Identification and characteristics of patients with potential difficult-to-treat psoriatic arthritis: exploratory analyses of the Greek PsA registry.

OBJECTIVE: To present the characteristics of patients with potential difficult-to-treat (D2T) PsA. METHODS: We used data from the Greek multicentre registry of PsA patients. D2T PsA was defined as follows: patients with at least 6 months' disease duration, who have failed to at least one conventional synthetic DMARD and at least two biologic DMARDs/targeted synthetic DMARDs with a different mechanism of action and have either at least moderate disease activity (MODA) defined as DAPSA (Disease Activity index in PSoriatic Arthritis) >14, and/or are not at minimal disease activity (MDA). Demographic and clinical characteristics were compared between D2T and non-D2T PsA patients. In two sensitivity analyses, patients classified as D2T solely according to the MODA or MDA criterion were examined separately. RESULTS: Among 467 patients included, 77 (16.5%) were considered D2T and 390 non-D2T PsA. Compared with non-D2T, patients with D2T PsA presented more commonly with extensive psoriasis (P < 0.0001) and were more likely to have higher BMI (P = 0.023) and a history of IBD (P = 0.026). In the MODA and MDA sensitivity analyses, 7.5% and 12.5% of patients were considered D2T, respectively. In both sensitivity analyses, extensive psoriasis was again identified as an independent variable for D2T PsA (P = 0.001 and P = 0.008, respectively). Moreover, female gender (P = 0.034) in the MODA analysis and axial disease (P = 0.040) in the MDA analysis were independent variables for D2T PsA. CONCLUSION: Despite the availability of therapies, D2T PsA is common in real-life cohorts of patients with PsA and extensive psoriasis. High BMI, female gender, axial disease and history of IBD were also associated with D2T PsA.

Endothelial dysfunction and complement activation are independently associated with disease duration in patients with systemic vasculitis.

OBJECTIVES: Systemic vasculitis is a heterogenous group of autoimmune diseases characterized by enhanced cardiovascular mortality. Endothelial dysfunction is associated with accelerated vascular damage, representing a core pathophysiologic mechanism contributing to excess CV risk. Recent studies have also shown that complement activation holds significant role in the pathogenesis of Anti-Neutrophilic Cytoplasmic Autoantibody (ANCA) -associated vasculitis (AAV). Given the potential crosstalk between the endothelium and complement, we aimed to assess, for the first time simultaneously, easily accessible biomarkers of endothelial dysfunction and complement activation in SV. METHODS: We measured circulating endothelial microvesicles (EMVs) and soluble complement components representative of alternative, classical and terminal activation (C5b-9, C1q, Bb fragments, respectively) in a meticulously selected group of patients with systemic vasculitis, but without cardiovascular disease. Individuals free from systemic diseases, who were matched with patients for cardiovascular risk factors(hypertension, diabetes, smoking, dyslipidemia), comprised the control group. RESULTS: We studied 60 individuals (30 in each group). Patients with systemic vasculitis had elevated EMVs, higher levels of C5b-9 [536.4(463.4) vs 1200.94457.3), p = 0.003] and C1q [136.2(146.5 vs 204.2(232.9), p = 0.0129], compared to controls [232.0 (243.5) vs 139.3(52.1), p < 0.001]. In multivariate analysis both EMVs and C5b-9 were independently associated with disease duration (p = 0.005 and p = 0.004 respectively), yet not with disease activity. CONCLUSION: Patients with systemic vasculitis exhibit impaired endothelial function and complement activation, both assessed by easily accessible biomarkers, even in the absence of cardiovascular disease manifestations. EMVs and soluble complement components such as C5b-9 and C1q could be used as early biomarkers of endothelial dysfunction and complement activation, respectively, in clinical practice during the course of SV, yet their predictive value in terms of future cardiovascular disease warrants further verification in appropriately designed studies.

Microcirculation dynamics in systemic vasculitis: evidence of impaired microvascular response regardless of cardiovascular risk factors.

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 < 0.001) and lower percentage cutaneous vascular conductance increase (mean (s.d.) 190.0 [49.6]% vs 149.6 [48.9]%, P = 0.002) as compared with controls. Importantly, microvascular damage was correlated with disease duration (P < 0.001, r = -0.563 and P < 0.001, r = 0.442, respectively). 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.

Decreased flow-mediated dilation in gestational diabetes in pregnancy and post-partum. A systematic review and meta-analysis.

AIMS: 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). MATERIALS AND METHODS: Eligible studies (cohort and observational) published until October 2021 were identified in the MEDLINE, Scopus, Cochrane Library database and grey literature sources were searched. RESULTS: 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). CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42021283113 (www. CLINICALTRIALS: gov).

Depression in systemic lupus erythematosus: A manifestation of microcirculation dysfunction?

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 <9 the SLE-non-depression group. All participants underwent a protocol involving a seated rest, a 3-min handgrip exercise (at 30% of maximal strength), and a 3-min recovery. NIRS was used to monitor changes in cerebral oxygenated hemoglobin (O2Hb), deoxygenated (HHb), and total hemoglobin (tHb). VCAM-1 levels were measured in serum samples. 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.

Skin microcirculation dynamics are impaired in patients with rheumatoid arthritis and no cardiovascular comorbidities.

OBJECTIVES: Rheumatoid arthritis (RA) is associated with increased cardiovascular disease (CVD) risk. Microvascular endothelial dysfunction contributes to the development of vascular injury and subsequent CVD. We hypothesised that RA patients exhibit blunted microvascular reactivity regardless of CVD risk factors and investigated potential associations with coronary microvascular perfusion and surrogate markers of CVD. METHODS: This case-control study recruited RA patients and non-RA individuals in the absence of cardiovascular comorbidities. Skin microvascular reactivity was dynamically assessed using laser speckle contrast imaging coupled with post-occlusive reactive hyperaemia protocol. Applanation tonometry was applied to assess subendocardial viability ratio, an index of myocardial microvascular perfusion, and central arterial stiffness [carotid-femoral pulse wave velocity (PWV), augmentation index]. Peripheral arterial stiffness (carotid PWV, ß-stiffness index) and carotid atherosclerosis (intima-media thickness) were assessed with carotid ultrasound software. RESULTS: Skin microvascular responses before and following reperfusion [baseline flux, occlusion flux, time-to-peak, peak magnitude, peak-to-baseline magnitude, baseline cutaneous vascular conductance (CVC), and percentage increase in CVC] were significantly impaired in RA patients (n=35) compared to controls (n=35). Presence of RA independently predicted altered microvascular reactivity in multivariate analysis. Skin microcirculation dynamics significantly correlated with coronary microvascular perfusion and peripheral arterial stiffness, yet not carotid atherosclerosis, even after adjustment for CVD risk factors. CONCLUSIONS: Patients with RA present impaired microvascular reactivity regardless of CVD risk factors at a preclinical stage preceding CVD. Assessment of skin microvascular dysfunction may reflect a state of generalised vasculopathy, including myocardial microvascular abnormalities, and serve as a non-invasive surrogate indicator of CVD risk in RA.

Blunted cerebral oxygenation during exercise in systemic lupus erythematosus patients.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 (p<0.01). CONCLUSIONS: 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.

Assessment of vascular damage in children and young adults with Familial Mediterranean Fever.

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.

Skin microvascular dysfunction in systemic lupus erythematosus patients with and without cardiovascular risk factors.

OBJECTIVES: Patients with SLE have increased cardiovascular mortality. Alterations in both macro- and micro-circulation have been associated with cardiovascular disease. We sought to assess skin microvascular function by using laser speckle contrast analysis (LASCA) in patients with SLE, with and without cardiovascular disease and risk factors. METHODS: Continuous blood flow was recorded using a LASCA device during baseline, a 5-min arterial occlusion and a 5-min reperfusion period. RESULTS: Thirty-five patients with SLE (85.7% women) with a median disease duration 12.0 (6.5-17.5) years and a mean age of 46.3 (8.6) years and 31 controls matched for age, sex and BMI were enrolled. During reperfusion, SLE patients exhibited a smaller peak magnitude compared with controls (161.0 (47.1) vs 197.2 (41.4)%, respectively, P =0.002). Results remained unchanged among 24 SLE patients without cardiovascular disease compared with the control group (169.2 (48.1) vs 195.6 (34.0)%, respectively, P =0.002). CONCLUSION: Our study shows, for the first time, that patients with SLE, even without overt cardiovascular disease or risk factors, exhibit a blunted microvascular reactivity during reperfusion compared with controls. These results show that skin microvascular dysfunction is present in SLE independently of the CV burden that these patients bear and may represent an early sign of vascular damage.

Dietary nitrate improves muscle microvascular reactivity and lowers blood pressure at rest and during isometric exercise in untreated hypertensives.

OBJECTIVE: This double-blind, cross-over study examined in drug-naïve hypertensives the effects of a single dose of dietary nitrate (beetroot juice, BRJ) on (a) office/ambulatory BP and arterial stiffness, (b) muscle microvascular function, and (c) hemodynamic responses and cardiovagal baroreceptor sensitivity (cBRS) at rest and during isometric exercise. METHODS: Eighteen untreated hypertensives (44.0 ± 2.6 years) consumed randomly, a nitrate-rich (8.1 mmol-BRJnitrate ) and a nitrate-depleted (BRJplacebo ) BRJ. Office BP and pulse wave velocity were assessed before/after BRJ. An occlusion-reperfusion maneuver with continuous monitoring of muscle oxygenated hemoglobin (O2 Hb) and total hemoglobin (tHb), via NIRS, followed. Participants performed submaximal isometric handgrip with beat-by-beat monitoring of hemodynamics and cBRS. Ambulatory BP assessment followed. RESULTS: During reperfusion, following arterial occlusion, the magnitude and rate of muscle microvascular reoxygenation (O2 Hb) and red blood cell content (tHb) were higher in BRJnitrate vs BRJplacebo (P < 0.05), suggesting improved microvascular reactivity. Office/ambulatory BP were lower following BRJnitrate vs BRJplacebo (P < 0.05); pulse-wave-velocity was not altered. During isometric handgrip, BP and peripheral resistance rise were smaller in BRJnitrate vs BRJplacebo (P < 0.01-0.05), with no differences in cBRS. CONCLUSIONS: In drug-naïve hypertensives, a single dose of BRJ induces (a) short-term reductions in resting/ambulatory BP, (b) acute improvements in muscle microvascular function, and (c) attenuation in BP and peripheral resistance responses during isometric exercise.

Association of non-invasive hemodynamics with arterial stiffness in rheumatoid arthritis.

OBJECTIVES: Arterial stiffness has emerged as a surrogate marker of cardiovascular disease. We investigated the role of myocardial performance and hemodynamic parameters in arterial stiffness in patients with rheumatoid arthritis (RA), which is accompanied by excess cardiovascular risk. DESIGN: Arterial stiffness was evaluated with pulse wave velocity (PWV) in RA patients and controls. Cardiac and hemodynamic characterization was based on impedance cardiography. Cardiovascular risk factors, inflammatory markers and disease-related parameters were assessed. RESULTS: PWV (8.2 ± 2.1 vs 7.4 ± 1.4 m/s, p = .016) was higher among RA patients (n = 104) compared to controls (n = 52). In the RA group, PWV correlated with markers of cardiac contractibility (acceleration and velocity index), myocardial blood flow (cardiac output and stroke volume), preload (thoracic fluid content) and afterload (systemic vascular resistance) (p < .05 for all). PWV tended to increase with decreasing oxygen delivery to the myocardium (r = 0.055), as well as with shortening of the ejection duration of the left ventricle (p = .058). However, these associations no longer remained significant after adjustment for classical cardiovascular risk factors, inflammation and corticosteroid use, which were independently associated with PWV. CONCLUSIONS: Among patients with RA, arterial stiffness appears as the composite of cardiovascular risk factors and inflammation, while corticosteroid use emerges as an additional adverse factor.

Retinal vessel morphology in rheumatoid arthritis: Association with systemic inflammation, subclinical atherosclerosis, and cardiovascular risk.

OBJECTIVE: Quantification of retinal vessel morphology has emerged as a marker of cardiovascular health. We examined retinal microvascular diameters in RA, particularly in regard to systemic inflammation, subclinical atherosclerosis, and cardiovascular risk. METHODS: Retinal images from RA patients and controls were processed using computerized software, to obtain CRAE and CRVE and AVR. Subclinical atherosclerosis was assessed with cIMT, and 10-year risk of general cardiovascular disease was calculated. RESULTS: Both CRAE (78.8 ± 8.9 vs 90.2 ± 9.9 µm, P < .001) and AVR (0.69 ± 0.09 vs 0.81 ± 0.09, P < .001) were decreased in RA patients (n = 87) compared to controls (n = 46), whereas CRVE did not differ. Among RA patients, CRAE and AVR were inversely associated with both cIMT and CRP, whereas CRVE positively correlated with CRP (P < .05 for all). CRAE additionally correlated with cardiovascular risk score (r = -.396, P = .001). In the multivariate analysis, cardiovascular risk was associated with CRAE; age with CRVE, while CRP independently predicted AVR. CONCLUSIONS: Our study shows altered retinal microvascular morphology in RA patients. Inflammation appears as the biological link for the observed association between retinal microvascular abnormalities and subclinical atherosclerosis. Retinal arteriolar narrowing might play its own role in cardiovascular risk prediction in RA.

Neutrophil extracellular traps as immunofibrotic mediators in RA-ILD; pilot evaluation of the nintedanib therapy.

Objective: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a significant pulmonary complication of RA. This study tried to elucidate the mechanisms enhancing inflammation and causing lung injury in RA-ILD, focusing on the role of neutrophil extracellular traps (NETs). The study also investigated the potential benefits of nintedanib in advanced disease. Methods: Nine RA-ILD patients and nine healthy controls were included in the study. Inflammatory markers in patients' circulation were evaluated with immunoassays. The formation of NETs was examined using a citrullinated histone H3 (CitH3) ELISA and cell immunofluorescence. Inflammatory proteins expressed in neutrophils/NETs were studied with real-time qPCR and NET ELISA. To assess the effect of nintedanib, an intracellular tyrosine kinase inhibitor with antifibrotic properties, in RA-ILD a paired study was conducted in five patients before treatment administration and 16 weeks later. Results: The soluble terminal complement complex sC5b-9 and the levels of CitH3 were significantly elevated in patients with RA-ILD, compared to healthy controls. In addition, neutrophils isolated from RA-ILD patients released NETs enriched with tissue factor and interleukin-17A. Inflammatory NETs had a dynamic role, increasing the fibrotic potential of human pulmonary fibroblasts (HPFs). On the other hand, nintedanib treatment decreased NETs and sC5b-9 levels in RA-ILD patients. Conclusion: The findings propose an interplay between circulating NETs and HPFs, establishing the immunofibrotic aspects of RA-ILD. They also support the effectiveness of nintedanib in reducing key pathological processes of the disease. Further research is needed to fully understand these mechanisms and optimize treatment strategies for RA-ILD.

Skin Microvascular Dysfunction in Type 2 Diabetes Mellitus Using Laser Speckle Contrast Analysis and Association with Carotid Intima-Media Thickness.

Background: It is established that diabetes mellitus (DM) is characterized by increased cardiovascular risk associated with subclinical atherosclerosis as well as microvascular alterations. Laser speckle contrast analysis (LASCA) is an innovative, non-invasive method for assessing skin microvascular function. Objectives: We sought to assess skin microvascular function in patients with type 2 DM and matched controls. Methods: Consecutive patients with DM and individuals matched for age, sex and BMI were included in the study. Skin microvascular perfusion was assessed, using LASCA, during baseline, a 5 min occlusion period and a 5 min reperfusion period. Carotid intima-media thickness (cIMT) was measured as a surrogate marker of macrocirculation. Results: In total, 18 patients with DM and 22 in the control group were enrolled. No statistically significant differences were observed in baseline flux, peak flux and percentage decrease during arterial occlusion. During reperfusion, individuals with DM exhibited a smaller peak magnitude compared to controls (147.0 ± 64.7% vs. 189.4 ± 46.0%, respectively; p < 0.05). Moreover, cIMT was higher in patients with DM compared to controls (0.68 ± 0.09 mm vs. 0.60 ± 0.08 mm, respectively, p < 0.01) and was negatively correlated with skin microvascular reactivity in the univariate analysis. In the multivariate analysis, glucose and office systolic blood pressure levels remained significant predictors of microvascular reactivity. Conclusions: Our study shows that patients with type 2 DM exhibit impaired skin microvascular function compared to controls. Furthermore, glucose levels and blood pressure play a key role in microvascular dysfunction. However, additional studies are needed to address the clinical significance of early microvascular changes in DM.

State of the Art Review on the Treatment of Psoriatic Disease.

Introduction: Psoriasis is an inflammatory skin disease that in some cases is accompanied by systemic manifestations. Given the varied clinical manifestations, the term psoriatic disease probably better reflects the clinical picture of these patients. Literature review: In most cases, the skin lesions precede joint involvement as well as other potentially involved organs such as the intestine and the eye. Various immune-mediated cellular pathways such as that of TNFα, IL-23, IL-17 as well as other cytokines are involved in the pathophysiology of the psoriatic disease. Future insights: A better understanding of the way they interfere with our immune system has led to remarkably better disease control and outcomes. This review aims to highlight the newest treatments for psoriatic disease, which are expected to significantly reduce unmet needs and treatment gaps.

Accumulation of Microvascular Target Organ Damage in Systemic Lupus Erythematosus Patients Is Associated with Increased Cardiovascular Risk.

Background: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease associated with increased cardiovascular (CV) burden. Besides increased arterial stiffness and subclinical atherosclerosis, microvascular dysfunction is considered an important component in the pathophysiology of CV disease. However, there is a lack of data regarding the effect of multiple target organ damage (TOD) on CV health. Objectives: This study aimed to evaluate (i) the presence of microvascular changes in SLE in various vascular beds, (ii) the possible associations between the accumulation of microvascular TOD and CV risk and (iii) whether Galectin-3 represents a predictor of combined microvascular TOD. Methods: Participants underwent (i) evaluation of skin microvascular perfusion (laser speckle contrast analysis), (ii) fundoscopy (non-mydriatic fundus camera), (iii) indirect assessment of myocardial perfusion (subendocardial viability ratio) and (iv) determination of urine albumin-to-creatinine ratio (UACR). CV risk was calculated using the QResearch Risk Estimator version 3 (QRISK3). Serum Galectin-3 levels were determined. Results: Forty-seven SLE patients and fifty controls were studied. SLE patients demonstrated impaired skin microvascular reactivity (160.2 ± 41.0 vs. 203.6 ± 40.1%), retinal arteriolar narrowing (88.1 ± 11.1 vs. 94.6 ± 13.5 µm) and higher UACR levels compared to controls. Furthermore, SLE individuals had significantly higher Galectin-3 levels [21.5(6.1) vs. 6.6(6.6) ng/dL], QRISK3 scores [7.0(8.6) vs. 1.3(3.6)%] and a greater chance for microvascular dysfunction. In the SLE group, patients with multiple TOD exhibited higher QRISK3. In the multivariate analysis, the accumulation of TOD correlated with disease activity and Galectin-3 (p < 0.05). Conclusions: Our study showed for the first time that SLE patients exhibit a greater number of cases of TOD. The accumulation of TOD was associated with increased CV risk. Clinicians dealing with SLE should be aware and seek microvascular alterations.

Microvascular and Endothelial Dysfunction in Prediabetes.

Prediabetes is a significant metabolic status since there is high potential for future progression of diabetes mellitus (DM). People with prediabetes are at increased risk of cardiovascular disease (CVD) and mortality. Endothelial and microvascular dysfunction is considered a key step towards the development and progression of CVD. Importantly, endothelial and microvascular dysfunction can be detected and monitored using non-invasive procedures in peripheral organs and tissues, including the retina, kidney, skin and skeletal muscle. Structural and functional alterations of the microvasculature have been consistently documented in the above microvascular beds in patients with diabetes mellitus. In contrast, such alterations remain understudied in prediabetes, but are currently receiving attention as markers of subclinical and future CVD. The aim of this review is to summarize available evidence regarding the presence of subclinical microvascular and endothelial dysfunction in prediabetes and their impact on cardiovascular risk.

Relationship of 24-h ambulatory blood pressure variability with micro and macrovascular parameters and hypertension status.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Short-term BPV as assessed by ARV is independently associated with macrovascular parameters in untreated hypertensive patients, and with microvascular parameters in normotensive individuals.

Clinical, Serological, and Immunological Characteristics of Greek Patients with Polymyalgia Rheumatica and/or Giant Cell Arteritis: A Research Protocol.

Polymyalgia Rheumatica (PMR) and Giant Cell Arteritis (GCA) are chronic inflammatory disorders that usually affect older people. Although the aetiology of these diseases remains unknown, genetic, environmental, and immune factors have been implicated. Specific cytokines such as the IL-6, IL-1ß, IL-12, IL-17, and interferon -γ seem to play an essential role. The diagnosis of the disease is usually based on clinical manifestations and the use of histology or imaging, while disease monitoring is based on physical examination, laboratory, and imaging findings. However, there is the unmet need in identifying possible biomarkers that could help the diagnosis and the monitoring as well. The present study aims to investigate the epidemiological, clinical, and immunological characteristics of PMR and/or GCA patients in the region of northwest Greece and to evaluate the role of specific molecules associated with the pathogenesis of the diseases, giving evidence to possible future biomarkers.

Uterine Arteries Resistance in Pregnant Women with Gestational Diabetes Mellitus, Diabetes Mellitus Type 1, Diabetes Mellitus Type 2, and Uncomplicated Pregnancies.

BACKGROUND: The examination of the uterine arteries using Doppler in the first trimester of pregnancy serves as a valuable tool for evaluating the uteroplacental circulation. Diabetes mellitus is associated with altered placental implantation and pregnancy-related pathologies, such as preeclampsia. The aim of this study was to compare the uterine arteries' pulsatility indices (UtA PI) in women with diabetes mellitus type 1 (DM1), diabetes mellitus type 2 (DM2), gestational diabetes mellitus (GDM), and uncomplicated pregnancies. METHODS: This was a retrospective case-control trial including pregnant women with DM1, DM2, GDM, and uncomplicated pregnancies, presenting for first-trimester ultrasound screening in two tertiary university hospitals between 2013 and 2023. The first-trimester UtA pulsatility index (PI), expressed in multiples of medians (MoMs), was compared between the four groups. RESULTS: Out of 15,638 pregnant women, 58 women with DM1, 67 women with DM2, 65 women with GDM, and 65 women with uncomplicated pregnancies were included. The mean UtA PI were 1.00 ± 0.26 MoMs, 1.04 ± 0.32 MoMs, 1.02 ± 0.31 MoMs, and 1.08 ± 0.33 MoMs in pregnant women with DM1, DM2, GDM, and uncomplicated pregnancies, respectively (p > 0.05). CONCLUSIONS: Potential alterations in the implantation of the placenta in pregnant women with diabetes were not displayed in the first-trimester pulsatility indices of the uterine arteries, as there were no changes between the groups.