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Background. Phentermine is an internationally recognised amphetamine derivative with significant appetite-suppressing properties. The drug is indicated for the short-term management of obesity, as the long-term (LT) use of phentermine may potentially be associated with severe cardiovascular side-effects, abuse and dependence. The LT use hereinafter describes periods exceeding 12 consecutive weeks. This use may also be associated with potential drug-drug interactions (PDDIs), which may result in adverse drug reactions (ADRs). The literature reports that phentermine is often prescribed LT and for several other off-label indications, increasing the risk for individuals to experience adverse drug events (ADEs) and drug-drug interactions (DDIs). There are, to our knowledge, no South African (SA) studies investigating the prevalence of co-prescribing LT phentermine with drugs that may potentially cause DDIs. Objective. To determine the prevalence of mild, moderate and severe DDIs with phentermine use when the duration of therapy in private healthcare exceeded 12 consecutive weeks. Methods. A cross-sectional drug utilisation review (DUR) was done by using data obtained from a SA pharmacy benefit management (PBM) company’s database. Retrospective data of medicine claims for phentermine, from 1 January 2015 to 31 December 2019, were extracted for analysis. The number of days phentermine was supplied was used to identify the study population, in other words, those patients who received the drug LT. A drug interaction checker (Drugs.com) was used to identify potential mild, moderate and severe DDIs when using phentermine and co-prescribed drugs concurrently. Results. A total of 889 patients received phentermine LT. The top 20 drugs identified as being frequently co-prescribed in this study population demonstrated no mild PDDI, 15 (75%) moderate PDDIs and 5 (25%) severe PDDIs. The most common co-prescribed drug in the moderate group was dextromethorphan (n=282, 31.72%) and the least co-prescribed was formoterol (n=52, 5.85%). Among the drug group ‘severe PDDIs’, tramadol (n=416, 46.79%) was most frequently prescribed, whereas phenylpropanolamine (n=69, 7.76%) was the least prescribed to patients in this group. Conclusion. There are patients who receive LT phentermine therapy despite the potential severe consequences that may result. These patients may receive concomitant therapy with phentermine and other pharmaceutical constituents, which may potentially cause DDIs, more specifically, moderate and severe DDIs. As such, these patients are not only confronted with the consequences of DDIs but are also at risk to experience ADRs as the residual effect of PDDIs.

Objective REFLECT is the first randomised, double-masked, placebo-controlled multicentre phase 3 clinical trial that evaluated the efficacy and safety of bilateral intravitreal (IVT) injection of lenadogene nolparvovec in subjects with Leber hereditary optic neuropathy carrying the m.11778G>A mutation.Methods and analysis A total of 98 subjects were enrolled with vision loss of ≤12 months. The subjects were randomised to one of two treatment arms with all subjects receiving an intravitreal (IVT) injection of lenadogene nolparvovec in their first affected eye and the second-affected eye randomised to receive IVT of either lenadogene nolparvovec or placebo.Results The majority of subjects were male with a mean duration of vision loss of 8.3 months. All but one subject experienced bilateral loss of vision at the time of injection. The mean best-corrected visual acuity of first-affected eyes was worse compared with second/not-yet-affected eyes. Analysis of retinal anatomical parameters showed increased thinning in the first-affected eyes when compared with the second/not-yet-affected eyes with both treatment arms showing significant changes compared with unaffected individuals.Conclusion The REFLECT trial is the third and the largest phase 3 clinical study evaluating lenadogene nolparvovec in m.11778G>A Leber hereditary optic neuropathy (LHON) subjects. The observed demographics in REFLECT are consistent with previous reports in LHON subjects in the acute and dynamic phases of LHON disease. Combined with the visual function and anatomical parameters obtained in the previous RESCUE and REVERSE trials, REFLECT has provided a uniformly collected data set that should help direct future LHON clinical trials.

Nearly 35 years after its initial publication in 1989, the Italian Society of Sports Cardiology and the Italian Federation of Sports Medicine (FMSI), in collaboration with other leading Italian Cardiological Scientific Associations (ANCE - National Association of Outpatient Cardiology, ANMCO - National Association of Inpatient Cardiology, SIC - Italian Society of Cardiology), proudly present the 2023 version of the Cardiological Guidelines for Competitive Sports Eligibility. This publication is an update of the previous guidelines, offering a comprehensive and detailed guide for the participation of athletes with heart disease in sports. This edition incorporates the latest advances in cardiology and sports medicine, providing current information and recommendations. It addresses various topics, including the details of the pre-participation screening in Italy and recommendations for sports eligibility and disqualification in competitive athletes with various heart conditions. This revised version of the Cardiological Guidelines for Competitive Sports Eligibility, recorded in the Italian Guidelines Registry of the Italian Minister of Health, stands as a crucial resource for sports medicine professionals, cardiologists, and healthcare providers, marked by its completeness, reliability, and scientific thoroughness. It is an indispensable tool for those involved in the care, management and eligibility process of competitive athletes with heart conditions.

Objective: To investigate the reproducibility of ambulatory BP sub-periods and nocturnal dipping phenotypes assessed twice 3 months apart in young-to-middle-age untreated individuals screened for stage 1 hypertension., Design and Methods: We investigated 1096, 18-to-45-year old participants from the HARVEST. Their office BP was 145.8 ± 10.4/93.7 ± 5.7 mmHg. Office BP and 24 h BP were measured at baseline and after 3 months. Office, 24-h, daytime and night-time hypertensions, and nocturnal dipping patterns were defined according to the 2023 ESH guidelines. Between-recording agreement was evaluated with kappa statistics., Results: Reproducibility evaluated with weighted kappa was moderate for both 24 h hypertension ( K  = 0.48) and daytime hypertension ( K  = 0.50) and was only fair for night-time hypertension ( K  = 0.36). Between-measurement agreement was even worse for isolated night-time hypertension ( K  = 0.24), and was poor for office hypertension ( K  = 0.14). The better reproducibility of daytime than night-time period was confirmed by the analysis of BP as continuous variable (all between-period differences, P  < 0.001). Nondipping was present in 31.8%, and showed a fair agreement ( K  = 0.28,). Poorer agreement was shown by extreme dipping ( K  = 0.18) and reverse dipping ( K  = 0.07)., Conclusions: These data show that within the ambulatory sub-periods, daytime hypertension has a better reproducibility than night-time hypertension. This suggests that the better association with adverse outcomes shown by sleep BP compared to wake BP in observational studies is not due to a better reproducibility of the former. The between-measurement agreement is even worse for isolated nocturnal hypertension and dipping patterns, especially for extreme and reverse dipping. Thus, these BP phenotypes should be confirmed with repeat ambulatory BP monitoring., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The Coronavirus-19 disease (COVID-19) related pandemic have deeply impacted human health, economy, psychology and sociality. Possible serious cardiac involvement in the infection has been described, raising doubts about complete healing after the disease in many clinical settings. Moreover, there is the suspicion that the vaccines, especially those based on mRNA technology, can induce myopericarditis. Myocarditis or pericarditis related scars can represent the substrate for life-threatening arrhythmias, triggered by physical activity. A crucial point is how to evaluate an athlete after a COVID-19 infection ensuring a safe return to play without increasing the number of unnecessary disqualifications from sports competitions. The lack of conclusive scientific data significantly increases the difficulty to propose recommendations and guidelines on this topic. At the same time, the psychological and physical negative consequences of unnecessary sports restriction must be taken into account. The present document aims to provide an updated brief review of the current knowledge about the COVID-19 cardiac involvement and how to recognize it and to offer a roadmap for the management of the athletes after a COVID-19 infections, including subsequent impact on exercise recommendations. Our document exclusively refers to cardiovascular implications of the disease, but pulmonary consequences are also considered.

Aims: To investigate the prevalence of metabolically healthy overweight/obesity and to study its longitudinal association with major adverse cardiovascular and renal events (MARCE)., Methods and Results: The study was conducted in 1210 young-to-middle-age subjects grouped according to their BMI and metabolic status. The risk of MARCE was evaluated during 17.4 years of follow-up. Forty-eight-percent of the participants had normal weight, 41.9% had overweight, and 9.3% had obesity. Metabolically healthy status was found in 31.1% of subjects with normal weight and in 20.0% of those with overweight/obesity. During the follow-up, there were 108 MARCE. In multivariate Cox analysis adjusted for confounders and risk factors, no association was found between MARCE and overweight/obesity (p = 0.49). In contrast, metabolic status considered as a two-class variable (0 versus at least one metabolic abnormality) was a significant predictor of MARCE (HR, 2.11; 95%CI, 1.21-3.70, p = 0.009). Exclusion of atrial fibrillation from MARCE (N = 87) provided similar results (HR, 2.11; 95%CI, 1.07-4.16, p = 0.030). Inclusion of average 24 h BP in the regression model attenuated the strength of the associations. Compared to the group with healthy metabolic status, the metabolically unhealthy overweight/obesity participants had an increased risk of MARCE with an adjusted HR of 2.33 (95%CI, 1.05-5.19, p = 0.038). Among the metabolically healthy individuals, the CV risk did not differ according to BMI group (p = 0.53)., Conclusion: The present data show that the risk of MARCE is not increased in young metabolically healthy overweight/obesity suggesting that the clinical approach to people with high BMI should focus on parameters of metabolic health rather than on BMI., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Whether healthy metabolic status is stable or only temporary is still controversial. The aim of the present study was to determine the frequency of the transition from metabolically healthy to metabolically unhealthy status, or vice versa, over the long term., Methods: We examined 970 individuals of 18 to 45 years of age. The participants' mean age was 33.1 ± 8.6 years and mean BP was 145.5 ± 10.6/93.5 ± 5.7 mmHg. Participants were classified into four groups according to whether they had normal weight or overweight/obesity (OwOb) and were metabolically healthy or unhealthy. After 7.5 years, 24.3% of men and 41.9% of women in the metabolically healthy normal-weight group remained metabolically healthy ( p < 0.0001). Among the metabolically healthy OwOb participants, 31.9% remained metabolically healthy, with a similar frequency in men and women. However, more OwOb women (19.1%) than men (5.7%) achieved normal weight ( p < 0.0001). Among the metabolically unhealthy OwOb subjects, 81.8% of men and 69.3% of women remained metabolically unhealthy, 7.4% of men and 12.0% of women transitioned to OwOb healthy status, and 10.7% of men and 18.7% of women achieved normal weight (men versus women, p < 0.0001). Predictors of transition to unhealthy status were high BP, high BMI, and smoking. Male sex was a borderline predictor of progression to unhealthy status in OwOb participants ( p = 0.073)., Conclusion: These data show that metabolically healthy status is a highly unstable condition in both normal-weight and OwOb individuals. The impairment of metabolic status was more frequent in men than in women. Lifestyle counseling produced beneficial effects in almost one-third of metabolically unhealthy OwOb women and in less than one-fifth of men.

Purpose: Exercise prescription based on fixed heart rate (HR) values is not associated with a specific work rate (WR) during prolonged exercise. This phenomenon has never been evaluated in cardiac patients and might be associated with a slow component of HR kinetics and β-adrenergic activity. The aims were to quantify, in cardiac patients, the WR decrease at a fixed HR and to test if it would be attenuated by β-blockers., Methods: Seventeen patients with coronary artery disease in stable conditions (69 ± 9 yr) were divided into two groups according to the presence (BB) or absence (no-BB) of a therapy with β-blockers, and performed on a cycle ergometer: an incremental exercise (INCR) and a 15-min "HR CLAMPED " exercise, in which WR was continuously adjusted to maintain a constant HR, corresponding to the gas exchange threshold +15%. HR was determined by the ECG signal, and pulmonary gas exchange was assessed breath-by-breath., Results: During INCR, HR peak was lower in BB versus no-BB ( P < 0.05), whereas no differences were observed for other variables. During HR CLAMPED , the decrease in WR needed to maintain HR constant was less pronounced in BB versus no-BB (-16% ± 10% vs -27 ± 10, P = 0.04) and was accompanied by a decreased V̇O 2 only in no-BB (-13% ± 6%, P < 0.001)., Conclusions: The decrease in WR during a 15-min exercise at a fixed HR (slightly higher than that at gas exchange threshold) was attenuated in BB, suggesting a potential role by β-adrenergic stimulation. The phenomenon may represent, also in this population, a sign of impaired exercise tolerance and interferes with aerobic exercise prescription., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Purpose: To investigate the prevalence of orthostatic hypertension and the association of the blood pressure (BP) level, supine BP decline, and white-coat effect with the orthostatic pressor response., Methods: We studied 1275 young-to-middle-age individuals with stage-1 hypertension. Orthostatic response was assessed three times over a 3 month period. The white-coat effect was assessed at baseline and after 3 months, and was calculated as the difference between office and average 24 h BP. In 660 participants, urinary epinephrine and norepinephrine were also measured., Results: An orthostatic systolic BP increase ≥ 20 mmHg was observed in 0.6-1.2% of the subjects during the three visits. Using the 20 mmHg cut-off, the prevalence of orthostatic hypertension was 0.6%. An orthostatic BP increase of ≥ 5 mmHg was found in 14.4% of participants. At baseline, the orthostatic response to standing showed an independent negative association with the supine BP level (p < 0.001), the supine BP change from the first to third measurement (p < 0.001), and the white-coat effect (p < 0.001). Similar results were obtained in the 1080 participants assessed at the third visit. Urinary epinephrine showed higher values in the top BP response decile (systolic BP increase ≥ 6 mmHg, p = 0.002 versus rest of the group)., Conclusion: An orthostatic systolic BP reaction ≥ 20 mmHg is rare in young adults. However, even lower BP increases may be clinically relevant. The BP level, the supine BP decline over repeated measurement, and the white-coat effect can influence the estimate of the BP response to standing and should be considered in clinical and pathogenetic studies., (© 2023. The Author(s).)

Three-dimensional electroanatomical mapping (EAM) has the potential to identify the pathological substrate underlying ventricular arrhythmias (VAs) in different clinical settings by detecting myocardial areas with abnormally low voltages, which reflect the presence of different cardiomyopathic substrates. In athletes, the added value of EAM may be to enhance the efficacy of third-level diagnostic tests and cardiac magnetic resonance (CMR) in detecting concealed arrhythmogenic cardiomyopathies. Additional benefits of EAM in the athlete include the potential impact on disease risk stratification and the consequent implications for eligibility to competitive sports. This opinion paper of the Italian Society of Sports Cardiology aims to guide general sports medicine physicians and cardiologists on the clinical decision when to eventually perform an EAM study in the athlete, highlighting strengths and weaknesses for each cardiovascular disease at risk of sudden cardiac death during sport. The importance of early (preclinical) diagnosis to prevent the negative effects of exercise on phenotypic expression, disease progression, and worsening of the arrhythmogenic substrate is also addressed., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: To evaluate the association of alcohol and smoking combined with cardiovascular and renal events and investigate whether moderate and heavy alcohol consumption have a different impact on this association., Methods: The study was conducted in 1208 young-to-middle-age stage 1 hypertensive patients. Subjects were classified into three categories of cigarette smoking and alcohol use, and the risk of adverse outcomes was assessed over a 17.4-year follow-up., Results: In multivariable Cox models, smoking showed a different prognostic impact on alcohol drinkers and abstainers. In the former, an increase in the risk of cardiovascular and renal events was observed compared to nonsmokers (hazard ratio, 2.6, 95% CI, 1.5-4.3, p < 0.001), whereas in the latter, the risk did not achieve the level of statistical significance ( p = 0.27) with a significant interaction between smoking and alcohol use ( p < 0.001). Among the heavy smokers who also drank alcoholic beverages, the hazard ratio from the fully adjusted model was 4.3 (95% CI, 2.3-8.0, p < 0.0001). In the subjects with moderate alcohol consumption, the risk of smoking and alcohol combined was similar to that found in the whole population (hazard ratio, 2.7; 95% CI, 1.5-3.9, p < 0.001). Among the subjects with heavy alcohol consumption, the hazard ratio was 3.4 (95% CI, 1.3-8.6, p = 0.011)., Conclusion: These findings indicate that the detrimental cardiovascular effects of smoking can be worsened by concomitant alcohol use. This synergistic effect occurs not only for heavy alcohol consumption but also for moderate use. Smokers should be aware of the increased risk associated with concomitant alcohol consumption.

(1) Aim. The aim of the study was to investigate the reproducibility of white-coat hypertension (WCH) and its predictive capacity for hypertension needing antihypertensive treatment (HT) in young to middle-age subjects. (2) Methods. We investigated 1096 subjects from the HARVEST. Office and 24 h blood pressures (BP) were measured at baseline and after 3 months. The reproducibility of WCH was evaluated with kappa statistics. The predictive capacity of WCH was tested in multivariate Cox models (N = 1050). (3) Results. Baseline WCH was confirmed at 3-month assessment in 33.3% of participants. Reproducibility was fair (0.27, 95%CI 0.20-0.37) for WCH, poor (0.14, 95%CI 0.09-0.19) for office hypertension, and moderate (0.47, 95%CI 0.41-0.53) for ambulatory hypertension. WCH assessed either at baseline or after 3 months (unstable WCH) was not a significant predictor of HT during 17.4 years of follow-up. However, participants who had WCH both at baseline and after 3 months (stable WCH) had an increased risk of HT compared to the normotensives (Hazard ratio, 1.50, 95%CI 1.06-2.1). (4) Conclusions. These results show that WCH has limited reproducibility. WCH diagnosed with two BP assessments but not with one showed an increased risk of future HT. Our data indicate that WCH should be identified with two sets of office and ambulatory BP measurements.

Mitral valve prolapse (MVP) is the most frequent valvulopathy in the general population, with usually a favourable prognosis. Although it can be associated with some complications, ventricular arrhythmias (VA) and sudden cardiac death (SCD) are the most worrying. The estimated risk of SCD in MVP is between 0.2% to 1.9% per year, including MVP patients with and without severe mitral regurgitation (MR). The association between SCD and MVP is expressed by a phenotype called "malignant MVP" characterized by transthoracic echocardiography (TTE) findings such as bileaflet myxomatous prolapse and mitral annulus disjunction (MAD), ECG findings such as repolarization abnormalities, complex ventricular arrhythmias (c-VAs) and LV fibrosis of papillary muscles (PMs) and inferobasal wall visualized by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Therefore, attention is raised for patients with "arrhythmic MVP" characterized from an ECG point of view by frequent premature ventricular contractions (PVCs) arising from one or both PMs as well as by T-wave inversion in the inferolateral leads. In athletes, SCD is the most frequent medical cause of death and in young subjects (< 35 years) usually is due to electrical mechanism affecting who has a silent cardiovascular disease and are not considered per se a cause of increased mortality. In MVP, SCD was reported to happen during sports activity or immediately after and valve prolapse was the only pathological aspect detected. The aim of the present paper is to explore the association between SCD and MVP in athletes, focusing attention on ECG, TTE in particular, and CMR findings that could help to identify subjects at high risk for complex arrhythmias and eventually SCD. In addition, it is also examined if sports activity might predispose patients with MVP to develop major arrhythmias., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The pathophysiologic mechanisms of masked hypertension are still debated. The aim of this study was to investigate whether the blood pressure response to standing is a determinant of masked hypertension in young individuals., Design and Methods: We studied 1078 individuals (mean age 33.2 ± 8.5 years) with stage-1 untreated hypertension at baseline. Orthostatic response was defined as the difference between six SBP measurements in the orthostatic and supine postures. People with a response more than 6.5 mmHg (upper decile) were defined as hyperreactors. After 3 months of follow-up, 24-h ambulatory BP was measured and the participants were classified as normotensives (N = 120), white-coat hypertensive individuals (N = 168), masked hypertensive individuals (N = 166) and sustained hypertensive individuals (N = 624). In 591 participants, 24-h urinary epinephrine was also measured., Results: Orthostatic response was an independent predictor of masked hypertension after 3 months (P = 0.001). In the whole group, the odds ratio for the Hyperreactors was 2.5 [95% confidence interval (95% CI) 1.5-4.0, P < 0.001]. In the participants stratified by orthostatic response and urinary epinephrine, the odds ratio for masked hypertension was 4.2 (95% CI, 1.8-9.9, P = 0.001) in the hyperreactors with epinephrine above the median and was 2.6 (95% CI, 0.9-7.3, P = 0.069) in those with epinephrine below the median. The association between orthostatic response and masked hypertension was confirmed in the cross-sectional analysis after 3 months (P < 0.001)., Conclusion: The present findings indicate that hyperreactivity to standing is a significant determinant of masked hypertension. The odds ratio for masked hypertension was even quadrupled in people with an orthostatic response more than 6.5 mmHg and high urinary epinephrine suggesting a role of sympathoadrenergic activity in the pathogenesis of masked hypertension., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Molecular genetic testing is an increasingly available test to support the clinical diagnosis of inherited cardiovascular diseases through identification of pathogenic gene variants and to make a preclinical genetic diagnosis among proband's family members (so-called "cascade family screening"). In athletes, the added value of molecular genetic testing is to assist in discriminating between physiological adaptive changes of the athlete's heart and inherited cardiovascular diseases, in the presence of overlapping phenotypic features such as ECG changes, imaging abnormalities or arrhythmias ("grey zone"). Additional benefits of molecular genetic testing in the athlete include the potential impact on the disease risk stratification and the implications for eligibility to competitive sports. This position statement of the Italian Society of Sports Cardiology aims to guide general sports medical physicians and sports cardiologists on clinical decision as why and when to perform a molecular genetic testing in the athlete, highlighting strengths and weaknesses for each inherited cardiovascular disease at-risk of sudden cardiac death during sport. The importance of early (preclinical) diagnosis to prevent the negative effects of exercise on phenotypic expression, disease progression and worsening of the arrhythmogenic substrate is also addressed., (Copyright © 2022. Published by Elsevier B.V.)

Aim. To assess the effect of leisure time versus vigorous long-term dynamic physical activity (PA) on carotid stiffness in normotensive versus hypertensive subjects. Methods. The study was conducted on 120 leisure-time exercisers and 120 competitive athletes. One hundred and twenty sedentary subjects served as controls. In addition, participants were classified according to whether their systolic blood pressure was ≥130 mmHg (hypertensives, n = 120) or normal (normotensives, n = 240) according to the ACC/AHA 2017 definition. Carotid artery stiffness was assessed with an echo-tracking ultrasound system, using the pressure-strain elastic modulus (EP) and one-point pulse wave velocity (PWVβ) as parameters of stiffness. Results. The effect of the two levels of PA differed in the normotensives and the hypertensives. Among the normotensives, there was an ongoing, graded reduction in EP and PWVβ from the sedentary subjects to the athletes. By contrast, among the hypertensives, the lowest levels of EP and PWVβ were found among the leisure-time PA participants. EP and PWVβ did not differ between the hypertensive sedentary subjects and the athletes. A significant interaction was found between PA and BP status on EP ( p = 0.03) and a borderline interaction on PWVβ ( p = 0.06). In multiple regression analyses, PA was a negative predictor of EP ( p = 0.001) and PWVβ ( p = 0.0001). The strength of the association was weakened after the inclusion of heart rate in the models ( p = 0.04 and 0.007, respectively). Conclusions. These data indicate that in people with hypertension, leisure-time PA has beneficial effects on carotid artery stiffness, whereas high-intensity chronic PA provides no benefit to vascular functions.

Aims: The role of increased blood pressure (BP) variability and a blunted day-night BP drop is still being debated, particularly in young hypertensive subjects. We investigated the contribution of BP variability and day-night BP changes combined to cardiovascular events in initially untreated young hypertensive individuals., Methods and Results: We selected 1794 subjects aged ≤45 years from the HARVEST and the PIUMA studies, two long-term observational studies in subjects with hypertension. The outcome was a composite pool of non-fatal myocardial infarction or stroke, heart failure needing hospitalization, death from cardiovascular causes, and myocardial or limb revascularization procedures. During an 11.3-year follow-up, 140 cardiovascular events were accrued. A multivariable Cox model which included BP variability and non-dipping was more informative (Akaike Information Criterion = 1536.9) than the model which included average of 24-h BP (Akaike Information Criterion = 1553.6). A higher hazard ratio (HR) was observed for non-dipping [HR 2.22; 95% confidence interval (CI): 1.55-3.17; P &lt; 0.0001] and for high BP variability (HR 1.84; 95% CI: 1.26-2.65; P = 0.0015) than for high average 24-h BP (HR 1.58; 95% CI: 1.07-2.33; P = 0.020). When average 24-h ambulatory BP was included in a nested model, the -2log likelihood decreased from 1524.9 to 1519.3, and there was a tendency for an interactive effect between 24-h BP and non-dipping on risk of cardiovascular events (P = 0.092)., Conclusion: In young hypertensive individuals, prognostic models including BP variability and non-dipping pattern provide better information than models with average 24-h ambulatory BP alone. More consideration should be given to BP variability and the day-night BP pattern beyond the average 24-h ambulatory BP in young hypertensive subjects., Competing Interests: Conflict of interest: none declared., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

The prognostic significance and the mechanisms of blood pressure (BP) hyperreactivity to standing remain controversial. This study aims to evaluate the association of orthostatic hyperreactivity with major adverse cardiovascular and renal events in a cohort of young hypertensive subjects. We studied 1207 untreated subjects screened for stage I hypertension with a mean age of 33.1±8.6 years. The orthostatic BP change was calculated as the difference between 6 standing and 6 supine BP readings obtained during 2 separate visits. Hyperreactivity to standing was defined as the standing-supine systolic BP difference in the top decile. The mean difference in the whole group was -2.5±7.3/4.6±5.4 mm Hg. Ambulatory hypertension evaluated with 24-hour recordings was more common in Hyperreactors than Normoreactors (90.8% versus 76.4%, P =0.001). In 630 participants in whom 24-hour urinary catecholamines were measured, epinephrine/creatinine ratio was higher in hyperreactors (118.4±185.6 versus 77.0±90.1 nmol/mol, P =0.005). During a 17.2-year follow-up, 105 major adverse cardiovascular and renal events were accrued. In a multivariate Cox model, hyperreactivity to standing was an independent predictor of major adverse cardiovascular and renal events with a hazard ratio of 1.97 (95% CI, 1.10-3.52). Hyperreactivity remained an independent predictor of adverse events even when ambulatory BP data and incident hypertension during follow-up were included in the Cox model (hazard ratio, 1.94 [95% CI, 1.10-3.44]). Our data indicate that in young-to-middle-age hypertensive subjects an exaggerated systolic BP response to standing is associated with sympatho-adrenergic hyperreactivity and is an independent predictor of major adverse cardiovascular and renal events. Orthostatic BP assessment gives the advantage of simple acquisition and provides prognostic information on top of ambulatory BP.

Since 1989, SIC Sport and a FMSI, in partnership with leading Italian Cardiological Scientific Associations (ANCE, ANMCO and SIC) have produced Cardiological Guidelines for Completive Sports Eligibility for athletes with heart disease (COCIS -- 1989, 1995, 2003, 2009 and 2017). The English version of the Italian Cardiological Guidelines for Competitive Sports Eligibility for athletes with heart disease was published in 2013 in this Journal. This publication is an update with respect to the document previously published in English in 2013. It includes the principal innovations that have emerged over recent years, and is divided into five main chapters: arrhythmias, ion channel disorders, congenital heart diseases, acquired valve diseases, cardiomyopathies, myocarditis and pericarditis and ischemic heart disease. Wherever no new data have been introduced with respect to the 2013 publication, please refer to the previous version. This document is intended to complement recent European and American guidelines but an important difference should be noted. The European and American guidelines indicate good practice for people engaging in physical activity at various levels, not only at the competitive level. In contrast, the COCIS guidelines refer specifically to competitive athletes in various sports including those with high cardiovascular stress. This explains why Italian guidelines are more restrictive than European and USA ones. COCIS guidelines address 'sports doctors' who, in Italy, must certify fitness to participate in competitive sports. In Italy, this certificate is essential for participating in any competition., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)