Exosomal miR-17-5p, miR-146a-3p, and miR-223-3p Correlate with Radiologic Sequelae in Survivors of COVID-19-Related Acute Respiratory Distress Syndrome.

We investigated the association between circulating microRNAs (miRNAs) potentially involved in the lung inflammatory process and fibrosis development among COVID-19-related acute respiratory distress syndrome (ARDS) survivors. At 4 ± 2 months from clinical recovery, COVID-19-related ARDS survivors matched for age, sex, and clinical characteristics underwent chest high-resolution computerized tomography (HRCT) and were selected based on imaging pattern evolution into fully recovered (N = normal), pulmonary opacities (PO) and fibrosis-like lesions (FL). Based on the previous literature, we performed plasma miRNA profiling of exosomal miRNAs belonging to the NLRP3-inflammasome platform with validated (miR-17-5p, miR-223-3p) and putative targets (miR-146a-5p), miRNAs involved in the post-transcriptional regulation of acute phase cytokines (miR128-3p, miR3168, miR125b-2-3p, miR106a-5p), miRNAs belonging to the NLRP4-inflammasome platform (miR-141-3p) and miRNAs related to post-transcriptional regulation of the fibrosis process (miR-21-5p). miR-17-5p, miR-223-3p, and miR-146a-5p were significantly down-regulated in patients with FL when compared to patients with PO. miR-146a-5p was also down-regulated in patients with FL than in N. The expression of the remaining miRNAs did not differ by group. In patients with long-term pulmonary radiological sequelae following COVID-19-related ARDS, a down-regulation of miR-17-5p, miR-146a-3p, and miR-223-3p correlated to fibrosis development in patients showing persistent hyper-reactivity to inflammatory stimulation. Our results support the hypothesis that NLRP3-Inflammasome could be implicated in the process of fibrotic evolution of COVID-19-associated ARDS.

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.

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.

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.

Relationship between echocardiographic and functional parameters in patients with heart failure undergoing cardiopulmonary exercise test.

BACKGROUND: HF patients typically show effort intolerance due to a reduction in peak exercise oxygen (peak VO2) consumption, which is related to inability to adapt systolic function to increased demand. Left ventricular ejection fraction (EF) is a surrogate marker of cardiac contractility and a powerful predictor of adverse prognosis in chronic heart failure (HF). The aim of the study was to explore the relationship between EF and other echocardiographic findings with peak VO2 in a population of HF individuals undergoing cardiopulmonary exercise testing (CPX). METHODS: We evaluated 101 patients (61% hypertensives, 74% with documented coronary artery disease) undergoing both resting echocardiography and symptom-limited CPX. RESULTS: Mean age was 58±13 years, 83% were males. Mean EF was 55±12%; 20% of the patients showed EF<40%. Mean test duration was 9.4±2.2 min. Average peak VO2 was 21±6 mL/kg/min. Peak VO2 showed a robust positive correlation with EF (R=0.42, P<0.001). Other independent predictors of peak VO2 were age, male sex, height and tricuspidal anular plane systolic excursion (TAPSE), this latter reflecting right ventricular dysfunction. When subjects were dichotomized according to predicted peak VO2values, those with higher-than-predicted peak VO2 showed significantly lower VE/VCO2 slope, and higher values of both oxygen pulse and VO2/WR slope. CONCLUSIONS: EF and TAPSE are associated with peak VO2 in HF patients independently from age, sex and height. The evaluation of potentially relevant mechanisms affecting exercise capacity in HF patients requires further investigation.

Effects of gravity-induced upper-limb blood pressure changes on wave transmission and arterial radial waveform.

BACKGROUND: Local blood pressure (BP) changes induced by arm tilting may influence pressure wave transmission and reflection. We investigated the effects of upper-limb tilting on radial augmentation index (rAIx) and related central measures [aortic augmentation index (aAIx)]. METHODS: In 45 volunteers (age 49 ±â€Š19 years), supine brachial BP and radial artery waveforms were obtained by applanation tonometry with the dominant arm stretched and gently supported in three different positions: at the heart level, with the BP cuff 15 cm above heart level (approximately +30°), and 15 cm below heart level (-30°). RESULTS: Brachial SBP/DBP was 120/68 ±â€Š17/8 mmHg. Mean arterial pressure changed predictably with arm tilting (99 ±â€Š12 mmHg at -30°, 88 ±â€Š10 mmHg at 0°, 77 ±â€Š11 mmHg at +30°, all P < 0.001). rAIx decreased at -30° (69 ±â€Š22%), and increased at +30° (93 ±â€Š20%) compared with 0° (82 ±â€Š20%, all P less than 0.001). Changes in rAIx (value at +30° minus value at -30°) showed an inverse relationship with age (r = -0.32, P = 0.03). Heart rate, BP and rAIx did not change in the contralateral arm, which was held at the heart level during the examination. aAIx followed the same pattern as rAIx (123 ±â€Š27% at -30°, 144 ±â€Š33% at +30°, 136 ±â€Š31% at 0°, all P less than 0.001); changes in rAIx and aAIx were strongly related each other (r = 0.82, P < 0.001). CONCLUSION: Acute gravitational upper-limb BP changes generate opposite, profound changes in rAIx, and major artifactual changes in aAIx. These findings provide a rationale for recommending to keep the upper limb at the heart level during radial waveform assessment.