Relationship between measures of adiposity, blood pressure and arterial stiffness in adolescents. The MACISTE study.

OBJECTIVE: Children and adolescents with adiposity excess are at increased risk of future cardiovascular (CV) disease. Fat accumulation promotes the development of elevated blood pressure (BP) and arterial stiffness, two main determinants of CV risk which are strongly inter-related. We aimed at investigating whether the association between overweight and arterial stiffness, taken at different arterial segments, is mediated by increased BP or is BP-independent. METHODS: Three hundred and twenty-two Italian healthy adolescents (mean age 16.9±1.4 years, 12% with overweight) attending the "G. Donatelli" High School in Terni, Italy, underwent measurement of arterial stiffness by arterial tonometry (aortic stiffness) and semiautomatical detection of pressure-volume ratio of the common carotid (carotid stiffness). The mediator effect of BP was tested for each anthropometric or biochemical measure of fat excess related to arterial stiffness. RESULTS: Both carotid and aortic stiffness showed positive correlations with body mass index, waist, hip, and neck circumferences (NC). Only carotid stiffness, but not aortic stiffness, was associated with serum markers of fat accumulation and metabolic impairment such as insulin, homeostatic model of insulin resistance (HOMA-IR), serum gamma-glutamyl transferase (sGGT) and uric acid. The association with NC was stronger for carotid than for aortic stiffness (Fisher z -to- R 2.07, P  = 0.04), and independent from BP. CONCLUSIONS: In healthy adolescents, fat accumulation is associated with arterial stiffness. The degree of this association differs by arterial segments, since carotid stiffness is more strongly associated to adipose tissue excess than aortic stiffness and shows a BP-independent association with NC whereas aortic stiffness does not.

Antihypertensive treatment changes and related clinical outcomes in older hospitalized patients.

BACKGROUND: Hypertension management in older patients represents a challenge, particularly when hospitalized. OBJECTIVE: The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients. METHODS: A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in-patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin-converting-enzyme-inhibitor (ACE-I) or an angiotensin-receptor-blocker (ARB) with a calcium-channel-blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE-I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all-cause death, cardiovascular (CV) hospitalization/death, CV death, non-CV death, evaluated according to the presence of MT at discharge. RESULTS: Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all-cause death, all-cause death/hospitalization, CV death, CV death/hospitalization and non-CV death. CONCLUSIONS: Guidelines-suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients.

Handgrip strength is associated with adverse outcomes in patients hospitalized for COVID-19-associated pneumonia.

Handgrip strength (HGS), a simple tool for the evaluation of muscular strength, is independently associated with negative prognosis in many diseases. It is unknown whether HGS is prognostically relevant in COVID-19. We evaluated the ability of HGS to predict clinical outcomes in people with COVID-19-related pneumonia. 118 patients (66% men, 63 ± 12 years), consecutively hospitalized to the "Santa Maria" Terni University Hospital for COVID-19-related pneumonia and respiratory failure, underwent HGS measurement (Jamar hand-dynamometer) at ward admission. HGS was normalized to weight2/3 (nHGS) The main end-point was the first occurrence of death and/or endotracheal intubation at 14 days. Twenty-two patients reached the main end-point. In the Kaplan-Meyer analysis, the Log rank test showed significant differences between subjects with lower than mean HGS normalized to weight2/3 (nHGS) (< 1.32 kg/Kg2/3) vs subjects with higher than mean nHGS. (p = 0.03). In a Cox-proportional hazard model, nHGS inversely predicted the main end-point (hazard ratio, HR = 1.99 each 0.5 kg/Kg2/3 decrease, p = 0.03), independently from age, sex, body mass index, ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO2/FiO2 ratio), hypertension, diabetes, estimated glomerular filtration rate and history of previous cardiovascular cardiovascular disease. These two latter also showed independent association with the main end-point (HR 1.30, p = 0.03 and 3.89, p < 0.01, respectively). In conclusion, nHGS measured at hospital admission, independently and inversely predicts the risk of poor outcomes in people with COVID-19-related pneumonia. The evaluation of HGS may be useful in early stratifying the risk of adverse prognosis in COVID-19.

Importance of central BP assessment in ISH of the young. Which devices are best suited for practical use?

Isolated systolic hypertension (ISH), defined as brachial systolic blood pressure (bSBP) ≥140 mmHg and diastolic blood pressure (DBP) <90 mmHg, is highly prevalent among young subjects and in the elderly. The prognostic significance of ISH in young individuals remains the object of large debate which might be solved, at least in part, if considering the prognostic role of central BP. For any given value of pBP, the cardiovascular (CV) risk is better defined by central BP (cBP). Young individuals with ISH have long been considered at low CV risk, given the assumption that a "spurious hypertension" phenotype characterized by elevated peripheral (brachial) BP (pBP), normal cBP, and elevated BP amplification was often found in this population. However, this remains to be proven, because many other studies found no differences in BP amplification between ISH and sisto-diastolic hypertension. Despite numerous attempts, methodologies for cBP assessment by non-invasive devices are currently not standardized. As a result, different devices could provide different cBP values despite using the same biological signals. Devices providing accurate estimates of BP amplification as a dimensionless ratio between amplitudes of central and peripheral arterial waveforms might be well suited for clinical purposes in young individuals with ISH. There is urgent need of well-designed prospective studies aiming at longitudinally evaluating the amount of CV risk associated with elevated cBP in young subjects with ISH and their related incremental prognostic value.

Vaccine-induced massive pulmonary embolism and thrombocytopenia following a single dose of Janssen Ad26.COV2.S vaccination.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side effect of adenoviral vector-based vaccines against coronavirus disease 2019 (COVID-19), and is most frequently reported after use of the Vaxzevria (AstraZeneca) vaccine. This report describes a case of severe thrombocytopenia associated with massive pulmonary embolism and portal vein thrombosis occurring 13 days after the administration of the single-dose adenoviral vector-based vaccine Ad26.COV2.S (Janssen Vaccines). Based on early clinical suspicion, the patient quickly received treatment with corticosteroids and intravenous immunoglobulin, followed by a rapid increase in platelet count that allowed timely administration of full-dose anticoagulation. Treatment with intravenous immunoglobulin, however, could mask the ability of anti-platelet factor 4-heparin antibodies to bind and activate platelets in the presence of heparin, leading to false-negative results on the immunoassay functional test. Therefore, if VITT is suspected, blood samples for diagnostic confirmation should be collected prior to any treatment to improve diagnostic performance.

Mid-term impact of mild-moderate COVID-19 on cardiorespiratory fitness in élite athletes.

BACKGROUND: Mid- and long-term sequelae of COVID-19 on cardiorespiratory fitness are unknown. Aim of the study was to assess the mid-term impact of mild-moderate COVID-19 on cardiorespiratory fitness evaluated by cardiopulmonary exercise testing (CPET) in élite athletes. METHODS: 13 elite cross-country skiers with previous mild-moderate COVID-19 symptoms underwent CPET before resuming seasonal training (COVID athletes). 13 élite detrained cross-country skiers, matched for principal confounding factors, were taken as controls (control group). Resting peripheral oxygen saturation, pulmonary function test, echocardiography, bioelectrical impedance analysis and CPET (modified XELG2, Woodway, USA) were performed in all participants. RESULTS: Median recovery time in COVID athletes was 34 days (IQR 33-38 days). COVID athletes reached earlier the onset of the aerobic threshold (4'48" vs. 6'28", R2=0.15, F=4.37, P<0.05) than controls, whereas the time to anaerobic threshold and maximal efforts did not significantly differ between groups. Oxygen consumption was lower at the aerobic threshold in COVID athletes than controls (VO2/kg 28.6 mL/min vs. 38.9 mL/min, R2=0.39, F=15.34, P<0.01), whereas no significant difference between groups was found both at the aerobic threshold and at peak exercise (all P<0.05). Findings from resting echocardiography and pulmonary function test were similar between the two groups. CONCLUSIONS: Élite cross-country athletes, previously affected by mild-moderate COVID-19, reached earlier the aerobic threshold than controls, whereas the remaining CPET parameters did not differ between groups. Such changes were not associated with any detectable difference in resting pulmonary and cardiac examination. Subjects affected by mild-moderate COVID-19 may require a longer time course of re-adaptation to aerobic exercise.

Efficacy of convalescent plasma therapy in immunocompromised patients with COVID-19: A case report.

BACKGROUND: Management of immunocompromised COVID-19 patients is the object of current debate. Accumulating evidence suggest that treatment with high-titer COVID-19 convalescent plasma (CCP) may be effective in this characteristic clinical scenario. CASE REPORT: A 52-years old immunocompromised female patient, previously treated with rituximab for low grade B-cell lymphoma, showed prolonged SARS-CoV-2 shedding and a long-term course of signs of severe COVID-19. A first cycle of treatment with remdesivir, a nucleotide analogue prodrug effective in inhibiting SARS-CoV-2 replication, did not provide fully and sustained clinical remission. A second hospitalization was deemed necessary after 10 days from the first hospital discharge due to recrudescence of symptoms of severe COVID-19 and the evidence of bilateral interstitial pneumonia at the chest-CT scan. Clinical and radiological findings completely disappeared after CCP administration. The viral culture confirmed the absence of SARS-CoV-2-related cytopathic effect. The clinical evaluation, performed two months after hospital discharge, was unremarkable. RESULTS: Findings from our case report suggest that the host T-cell specific response to SARS-CoV-2 is not sufficient to reduce viral load in the absence of neutralizing antibodies. Acquired immune antibodies and/or related components passively infused with CCP might help in boosting the plasma recipient response to the virus and promoting complete viral clearance. CONCLUSIONS: Independently from negative results in immunocompetent individuals, the potential effectiveness of CCP infusion in selected cohorts of patients with primary or secondary impaired immune response should be tested. Further research about mechanisms of host response in immunocompromised patients with SARS-CoV-2 infection is required.

Association between Ideal Cardiovascular Health and aortic stiffness in Italian adolescents. The MACISTE study.

BACKGROUND AND AIMS: Ideal Cardiovascular Health (ICH), defined as optimal levels of cardiovascular (CV) health factors and behaviors, has been reported to be very low in adults and children, with consequent several negative health outcomes and higher CV risk. The present study investigated the burden of ICH among Italian adolescents and its association with carotid-femoral pulse wave velocity (cf-PWV). METHODS AND RESULTS: 387 healthy adolescents (mean age 17.1 ± 1.4 years) attending the "G. Donatelli" High School in Terni, Italy, were evaluated. ICH was assessed through clinical evaluation, laboratory measures and interviewer-administered questionnaires. Cf-PWV was measured by arterial tonometry (SphygmoCor). For each ICH metric, a score of 2 was assigned for ideal levels, 1 for intermediate, and 0 for poor. All subjects showed at least one ICH metric, whereas none showed all ICH 7 metrics. The average number of ICH metrics was 4.3 ± 1.1. The highest rates were observed for fasting blood glucose (98%), whereas an ideal healthy diet was achieved only by 8% of subjects. The Cf-PWV was inversely and linearly associated with the sum of ICH metrics (p = 0.03) and the ICH score (p < 0.01). At the multivariate analysis, the association between ICH score and cf-PWV remained significant after adjustment for age, sex, heart rate, mean arterial pressure and other confounders (p = 0.04). CONCLUSION: ICH is relatively uncommon among Italian adolescents and inversely related to cf-PWV. Our results showed a detrimental association between CV unhealthy factors and behaviors with increased aortic stiffness, which starts developing at an early stage of the lifespan.

Screening for atrial fibrillation during automated blood pressure measurement among patients admitted to internal medicine ward.

Atrial fibrillation (AF), the commonest sustained cardiac arrhythmia affecting the adult population, is often casually discovered among hospitalized people. AF onset is indeed triggered by several clinical conditions such as acute inflammatory states, infections, and electrolyte disturbance, frequently occurring during the hospitalization. We aimed to evaluate whether systematic AF screening, performed through an automated oscillometric blood pressure (BP) device (Microlife WatchBP Office AFIB, Microlife AG, Switzerland), is effective for detecting AF episodes in subjects admitted to an Internal Medicine ward. 163 patients consecutively hospitalized at the Unit of Internal Medicine of the "Santa Maria" Terni University Hospital between November 2019 and January 2020 (mean age ± standard deviation: 77 ± 14 years, men proportion: 40%) were examined. Simultaneously with BP measurement and AF screening, a standard 12-lead electrocardiogram (ECG) was performed in all subjects. AF was diagnosed by ECG in 29 patients (18%). AF screening showed overall 86% sensitivity and 96% specificity. False negatives (n = 4) had RR-interval coefficient of variation lower than true positives (n = 25, p < 0.01), suggesting a regular ventricular rhythm during AF. The repeated evaluation substantially confirmed the same level of agreement. AF screening was positive in all patients with new-onset AF (n = 6, 100%). Systematic AF screening in patients admitted to Internal Medicine wards, performed using the Microlife WatchBP Office AFIB, is feasible and effective. The opportunity to implement such technology in daily routine clinical practice to prevent undiagnosed AF episodes in hospitalized patients should be the subject of further research.

Relationship between serum myostatin levels and carotid-femoral pulse wave velocity in healthy young male adolescents: the MACISTE study.

Serum myostatin (sMSTN) is a proteic compound that regulates skeletal muscle growth, adipogenesis, and production of extracellular matrix. Its relationship with functional and structural properties of the arterial wall is still understudied. We aimed at evaluating the association between sMSTN and carotid-femoral pulse wave velocity (cf-PWV), a measure of aortic stiffness, in a cohort of healthy male adolescents. Fifteen healthy male adolescents were recruited among the participants of the Metabolic And Cardiovascular Investigation at School, TErni (MACISTE) study, a cross-sectional survey conducted at the "Renato Donatelli" High School in Terni, Italy. sMSTN was measured through enzyme-linked immunosorbent assay. cf-PWV was measured through high-fidelity applanation tonometry. Muscle strength and body composition were measured through handgrip and bioimpedentiometry, respectively. sMSTN levels showed a skewed distribution (median: 6.0 ng/mL, interquartile range: 2.2-69.2 ng/mL). Subjects with sMSTN above median value showed higher values of brachial diastolic blood pressure and increased cf-PWV (6.1 ± 1.1 m/s vs. 4.6 ± 0.7 m/s, P < 0.01) values, compared with their counterparts. Such difference remained significant after controlling for age, mean BP, heart rate, body mass index z-score, waist-to-height ratio, body mass/lean mass ratio, and amount of physical activity (P = 0.02). The association between log-transformed sMSTN and cf-PWV was direct and linear, and independent from the effect of confounders at the multivariate analysis (P = 0.02). In this preliminary report, sMSTN was independently associated with cf-PWV, a measure of aortic stiffness, in healthy male adolescents. Our results shed lights on the potential role of myokines in the pathogenesis of systemic hypertension and atherosclerosis.NEW & NOTEWORTHY Serum myostatin, a proteic compound known to regulate skeletal muscle growth and production of extracellular matrix, is independently associated with increased aortic stiffness in healthy male adolescents. This result sheds lights on the potential novel role of myokines in the early development of systemic hypertension and early vascular aging, as well as on their inhibition as a hypothetical therapeutic strategy to counteract vascular aging at an early stage of physical development.

The Multifaceted Actions of Curcumin in Obesity.

Obesity remains a pervasive health concern worldwide with concomitant comorbidities such as cardiovascular diseases, diabetes, inflammation, and other metabolic disorders. A wealth of data validates dietary and lifestyle modifications such as restricting caloric intake and increasing physical activity to slow the obesity development. Recently, the advent of phytochemicals such as curcumin, the active ingredient in turmeric, has attracted considerable research interest in tracking down their possible effects in protection against obesity and obesity-related comorbidities. According to the existing literature, curcumin may regulate lipid metabolism and suppress chronic inflammation interacting with white adipose tissue, which plays a central role in the complications associated with obesity. Curcumin also inhibits the differentiation of adipocyte and improves antioxidant properties. In the present review, we sought to deliberate the possible effects of curcumin in downregulating obesity and curtailing the adverse health effects of obesity.

Very Low-Carbohydrate Ketogenic Diet for the Treatment of Severe Obesity and Associated Non-Alcoholic Fatty Liver Disease: The Role of Sex Differences.

Very low-carbohydrate ketogenic diets (VLCKDs) are an emerging nutritional treatment for severe obesity and are associated with a significant improvement in non-alcoholic fatty liver disease (NAFLD). Little is known about the effect of sex differences on weight loss induced by following a VLCKD. The aim of this study was to investigate the effects of sex differences on weight loss and NAFLD improvement in patients with severe obesity undergoing a VLCKD. Forty-two females and 28 males with severe obesity underwent a 25-day VLCKD. Anthropometric parameters, bioimpedentiometry, degree of liver steatosis measured by ultrasonography, liver function tests, and glucose homeostasis were measured before and after the VLCKD. Males experienced a significantly larger excess body weight loss (EBWL) and a greater reduction in γ-glutamyl transferase (γGT) than females. Dividing the female group by menopausal status, a significant difference between males and pre-menopausal females was found for both EBWL and γGT. No significant difference between groups was observed for improvement in the Edmonton stage or in the degree of steatosis. We conclude that the efficacy of following a VLCKD in severe obesity is affected by sex differences and, for females, by menopausal status. Males seem to experience larger benefits than females in terms of EBWL and NAFLD improvement. These differences are attenuated after menopause, probably because of changes in hormonal profile and body composition.

Assessment of nocturnal hypertension by ambulatory blood pressure monitoring at the forearm in people with morbid obesity.

Blood pressure (BP) measurement at the forearm (FA) has been proposed as alternative site to upper arm (UA) in people with morbid obesity (MO). We compared nocturnal BP readings simultaneously taken at FA and UA by ambulatory blood pressure monitoring (ABPM). Fourteen individuals with MO and seven normal-weight controls underwent nocturnal ABPM with two devices placed at the UA and contralateral FA, respectively. Agreement between FA-UA BP, diagnosis of nocturnal hypertension, and potential determinants of BP differences were evaluated. BP at the FA was significantly higher than UA in both people with MO and controls. FA-UA differences in systolic and diastolic BP were similar in people with MO and controls. Nocturnal hypertension was diagnosed in 10 subjects (48%) according to UA BP and in 13 subjects (62%) according to FA BP (concordance 76%, moderate agreement). ΔFA-UA systolic BP was associated with ratio between FA/UA circumferences (R = 0.45, P < .05) and with cuff-UA slant angle difference (R = 0.44, P < .05). In conclusions, in people with MO, the agreement between FA and UA nighttime BP measured by ABPM is sub-optimal. Our results raise uncertainty in using ABPM at the FA as an alternative to UA placement in people with MO for the diagnosis of nocturnal hypertension.

Chemerin predicts carotid intima-media thickening in severe obesity.

BACKGROUND AND AIMS: Chemerin is an adipokine with an emerging role in the crosstalk between adipose tissue and immune system. It is overexpressed in severe obesity, affects adipogenesis and glucose homeostasis and it correlates with early vascular damage. The aim of this study is to investigate the correlation between circulating levels of chemerin and early vascular damage in subjects with severe obesity, before and after laparoscopic sleeve gastrectomy (LSG). METHODS: Fifty-six obese subjects eligible for LSG were enrolled in the study. The following parameters were evaluated: body mass index (BMI), glycemia, insulinemia, glycated haemoglobin, lipid profile, plasma chemerin levels and carotid intima-media thickness (cIMT). Fifty-four subjects were evaluated 1 year after the intervention. RESULTS: Univariate analysis showed a direct and significant correlation between chemerin and waist circumference, insulin resistance, glycated haemoglobin and cIMT. Chemerin was a better predictor of intima-media thickening than waist circumference and glycated haemoglobin at the ROC curve analysis, with a cut-off value for chemerin of 140 ng/mL. The reduction of chemerin is independently associated with the reduction of cIMT and the improvement of insulin sensitivity after LSG. CONCLUSION: Chemerin is involved in the development and progression of early vascular damage and insulin resistance in subjects with severe obesity, and in their healing after bariatric surgery. Chemerin could also have a role in the assessment of cardiovascular risk in subjects with severe obesity.

Increased plasmatic NETs by-products in patients in severe obesity.

Neutrophil extracellular traps (NETs) are DNAs products involved in immune process. Obesity through a low-grade chronic inflammation determines neutrophil activation, but it is still unclear its role in NETs formation. Here we analyzed the NETs levels in healthy and morbid obese, their association with anthropometric and glyco-metabolic parameters and their changes after bariatric surgery. For this study, we enrolled 73 patients with morbid obesity (BMI ≥40 kg/m2 or ≥35 kg/m2 + comorbidity) eligible to sleeve gastrectomy. In parallel, 55 healthy subjects and 21 patients with severe coronary artery disease were studied as controls. We evaluated anthropometric parameters, peripheral blood pressure, biochemical and serum analysis at the enrollment and at twelve months after surgery. Plasmatic levels of MPO-DNA complexes were assessed by ELISA. NETs levels were higher in obese than in control group (p < 0.001) and correlated with the main anthropometric variable (BMI, waist, hip), glyco-metabolic variables and systolic blood pressure. NETs trend after intervention was uneven. The reduction of NETs correlated with the entity of reduction of BMI (ρ = 0.416, p < 0.05), visceral fat area (ρ = 0.351, p < 0.05), and glycemia (ρ = 0.495, p < 0.001). In medical history of patients in whom NETs increased, we observed a higher number of thromboembolic events. Our observations indicate that severe obesity is associated with increased generation of NETs, which in turn could influence the patients' systemic inflammatory state. Weight loss and in particular, loss of adipose tissue after bariatric surgery does not in itself correct NET's dysregulated production. Finally, patients in whom NETs accumulation persists after surgery are probably those at the highest risk of cardiovascular events.