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Aim To investigate the associations of blood pressure variability (BPV), expressed as long‐term (visit‐to‐visit) and short‐term (ambulatory blood pressure monitoring [ABPM] and home blood pressure monitoring [HBPM]) and all‐cause mortality, major adverse cardiovascular events (MACEs), extended MACEs, microvascular complications (MiCs) and hypertension‐mediated organ damage (HMOD) in adult patients with type 2 diabetes. Materials and methods PubMed, Medline, Embase, Cinahl, Web of Science, http://clinicaltrials.gov and grey literature databases were searched for studies including patients with type 2 diabetes, at least one variable of BPV (visit‐to‐visit, HBPM, ABPM) and evaluation of the incidence of at least one of the following outcomes: all‐cause mortality, MACEs, extended MACEs and/or MiCs and/or HMOD. The extracted information was analyzed using random effects meta‐analysis and meta‐regression. Results Data from a total of 377 305 patients were analyzed. Systolic blood pressure (SBP) variability was associated with a significantly increased risk of all‐cause mortality (HR 1.12, 95% CI 1.04–1.21), MACEs (HR 1.01, 95% CI 1.04–1.17), extended MACEs (HR 1.07, 95% CI 1.03–1.11) and MiCs (HR 1. 12, 95% CI 1.01–1.24), while diastolic blood pressure was not. Associations were mainly driven from studies on long‐term SBP variability. Qualitative analysis showed that BPV was associated with the presence of HMOD expressed as carotid intima‐media thickness, pulse wave velocity and left ventricular hypertrophy. Results were independent of mean blood pressure, glycaemic control and serum creatinine levels. Conclusions Our results suggest that BPV might provide additional information rather than mean blood pressure on the risk of cardiovascular disease in patients with type 2 diabetes.

Purpose of Review To examine the state of the art on the pathogenesis of endothelial dysfunction in the microcirculation of patients with obesity, focusing on the complex relationship between the consolidated and the novel mechanisms involved in this alteration.Recent Findings Human obesity is associated with vascular endothelial dysfunction, caused by a reduced nitric oxide availability secondary to an enhanced oxidative stress production. Pro-inflammatory cytokine generation, secreted by perivascular adipose tissue, is a major mechanism whereby obesity is associated with a reduced vascular NO availability. Vasculature also represents a source of low-grade inflammation and oxidative stress which contribute to endothelial dysfunction in obese patients. Recently, a direct influence of arginase on endothelial function by reducing nitric oxide availability was demonstrated in small vessels from patients with severe obesity. This effect is modulated by ageing and related to the high levels of vascular oxidative stress. Summary Oxidative stress, inflammation, and enzymatic pathways are important players in the pathophysiology of obesityrelated vascular disease. The identification of new therapeutic approaches able to interfere with these mechanisms will result in more effective prevention of the cardiovascular complications associated with obesity.

Aims The relationship between resistance artery remodelling and endothelial function remains unknown. In this study, we assessed (i) the capacity of endothelial function and nitric oxide (NO) availability to provide more information on the severity of resistance artery remodelling than common cardiovascular risk factors in subjects at low or high cardiovascular risk; and (ii) differences between patterns of resistance artery remodelling associated with deficit of NO availability and with exposure to cardiovascular risk factors. Methods and results All analyses were conducted on the microvascular data set of the Italian Society for Arterial Hypertension (SIIA) that includes 356 patients with measures of small resistance arteries remodelling acquired with pressure or wire myography. Information on endothelial function and NO availability were also available in 116 patients. The European Heart Score (HS) was used to define the total cardiovascular risk of each patient. Endothelial function was inversely related with the severity of the resistance artery remodelling, and this association remained significant after adjustment for the HS. By contrast, the HS lost its significant association with the media-to-lumen (M/L) ratio and the media cross-sectional area after adjustment for endothelial function. The strength of these associations was similar in subjects at high and low cardiovascular risk. The addition of endothelial function and NO availability to the HS significantly improved the identification of subjects at more and less severe resistance artery remodelling. A severe deficit of NO availability was associated with hypertrophic remodelling, while a higher HS was more clearly associated with eutrophic remodelling. Conclusion Resistance artery endothelial function and NO availability might represent important factors involved in resistance artery remodelling, independently from cardiovascular risk factor exposure.

Aim To investigate the impact of epicardial adipose tissue (EAT) thickness on cardiopulmonary performance in patients with type 2 diabetes (T2D) and normal heart function. Materials and methods We analysed EAT thickness in subjects with T2D and normal biventricular systo‐diastolic functions undergoing a maximal cardiopulmonary exercise test combined with stress echocardiography, speckle tracking and pulmonary function assessment, as well as serum N‐terminal pro B‐type natriuretic peptide (NT‐proBNP). Results In the 72 subjects enrolled, those with EAT thickness above the median (> 5 mm) showed higher body fat mass, smaller indexed left ventricular dimensions and marginally reduced diastolic function variables at rest. Higher EAT thickness was associated with lower peak oxygen uptake (VO2peak 17.1 ± 3.6 vs. 21.0 ± 5.7 ml/min/kg, P = .001), reduced systolic reserve (ΔS′ 4.6 ± 1.6 vs. 5.8 ± 2.5 m/s, P = .02) and higher natriuretic peptides (NT‐proBNP 64 [29‐165] vs. 31 [26‐139] pg/ml, P = .04), as well as chronotropic insufficiency and impaired heart rate recovery. Ventilatory variables and peripheral oxygen extraction were not different between groups. EAT was independently associated with VO2peak and linearly and negatively correlated with peak heart rate, heart rate recovery, workload, VO2 at the anaerobic threshold and at peak, and cardiac power output, and was directly correlated with natriuretic peptides. Conclusion Higher EAT thickness in T2D is associated with worse cardiopulmonary performance and multiple traits of subclinical cardiac systolic dysfunction.

Longer life span and increased prevalence of chronic, noncommunicable, inflammatory diseases fuel cardiovascular mortality. The microcirculation is central in the cross talk between ageing, inflammation, cardiovascular, and metabolic diseases. Microvascular dysfunction, characterized by alteration in the microvascular endothelial function and wall structure, is described in an increasing number of chronic age-associated diseases, suggesting that it might be a marker of ageing superior to chronological age. The aim of this review is to thoroughly explore the connections between microvascular dysfunction, ageing, and metabolic disorders by detailing the major role played by inflammation and oxidative stress in their evolution. Older age, hypertension, nutrient abundance, and hyperglycemia concur in the induction of a persistent low-grade inflammatory response, defined as meta-inflammation or inflammageing. This increases the local generation of reactive oxygen species that further impairs endothelial function and amplifies the local inflammatory response. Mitochondrial dysfunction is a hallmark of many age-related diseases. The alterations of mitochondrial function promote irreversible modification in microvascular structure. The interest in the hypothesis of chronic inflammation at the center of the ageing process lies in its therapeutic implications. Inhibition of specific inflammatory pathways has been shown to lower the risk of many age-related diseases, including cardiovascular disease. However, the whole architecture of the inflammatory response underpinning the ageing process and its impact on the burden of age-related diseases remain to be fully elucidated. Additional studies are needed to unravel the connection between these biological pathways and to address their therapeutic power in terms of cardiovascular prevention.

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Background Remdesivir, an antiviral agent able to reduce inflammatory cascade accompanying severe, life-threatening pneumonia, became the first drug approved by the Food and Drug Administration for the treatment of hospitalized patients with coronavirus 2 related severe acute respiratory syndrome (SARS CoV2). As from its previously known clinical indications, the use of remdesivir in the presence of severe renal impairment is contraindicated; however, the impact of remdesivir on renal function in aging patients has not been elucidated. Subjects and Methods This retrospective observational study involved 109 individuals consecutively admitted in internal medicine section, Azienda Ospedaliero Universitaria Pisana hospital, in November–December 2020 due to a confirmed diagnosis of SARS CoV2 and receiving remdesivir according to international inclusion criteria. Biochemical variables at admission were evaluated, together with slopes of estimated glomerular filtration rate (eGFR) built during remdesivir treatment. Participants were followed until discharge or exitus. Results Patients were stratified according to age (80 formed the study cohort and 29 served as controls); CKD stage III was present in 46% of them. No patients showed any sign of deteriorated renal function during remdesivir. Fourteen patients in the elderly cohort deceased; their eGFR at baseline was significantly lower. Recovered patients were characterized by a relevant eGFR gaining during remdesivir treatment. Conclusion We show here for the first time as remdesivir does not influence eGFR in a cohort of elderly people hospitalized for SARS CoV2, and that eGFR gain during such treatment is coupled with a better prognosis.