Search

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.

Familial Mediterranean Fever (FMF) is the most frequent autoinflammatory disease. This study aimed to evaluate the risk of subclinical vascular damage in FMF children, and young adults, using both imaging and laboratory tests. Forty-five FMF patients (mean age 14.3 ± 9.5 years, 33 children) and 44 healthy controls(mean age 13.3 ± 8.6 years, 36 children) were included in the study. The patients were diagnosed according to Tel-Hashomer criteria, were positive for MEFV gene mutation, were treated with colchicine and were evaluated during an attack free-period. The arterial stiffness parameters studied were carotid-femoral pulse wave velocity (PWV), Augmentation Index (Aix), subendocardial viability ratio (SEVR) and carotid intima-media thickness (cIMT). Laboratory parameters, inflammation markers and lipid profile were also evaluated for all participants. There were no significant differences between patients and healthy individuals, as well as in our children population regarding PWV, SEVR, Aix and cIMT. However, significantly higher ESR, CRP and fibrinogen levels were detected in the total population of FMF patients and higher amyloid levels in FMF children, compared to controls. Atherogenic Index of Plasma was significantly higher both in the total patient population and in the subgroup of children, compared to controls. Furthermore, a significant positive correlation between Aix and CRP and a negative correlation between SEVR and ESR became apparent in the pediatric subgroup. Our study demonstrated no significant differences in vascular measurements between FMF patients and controls. The above could be attributed to the regular colchicine treatment, which seems to have a cardioprotective role against vascular damage.

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.

Pheochromocytoma is a rare tumor frequently overlooked mainly due to the wide range of its clinical presentation, which may vary from entirely untypical signs and symptoms to life-threatening complications.The present study aims to present a case series recently treated in our center, with emphasis placed on patients' specific characteristics, clinical presentation and diagnostic evaluation. Relevant literature and current guidelines are being briefly reviewed to summarize screening for pheochromocytoma and appropriate diagnostic procedures.While the classic symptoms include headache, palpitations and sweating with permanent or paroxysmal hypertension, a wide range of clinical manifestations may be attributed to pheochromocytoma. The initial screening test is measurement of plasma or 24-hour urine metanephrine levels. Abdominal computerized tomography with intravenous contrast infusion is suggested as the imaging examination of choice, whereas magnetic resonance imaging should be preferred over CT in exceptional cases. 123I-metaiodobenzylguanidine scintigraphy is particularly useful for establishing the diagnosis of pheochromocytoma and should be further applied to detect or exclude possible metastatic lesions.Early diagnosis of pheochromocytoma is of great significance not only because it represents a curable form of secondary hypertension, but also because it is often related to familial syndromes, malignancy or metastatic disease. Physicians need to be familiar with relevant clinical manifestations and diagnostic steps to raise clinical suspiction of pheochromocytoma and establish a timely diagnosis.

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 (

Gestational diabetes mellitus (GDM) is associated with an increased risk for maternal and fetal complications. Patients with GDM have an increased cardiovascular risk in later life. The aim of this study was to investigate cardiac autonomic nervous system (ANS) function at rest and during exercise in women with GDM vs. women with uncomplicated pregnancies. Thirty-six normotensive pregnant women (21 with GDM and 15 age- and parity-matched women with an uncomplicated pregnancy) were enrolled in this case–control study. Continuous beat-by-beat blood pressure (BP) measurements were recorded during rest, intermittent handgrip exercise, and recovery (via photoplethysmography, Finapres®). Heart rate variability (HRV) (Kubios®) was used for the assessment of autonomic nervous system function. The groups were similar in age, gestational week, and handgrip strength. At rest, no differences in HRV indices [root mean square of successive differences (RMSSD), standard deviation Poincare plot 1, and 2 (SD1, SD2), SD2/SD1 ratio] were detected between women with GDM and women with an uncomplicated pregnancy. However, during exercise, a different pattern in the HRV responses was detected: in the control group, RMSSD and SD1 (indices of parasympathetic function) significantly decreased (p

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.

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.

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.

Arterial stiffness is a strong predictor of death and cardiovascular (CV) events in hemodialysis patients. Only few studies tested interventions aiming to improve arterial stiffness in this population. This study examines the effect of dry-weight reduction with a standardized lung-ultrasound-guided strategy on ambulatory aortic blood pressure (BP) and arterial stiffness parameters in hemodialysis. Seventy-one clinically euvolemic hemodialysis patients with hypertension, were included in this single-blind randomized clinical-trial. Patients were randomized in the active group (n = 35), following dry-weight reduction guided by the total number of US-B lines before a mid-week dialysis session and the control group (n = 36), following standard treatment. Patients underwent office evaluation of arterial stiffness and 48-h ABPM to capture ambulatory central systolic (cSBP) and diastolic BP (cDBP) and arterial stiffness indexes at baseline and after 8-weeks. US-B lines decreased in the active and slightly increased in the control group (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.

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

Background and Aims: This study investigated the possible correlation between elevated lipoprotein (a) (Lp(a)) levels and early vascular aging biomarkers in healthy children and adolescents. Methods: Twenty-seven healthy children/adolescents, mean age 9.9 ± 3.7 years, with high Lp(a) levels without other lipid abnormalities and 27 age- and sex-matched controls with normal Lp(a) levels, were included in the study. The investigation of possible early vascular aging was assessed by measuring vascular function indices: carotid intima-media thickness (c-IMT), pulse wave velocity (PWV), augmentation index (AIx), and subendocardial viability ratio (SEVR). Results: Although serum lipid values were within normal levels, mean values of total cholesterol and apolipoprotein B were higher in the group of children with high Lp(a) levels than controls (p = 0.006 and p < 0.001, respectively). Vascular function indices did not show significant differences, neither between the 2 groups nor in the subgroups of children with increased Lp(a) levels. These subgroups were defined by the presence or absence of family history of premature coronary artery disease. Lp(a) levels did not show a significant correlation with the other parameters studied, both regarding the whole sample (patients and controls), as well as in the subgroups of elevated Lp(a) levels. However, in the group of children with high Lp(a) levels, c-IMT and PWV were positively correlated with diastolic blood pressure (r = 0.427, p = 0.026 and r = 0.425, p = 0.030, respectively), while SEVR was negatively correlated with AIx (r = −0.455, p = 0.017). Conclusions: Healthy children and adolescents with high Lp(a) levels do not yet have impaired vascular indices, compared to controls. However, in order to prevent early atherosclerosis, it is crucial to early identify and follow up children with high Lp(a) levels and positive family history of premature coronary disease or other cardiovascular risk factors.

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.

Familial Mediterranean fever is a chronic inflammatory disease characterized by periodic and self-limited episodes of fever and aseptic polyserositis. Although colchicine treatment has altered the course of the disease, it is believed that subclinical inflammation is still present, leading to endothelial dysfunction and atherosclerosis in the course of time. In this review, following the published recommendations, we queried online databases such as MEDLINE Pubmed, Scopus, and Web of science for peer-reviewed studies and reviews written in English language, using the following keywords: familial Mediterranean fever, children, endothelial dysfunction, atherosclerosis, cardiovascular disease. The objective of this review is to highlight the correlation between familial Mediterranean fever and atherosclerosis, and moreover to describe new serum inflammatory markers and non-invasive methods of endothelial dysfunction, to detect the atherosclerosis process early starting from childhood.

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.