glycocalyx assessment times included ranged from 0 to 90min post-exercise. Our findings showed that endothelial glycocalyx increases after acute effect of exercise in healthy population (.56, 95% CI: .38, .74). The acute effect of exercise on endothelial glycocalyx components were .47 (95% CIs: .27, .67) for glycosaminoglycans, .67 (95% CIs: .08, 1.26) for proteoglycans and .61 (95% CIs: .35, .86) for glycoproteins. Conclusions: In a healthy population, various types of exercise showed an acute improvement of the endothelial glycocalyx and its individual components

Effect of Behavioral Weight Management Interventions Using Lifestyle mHealth Self‐Monitoring on Weight Loss: A Systematic Review and Meta‐Analysis

Alongside an increase in obesity, society is experiencing the development of substantial technological advances. Interventions that are easily scalable, such as lifestyle (including diet and physical activity) mobile health (mHealth) self‐monitoring, may be highly valuable in the prevention and treatment of excess weight. Thus, the aims of this systematic review and meta‐ analysis were to estimate the following: (i) the effect of behavioral weight management interventions using lifestyle mHealth self‐monitoring on weight loss and (ii) the adherence to behavioral weight management interventions using lifestyle mHealth self‐monitoring. MEDLINE via PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and the Web of Science databases were systematically searched. The DerSimonian and Laird method was used to estimate the effect of and adherence to behavioral weight management interventions using lifestyle mHealth self‐monitoring on weight loss. Twenty studies were included in the systematic review and meta‐ analysis, yielding a moderate decrease in weight and higher adherence to intervention of behavioral weight management interventions using lifestyle mHealth self‐monitoring, which was greater than other interventions. Subgroup analyses showed that smartphones were the most effective mHealth approach to achieve weight management and the effect of behavioral weight management interventions using lifestyle mHealth self‐monitoring was more pronounced when compared to usual care and in the short‐term (less than six months). Furthermore, behavioral weight management interventions using lifestyle mHealth self‐monitoring showed a higher adherence than: (i) recording on paper at any time and (ii) any other intervention at six and twelve months

Intranasal insulin effect on cognitive and/or memory impairment: a systematic review and meta-analysis

Background: Cognitive impairment, characterized by deficits in cognitive functions and loss of delayed and immediate recall, disproportionately affects individuals aged 65 years and older, particularly those with comorbid cardiovascular conditions such as hypertension and diabetes mellitus. Objective: This study aimed to investigate the potential association between intranasal insulin and cognitive and/or memory impairment, with a specific focus on delayed and immediate recall, considering the rising prevalence of cognitive disorders in the aging population. Methodology: Employing a rigorous systematic approach, we conducted a thorough search of MEDLINE, Scopus, the Cochrane database, and Web of Science from inception to November 23, 2022, identifying relevant randomized clinical trials. Our analyses encompassed three key aspects: (i) assessing the impact of intranasal insulin on cognitive impairment, (ii) evaluating its effect on delayed recall, and (iii) examining its influence on immediate recall. Results: Five studies meeting the inclusion criteria were included. The results underscored a statistically significant effect of intranasal insulin on delayed memory (effect size: 1.37; 95% CI: 0.65 to 2.09) and overall cognition (effect size: 0.58; 95% CI: 0.08 to 1.08). However, no statistically significant effect was observed for immediate memory (effect size: 0.48; 95% CI: -0.00 to 0.96). Conclusions: This study provides compelling evidence supporting the significance and efficacy of intranasal insulin in enhancing delayed recall and overall cognition. The observed effects hold promise for potential therapeutic interventions in addressing cognitive deficits associated with aging and comorbid conditions. The findings emphasize the need for further research to elucidate the underlying mechanisms and optimize the application of intranasal insulin in cognitive enhancement strategies

Association Between Eating Habits and Perceived School Performance: A Cross-Sectional Study Among 46,455 Adolescents From 42 Countries

PURPOSE: This study analyzed the association between selected self-reported eating habits and perceived school performance in adolescents by gender. METHODS: A cross-sectional analysis was conducted with data from a large representative sample of adolescents from 42 different countries. Participants answered questions about their weekly frequency of fruit, vegetable, sweets, and soft drink consumption, as well as the frequency of breakfast consumption and family meals. The adolescents subjectively rated their school performance compared to that of their classmates. Logistic regression models were adjusted for region, age, body mass index (z-score), socioeconomic status, physical activity, recreational screen time, and sleep difficulties. RESULTS: Among the 46,455 (53.5% female, mean age of 13.7 ± 1.6 years) adolescents studied, 20.6% of males and 25.5% of females reported high perceived school performance. In the results of the fully adjusted analyses, the higher the frequency of all healthy eating habits studied, the higher the perceived school performance in both males and females. Specifically, both males and females reporting a higher frequency of fruit and vegetable consumption, a lower frequency of sweets and soft drink consumption, more frequent breakfast consumption, and more frequent family meals (breakfast and dinner) were more likely to perceive their school performance as higher compared to their classmates. In addition, having breakfast regularly on weekends and the frequency of family dinner were associated with better school performance in both males and females. CONCLUSIONS: In summary, this study provide cross-sectional evidence on the association between healthy eating habits and perceived school performance. Considering that school performance is an indicator of healthy development in adolescence, our findings reinforce and extend the evidence on the importance of healthy eating at this stage of life

Non-invasive skin autofluorescence as a screening method for diabetic retinopathy

Diabetic retinopathy (DR) is a public health problem and a common cause of blindness. It is diagnosed by fundus examination; however, this is a costly and time-consuming method. Non-invasive skin autofluorescence (SAF) may be an accessible, fast and simple alternative for screening and early diagnosis of DR. The aim of this study was to evaluate the accuracy of SAF as a screening method for DR. A systematic search of MEDLINE, Scopus, and Web of Science databases was performed. Random effects models for sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio (dOR) value and 95% CIs were used to calculate test accuracy. In addition, hierarchical summary receiver operating characteristic curves (HSROC) were used to summarise the overall test performance. Four studies were included in the meta-analysis. Pooled sensitivity and specificity were 0.79 (95% CI 0.72–0.88; I2 = 0.0%) and 0.54 (95% CI 0.32–0.92; I2 = 97.0%), respectively. The dOR value for the diagnosis of DR using SAF was 5.11 (95% CI 1.81–14.48: I2 = 85.9%). The PRL was 2.17 (95% CI 0.62–7.64) and the NRL was 0.27 (95% CI 0.07–1.03). Heterogeneity was not relevant in sensitivity and considerable in specificity. The 95% confidence region of the HSROC included all studies. SAF as a screening test for DR shows sufficient accuracy for its use in clinical settings. SAF may be an appropriate method for DR screening, and further research is needed to recommend it as a diagnostic method

The effect of smoking and smoking cessation on arterial stiffness: a systematic review and meta-analysis.

Aims: One of the most important mechanisms by which smoking contributes to cardiovascular disease is endothelial dysfunction, including arterial stiffness. However, the effects of smoking and smoking cessation on arterial stiffness remain unclear. This meta-analysis aimed to evaluate the effect of smoking and smoking cessation on arterial stiffness in the adult population. Methods and results: Random effects models were used to compute pooled estimates of effect size (ES) and their respective 95% confidenceintervals (95% CIs) and change in pulse wave velocity (PWv) (m/s) for the acute and chronic effect of smoking and smoking cessation, and for the effect of smoking cessation vs. the pooled ES estimate for the effect of smoking cessation vs. maintaining this behaviour. Thirteen studies were included in the meta-analysis. Smoking cessation decreased the PWv (ES 0.52, 95% CI 1.02 to 0.03, 3.5% m/s) compared to those maintaining this behaviour. Pooled estimates of both smoking conventional cigarettes and vaping significantly increased the PWv (ES 0.68, 95% CI 0.39–0.98, 10.0% m/s; and ES 0.37, 95% CI 0.14–0.61, 4.7% m/s, respectively). In addition, smoking cessation was effective in reducing arterialstiffness but only in healthy subjects (ES 0.95, 95% CI 1.85 to 0.05, 6.7% m/s). The chronic effect of smoking showed non-significant results on arterial stiffness. Conclusion: Our results show that arterial stiffness levels decrease after smoking cessation. These findings are of clinical importance, as smoking cessation partially reverses the effects of smoking on arterial stiffness

Association between severe hypoglycaemia and risk of dementia in patients with type 2 diabetes mellitus: A systematic review and meta-analysis

The aim of this systematic review was to analyse whether there is an association between severe hypoglycaemia and the incidence of dementia in patients with type 2 diabetes mellitus. We systematically searched the MEDLINE, Scopus, and Cochrane databases from their inception until September 2022 for observational studies on the association between hypoglycaemia and the risk of dementia. The DerSimonian and Laird method was used to compute a pooled estimate of the risk for such association. Risk ratio (RR) and its respective 95% confidence interval (95% CI). Two analyses were performed to estimate the risk of dementia: (i) any hypoglycaemia versus no hypoglycaemia and (ii) a dose–response analysis for one, two, or more than three hypoglycemic events versus no hypoglycaemia. PROSPERO registration number CRD42020219200. Seven studies were included. The pooled RR for the association of severe hypoglycaemia and risk of dementia was 1.47 (95% CI: 1.24–1.74). When the dose–response trend was analysed, the pooled RR for the risk of dementia was increased according to the hypoglycaemia events as follows: 1.29 (95% CI: 1.15–1.44) for one hypoglycemic event; 1.68 (95% CI: 1.38–2.04) for two hypoglycemic events; and 1.99 (95% CI: 1.48–2.68) for three or more hypoglycemic events. Our study demonstrates a 54% higher risk of dementia among people who suffer a hypoglycaemia event compared to nonhypoglycaemia. Considering our results and the prevalence of people suffering from diabetes mellitus, health education for both newly diagnosed and already diagnosed people could be a useful tool for glycaemic control, thus avoiding hypoglycaemic events

The Acute Effect of Exercise on Arterial Stiffness in Healthy Subjects: A Meta-Analysis

Arterial stiffness has been shown to be a subclinical marker associated with cardiovascular disease. Meanwhile, long-term exercise has been demonstrated to reduce arterial stiffness, providing a decrease in cardiovascular risk. However, the acute effect of exercise on arterial stiffness is unclear. This systematic review and meta-analysis aimed to assess the acute effect of exercise interventions on arterial stiffness in healthy adults. We searched the Cochrane Central Register of Controlled Trials, MEDLINE (via Pubmed), Scopus, and Web of Science databases, from their inception to 30 June 2020. A meta-analysis was performed to evaluate the acute effect of exercise on arterial stiffness using random-effects models to calculate pooled effect size estimates and their corresponding 95% CI. Pulse wave velocity was measured as an arterial stiffness index. The 30 studies included in the meta-analysis showed that pulse wave velocity was not modified immediately after exercise (0 min post) (ES: 0.02; 95% CI: -0.22, 0.26), but subsequently decreased 30 min after exercise (ES: -0.27; 95% CI: -0.43, -0.12). Thereafter, pulse wave velocity increased to its initial value 24 h after exercise (ES: -0.07; 95% CI: -0.21, 0.07). Our results show that, although there is a significant reduction in pulse wave velocity 30 min after exercise, the levels of arterial stiffness return to their basal levels after 24 h. These findings could imply that, in order to achieve improvements in pulse wave velocity, exercise should be performed on a daily basis

Association Between Wine Consumption and Cognitive Decline in Older People: A Systematic Review and Meta-Analysis of Longitudinal Studies. 2022, 9, 863059.

Background: Low-to-moderate alcohol consumption appears to have potential health benefits. Existing evidence concludes that winemay be associated with a lower incidence of certain diseases. This systematic review and meta-analysis aim to examine evidence on the association between wine consumption and cognitive decline and to analyze whether this association varies depending on the wine consumption level or is affected by individual and study characteristics, including mean age, percentage of women participants, and follow-up time. Methods: In this systematic review and meta-analysis, we undertook a search in MEDLINE (via PubMed), Scopus, Cochrane, and Web of Science databases for longitudinal studies measuring the association between wine consumption and cognitive decline from their inception to May 2021. Effect sizes were calculated using the DerSimonian and Laird and Hartung-Knapp-Sidik-Jonkman methods. Results: The search retrieved 6,055 articles, 16 of which were included in this systematic review. In total, 12 studies were included in themeta-analysis. The studies were published between 1997 and 2019. They were conducted in nine different countries. The sample size of the included studies ranged from 360 to 10,308 with a mean age of 70 years old. Using the DerSimoniand and Laird method, the pooled RR for the effect of wine consumption on cognitive decline was 0.72 (95%CI 0.63–0.80; I2 = 82.4%; 2: 0.0154). Using the Hartung-Knapp-Sidik-Jonkman method, the RR was 0.65 (95% CI 0.52–0.79; I2 = 94,531%; 2: 0.057). Conclusions: This study may show a protective effect of wine consumption against cognitive decline. However, it would be important for future research to differentiate the types of wine within consumption