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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

BACKGROUND Aortic stiffness as measured by carotid–femoral pulse wave velocity (cfPWV) is known to depend on blood pressure (BP), and this dependency may change with age. Therefore, the hydrostatic BP gradient resulting from a change in body posture may elicit a cfPWV change that is age-dependent. We aimed to analyze the relationship between BP gradient—induced by head-up body tilting—and related changes in cfPWV in individuals of varying age. METHODS cfPWV and other hemodynamic parameters were measured in 30 healthy individuals at a head-up tilt of 0° (supine), 30°, and 60°. At each angle, the PWV gradient and resulting cfPWV were also estimated (predicted) by assuming a global nonlinear, exponential, pressure–diameter relationship characterized by a constant β0, and taking into account that (diastolic) foot-to-foot cfPWV acutely depends on diastolic BP. RESULTS cfPWV significantly increased upon body tilting (8.0 ± 2.0 m/s supine, 9.1 ± 2.6 m/s at 30°, 9.5 ± 3.2 m/s at 60°, P for trend CONCLUSIONS Under a hydrostatic pressure gradient, the pulse wave traveling along the aorta undergoes an age-related, nonlinear PWV increase exceeding the increase predicted from BP dependency.

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 elite athletes. Methods 13 elite cross-country skiers with previous mild-moderate COVID-19 symptoms underwent CPET before resuming seasonal training (COVID athletes). 13 elite 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 Conclusions Elite 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.

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

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 participants of the MACISTE study, a cross-sectional survey conducted at the "Renato Donatelli" High School in Terni, Italy. sMSTN was measured through Enzyme-Linked Immunosorbent Assay (ELISA). 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 DBP and increased cf-PWV (6.1±1.1 m/s vs 4.6±0.7 m/s, p

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide determining dramatic impacts on healthcare systems. Early identification of high-risk parameters is required in order to provide the best therapeutic approach. Coronary, thoracic aorta and aortic valve calcium can be measured from a non-gated chest computer tomography (CT) and are validated predictors of cardiovascular events and all-cause mortality. However, their prognostic role in acute systemic inflammatory diseases, such as COVID-19, has not been investigated. OBJECTIVES: The aim was to evaluate the association of coronary artery calcium and total thoracic calcium on in-hospital mortality in COVID-19 patients. METHODS: 1093 consecutive patients from 16 Italian hospitals with a positive swab for COVID-19 and an admission chest CT for pneumonia severity assessment were included. At CT, coronary, aortic valve and thoracic aorta calcium were qualitatively and quantitatively evaluated separately and combined together (total thoracic calcium) by a central Core-lab blinded to patients' outcomes. RESULTS: Non-survivors compared to survivors had higher coronary artery [Agatston (467.76 ​± ​570.92 vs 206.80 ​± ​424.13 ​mm2, p ​

Background and aims The potential impact of coronary atherosclerosis, as detected by coronary artery calcium, on clinical outcomes in COVID-19 patients remains unsettled. We aimed to evaluate the prognostic impact of clinical and subclinical coronary artery disease (CAD), as assessed by coronary artery calcium score (CAC), in a large, unselected population of hospitalized COVID-19 patients undergoing non-gated chest computed tomography (CT) for clinical practice. Methods SARS-CoV 2 positive patients from the multicenter (16 Italian hospitals), retrospective observational SCORE COVID-19 (calcium score for COVID-19 Risk Evaluation) registry were stratified in three groups: (a) “clinical CAD” (prior revascularization history), (b) “subclinical CAD” (CAC >0), (c) “No CAD” (CAC=0). Primary endpoint was in-hospital mortality and the secondary endpoint was a composite of myocardial infarction and cerebrovascular accident (MI/CVA). Results Amongst 1625 patients (male 67.2%, median age 69 [interquartile range 58-77] years), 31%, 57.8% and 11.1% had no, subclinical and clinical CAD, respectively. Increasing rates of in-hospital mortality (11.3% vs. 27.3% vs. 39.8%, p400, respectively, p, Graphical abstract Image 1

Background Coronavirus disease 2019 (COVID-19) has spread worldwide determining a dramatic impact on the healthcare system. Aim of this study is to evaluate mid-term clinical impact of COVID-19 on respiratory function. Methods 379 patients were evaluated 4 months after SARS-COV-2 diagnosis. Patients were divided in two groups based on the presence of pneumonia during COVID. Clinical conditions, quality of life, symptomatology, 6-min walking test, pulmonary function test with spirometry and diffusing capacity of carbon monoxide were analysed. Data were compared to clinical evolution during COVID (development of acute respiratory distress syndrome [ARDS], needing of invasive mechanical ventilation [IMV], partial oxygen saturation/ fraction of inspired oxygen [SpO2/FiO2] ratio and pneumonia severity index [PSI]). Results After a median of 135 days, 260 (68.6%) of 379 patients referred almost one symptom. Patients who developed pneumonia during COVID-19 showed lower SpO2 at rest (p, COVID-19 severe lung involvement can reduce respiratory performance at a mid/long-term. Respiratory rehabilitation is recommended in COVID-19 survivors who showed severe clinical and radiological signs of the disease.

Introduction: Acute, gravity-induced blood pressure (BP) changes during head-up tilt may generate concomitant variations in carotid-femoral pulse wave velocity (cf-PWV). We aimed to separate the pressure-dependent and -independent components of cf-PWV changes observed during head-up tilt. Methods: 30 healthy individuals (age 48 ± 18 years (mean ± SD), 38% males, BP 130/74 ± 12/8 mmHg) underwent head-up passive tilting at a = 0°, 30°, and 60°. BP was taken at the upper arm, constantly kept at heart level. Aortic BP was reconstructed from radial tonometry (SphygmoCor). Stiffness index b0 was estimated at 0°. 1 Assumptions: [1] from MRI2, the effective cf-PWV travel distance (ETD, 80% of straight carotid-to-femoral distance) begins at heart level; [2] the change in DBP along the aorta is predictable from the hydrostatic pressure gradient (0.73 mmHg/cm) 3; [3] cf-PWV and hydrostatic pressure relate linearly, hence predicted cf-PWV can be calculated as the average of aortic (PWVaorta, using b0 and aortic DBP) and femoral (PWVfem, using b0 and femoral DBP, corresponding to aortic DBP + (ETD × sin(a)*0.73)) PWVs. Results: Both young (24–48 years) and old (48–82 years) individuals showed increasing trends for peripheral SBP, DBP, PP, and central DBP with tilting; central SBP remained unchanged. Heart rate (HR) and cf-PWV increased with body tilt in both groups (Figure, left). b0 linearly correlated with age (R = 0.70, p < 0.01). After adjustment for HR4, observed-vs-predicted cf-PWV exponentially increased as a function of age (R2 = 0.38, p < 0.01 for quadratic equation, p = 0.04, vs. linear; Figure, right). Conclusion: With aging, the acute relationship between BP and cf-PWV becomes progressively nonlinear.

OBJECTIVE An excess morning blood pressure surge (MBPS) may portend an increased cardiovascular risk, but the mechanisms thereof have been little investigated. The link between MBPS, short-term blood pressure (BP) variability, and arterial stiffness has not been entirely defined. METHODS In 602 consecutive untreated hypertensive patients (48 ± 12 years, 61% men, office BP 149/93 ± 17/10 mmHg), we measured carotid-femoral pulse wave velocity (cf-PWV, SphygmoCor) and 24-h ambulatory BP. Using self-reported sleep and wake times, MBPS was defined as sleep-trough (ST-MBPS), prewaking, rising. Short-term BP variability was calculated as weighted 24-h SBP SD and average real variability of 24-h SBP (ARV), that is, average of absolute differences between consecutive SBP readings. RESULTS ST-MBPS (r = 0.16, P

Background: the MACISTE study (Metabolic and Cardiovascular Investigation at School, Terni) aimed at evaluating the metabolic and cardiovascular abnormalities and behaviors in healthy adolescents attending a High School. We evaluated the prevalence of smoking habits and the relationship between smoking and physical activity. Methods: 539 students (302 boys, 237 girls) were evaluated through: 1- self-reported questionnaires about lifestyles, smoking and physical habits, 2-measurement of exaled carbon-monoxide. Results: 65 subjects (12%) did not answer about smoking. Among the 474 subjects, 125 subjects (26%) were smokers, and 349 (74%) were non-smokers. Smoking prevalence significantly increased among the female sex and age-groups (R. 14 - 19)(Figure). 97 subjects (21%) reported sedentary lifestyle, 157 (33%) were involved in non-competitive physical activities, and 220 (46%) were involved in competitive sports. Smoking was more prevalent in sedentaries (37%), than in non-agonistic athletes (27%), and in athletes (21%, ANOVA p=0.009). The measurement of exaled carbon-monoxide, available in 250 subjects, was in agreement with self-reported data about smoking habits. Conclusions: smoking prevalence is disproportionately high among young Italian adolescents. Phisical activity is associated with a lower prevalence of smoking. However, the unacceptably high rate of smokers among athletes requires dedicated educational interventions.

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 ± 19 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 ± 17/8 mmHg. Mean arterial pressure changed predictably with arm tilting (99 ± 12 mmHg at -30°, 88 ± 10 mmHg at 0°, 77 ± 11 mmHg at +30°, all P

Objective: Pulse pressure (PP) is a complex physiologic trait affected by many variables, including LV contractility (reflected by stroke volume), arterial stiffness, and central-to-brachial amplification.The impact of age on the relationship between stroke volume and central or brachial PP has not been investigated. Methods: 3765 untreated hypertensive adults (men 56%, age 50 ± 12 years) underwent 24-hour ambulatory BP monitoring (SpaceLabs) and M-mode echocardiography. In a subset of 982 subjects in whom central PP was measured by applying a transfer function to radial pulse wave (SphygmoCor), we also estimated central office (or 24 h) PP by regression equations based on office (or 24 h) PP and MAP, heart rate, age, height and sex (R2 = 0.92 between estimated and measured central PP).The same equations were then applied to the original population to obtain estimated central PP. Results: Stroke volume had a significant direct association with both brachial and central 24 h PP up to the age of 39 years. The above relationship weakened with age and became mostly non-significant after the age of 40 (all r < 0.10). Similar, although weaker, trends were observed for office PP (both brachial and central). Conclusions: 24-h PP has a strong direct association with LV stroke volume in the young only, and might more exclusively depend on arterial stiffness later in life. Since the above relationship was also observed with estimated central PP, it may not depend on PP amplification. The “young” and “old” pathophysiological patterns of PP may help to explain the increasingly adverse prognostic value of PP observed with advancing age.

Hypothesis: increased arterial stiffness has been reported in subjects with systemic lupus erythematosus (SLE) compared with healthy controls. In SLE, indexes of organ damage are related to a poor clinical status and worse prognosis independently from the activity of the disease. Data are controversial about the association between SLE-related organ damage and arterial stiffness. Methods: 40 subjects with history of SLE (mean age 45±12 years, 90% women) and a median disease duration of 12 years (IQR 5–19), underwent assessment of carotid-femoral pulse wave velocity (cf-PWV) by means of applanation tonometry (SphygmoCor). A comprehensive clinical, metabolic and immunological assessment was performed. Irreversible organ damage, not related to active inflammation, was assessed through the Systemic Lupus International Collaborating Clinics (SLICC) damage index. Results: mean BP was 128/75±16/10 mmHg. 9 subjects (23%) were on anti-hypertensive treatment, 4 (10%) had had previous cardiovascular events, 17 (42%) were treated with steroids, 29 (71%) with hydroxychloroquine, 15 (37%) with other immunosuppressants. Median SLICC index was 2 (IQR 1–3), average cf-PWV was 7.5±1.9 m/s. cf-PWV significantly increased across SLICC damage index categories (F=3.141, p

BACKGROUND: Vascular endothelial growth factor (VEGF)-B activates cytoprotective/antiapoptotic and minimally angiogenic mechanisms via VEGF receptors. Therefore, VEGF-B might be an ideal candidate for the treatment of dilated cardiomyopathy, which displays modest microvascular rarefaction and increased rate of apoptosis. OBJECTIVES: This study evaluated VEGF-B gene therapy in a canine model of tachypacing-induced dilated cardiomyopathy. METHODS: Chronically instrumented dogs underwent cardiac tachypacing for 28 days. Adeno-associated virus serotype 9 viral vectors carrying VEGF-B167 genes were infused intracoronarily at the beginning of the pacing protocol or during compensated heart failure. Moreover, we tested a novel VEGF-B167 transgene controlled by the atrial natriuretic factor promoter. RESULTS: Compared with control subjects, VEGF-B167 markedly preserved diastolic and contractile function and attenuated ventricular chamber remodeling, halting the progression from compensated to decompensated heart failure. Atrial natriuretic factor-VEGF-B167 expression was low in normally functioning hearts and stimulated by cardiac pacing; it thus functioned as an ideal therapeutic transgene, active only under pathological conditions. CONCLUSIONS: Our results, obtained with a standard technique of interventional cardiology in a clinically relevant animal model, support VEGF-B167 gene transfer as an affordable and effective new therapy for nonischemic heart failure.

(0.16 1.9 vs -0.12 2.2 m/s; PZ0.4), or any other haemodynamic variable relative to control at six or 12 months (all P > 0.05). Conclusions: Despite many observational studies to suggest that vitamin D supplementation could be a useful therapy for improving aortic stiffness and associated haemodynamic indices, 12-months intervention yielded no improvement in older people with vitamin D deficiency. These results do not support use of vitamin D supplementation to improve cardiovascular health in this patient population.

Imatinib mesylate is a selective tyrosine-kinase inhibitor used in the treatment of multiple cancers, most notably chronic myelogenous leukemia. There is evidence that imatinib can induce cardiotoxicity in cancer patients. Our hypothesis is that imatinib alters calcium regulatory mechanisms and can contribute to development of pathological cardiac hypertrophy.Neonatal rat ventricular myocytes (NRVMs) were treated with clinical doses (low: 2 μM; high: 5 μM) of imatinib and assessed for molecular changes. Imatinib increased peak systolic Ca(2+) and Ca(2+) transient decay rates and Western analysis revealed significant increases in phosphorylation of phospholamban (Thr-17) and the ryanodine receptor (Ser-2814), signifying activation of calcium/calmodulin-dependent kinase II (CaMKII). Imatinib significantly increased NRVM volume as assessed by Coulter counter, myocyte surface area, and atrial natriuretic peptide abundance seen by Western. Imatinib induced cell death, but did not activate the classical apoptotic program as assessed by caspase-3 cleavage, indicating a necrotic mechanism of death in myocytes. We expressed AdNFATc3-green fluorescent protein in NRVMs and showed imatinib treatment significantly increased nuclear factor of activated T cells translocation that was inhibited by the calcineurin inhibitor FK506 or CaMKII inhibitors.These data show that imatinib can activate pathological hypertrophic signaling pathways by altering intracellular Ca(2+) dynamics. This is likely a contributing mechanism for the adverse cardiac effects of imatinib.

The relationship between arterial stiffness, measured as pulse wave velocity (PWV), and the left ventricle is confounded by the effects of blood pressure. We evaluated the relationship between carotid-femoral PWV and cardio-ankle vascular index (CAVI), a less pressure-dependent measurement of the stiffness constant (β) of the aorta and the iliac, femoral and tibial arteries, and obtained prognostically relevant measurements of left ventricular structure and systolic function. CAVI, carotid-femoral PWV and echocardiographic left ventricular mass and systolic function were determined in 133 subjects with either hypertension or high-normal blood pressure (33% treated; 56 ± 16 years, blood pressure 145/89 ± 21/12 mm Hg). Carotid-femoral PWV exhibited a direct relationship with systolic and diastolic blood pressure (r = 0.33/0.26, P0.001/0.014), whereas CAVI demonstrated no such relationship (r = 0.12/-0.05, both P0.1). Both CAVI and PWV correlated significantly with left ventricular mass index (r = 0.31, P0.001; r = 0.21, P = 0.014). Subjects with inappropriately high left ventricular masses for a given cardiac workload (n = 44) had higher CAVI values (9.1 ± 2.0 vs. 7.9 ± 1.6, P0.001), but not higher PWV values (8.5 ± 2.5 vs. 8.7 ± 2.4, P0.1). In a multivariate regression model, CAVI was independently associated with inappropriate left ventricular mass (β = 0.40, P0.001), along with body mass index. CAVI also demonstrated a negative relationship with left ventricular midwall fractional shortening (r = -0.41, P = 0.001) that was independent of age, sex, blood pressure and left ventricular mass in a multivariate analysis. In conclusion, a high CAVI is associated with inappropriately high left ventricular mass and low midwall systolic function. As a marker of arterial diastolic-to-systolic stiffening, CAVI may have a relationship with left ventricular structure and function that is independent of blood pressure levels.