Sex- and Gender-Related Aspects in Pulmonary Hypertension.

Biological sex and sociocultural gender are emerging as pivotal modifiers of health and diseases. Sex-based differences exist in the development, pathogenesis, and management of individuals with pulmonary arterial hypertension (PAH). The interplay between gender domains (ie, identity, roles, relations, and institutionalized gender) and PAH has been barely investigated. The aim of this narrative review is to describe up-to-date evidence on the integration of sex and gender in PAH research, highlighting areas for future investigation.

Effects of 3-month high-intensity interval training vs. moderate endurance training and 4-month follow-up on fat metabolism, cardiorespiratory function and mitochondrial respiration in obese adults.

PURPOSE: The purpose of this study was to investigate, in obese adults, changes in body composition, physical capacities, fat oxidation and ex vivo mitochondrial respiration induced by a 3-month either moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT); afterwards, the patients were followed for four months. METHODS: Thirty-two patients (mean age 39 years; mean body mass index [BMI] 36 kg∙m-2) participated in this study attending ~ 34 sessions of training. At baseline (PRE), at the end of the program (POST) and after follow-up, body composition, peak O2 uptake (V'O2peak) and fat oxidation rate were measured. Vastus lateralis biopsies for the evaluation of mitochondrial respiration were performed only at PRE and POST. RESULTS: At POST, body mass (BM) and fat mass (FM) decreased (- 6 and - 14%, respectively, P < 0.05) in MICT and HIIT; V'O2peak increased in both groups (+ 6 and + 16%, respectively, P < 0.05). Maximal fat oxidation rate increased only after HIIT (P < 0.001). Maximal ADP-stimulated mitochondrial respiration normalized by citrate synthase increased (P < 0.05) by 67% and 36% in MICT and HIIT, respectively, without significant difference. After follow-up, BM and FM were still lower (- 4 and - 20%, respectively, P < 0.050) compared with baseline in both groups. Only after HIIT, V'O2peak (+ 8%) and maximal fat oxidation rate were still higher (P < 0.05). CONCLUSIONS: HIIT was more effective in improving and maintaining V'O2peak and fat oxidation. These results may be relevant for an appropriate prescription of training programs designed to optimize aerobic fitness in obese subjects.

Dyslipidemia, Cholangitis and Fatty Liver Disease: The Close Underexplored Relationship: A Narrative Review.

In assessing individual cardiovascular risk, dyslipidemia is known for emerging as a pivotal factor significantly contributing to major cardiovascular events. However, dyslipidemic patients frequently present with concurrent medical conditions, each with varying frequencies of occurrence; cholangitis, whether acute or chronic, and hepatic steatosis, along with associated conditions, are strongly associated with specific forms of dyslipidemia, and these associations are reasonably well elucidated. Conversely, evidence linking biliary disease to hepatic steatosis is comparatively scant. This narrative review aims to bridge this gap in knowledge concerning the interplay between dyslipidemia, cholangitis, and hepatic steatosis. By addressing this gap, clinicians can better identify patients at heightened risk of future major cardiovascular events, facilitating more targeted interventions and management strategies. The review delves into the intricate relationships between dyslipidemia and these hepatic and biliary clinical conditions, shedding light on potential mechanisms underlying their associations. Understanding these complex interactions is crucial for optimizing cardiovascular risk assessment as well and devising tailored treatment approaches for patients with dyslipidemia and associated hepatic disorders. Moreover, elucidating these connections empowers clinicians with the knowledge needed to navigate the multifaceted landscape of cardiovascular risk assessment and management effectively. By exploring the intricate relationships between dyslipidemia, cholangitis, and hepatic steatosis (without forgetting the possible clinical consequences of hepatic steatosis itself), this review not only contributes to the existing body of knowledge but also offers insights into potential avenues for further research and clinical practice. Thus, it serves as a valuable resource for healthcare professionals striving to enhance patient care and outcomes in the context of cardiovascular disease and associated hepatic conditions.

Cholesterol efflux capacity is increased in subjects with familial hypercholesterolemia in a retrospective case-control study.

Familial Hypercholesterolemia (FH) is characterized by an increase in Low-Density Lipoprotein Cholesterol (LDL-C) and by premature Cardiovascular Disease (CVD). However, it remains to be fully elucidated if FH impairs cholesterol efflux capacity (CEC), and whether CEC is related to lipoprotein subfraction distribution. This study aimed at comparing FH patients and age, sex and BMI matched controls in terms of LDL and HDL subfraction distribution as well as CEC. Forty FH patients and 80 controls, matched for age, sex and BMI, were enrolled in this case-control study. LDL and HDL subfractions were analyzed using the Quantimetrix Lipoprint System. CEC was evaluated as aq-CEC and ABCA1-CEC. FH subjects showed a significantly higher concentration of all LDL subfractions, and a shift from large to small HDL subfraction pattern relative to controls. FH subjects with previous CVD event had smaller LDL lipoproteins than controls and FH subjects without previous CVD event. Both aq-CEC and ABCA1-CEC were increased in FH patients with respect to controls. To conclude, FH subjects had a metabolic profile characterized not only by higher LDL-C but also by shift from large to small HDL subfraction phenotype. However, FH subjects showed an increase CEC than controls.

Paraoxonase-1 (PON-1) Arylesterase Activity Levels in Patients with Coronary Artery Disease: A Meta-Analysis.

Aim: To review and compare the PON-1 arylesterase activity between coronary artery disease (CAD) and non-CAD patients. Methods: Data were obtained by searching MEDLINE and Scopus for all investigations published between January 1, 2000 and March 1, 2021 comparing PON-1 arylesterase activity between CAD and controls. Results: Twenty studies, based on 5417 patients, met the inclusion criteria and were included in the analysis. A random effect model revealed that PON-1 arylesterase activity was significantly lower in the CAD group compared to controls (SMD = -0.587, 95%CI = -0.776 to -0.339, p < 0.0001, I 2 = 92.3%). In CAD patients, the PON-1 arylesterase activity was significantly higher among CAD patients without diabetes mellitus (DM) compared to those with diabetes (SMD: 0.235, 95% CI: 0.014 to 0.456, p = 0.03, I 2 = 0%). Conclusions: PON-1 activity is significantly lower in CAD patients, and those without DM presented a significantly higher PON-1 arylesterase activity.

Skeletal Muscle Mitochondrial and Perilipin Content in a Cohort of Obese Subjects Undergoing Moderate and High Intensity Training.

Obesity is a complex condition characterized by abnormal and excessive fat accumulation, resulting in an increased risk for severe health problems. Skeletal muscles play a major role in movement and fat catabolism, but the insulin resistance that comes with obesity makes it difficult to fulfill these tasks. In this study, we analyse two types of training protocols, moderate intensity continuous training (MICT) versus high intensity interval training (HIIT), in a cohort of obese subjects to establish which muscle adaptations favour fat consumption in response to exercise. Mitochondria play a role in fat oxidation. We found protein upregulation of mitochondrial biomarkers, TOMM20 and Cox-4, in HIIT but not in MICT, without detecting any shifts in fibre composition phenotype of the vastus lateralis in both training groups. Interestingly, both MICT and HIIT protocols showed increased protein levels of perilipin PLIN2, which is involved in the delivery and consumption of fats. HIIT also augmented perilipin PLIN5. Perilipins are involved in fat storage in skeletal muscles and their upregulation, along with the analysis of circulatory lipid profiles reported in the present study, suggest important adaptations induced by the two types of training protocols that favour fat consumption and weight loss in obese subjects.

Biological Response of Irisin Induced by Different Types of Exercise in Obese Subjects: A Non-Inferiority Controlled Randomized Study.

Background: Weight loss through physical exercise is warranted among obese individuals. Recently, a greater benefit in cardiorespiratory fitness was achievable with high-intensity interval training (HIIT) as compared with moderate intensity continuous training. The beneficial effect of training on CV health might be related to a specific modulation of circulating irisin, an adypo-myokine implicated in the regulation of energy expenditure. Methods: The present study investigates the circulating plasma levels of irisin at baseline and in response to 12-week of training program either with HIIT or moderate-intensity continuous training (MICT) among young female and male obese subjects. Clinical, anthropometric, and training characteristics for each participant were available. A sex-disaggregated data for circulating plasma levels of irisin pre- and post-training are provided as well as an adjusted multivariate linear regression model to identify the determinants of post-training irisin levels. Results: Data from a total of 32 obese healthy individuals (47% female, mean age 38.7 years, mean BMI 35.6 kg/m2), randomized in a 1:1 manner to HIIT or MICT were analyzed. Circulating plasma levels of irisin similarly and significantly decreased in both MICT and HIIT interventional groups. Females had higher post-exercise irisin levels than males (6.32 [5.51-6.75] vs. 4.97 [4.57-5.72] µg/mL, p = 0.001). When stratified by an interventional group, a statistically significant difference was observed only for the MICT group (male, 4.76 [4.20-5.45] µg/mL vs. female 6.48 [4.88-6.84] µg/mL p = 0.03). The circulating post-training level of irisin was independently associated with post-training fat-free mass (ß -0.34, 95% confidence interval, CI -0.062, -0.006, p = 0.019) in a model adjusted confounders. When female sex was added into the adjusted model, it was retained as the only factor independently associated with irisin levels (ß 1.22, 95% CI, 0.50, 1.93, p = 0.002). Conclusions: In obese healthy subjects, circulating irisin levels were reduced in response to 12-weeks of exercise involving either HIIT or MICT. A sex-specific differences in circulating irisin levels at baseline and as biological response to chronic exercise was described. Sex-specific biological response of irisin to exercise should be further explored to tailor sex-specific training approaches for improving the cardiovascular health of obese healthy subjects.

Physical capacities and leisure activities are related with cognitive functions in older adults.

BACKGROUND: This study aimed to evaluate the relationship between physical activity habits, physical performance and cognitive capacity in older adults' population of Italy and Slovenia. METHODS: Anthropometric characteristics and body composition bioelectrical impedance analysis were evaluated in 892 older adults (60-80 y). Aerobic capacity was measured using the 2-km walk test and handgrip and flexibility tests were performed. Physical activity habits and cognitive functions were evaluated by the Global-Physical-Activity-Questionnaires (GPAQ) and by Montreal-Cognitive-Assessment (MoCA) questionnaires, respectively. RESULTS: GPAQ scores were associated with lower BMI (r=-0.096; P=0.005), lower percentage of fat-mass (r=-0.138; P=0.001), better results in the 2-km walk test (r=-0.175; P=0.001) and a higher percentage of fat-free mass (r=0.138; P=0.001). We also evaluated that a higher MoCA Score correlates with age (r=-0.208; P=0.001), 2-km walk test (r=-0.166; P=0.001), waist-hip ratio (r=-0.200; P=0.001), resting heart-rate (r=-0.087; P=0.025) and heart-rate at the end of 2-km walk test (r=0.189; P=0.001). CONCLUSIONS: Older adults with a higher level of daily physical activity showed reduction in fat-mass and BMI, and higher aerobic fitness; these characteristics have a protection effect on cognitive function.

Irisin Attenuates Muscle Impairment during Bed Rest through Muscle-Adipose Tissue Crosstalk.

The detrimental effect of physical inactivity on muscle characteristics are well known. Irisin, an exercise-induced myokine cleaved from membrane protein fibronectin type III domain-containing protein-5 (FNDC5), mediates at least partially the metabolic benefits of exercise. This study aimed to assess the interplay between prolonged inactivity, circulating irisin, muscle performance, muscle fibers characteristics, as well as the FNDC5 gene expression (FNDC5ge) in muscle and adipose tissue among healthy subjects. Twenty-three healthy volunteers were tested before and after 14 days of Bed Rest, (BR). Post-BR circulating levels of irisin significantly increased, whereas body composition, muscle performance, and muscle fiber characteristics deteriorated. Among the subjects achieving the highest post-BR increase of irisin, the lowest reduction in maximal voluntary contraction and specific force of Fiber Slow/1, the highest increase of FNDC5ge in adipose tissue, and no variation of FNDC5ge in skeletal muscle were recorded. Subjects who had the highest FNDC5ge in adipose tissue but not in muscle tissue showed the highest circulating irisin levels and could better withstand the harmful effect of BR.

Effectiveness of high-intensity interval training for weight loss in adults with obesity: a randomised controlled non-inferiority trial.

INTRODUCTION: Obesity treatment guidelines suggest moderate-intensity continuous training (MICT), but the patient's compliance to this indication remains low. High-intensity interval training (HIIT) is a time sparing training mode whose metabolic effects are not clear. This study aimed to determine whether a 12-week HIIT was more effective than MICT for weight loss in obese adults. METHODS: 44 obese subjects were randomised and trained with isoenergetic treadmill exercises for 12 weeks: MICT (60% of maximal oxygen peak, VO2peak) or HIIT (3-7 repetition of 3 min 100% of VO2peak interspersed by 1.5 min 50% of VO2peak). The primary outcome was a change in body weight; the secondary outcomes were changes in body composition, blood pressure, lipid profile, glycaemia, insulin and VO2peak. RESULTS: 32 subjects (53% male, mean age: 38.5 years, mean body mass index: 35.5 kg/m2) completed the trial. MICT and HIIT showed comparable effect within groups in weight loss (-6.0 kg (-9.0 kg to -3.0 kg) vs -5.7 kg (-8.3 kg to -3.1 kg)), changes in fat mass (-2.9% (-4.4% to -1.4%) vs -3.6% (-5.9% to -1.2%)), fat free mass (-5.3% (-7.8% to -2.8%) vs -5.5% (-8.3% to -2.6%)), diastolic blood pressure (-5.5 mm Hg (-10.6 mm Hg to -0.3 mm Hg) vs -5.8 mm Hg (-11.3 mm Hg to -0.3 mm Hg)) and low-density lipoprotein cholesterol (-16.4 mg/dL (-30.8 mg/dL to -2.0 mg/dL) vs -14.7 mg/dL (-25.6 mg/dL to -3.8 mg/dL)). There was a significant change between groups in VO2peak (HIIT: +461.6 mL (329.3‒593.8 mL); MICT: +170.5 mL (86.7-254.4 mL); p<0001) and duration of sessions (HIIT: 35.0 min (31.7 ‒35.6 min); MICT: 46.5 min (40.2‒48.3 min); p<0.001). No significant changes in systolic blood pressure, high-density lipoprotein cholesterol, triglycerides, glycaemia or plasma insulin were observed. CONCLUSIONS: In healthy adults with obesity, HIIT compared with MICT induced similar weight loss and cardiovascular risk factors improvement but resulted in a larger increase in cardiorespiratory fitness over a shorter period.

Rethinking of osteoporosis through a sex- and gender-informed approach in the COVID-19 era.

Standards and models of reference for osteoporosis (OP) have been developed for female individuals as they are more likely to be affected by the disease. Nonetheless, OP is also responsible for one-third of hip fractures in male individuals suggesting that a sex-blinded approach to OP may lead to miss opportunities for equity in bone health. OP-related fractures, especially hip fractures, are a matter of immediate concern as they are associated with limited mobility, chronic disability, loss of independence, and reduced quality of life in both sexes. When it comes to sociocultural gender, the effect of gender domains (i.e., identity, roles, relations, and institutionalized gender) on development and management of OP is largely overlooked despite risk factors or protective conditions are gendered. Clinical trials testing the efficacy and safety of anti-OP drugs as well as non-pharmacological interventions have been conducted mainly in female participants, limiting the generalizability of the findings. The present narrative review deals with the sex and gender-based challenges and drawbacks in OP knowledge and translation to clinical practice, also considering the impact of coronavirus disease 2019 pandemic.

Role of Statins in Coronavirus-Related Disease (COVID-19): A Retrospective Cohort Study in Northern Italy.

INTRODUCTION: The outbreak by SARS-CoV-2 has rapidly spread worldwide. The need for specific treatments to adequately stop the inflammatory response and its sequelae is day by day more urgent and many therapeutic strategies were performed since COVID-19 burst in the last months. Statins were thought to be effective against this novel coronavirus for their anti-inflammatory properties, even if the real effects on COVID patients are still partially unexplored. METHODS: We retrospectively evaluated 501 adult patients, consecutively admitted to the two COVID-hospitals of Ferrara's territory, and divided them into two groups: ST = patients on statin therapy on admission and NST=patients not on statin therapy on admission. We searched for differences between groups in terms of anamnestic, clinical and laboratory data and then in terms of COVID-19 outcomes. RESULTS: We found significant differences between groups in terms of age, comorbidities, procalcitonin and CPK serum levels: ST patients were older, more comorbid, with lower procalcitonin and higher CPK serum levels. Male sex was, together with the Charlson Comorbidity Index, an independent predictor of needing intensification of care, while age only was a good predictor of in-hospital and 100-day mortality. Differences were also found in the survival functions between the two groups. CONCLUSIONS: After a period of observation of 100 days, ST patients, despite their older age and their greater load of comorbidities, have similar survival functions to NST patients. If adjusted for age and CCI the survival functions of ST group are considerably more favourable than those of the second group.

Levels and Factors Associated with Resilience in Italian Healthcare Professionals during the COVID-19 Pandemic: A Web-Based Survey.

BACKGROUND: Resilience is defined as the capacity to cope successfully with change or adversity. The aims of our study were to investigate levels of resilience in Italian healthcare professionals (HCPs) during the Coronavirus disease 2019 (COVID-19) pandemic and to identify potential predictors of resilience. METHODS: We performed a web-based survey of HCPs (n = 1009) working in Italian hospitals during the COVID-19 pandemic. The survey contained a 14-item resilience scale (RS14) and questionnaires to evaluate depression and anxiety symptoms. Non-HCP individuals (n = 375) from the general population were used for comparison. RESULTS: HCPs showed significantly lower resilience compared to the control group (p = 0.001). No significant differences were observed after stratification for geographical area, work setting, role, or suspected/confirmed diagnosis of COVID-19. In a linear regression analysis, RS14 was inversely correlated with depression (R2 = 0.227, p < 0.001) and anxiety (R2 = 0.117, p < 0.001) and directly correlated with age (R2 = 0.012, p < 0.001) but not with body mass index (BMI, R2 = 0.002, p = 0.213). In male HCPs, higher depression score (odds ratio (OR) 1.147, p < 0.001) or BMI (OR 1.136, p = 0.011) significantly predicted having low resilience. In female HCPs, higher depression score (OR 1.111, p < 0.0001) and working in a COVID-19 free setting (OR 2.308, p = 0.002) significantly predicted having low resilience. HCPs satisfied with personal protective equipment had higher levels of resilience (p < 0.010). CONCLUSIONS: Our findings suggest that resilience was lower in Italian HCPs than in the general population after the first COVID-19 wave. Specific factors can be identified, and targeted interventions may have an important role to foster resilience of HCPs.