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Background The objective of this systematic review and meta-analysis is to investigate whether nocturnal blood pressure fall, expressed by dipping patterns according to 24 h ambulatory blood pressure monitoring (ABPM), is associated with abnormal cognitive function (cognitive impairment or dementia). Methods We systematically searched PubMed, Embase, and Cochrane databases to identify original articles through December 2022. We included any study with at least ten participants reporting on all-cause dementia or cognitive impairment incidence (primary outcome) or validated cognitive tests (secondary outcome) among ABPM patterns. We assessed risk of bias using Newcastle–Ottawa Quality Assessment Scale. We pooled odds ratios (OR) and standardized mean differences (SMD) using random-effect models for primary and secondary outcome, respectively. Results In the qualitative synthesis, 28 studies examining 7595 patients were included. The pooled analysis of 18 studies showed that dippers had a 51% [OR 0.49(0.35–0.69)] lower risk of abnormal cognitive function and a 63% [OR 0.37(0.23–0.61)] lower risk of dementia alone, compared to non-dippers. Reverse dippers presented an up to sixfold higher risk [OR 6.06(3.15–11.64)] of abnormal cognitive function compared to dippers and an almost twofold higher risk [OR 1.81(1.26–2.6)] compared to non-dippers. Reverse dippers performed worse in global function neuropsychological tests compared with both dippers [SMD − 0.66(− 0.93 to − 0.39)] and non-dippers [SMD − 0.35(− 0.53 to − 0.16)]. Conclusion Dysregulation of the normal circadian BP rhythm, specifically non-dipping and reverse dipping is associated with abnormal cognitive function. Further studies are required to determine potential underlying mechanisms and possible prognostic or therapeutic implications. Protocol registration PROSPERO database (ID: CRD42022310384).

Objectives Depression is highly prevalent among systemic lupus erythematosus (SLE) patients. Brain hypoperfusion in neuropsychiatric SLE patients might be associated with emotional difficulties. However, no previous study examined possible associations of depression with brain oxygenation during a mild physical stress in non-neuropsychiatric SLE patients. Our study aimed to identify possible differences in cerebral oxygenation during exercise in SLE patients with and without depressive symptoms using near-infrared spectroscopy (NIRS) and examine possible underlying mechanisms through evaluation of vascular cell adhesion molecule 1 (VCAM-1) levels. Methods SLE patients without a known neuropsychiatric history or treatment with antidepressants or antipsychotic drugs were enrolled. Participants were assigned into groups based on Beck’s Depression Inventory I (BDI-I). Patients with BDI-I score ≥10 comprised the SLE-depression group and those with BDI-I score Results Twenty-three patients were enrolled. During exercise, the SLE-depression group exhibited a significantly lower increase in cerebral O2Hb [(peak-O2Hb ( p = 0.039); O2Hb-area under the curve, AUC, p = 0.027) vs. SLE-non-depression group. BDI-I score was inversely correlated with AUC (rho = −0.493, p = 0.017) and positively correlated with VCAM-1 levels (rho = 0.501, p = 0.034). Conclusion This study suggests a possible association between emotional abnormalities and microvascular impairment (cerebral oxygenation and endothelial dysfunction) in SLE However, larger studies are needed to confirm these results.

Increased blood pressure variability (BPV) has been associated with an increased risk of subclinical organ damage and cardiovascular events, independently of elevated average BP values. We aimed to investigate the association of BPV indices with micro- and macrovascular parameters, some of them not previously studied.We evaluated 344 individuals (233 never-treated/newly diagnosed hypertensive and 111 normotensive individuals). BPV was assessed using average real variability (ARV) during 24-h, daytime and night-time ambulatory blood pressure monitoring, and systolic weighted standard deviation (wSD). Retinal microvascular diameter was assessed by nonmydriatic retinal photography. Arterial stiffness was assessed by pulse wave velocity (PWV) and aortic augmentation index (AIx); subendocardial variability ratio (SEVR) was used as an index of myocardial perfusion. Carotid intima-media thickness (cIMT) was measured by ultrasound. Data were analyzed using multiple regression analysis.After adjusting for potential confounders, PWV and cIMT were independently associated with ARV components in the total sample (P 0.023 and P 0.014, respectively). Within hypertensives only PWV and cIMT were independently associated with ARV components (P 0.002 for PWV and P 0.003 for cIMT). In contrast, within normotensives, only retinal parameters and AIx were associated with ARV components (P 0.017 and P = 0.013, respectively). None of the univariate correlations between vascular parameters and wSD remained significant after adjustment for potential confounders.Short-term BPV as assessed by ARV is independently associated with macrovascular parameters in untreated hypertensive patients, and with microvascular parameters in normotensive individuals.

Background The brain is one of the main target organs affected by hypertension. Impaired cerebral oxygenation during exercise is an indicator of cerebral dysfunction. We aimed to investigate whether cerebral oxygenation during exercise correlates with subclinical markers of early target organ damage in a population of middle-aged, newly diagnosed hypertensive and healthy individuals. Methods Carotid intima–media thickness (cIMT) was measured using ultrasound, arterial stiffness was estimated measuring the augmentation index and pulse wave velocity, and retinal vessel diameter was assessed via the central retinal-arteriolar and vein equivalent and retinal-arteriovenous ratio. Participants (n = 93) performed a 3-minute isometric handgrip exercise. Cerebral prefrontal oxygenation was measured continuously using near infrared spectroscopy. The average exercise responses in oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), and total hemoglobin (tHb) were assessed. Univariate analyses were performed; partial correlation was used to account for traditional cardiovascular risk factors to identify independent associations between cerebral-oxygenation indices and early markers of target organ damage. Results Mean cIMT was negatively correlated with the average exercise response in cerebral oxygenation (rhoO2Hb = −0.348, PO2Hb = 0.001; rhotHb = −0.253, Pthb = 0.02). Augmentation index was negatively correlated with cerebral oxygenation during exercise (rhoO2Hb = −0.374, P < 0.001; rhotHb = −0.332, P = 0.02), whereas no significant correlation was observed between pulse wave velocity and cerebral-oxygenation indices. In the adjusted analysis, cerebral oxygenation was correlated with central retinal arteriolar diameter (CRAE r = 0.233, P = 0.043). Conclusions Our novel findings suggest that indices of lower cerebral oxygenation during a submaximal physical task are associated with markers of early, subclinical target organ damage, namely increased cIMT, arterial stiffness, and arteriolar retinal narrowing in newly diagnosed, untreated, hypertensive individuals.

Allogeneic hematopoietic cell transplantation (alloHCT) survivors have been recently recognized as patients at increased cardiovascular risk. We hypothesized that vascular function remains impaired in alloHCT survivors free of graft-versus-host-disease or relapse. We enrolled consecutive adult alloHCT survivors and non-HCT control individuals (January 2019-March 2020), matched for traditional cardiovascular risk factors. Microvascular dysfunction was dynamically assessed in real time by Laser Speckle Contrast Analysis (LASCA). Carotid-femoral pulse-wave velocity (PWV) and carotid intima media thickness (IMT) were assessed as surrogate markers of cardiovascular disease. We studied 75 patients after a median of 3.2 (range 2.1-4.9) years from alloHCT, who had suffered from grade 2 to 3 acute (20%) and/or moderate/severe chronic GVHD (42%), and 75 controls. Although traditional cardiovascular risk factors and surrogate markers of cardiovascular disease did not differ between groups, alloHCT survivors showed significantly impaired microvascular function (baseline and peak flux, time to peak, base to peak and base to occlusion change). LASCA indices were also independently associated with alloHCT. Our study shows for the first-time impaired microcirculation dynamics in alloHCT survivors, independently of cardiovascular risk factors. Additional studies are needed to address the role of novel markers in cardiovascular risk prediction, along with effects of disease type, phase, and pre-transplant treatments.

Gestational diabetes mellitus (GDM) is a common medical complication during pregnancy. Endothelial dysfunction is considered an early step in the progression of atherosclerosis that may contribute to subclinical target organ damage. This meta-analysis aimed to systemically review the existing data regarding endothelial dysfunction between women with and without GDM during pregnancy and post-partum using flow-mediated dilation (FMD).Eligible studies (cohort and observational) published until October 2021 were identified in the MEDLINE, Scopus, Cochrane Library database and grey literature sources were searched.The search yielded 2272 studies, of which 17 were fully reviewed and 12 studies (N = 740 pregnant women) were finally included. Pregnant women with GDM exhibited a significantly lower FMD compared to pregnant women without GDM (pooled mean difference -3.12; 95% CI -5.36 to -0.88). Moreover, in the immediate (1-6 months) post-partum period, women with previous GDM showed lower FMD compared to healthy women without GDM history (pooled mean difference -7.52; 95% CI -9.44 to -5.59), whereas FMD did not differ in the late post-partum period (more than 4 years).Flow-mediated dilation is decreased in women with GDM during pregnancy and in the immediate post-partum period, compared to women without GDM, indicating that the endothelial dysfunction noted during the pregnancy in those women persists in the immediate post-partum period too.PROSPERO CRD42021283113 (www.gov).

Patients with longstanding diabetes exhibit diminished nocturnal blood pressure (BP) drop, yet this phenomenon remains understudied in the early stages of the disease. Eighty patients with newly diagnosed (

Objectives Systemic vasculitides (SVs) are a highly inflammatory group of diseases characterized by significant cardiovascular (CV) mortality. Microvascular damage closely linked with accelerated atherosclerosis and thrombosis represents a core pathophysiological mechanism contributing to the excess CV risk of patients with SVs. Skin represents an easily accessible tissue facilitating non-invasive microvascular study. In this study we aimed to investigate microcirculation dynamics and associate them with disease-related factors in patients with SVs. Methods We assessed skin microcirculation using laser speckle contrast imaging (LSCI) and vascular reactivity by the post-occlusive reactive hyperaemia (PORH) protocol in a meticulously selected group of patients with SVs without CV disease and compared them to controls, matched for age, sex, BMI and smoking status. Results Sixty individuals were included in the study, 30 patients and 30 controls. Patients with SVs presented a lower peak magnitude during reperfusion phase (median [interquartile range] 207 [60.1] vs 143.7 [41.0] laser speckle perfusion units, P Conclusion For the first time we have shown that patients with SVs exhibit impaired microvascular function and blunted reactivity after occlusion, as this was demonstrated by the LSCI technique. Therefore, skin microcirculation may be a useful, non-invasive method in patients with SVs for the early detection of microvascular dysfunction, which is closely related to the high CV risk that these patients bear.

Hypertension remains a major public health issue with inadequate control worldwide. The May Measurement Month (MMM) initiative by the International Society of Hypertension was implemented in Greece in 2019 aiming to raise hypertension awareness and control. Adult volunteers (≥18 years) were recruited through opportunistic screening in five urban areas. Information on medical history and triplicate sitting blood pressure (BP) measurements were obtained using validated automated upper-arm devices. Hypertension was defined as systolic BP ≥140 mmHg and/or diastolic ≥90 mmHg, and/or self-reported use of drugs for hypertension. A total of 5727 were analysed [mean age 52.7 (SD 16.6) years, men 46.5%, 88.3% had BP measurement in the last 18 months]. The prevalence of hypertension was (41.6%) and was higher in men and in older individuals. Among individuals with hypertension, 78.7% were diagnosed, 73.1% treated, and 48.3% controlled. Awareness, treatment, and control of hypertension were higher in women and in older individuals. Hypertensives had a higher body mass index (BMI) and were more likely to have diabetes, myocardial infarction and stroke, and less likely to smoke than normotensives (all P

This study aimed to assess the reliability of opportunistic screening programs in estimating the prevalence, treatment, and control rate of hypertension in the general population. Two recent epidemiological surveys obtained data on hypertension in the adult general population in Greece. The EMENO (2013–2016) applied a multi-stage stratified random sampling method to collect nationwide data. The MMM (2019) collected data through opportunistic (voluntary) screening in five large cities. Hypertension was defined as blood pressure (BP) ≥ 140/90 mmHg (single occasion; average of 2nd–3rd measurement; electronic devices) and/or use of antihypertensive drugs. Data from a total of 10,426 adults were analyzed (EMENO 4,699; MMM 5,727). Mean age (SD) was 49.2 (18.6)/52.7 (16.6) years (EMENO/MMM, p

Rather than being mere biomarkers reflecting generalized vascular injury, endothelial- (EMVs) and platelet-derived (PMVs) microvesicles have emerged as potent regulators of intercellular communication with significant biologic effects in vascular homeostasis and several pathophysiological responses including inflammation and thrombosis. So far, studies in hypertension are scarce, whereas no studies exist in masked hypertension (MH). We measured EMVs and PMVs in untreated, newly diagnosed hypertensives (HTs) and MHs compared to normotensive controls (NTs), and associated them with various cardiovascular risk factors. Sustained hypertension (SHT) and MH were defined according to standard blood pressure (BP) criteria. All HTs were free of cardiovascular disease and medications. Microvesicles' quantitation and detection were performed by flow cytometry by using cell-specific antibodies and corresponding isotypes (anti-CD105 and anti-CD144 for EMVs, anti-CD42a for PMVs, and Annexin V-fluorescein isothiocyanate for all microvesicles). In this study, we included 59 HTs (44 SHTs and 15 MHs) and 27 NTs. HTs had significantly elevated EMVs (p = 0.004), but not PMVs compared to NTs. MHs had significantly elevated EMVs compared to NTs (p = 0.012) but not compared to SHTs. Furthermore, EMVs significantly correlated with ambulatory (r = 0.214-0.284), central BP (r = 0.247-0.262), and total vascular resistance (r = 0.327-0.361). EMVs are increased not only in SHTs but also in MHs, a hypertension phenotype with a cardiovascular risk close to SHT. EMVs have emerged as active contributors to thromboinflammation and vascular damage and may explain, in part, the adverse cardiovascular profile of SHTs and MHs.

Vascular aging, characterized by structural and functional alterations of the vascular wall, is a hallmark of aging and is tightly related to the development of cardiovascular mortality and age-associated vascular pathologies. Over the last years, extensive and ongoing research has highlighted several sophisticated molecular mechanisms that are involved in the pathophysiology of vascular aging. A more thorough understanding of these mechanisms could help to provide a new insight into the complex biology of this non-reversible vascular process and direct future interventions to improve longevity. In this review, we discuss the role of the most important molecular pathways involved in vascular ageing including oxidative stress, vascular inflammation, extracellular matrix metalloproteinases activity, epigenetic regulation, telomere shortening, senescence and autophagy.

Psoriasis is associated with increased cardiovascular risk. Endothelial, platelet, and erythrocyte microvesicles (MVs) are novel biomarkers of endothelial dysfunction and thromboinflammation. We explored whether MVs of different cell types are elevated in patients with psoriasis, and investigated potential associations with disease severity and macrovascular function. Endothelial, platelet and erythrocyte MVs were measured using a standardized flow cytometry protocol in psoriasis patients and controls free from established cardiovascular disease. Carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were measured as markers of subclinical atherosclerosis and arterial stiffness. Psoriasis severity was assessed with PASI (Psoriasis Area Severity Index). Both platelet (p 0.001) and erythrocyte MVs (p = 0.046), yet not endothelial MVs, were significantly increased in patients with psoriasis (n = 41) compared with controls (n = 41). Patients with higher PASI (≥10) presented significantly higher levels of ErMVs compared to those with lower PASI (10) (p = 0.047). Carotid IMT and PWV were comparable between psoriasis patients and controls and did not significantly correlate with MVs. In the multivariate analysis, psoriasis was identified as an independent predictor of both platelet (p 0.001) and erythrocyte MVs (p = 0.043), while hypertension was independently associated with endothelial MVs (p 0.001). Increased formation of platelet and erythrocyte MVs may be evident in psoriasis patients and is indicative of prothrombotic, proinflammatory microenvironment, even in the absence of subclinical macrovascular dysfunction and before the clinical onset of overt cardiovascular complications. Potential mechanistic links and prognostic implications of increased MVs in psoriasis warrant further investigation.

The objective of this systematic review and meta‐analysis is to determine whether nocturnal blood pressure fall, expressed by dipping patterns according to ambulatory blood pressure monitoring (ABPM), is a risk factor for cardiovascular events (CVEs) in untreated hypertensives. Α thorough systematic literature search at MEDLINE, Embase, Cochrane Library, and gray literature was conducted through March 2020. Two reviewers screened studies and assessed dipping patterns of untreated hypertensives using ABPM with a follow‐up >6 months. Newcastle‐Ottawa scale was used for risk of bias assessment. We initially identified 463 reports; of which, seven cohort studies were eligible for meta‐analysis enrolling 10 438 untreated hypertensives. Untreated patients classified as dippers at baseline (n = 7081) had significant lower risk of CVEs and total mortality compared to non‐dippers (n = 3,357) [RR = 0.67, 95% CI (0.49, 0.92); RR = 0.71, 95% CI (0.59, 0.86)]. However, when patients were further classified into four dipping groups, only reverse dippers, yet not extreme dippers or non‐dippers, were at increased risk for CVEs compared to dippers [RR = 0.47, 95% CI (0.33, 0.66)]. Likewise, only reverse dippers had a higher stroke risk than dippers [RR = 0.39, 95% CI (0.22, 0.72)]. When compared with the whole group of dippers (including extreme dippers), non‐dipping alone (excluding reverse dipping) was not a significant risk factor for CVEs [RR = 0.84, 95% CI (0.61, 1.16)] or total mortality [RR = 0.84, 95% CI (0.61, 1.16); RR = 0.78, 95% CI (0.53, 1.13), respectively]. Untreated hypertensives may benefit more from the evaluation of reverse dipping rather than the non‐dipping phenomenon in general.

Background Endothelial dysfunction is associated with cardiovascular events and mortality in various disease states, including end-stage renal disease (ESRD). Novel technological approaches have emerged for real-time assessment of endothelial reactivity. This study examined skin microcirculation using laser speckle contrast imaging (LSCI) before and after arterial occlusion in ESRD patients undergoing haemodialysis (HD) or peritoneal dialysis (PD). Methods The 38 HD patients were matched in a 1:1 ratio with 38 PD patients (for age, sex and dialysis vintage) and 38 controls (for age and sex). Skin microvascular reactivity parameters assessed with LSCI included baseline perfusion, occlusion perfusion and peak perfusion during post-occlusive reactive hyperaemia (PORH); time to peak perfusion; proportional change from baseline to peak perfusion; baseline and peak cutaneous vascular conductance (CVC); proportional change from baseline to peak CVC and amplitude of the PORH response (i.e. the difference between peak and baseline CVC). Results Baseline perfusion [HD: 46.97 ± 14.6; PD: 49.32 ± 18.07; controls: 42.02 ± 11.94 laser specle perfusion units (LSPU), P = 0.097] and peak post-occlusion perfusion (104.77 ± 28.68 versus 109.04 ± 40.77 versus 116.96 ± 30.96 LSPU, P = 0.238) did not differ significantly between groups. However, the post-occlusive vascular response was completely different since the proportional increase from baseline to peak perfusion (HD: 133 ± 66; PD: 149 ± 125; controls: 187 ± 61%, P = 0.001) was significantly lower in ESRD patients and time to peak response was lower in HD but similar in PD patients compared with controls (HD: 7.24 ± 6.99; PD: 10.68 ± 9.45; controls: 11.11 ± 5.1 s, Kruskal–Wallis P = 0.003; pairwise comparisons: HD versus controls, P = 0.002; HD versus PD, P = 0.154; PD versus controls, P = 0.406). ESRD patients also had lower levels of peak CVC, indicating the maximum capillary recruitment (HD: 1.05 ± 0.3; PD: 1.07 ± 0.44; controls: 1.57 ± 0.52 LSPU/mmHg, P Conclusions Using this novel non-invasive technology, endothelial post-occlusive forearm skin vasodilatory response was found to be similar between HD and PD patients and significantly impaired compared with controls. Future studies are needed to assess the prognostic implications of this microcirculatory functional defect.

BACKGROUND Ambulatory pulse-wave velocity (PWV), augmentation pressure, and augmentation index (AIx) are associated with increased cardiovascular events and death in hemodialysis. The intermittent nature of hemodialysis generates a distinct ambulatory pattern, with a progressive increase of augmentation pressure and AIx during the interdialytic interval. No study so far has compared the ambulatory course of central hemodynamics and PWV between peritoneal dialysis and hemodialysis patients. METHODS Thirty-eight patients under peritoneal dialysis and 76 patients under hemodialysis matched in a 1 : 2 ratio for age, sex and dialysis vintage underwent 48-h ambulatory blood pressure (BP) monitoring with the oscillometric Mobil-O-Graph device. Parameters of central hemodynamics [central SBP, DBP and pulse pressure (PP)], wave reflection [AIx, heart rate-adjusted AIx; AIx(75) and augmentation pressure] and PWV were estimated from the 48-h recordings. RESULTS Over the total 48-h period, no significant differences were observed between peritoneal dialysis and hemodialysis patients in mean levels of central SBP, DBP, PP, augmentation pressure, AIx, AIx(75) and PWV. However, patients under peritoneal dialysis and hemodialysis displayed different trajectories in all the above parameters over the course of the recording: in peritoneal dialysis patients no differences were noted in central SBP (125.0 ± 19.2 vs. 126.0 ± 17.8 mmHg, P = 0.25), DBP, PP, augmentation pressure (13.0 ± 6.8 vs. 13.7 ± 7. mmHg, P = 0.15), AIx(75) (25.9 ± 6.9 vs. 26.3 ± 7.8%, P = 0.54) and PWV (9.5 ± 2.1 vs. 9.6 ± 2.1 m/s, P = 0.27) from the first to the second 24-h period of the recording. In contrast, hemodialysis patients showed significant increases in all these parameters from the first to second 24 h (SBP: 119.5 ± 14.4 vs. 124.6 ± 15.0 mmHg, P

Hypertension is a major modifiable risk factor for cardiovascular disease. Autoimmune rheumatic diseases confer increased cardiovascular risk, which is at least partially mediated by traditional cardiovascular risk factors. We examined the prevalence, awareness, treatment, and control rates of hypertension in a large cohort of patients with rheumatic diseases. Consecutive patients attending the Rheumatology Οutpatient Clinics were studied. Hypertension was defined by both the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines and the 2017 American College of Cardiology/American Heart Association (ACC/AHA). In a total of 622 individuals, hypertension prevalence reached 54.5% according to the 2018 ESH/ESC guideline, with the highest rates observed in patients with osteoarthritis (69.6%), rheumatoid arthritis (60.9%), and psoriatic arthritis (57.8%). Among hypertensive individuals, 21.7% were unaware of high blood pressure levels, while 67.2% were treated. Only 48.6% of treated hypertensives reached the 2018 ESC/ESH treatment goals. Applying the 2017 ACC/AHA criteria would result in a substantial increase of hypertension prevalence (72.4%) for both genders and especially among younger individuals, accompanied by a dramatic drop in control rates among treated patients (16.7%). In conclusion, comorbid hypertension was highly prevalent in a large cohort of patients with rheumatic diseases according to ESH/ESC and especially, ACC/AHA guidelines. However, it remains underdiagnosed and undertreated in a significant portion, while control rates are far from optimal. Our findings highlight the importance of systematic screening and more aggressive treatment of hypertension among patients with rheumatic diseases.

Background Increased urinary albumin excretion (UAE) in diabetes is a sensitive marker of microvascular injury and a reliable predictor of cardiovascular outcomes. Hypertension-induced hemodynamic pressure load, diabetes-related metabolic processes and large artery stiffening have all been implicated in the development of microalbuminuria. We investigated whether hyperglycemia per se, or rather increased blood pressure (BP) and macrovascular dysfunction, is a stronger predictor of UAE at the earliest stages of diabetes. Methods Consecutive newly diagnosed patients with diabetes type 2, who were normoglycemic within a year’s time prior to diagnosis, were enrolled. UAE was estimated in 24-h urine samples. Both office and 24-h ambulatory BP was recorded. Arterial stiffness was evaluated by measurement of carotid-femoral pulse wave velocity (PWV) with applanation tonometry. Results Among 71 newly diagnosed patients with median diabetes duration of just 1 month, 15.5% presented microalbuminuria. UAE did not differ between hypertensive and normotensive diabetics; however, newly diagnosed patients for both hypertension and diabetes exhibited significantly higher levels of UAE, compared to diabetic patients with long-standing hypertension. UAE strongly and significantly correlated with office systolic BP, HbA1c, PWV and estimated glomerular filtration rate. However, in the multivariate analysis adjusting for these factors, only HbA1c was independently associated with UAE (beta = 0.278, p = 0.049). Conclusions Hyperglycemic state emerges as a powerful predictor of increased UAE even at the earliest stages of diabetes. The relative contribution of hypertension and macrovascular dysfunction to the development of microalbuminuria seems to be obscured by hyperglycemia, even in patients whose diabetes onset does not exceed a few months’ time.

Hematopoietic cells and their microvesicles have recently emerged as novel markers of cardiovascular risk [...]

Subclinical brain lesions have been reported in systemic lupus erythematosus (SLE) patients. Advanced neuroimaging techniques have revealed microstructural and microvascular alterations. Most studies examining structural or functional brain abnormalities were performed either at rest or during a mental task. Our study aimed to examine possible differences in cerebral oxygenation during exercise between SLE patients without known neuropsychiatric manifestations and age-matched controls, using near-infrared-spectroscopy (NIRS) and examine possible underlying mechanisms through evaluation of brain derived neurotrophic factor (BDNF) levels.The protocol involved a seated rest, a 3-min submaximal (30%) handgrip exercise, and a 3-min recovery. Continuous-NIRS was used to monitor changes in cerebral-oxygenated (O2Hb), de-oxygenated (HHb) and total-haemoglobin (tHb). BDNF levels were measured in serum samples.Twenty-six SLE patients and 27 matched controls were enrolled. No differences were observed in baseline characteristics. During exercise, cerebral-O2Hb increased in both groups. However, SLE patients exhibited a significantly lower average- (1.20 ± 0.89 vs. 2.69 ± 2.46, p=0.001) and peak-O2Hb response (2.89 ± 1.56 vs. 5.83 ± 4.59, p=0.004) compared to controls. Serum BDNF levels were significantly lower in SLE patients compared to controls (p0.01).To our knowledge, this is the first study to evaluate cerebral oxygenation during exercise using NIRS in SLE patients compared to age-matched controls. Our data show that SLE patients even without overt neuropsychiatric manifestations exhibit a blunted increase in cerebral-O2Hb during a submaximal exercise stimulus. Examining brain oxygenation during a simple exercise task may assist in identifying patients with early alterations in cerebral function.

Primary aldosteronism (PA) is associated with considerably higher cardiovascular risk and increased prevalence of organ damage compared to essential hypertension (EH). Laser speckle contrast imaging (LSCI) has emerged as a novel non-invasive tool to assess of skin microcirculation. Our aim was to evaluate skin microvascular function (SMF) using LSCI coupled with post-occlusive reactive hyperemia (PORH) in a group of PA patients (PAs) compared to patients with EH (EHs) and normotensive controls (NTs). We enrolled PAs, age- and gender-matched with EHs and NTs. All participants underwent SMF assessment by LSCI with PORH. We enrolled 109 participants including 29 PAs, 47 EHs, and 33 NTs. SMF was significantly impaired in PAs, including peak time (p

Aim: To investigate the thrombotic microenvironment in early stages of type 2 diabetes mellitus measuring platelet-derived, endothelial-derived and erythrocyte-derived microvesicles. Methods: We recruited 50 newly diagnosed type 2 diabetes mellitus patients who did not receive glucose-lowering treatment except for metformin and 25 matched non-type 2 diabetes mellitus volunteers. Microvesicles were measured with flow cytometry, glycated haemoglobin with high-performance liquid chromatography and advanced glycation end products with enzyme-linked immunosorbent assay. Results: Type 2 diabetes mellitus patients showed significantly higher levels of platelet-derived microvesicles [195/μL (115–409) vs 110/μL (73–150), p = 0.001] and erythrocyte-derived microvesicles [26/μL (9–100) vs 9/μL (4–25), p = 0.007] compared to non-type 2 diabetes mellitus individuals. Platelet-derived microvesicles were positively associated with fasting blood glucose ( p = 0.026) and glycated haemoglobin ( p = 0.002). Erythrocyte-derived microvesicles were also positively associated with fasting blood glucose ( p = 0.018) but not with glycated haemoglobin ( p = 0.193). No significant association was observed between platelet-derived microvesicles ( p = 0.126) or erythrocyte-derived microvesicles ( p = 0.857) and advanced glycation end products. Erythrocyte-derived microvesicles predicted the presence of type 2 diabetes mellitus, independently of platelet-derived microvesicles. Conclusion: In newly diagnosed type 2 diabetes mellitus, ongoing atherothrombosis is evident during the early stages as evidenced by increased microvesicles levels. Furthermore, the association with glycemic profile suggests that microvesicles represent not only a novel mechanism by which hyperglycemia amplifies thrombotic tendency in type 2 diabetes mellitus but also early markers of thrombosis highlighting the need for earlier management of hyperglycemia.

Blood pressure levels are directly associated with cardiovascular and cerebrovascular morbidity and mortality, rendering arterial hypertension a major public health problem affecting almost 1 billion people worldwide. Several models have been used for cardiovascular risk prediction based on traditional cardiovascular risk factors. Among them, hypertension represents a factor that may be triggered by distinct pathogenetic mechanisms in specific disease populations. Accumulating evidence points towards an increased incidence of hypertension in patients with hematologic malignancies and recipients of hematopoietic cell transplantation. However, the role of hypertension in these entities remains under-reported in the relevant literature. In the complex setting of life-threatening conditions that need immediate and aggressive treatment, conditions that are common and easy to diagnose such as hypertension, may be neglected by treating physicians. However, hypertension may represent a key diagnostic and prognostic clinical finding in acute syndromes, such as thrombotic microangiopathy. Furthermore, hypertension may arise as a late effect of long-term survivors leading to increased morbidity and mortality across all age groups. Our concise review focuses on incidence, pathophysiology and management of hypertension in patients following hematopoietic cell transplantation and treatment for hematologic malignancies.

Cardiovascular risk is increased in patients with autoimmune rheumatic diseases. Endothelial, erythrocyte and platelet microvesicles (MVs) are elevated in patients with cardiovascular diseases and represent novel markers of endothelial dysfunction and thromboinflammation. We tested whether their levels are increased in patients with autoimmune rheumatic diseases (ARDs) in the absence of disease flare and cardiovascular comorbidities. Well-controlled patients with rheumatoid arthritis or systemic lupus erythematosus were studied, provided they were free from cardiovascular comorbidities and established cardiovascular disease. We additionally studied (a) a control group consisting of healthy volunteers and (b) a reference group including patients with stable coronary artery disease (CAD). MVs were measured using a standardized flow cytometry protocol. In a population of 74 participants, patients with ARDs (n = 17) presented increased levels of both endothelial (283.3 ± 195.0/μL vs 168.5 ± 54.8/μL, p = 0.029) and platelet MVs (374.0 ± 275.3/μL vs 225.7 ± 101.1/μL, p = 0.046) compared to controls (n = 34), whereas erythrocyte MVs did not significantly differ. In addition, patients with ARDs showed similar levels of endothelial MVs compared to CAD patients (n = 23) (283.3 ± 195.0/μL vs 297.0 ± 211.8/μL, p = 0.846). Platelet MVs were significantly associated with disease duration, and erythrocyte MVs with patients' perceived disease activity. In conclusion, increased levels of endothelial and platelet MVs may be evident in patients with ARDs, even in the absence of disease flares and before the establishment of cardiovascular complications. Levels of endothelial MVs resemble those of patients with profound atherothrombotic profile. The prognostic potential of MVs in terms of cardiovascular disease prevention warrants further investigation in patients with ARDs.

Patients with longstanding diabetes exhibit diminished nocturnal blood pressure (BP) drop, yet this phenomenon remains understudied in the early stages of the disease. Eighty patients with newly diagnosed (6 months) Diabetes Mellitus type 2 (T2DM) and 80 non-T2DM individuals underwent office and 24-h ambulatory BP measurements, estimation of hemodynamic parameters using impedance cardiography and blood tests. Ten-year atherosclerotic cardiovascular disease (ASCVD) risk score was calculated. T2DM patients exhibited higher nighttime systolic blood pressure (SBP) (p = 0.028) and lower dipping (p 0.001) compared to controls. In the total population, dipping correlated negatively with age, HbA

Innate immunity and chronic inflammation are involved in atherosclerosis and atherothrombosis leading to target organ damage in essential hypertension (EH). However, the role of neutrophils in EH is still elusive. We investigated the association between angiotensin II (Ang II) and neutrophil extracellular traps (NETs) in pathogenesis of EH. Plasma samples, kidney biopsies and surgical specimens of abdominal aortic aneurysms (AAA) from EH patients were used. Cell-based assays, NETs/human aortic endothelial cells co-cultures and in situ studies were performed. Increased plasma levels of NETs and tissue factor (TF) activity were detected in untreated, newly-diagnosed, EH patients. Stimulation of control neutrophils with plasma from untreated EH patients generated TF-enriched NETs promoting endothelial collagen production. Ang II induced NETosis in vitro via a reactive oxygen species (ROS)/peptidylarginine deiminase type 4 and autophagy-dependent pathway. Circulating NETs and thrombin generation levels were reduced significantly in EH patients starting treatment with Ang II receptor blockers, whereas their plasma was unable to trigger procoagulant NETs. Moreover, TF-bearing NETotic neutrophils/remnants were accumulated in sites of interstitial renal fibrosis and in the subendothelial layer of AAA. These data reveal the important pathogenic role of Ang II/ROS/NETs/TF axis in EH, linking thromboinflammation with endothelial dysfunction and fibrosis.