Left ventricular remodeling in twin pregnancy, noninvasively assessed using hemodynamic forces and pressure-volume relation analysis: prospective, cohort study.

This study was designed to prospectively investigate the pattern of intraventricular hemodynamic forces (HDFs) associated with left ventricular (LV) function and remodeling in women with uncomplicated twin pregnancy. Transthoracic echocardiography was performed on 35 women (aged 35.9 ± 4.7-yr old) during gestation (T1, <14 wk; T2, 14-27 wk; T3, >28 wk) and 6-7 mo after delivery (T0). LV HDFs were computed from echocardiography long-axis data sets using a novel technique based on endocardial boundary tracking, both in apex-base (A-B) and latero-septal (L-S) directions. HDF distribution was evaluated by L-S over A-B HDF ratio (L-S:A-B HDF ratio). At T1, L-S:A-B HDF ratio was higher than in T0 (P < 0.05) indicating HDF misalignment. At T2, a slight impairment of cardiac function was then recorded with a reduction of global longitudinal strain (GLS) and left ventricular end-systolic elastance (Ees) at pressure-volume relationship analysis versus T1 (both P < 0.05). Finally, at T3, when HDF misalignment and LV contractility reduction (GLS and Ees) were all restored, a rightward shift of the end-diastolic pressure-volume relationship (EDPVR) with an increase of ventricular capacitance was documented. In twin pregnancy, HDF misalignment in the first trimester precedes the slight temporary decrease in left ventricular systolic function in the second trimester; at the third trimester, a rightward shift of the EDPVR was associated with a realignment of HDF and normalization of ventricular contractility indexes. These coordinated changes that occur in the maternal heart during twin pregnancy suggest the role of HDFs in cardiac remodeling.NEW & NOTEWORTHY These changes indicate that 1) the misalignment of hemodynamic forces (HDFs) precedes a mild reduction in systolic function in twin pregnancy and 2) the positive left ventricular (LV) response to hemodynamic stress is mainly due to an improved diastolic function with enhanced LV cavity compliance.

Effects of a 24-Week Exercise Program on Functional Fitness, Oxidative Stress, and Salivary Cortisol Levels in Elderly Subjects.

Background and Objectives: Aging is a biological and irreversible process characterized by physiological alterations resulting in a progressive decline in biological functions, decreased resistance or adaptability to stress, and increased disease susceptibility. A decline in functional fitness, imbalance between pro- and antioxidant capacity, and/or hormonal dysregulation adversely impact physical capacity, emotional status, and overall quality of life, especially within the elderly population. On the other hand, regular physical activity is considered an effective strategy to prevent and reduce those changes associated with primary aging and concurrent chronic disease, while slowing age-related physical degeneration. However, there is still limited evidence-based information regarding both the intensity and interval of effective interventions on physical functioning in older adults. Thus, the aim of the study was to assess the effects of a 24-week regular multimodal exercise program on functional fitness, oxidative stress, salivary cortisol level, and self-perceived quality of life in a group of eighteen physically active elderly subjects (mean age 72.8 ± 7.5 years). Materials and Methods: A set of anthropometric and physical measurements (grip strength, chair sit to stand, sit and reach and back scratch) assessing the functional fitness performance were evaluated. Moreover, biochemical markers (derived-reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) tests, and salivary cortisol levels) and the EuroQoL 5-Dimension 3-Level (EuroQoL 5-D 3-L) self-perceived questionnaire of quality of life were measured before and after the intervention program. All measurements were normally distributed as assessed by D'Agostino and Pearson's omnibus normality test. Student's t-tests were used to evaluate the differences in all the parameters measured at baseline (T0) and after the 24-week physical program (T1). Results: The results showed that an age-tailored structured intervention exercise program (1 h per session, twice per week, for 24 weeks) was effective in improving flexibility and other biomechanical parameters, such as muscle strength and the dynamic balance fitness component, which are key to performing daily tasks independently. Moreover, biochemical analyses demonstrate that the proposed intervention program has beneficial effects on the balance between plasma ROS production and their neutralization. Conclusions: The results confirm the benefits of regular physical activity in older adults resulting in improved physical strength and flexibility in the functional fitness parameters, and in regulating anti- and pro-oxidant activity and cortisol (stress hormone) levels.

Gender differences in the impact on physical activity and lifestyle in Italy during the lockdown, due to the COVID-19 pandemic.

BACKGROUND AND AIMS: Italy responded to the Covid-19 pandemic early by forcing the entire population into a 2-month domestic confinement. The aim of this study was to assess gender differences in the impact of lockdown on physical activity and lifestyle habits. METHODS AND RESULTS: A cross-sectional web-based survey was conducted in April 2020 on a general population sample residing in Italy. Participants completed validated questionnaires. Gender differences were assessed using a multivariable adjusted logistic regression model using gender as independent and exposures as dependent variables. Metabolic equivalents-hour/week was used to evaluate physical activity. A total of 2218 participants (761 men and 1457 women) agreed to participate in the study and completed the questionnaire. The survey found that women compared to men showed 1) a lower level of physical activity before the institution of lockdown, 2) a lower tendency to reduce physical activity levels during the lockdown, when gender differences in compliance with guideline recommendations for physical activity disappeared, 3) and a worsening of sleep and stool passage; men experienced an increase in alcohol consumption. CONCLUSIONS: Women, who previously had a lower level of physical activity than men, showed a lower tendency to reduce it during lockdown, revealing greater resilience than men. However, the worsening in sleep, in stool passage, and a trend to weight increase revealed signs of psychological suffering after a protracted lockdown period.

Hyperglycemia and angiotensin II cooperate to enhance collagen I deposition by cardiac fibroblasts through a ROS-STAT3-dependent mechanism.

Cardiac fibroblasts significantly contribute to diabetes-induced structural and functional changes in the myocardium. The objective of the present study was to determine the effects of high glucose (alone or supplemented with angiotensin II) in the activation of the JAK2/STAT3 pathway and its involvement in collagen I production by cardiac fibroblasts. We observed that the diabetic environment 1) enhanced tyrosine phosphorylation of JAK2 and STAT3; 2) induced nuclear localization of tyrosine phosphorylated STAT3 through a reactive oxygen species-mediated mechanism, with angiotensin II stimulation further enhancing STAT3 nuclear accumulation; and 3) stimulated collagen I production. The effects were inhibited by depletion of reactive oxygen species or silencing of STAT3 in high glucose alone or supplemented with exogenous angiotensin II. Combined, our data demonstrate that increased collagen I deposition in the setting of high glucose occurred through a reactive oxygen species- and STAT3-dependent mechanism. Our results reveal a novel role for STAT3 as a key signaling molecule of collagen I production in cardiac fibroblasts exposed to a diabetic environment.

Need for better blood pressure measurement in developing countries to improve prevention of cardiovascular disease.

Hypertension is now the foremost cause of disability and is responsible for the highest percentage of attributable death among risk factors. These global changes are mainly due to the increase in the prevalence of hypertension in most low- and middle-income countries (LMICs) as a consequence of relevant socioeconomic changes occurring during the last decades. Implementation of global prevention efforts urgently needs to be accelerated because of the increasing incidence of haemorrhagic stroke, renal failure, and hypertensive heart disease in developing countries. Blood pressure (BP) measurement has different implications in epidemiological studies performed in low-resource settings. First, the frequency of blood pressure measurement is a simple but reliable indicator of access to healthcare in epidemiological studies, which may disclose the favourable effects of urbanization; the opportunity to have BP measured increases hypertension awareness, facilitates drug treatment, and leads to better achievement of BP control. Second, BP measurement is a key element in cardiovascular risk stratification, focusing solely on the preferred strategy in low-resource settings where costs of biochemical tests might be less sustainable. Third, the issue of obtaining reliable estimation of BP values is crucial to achieve sound data on the burden of hypertension in LMICs, and some aspects of BP measurement, such as the use of reliable automated devices, the number of measurements/visits to achieve a consistent diagnosis of hypertension, and the possible confounding effect of environmental factors, must be closely considered.

Time sequence of autonomic changes induced by daily slow-breathing sessions.

OBJECTIVE: Daily sessions of slow-breathing (6 breaths/min) significantly reduced 24-h ambulatory blood pressure (ABP) in patients with mild hypertension and this effect persisted at least 6 months after the interruption of sessions. The sequence of changes induced by slow-breathing (SB) daily sessions on the modulation of ambulatory blood pressure, renal resistive index, heart rate variability (HRV), and baroreflex sensitivity (BRS) was thus investigated in a randomized, controlled clinical trial. METHODS: Thirty-seven patients (30-75 years, grade I essential hypertension), untreated with antihypertensive drugs, were randomized to daily sessions (30 min) of music-guided SB (<10 breaths/min) (intervention, n = 24) or simple relaxation (control, n = 13). Office and ambulatory blood pressure monitoring renal Doppler ultrasound, assessment of BRS (sequence method and spectral analysis), and HRV (spectral power in the high- and low-frequency bands) were performed at baseline, and after 1, 4, and 8 weeks. Mixed model analysis was conducted on derived variables given by the difference between each measurement and the baseline value within subjects. RESULTS: After 1 week, the intervention enhanced the parasympathetic modulation (high-frequency power; at least p < 0.05 vs both control and baseline) and reduced renal vascular resistance (p < 0.05 for both comparisons); after 1 month, the enhancement of BRS (p < 0.05 for both comparisons at both methods) paralleled a significant reduction in 24 h ABP (p < 0.05 for all comparisons). INTERPRETATION: Repeated daily session of music-guided SB increased parasympathetic modulation and decreased renal resistive index early in the study. These changes were being followed by a positive modulation of BRS and blood pressure reduction.

Adiponectin as a tissue regenerating hormone: more than a metabolic function.

The great interest that scientists have for adiponectin is primarily due to its central metabolic role. Indeed, the major function of this adipokine is the control of glucose homeostasis that it exerts regulating liver and muscle metabolism. Adiponectin has insulin-sensitizing action and leads to down-regulation of hepatic gluconeogenesis and an increase of fatty acid oxidation. In addition, adiponectin is reported to play an important role in the inhibition of inflammation. The hormone is secreted in full-length form, which can either assemble into complexes or be converted into globular form by proteolytic cleavage. Over the past few years, emerging publications reveal a more varied and pleiotropic action of this hormone. Many studies emphasize a key role of adiponectin during tissue regeneration and show that adiponectin deficiency greatly inhibits the mechanisms underlying tissue renewal. This review deals with the role of adiponectin in tissue regeneration, mainly referring to skeletal muscle regeneration, a process in which adiponectin is deeply involved. In this tissue, globular adiponectin increases proliferation, migration and myogenic properties of both resident stem cells (namely satellite cells) and non-resident muscle precursors (namely mesoangioblasts). Furthermore, skeletal muscle could be a site for the local production of the globular form that occurs in an inflamed environment. Overall, these recent findings contribute to highlight an intriguing function of adiponectin in addition to its well-recognized metabolic action.

Changes in 24 h ambulatory blood pressure and effects of angiotensin II receptor blockade during acute and prolonged high-altitude exposure: a randomized clinical trial.

AIM: Many hypertensive subjects travel to high altitudes, but little is known on ambulatory blood pressure (ABP) changes and antihypertensive drugs' efficacy under acute and prolonged exposure to hypobaric hypoxia. In particular, the efficacy of angiotensin receptor blockers in this condition is unknown. This may be clinically relevant considering that renin-angiotensin system activity changes at altitude. The HIGHCARE-HIMALAYA study assessed changes in 24 h ABP under acute and prolonged exposure to increasing altitude and blood pressure-lowering efficacy and safety of an angiotensin receptor blockade in this setting. METHODS AND RESULTS: Forty-seven healthy, normotensive lowlanders were randomized to telmisartan 80 mg or placebo in a double-blind, parallel group trial. Conventional and Ambulatory BPs were measured at baseline and on treatment: after 8 weeks at sea level, and under acute exposure to 3400 and 5400 m altitude, the latter upon arrival and after 12 days (Mt. Everest base camp). Blood samples were collected for plasma catecholamines, renin, angiotensin, and aldosterone. In both groups, exposure to increasing altitude was associated with: (i) significant progressive increases in conventional and 24 h blood pressure, persisting throughout the exposure to 5400 m; (ii) increased plasma noradrenaline and suppressed renin-angiotensin-aldosterone system. Telmisartan lowered 24 h ABP at the sea level and at 3400 m (between-group difference 4.0 mmHg, 95% CI: 2.2-9.5 mmHg), but not at 5400 m. CONCLUSION: Ambulatory blood pressure increases progressively with increasing altitude, remaining elevated after 3 weeks. An angiotensin receptor blockade maintains blood pressure-lowering efficacy at 3400 m but not at 5400 m.

Environmental temperature and thermal indices: what is the most effective predictor of heat-related mortality in different geographical contexts?

The aim of this study is to identify the most effective thermal predictor of heat-related very-elderly mortality in two cities located in different geographical contexts of central Italy. We tested the hypothesis that use of the state-of-the-art rational thermal indices, the Universal Thermal Climate Index (UTCI), might provide an improvement in predicting heat-related mortality with respect to other predictors. Data regarding very elderly people (≥ 75 years) who died in inland and coastal cities from 2006 to 2008 (May-October) and meteorological and air pollution were obtained from the regional mortality and environmental archives. Rational (UTCI) and direct thermal indices represented by a set of bivariate/multivariate apparent temperature indices were assessed. Correlation analyses and generalized additive models were applied. The Akaike weights were used for the best model selection. Direct multivariate indices showed the highest correlations with UTCI and were also selected as the best thermal predictors of heat-related mortality for both inland and coastal cities. Conversely, the UTCI was never identified as the best thermal predictor. The use of direct multivariate indices, which also account for the extra effect of wind speed and/or solar radiation, revealed the best fitting with all-cause, very-elderly mortality attributable to heat stress.

[Design and arrangement of the CHIP (CHinese In Prato) study]. / Disegno e modalità di realizzazione dello studio CHIP (CHinese In Prato).

Following the rapid economic development, China is experiencing a progressive increase in the incidence of cardiovascular (CV) events and in the prevalence of CV risk factors. According to recent estimations, the prevalence of diabetes sharply increased from 1% in 1980 to 11% in 2013. Migration from China to Europe is now mainly concentrated in Countries of the Southern Europe, e.g., Italy and Spain. The largest Chinese community living in Italy is now settled in Prato, being also one of the largest Chinese community in Europe. Local authorities estimate a number of Chinese citizens living in Prato of over 40,000 individuals, including illegal immigrants. The availability of reliable data on the health needs of Chinese population is thus a recognised priority for the local health system. The creation of a participatory research where Chinese population directly participates in the formation of a group of citizens involved in designing and conducting the survey allows to overcome difficulties due to the lack of official demographic files. Secondly, and most important, this approach makes it possible to effectively pass a prevention message to an elusive population. The purpose of the CHIP (CHinese In Prato) survey is to investigate the prevalence of diabetes and cardiovascular risk factors among Chinese immigrants. Recruitment procedure was started on 8th July 2014.

Physical Activity and Oxidative Stress in Aging.

Biological aging, characterized by changes in metabolism and physicochemical properties of cells, has an impact on public health. Environment and lifestyle, including factors like diet and physical activity, seem to play a key role in healthy aging. Several studies have shown that regular physical activity can enhance antioxidant defense mechanisms, including the activity of enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. However, intense or prolonged exercise can also lead to an increase in reactive oxygen species (ROS) production temporarily, resulting in oxidative stress. This phenomenon is referred to as "exercise-induced oxidative stress". The relationship between physical activity and oxidative stress in aging is complex and depends on various factors such as the type, intensity, duration, and frequency of exercise, as well as individual differences in antioxidant capacity and adaptation to exercise. In this review, we analyzed what is reported by several authors regarding the role of physical activity on oxidative stress in the aging process as well as the role of hormesis and physical exercise as tools for the prevention and treatment of sarcopenia, an aging-related disease. Finally, we reported what has recently been studied in relation to the effect of physical activity and sport on aging in women.

Chronic lactate exposure promotes cardiomyocyte cytoskeleton remodelling.

We investigated the effect of growing on lactate instead of glucose in human cardiomyocyte assessing their viability, cell cycle activity, oxidative stress and metabolism by a proteomic and metabolomic approach. In previous studies performed on elite players, we found that adaptation to exercise is characterized by a chronic high plasma level of lactate. Lactate is considered not only an energy source but also a signalling molecule and is referred as "lactormone"; heart is one of the major recipients of exogenous lactate. With this in mind, we used a cardiac cell line AC16 to characterize the lactate metabolic profile and investigate the metabolic flexibility of the heart. Interestingly, our data indicated that cardiomyocytes grown on lactate (72 h) show change in several proteins and metabolites linked to cell hypertrophy and cytoskeleton remodelling. The obtained results could help to understand the effect of this metabolite on heart of high-performance athletes.

Cardiovascular risk and access to primary care: Comparisons among Chinese documented and undocumented immigrants.

AIMS: The aim of this study was to examine main risk factors of undocumented Chinese migrants living in Italy when compared with Chinese migrants registered with National Health Service (NHS). METHODS: A cohort of 3435 Chinese first-generation immigrants living in Prato underwent blood pressure (BP) measurement and blood tests. Hypertension was diagnosed for BP ≥ 140/90 mmHg at 2 visits, and/or antihypertensive drug use; type 2 diabetes (T2DM) for fasting glucose ≥ 126 mg/dL at 2 visits, and/or use of hypoglycemic drugs; hypercholesterolemia (HC) for cholesterol ≥ 240 mg/dL and/or statins use. Subjects diagnosed with hypertension, T2DM, or HC unaware of their condition were considered newly diagnosed. Comparisons were performed using multivariable adjusted logistic regression analysis. RESULTS: A large proportion of Chinese migrants were undocumented (1766, 51 %); newly diagnoses of risk factors were performed especially among undocumented migrants; registration with NHS was associated with higher level of awareness for hypertension and T2DM and with 6 times higher rate of treatment for T2DM. Only a small minority of subjects with high cholesterol were treated with statins. CONCLUSIONS: Undocumented immigrants had high prevalence of risk factors with lower levels of awareness than migrants registered with the NHS. Health policies targeting this hard-to-reach population needs to be improved.

Subclinical hypothyroidism predicts outcome in heart failure: insights from the T.O.S.CA. registry.

Subclinical hypothyroidism (SH), defined as increased serum thyroid-stimulating hormone (TSH) with normal free T4 (fT4) levels, is frequently observed in the general population. Prevalence ranges from 0.6% to 1.8% in the adult population, depending on age, sex, and iodine intake. Several studies reported a worse prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and SH, but they considered heterogeneous populations suffering mainly from severe SH. Aim of this study was to evaluate if SH was independently associated with the occurrence of cardiovascular death considering 30 months of follow-up. 277 HFrEF patients enrolled in the prospective, multicenter, observational T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, were included in this analysis. Patients were divided into two groups according to the presence of SH (serum TSH levels > 4.5 mIU/L with normal fT4 levels). Data regarding clinical status, echocardiography, and survival were analyzed. Twenty-three patients displayed SH (87% mild vs 13% severe), while 254 were euthyroid. No differences were found in terms of age, sex, HF etiology, and left ventricular ejection fraction. When compared with the euthyroid group, SH patients showed higher TSH levels (7.7 ± 4.1 vs 1.6 ± 0.9, p < 0.001), as expected, with comparable levels of fT4 (1.3 ± 0.3 vs 1.3 ± 0.3, p = NS). When corrected for established predictors of poor outcome in HF, the presence of SH resulted to be an independent predictor of cardiovascular mortality (HR: 2.96; 5-95% CI:1.13-7.74; p = 0.03). Since thyroid tests are widely available and inexpensive, they should be performed in HF patients to detect subclinical disorders, evaluate replacement therapy, and improve prognosis.

Effects of angiotensin II type 1 receptor antagonist and temperature on prolonged cardioplegic arrest in neonatal rat myocytes.

Cardioplegic arrest is a model of ischemia/reperfusion injury and results in the death of irreplaceable cardiac myocytes by a programmed cell death or apoptosis. Signal transducers and activators of transcription (STAT) signaling pathways play an important role in the modulation of apoptosis after ischemia and reperfusion. Angiotensin II type 1 (AT1) receptor antagonist added to cardioplegia could represent an additional modality for enhancing myocardial protection during cardioplegic arrest. To test that hypothesis, we studied the effect of AT1 receptor antagonism and cardioplegia temperature perfusion on STATs modulation during cardioplegic arrest in neonatal rat hearts. Isolated, nonworking hearts (n = 4 per group) from neonatal rats were perfused aerobically in the Langendorff mode according to the following scheme: Dulbecco's Modified Eagle's Medium solution (Group 1); cold (4°C) modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 2); cold (4°C) MSTH2 cardioplegic solution plus AT1 antagonist (Valsartan) (Group 3); and warm (34°C) MSTH2 cardioplegic solution (Group 4). Thus, myocytes were isolated by enzymatic digestion, and STAT1, STAT2, STAT3, and STAT5 were investigated in Western blot studies. Times to arrest after cardioplegia were 6-10 s for all groups with the exception of Group 1 (spontaneous arrest after 12-16 s). Total cardioplegia delivery volume was about 300 mL in 15 min. Perfusion with cold MSTH2 supplemented with AT1 receptor antagonist (Group 3) induced a significant reduction in STAT1, STAT2, and STAT5 tyrosine phosphorylation versus other groups (P < 0.05). The decreased activation of STAT1, STAT2, and STAT5 observed in Group 3 was accompanied by reduction of interleukin-1ß (P < 0.05). On the other hand, STAT3 activation was significantly reduced in Groups 1 and 4 (P < 0.05). Only perfusion with AT1 receptor antagonist supplemented with cold MSTH2 significantly decreases the inflammatory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by activation of STAT3. Therefore, AT1 receptor antagonist could play a pivotal role in cytoprotective effect and cardiac recovery in neonates and infants.

Interaction between Geographical Areas and Family Environment of Dietary Habits, Physical Activity, Nutritional Knowledge and Obesity of Adolescents.

There are marked differences in the regional distribution of childhood obesity in Italy. This study sought to investigate the interaction between geographical areas and family environment of dietary habits, physical activity, nutritional knowledge and obesity of adolescents. A cross-sectional study was conducted on 426 school-aged children and 298 parents residing in Central Italy (Florence, Tuscany) and Southern Italy (Corigliano, Calabria), in 2021. Survey questionnaire investigated anthropometry, eating behavior, nutritional knowledge and physical activity. BMI was determined and compared with reference percentile charts for adolescents. Multivariate regression analyses showed that: (1) an adolescent's BMI was directly influenced by their parents' BMI independently of parental nutritional knowledge and dietary or physical activity habits; (2) parents transmitted eating or physical activity habits to their children; (3) the geographic region of residence is not in itself an independent determinant of children's BMI. The clear message is that prevention of childhood obesity should consider family-based approaches. Parental obesity can be the point of convergence of the complex interactions between a parent's and child's habits and should be one of the most important factors to look for.

Chronic Training Induces Metabolic and Proteomic Response in Male and Female Basketball Players: Salivary Modifications during In-Season Training Programs.

The aim of this study was to characterize the salivary proteome and metabolome of highly trained female and male young basketball players, highlighting common and different traits. A total of 20 male and female basketball players (10 female and 10 male) and 20 sedentary control subjects (10 female and 10 male) were included in the study. The athletes exercised at least five times per week for 2 h per day. Saliva samples were collected mid-season, between 9:00 and 11:00 a.m. and away from sport competition. The proteome and metabolome were analyzed by using 2DE and GC-MS techniques, respectively. A computerized 2DE gel image analysis revealed 43 spots that varied in intensity among groups. Between these spots, 10 (23.2%) were differentially expressed among male athletes and controls, 22 (51.2%) between female basketball players and controls, 11 spots (25.6%) between male and female athletes, and 13 spots (30.2%) between male and female controls. Among the proteins identified were Immunoglobulin, Alpha-Amylase, and Dermcidin, which are inflammation-related proteins. In addition, several amino acids, such as glutamic acid, lysine, ornithine, glycine, tyrosine, threonine, and valine, were increased in trained athletes. In this study, we highlight that saliva is a useful biofluid to assess athlete performance and confirm that the adaptation of men and women to exercise has some common features, but also some different sex-specific behaviors, including differential amino acid utilization and expression of inflammation-related proteins, which need to be further investigated. Moreover, in the future, it will be interesting to examine the influence of sport-type on these differences.

Blood pressure variability: methodological aspects, clinical relevance and practical indications for management - a European Society of Hypertension position paper ∗.

Blood pressure is not a static parameter, but rather undergoes continuous fluctuations over time, as a result of the interaction between environmental and behavioural factors on one side and intrinsic cardiovascular regulatory mechanisms on the other side. Increased blood pressure variability (BPV) may indicate an impaired cardiovascular regulation and may represent a cardiovascular risk factor itself, having been associated with increased all-cause and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease, and dementia incidence. Nonetheless, BPV was considered only a research issue in previous hypertension management guidelines, because the available evidence on its clinical relevance presents several gaps and is based on heterogeneous studies with limited standardization of methods for BPV assessment. The aim of this position paper, with contributions from members of the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability and from a number of international experts, is to summarize the available evidence in the field of BPV assessment methodology and clinical applications and to provide practical indications on how to measure and interpret BPV in research and clinical settings based on currently available data. Pending issues and clinical and methodological recommendations supported by available evidence are also reported. The information provided by this paper should contribute to a better standardization of future studies on BPV, but should also provide clinicians with some indications on how BPV can be managed based on currently available data.

Sudden death in young athletes: Is it preventable?

Sudden death in young athletes is a rare but always dramatic condition. Unlike all other rare diseases, the estimate of its real incidence is made complex not only because of the uncertain number of correctly identified cases (numerator) but also because of the uncertain estimation of the real number of the reference population, the athletes (denominator). New elements of complexity are also emerging with regard to prevention. The current two pillars of prevention are pre-participation screening (proactive strategy) and promoting use / access to the automated external defibrillator (reactive strategy). The standardization of procedures implemented over the past two decades for pre-participation screening can now allow us to assess the impact of this approach. The result is complex to evaluate. While screening may allow the identification of conditions potentially associated with SDA, and therefore the adoption of specific treatments, in about 0.4% of screened subjects, a single study investigated the yield in terms of mortality showing a positive predictive value of 4.7% with 25% sensitivity. Conversely, the reactive strategy appears considerably effective, due to the widespread use of the automated external defibrillators in sports facilities, calling for a homogeneous implementation worldwide. On a broader perspective, the vast attention devoted to SDA prevention in the world of sports represents a major driver for transfer of a reactive prevention strategy to the general population.

Differential Influence of Physical Activity on Cardiopulmonary Performance and Stroke Volume Assessed at Cardiopulmonary Exercise Test in Pectus Excavatum: A Pilot Study.

BACKGROUND: Exercise training increases muscle VO2 by increasing O2 transport and O2 uptake while cardiac output increase might be limited by the conformation of the chest in subjects with pectus excavatum (PE). AIMS: The aim of the present study was to investigate the influence of physical activity (PA) on functional parameters of cardiopulmonary performance and stroke volume obtained at Cardiopulmonary Exercise Test (CPET) in PE. METHODS AND PROCEDURES: A cohort of adolescents (15 with PE and 15 age- and sex-matched healthy controls, HC) underwent Cardiopulmonary Exercise Test (CPET) and administration of the International Physical Activity Questionnaire - Short Form (IPAQ-SF) with estimation of weekly PA (METs h-1⋅week-1). Determinants of CPET parameters were investigated with multivariable linear regression analysis. RESULTS: As expected, when compared to HC, PE had lower VO2 max (37.2 ± 6.6 vs. 45.4 ± 6.4 mL⋅kg-1⋅min-1, p < 0.05), and VO2/HR max (O2 pulse, 12.1 ± 2.4 vs. 16.2 ± 3.6 mL⋅min-1⋅bpm-1, p < 0.05). Importantly, physical activity level was a predictor of VO2 max (adjusted for sex, body mass index, FEV1%, and presence of PE, ß = 0.085; 95% Cl 0.010 to 0.160, p = 0.029) whereas O2 pulse was independent from PA level (ß = 0.035; 95% Cl -0.004 to 0.074). CONCLUSION: Physical activity is a determinant of VO2 max (cardiopulmonary performance), whereas it appears not to affect O2 pulse (a measure of stroke volume at peak exercise) related to constrained diastolic filling in PE.