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.

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.

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.

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.

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.

Measurement and Changes in Cerebral Oxygenation and Blood Flow at Rest and During Exercise in Normotensive and Hypertensive Individuals.

PURPOSE OF REVIEW: Summarize the methods used for measurement of cerebral blood flow and oxygenation; describe the effects of hypertension on cerebral blood flow and oxygenation. RECENT FINDINGS: Information regarding the effects of hypertension on cerebrovascular circulation during exercise is very limited, despite a plethora of methods to help with its assessment. In normotensive individuals performing incremental exercise testing, total blood flow to the brain increases. In contrast, the few studies performed in hypertensive patients suggest a smaller increase in cerebral blood flow, despite higher blood pressure levels. Endothelial dysfunction and increased vasoconstrictor concentration, as well as large vessel atherosclerosis and decreased small vessel number, have been proposed as the underlying mechanisms. Hypertension may adversely impact oxygen and blood delivery to the brain, both at rest and during exercise. Future studies should utilize the newer, noninvasive techniques to better characterize the interplay between the brain and exercise in hypertension.

Familial Mediterranean fever and atherosclerosis in childhood and adolescence.

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.

The impact of hyperglycemia on urinary albumin excretion in recent onset diabetes mellitus type II.

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.

Urinary albumin excretion in rheumatoid arthritis is not associated with markers of vasculopathy in distal microvascular beds.

OBJECTIVE: Increased UAE is a marker of generalized vascular damage in high-cardiovascular risk patients. However, it remains unknown whether it corresponds to a state of diffuse vasculopathy in high-risk patients with RA. METHODS: UAE was estimated in 24-hour urine samples in RA and non-RA individuals. Retinal arteriolar and venular diameters were calculated from retinal images with computerized software. SEVR was estimated as an index of microvascular coronary perfusion with applanation tonometry. Dermal capillary density was measured from images obtained with nailfold capillaroscopy, using specifically designed software. RESULTS: In a total of 111 individuals, neither UAE (5.1 [2.8-10.8] vs 6.5 [3.0-11.7] mg/24 h) nor prevalence of microalbuminuria (11.0% vs 8.1%) significantly differed between patients (n = 74) and controls (n = 37). In the RA group, UAE was not significantly associated with inflammation, nor with any of the studied microvascular indices of the retinal microvasculature, the coronary microcirculation, and the dermal capillary network. CONCLUSION: Among RA patients, UAE was not associated with markers of vasculopathy in distal microvascular beds. Increased UAE in RA might be primarily considered as a manifestation of localized, compromised function of the renal microvasculature, rather than a marker of generalized microvascular impairment.

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.

Dermal capillary rarefaction as a marker of microvascular damage in patients with rheumatoid arthritis: Association with inflammation and disorders of the macrocirculation.

OBJECTIVE: Capillary rarefaction is observed in various cardiovascular diseases, yet it remains understudied in RA, a chronic inflammatory disease accompanied by excess cardiovascular risk. We quantified capillary density in RA patients and explored potential associations with macrocirculatory disorders, inflammation, and cardiovascular risk. METHODS: Dermal capillary density was assessed with nailfold capillaroscopy in RA and non-RA individuals, using specifically designed semiautomated software. Macrocirculation assessments included large artery stiffening, evaluated with PWV, and myocardial blood flow, calculated as cardiac index from impedance cardiography. Cardiovascular risk score was estimated from the Framingham Heart Study. RESULTS: The number of capillaries per visual field was lower in patients (n = 99) compared to controls (n = 35) (132.6 ± 30.3 vs 152.9 ± 25.2, P = .001). In the RA group, capillary density negatively correlated with CRP and PWV, and positively with HDL and cardiac index. In the multivariate analysis, CRP independently predicted capillary rarefaction (P = .044). Capillary density significantly correlated with cardiovascular risk, even after adjustment for inflammation (P = .030). CONCLUSION: Capillary rarefaction appears pronounced in RA and correlates with lower cardiac output, increased arterial stiffness, and cardiovascular risk. However, the associations with macrocirculatory disorders may be obscured by inflammation, which appears as the major contributor to capillary rarefaction in RA.

Beetroot Increases Muscle Performance and Oxygenation During Sustained Isometric Exercise, but Does Not Alter Muscle Oxidative Efficiency and Microvascular Reactivity at Rest.

OBJECTIVE: To examine the effects of beetroot juice (BRJ) on (i) in vivo skeletal muscle O2 consumption (mVO2) and microvascular reactivity at rest and (ii) muscle performance, muscle oxygenation, and mVO2 during sustained isometric handgrip exercise (IHG). METHODS: Sixteen young males consumed, randomly, a nitrate-rich (8.1 mmol BRJnitrate) or nitrate-depleted (BRJplacebo) BRJ. After 2.5 hours, they performed an occlusion-reperfusion maneuver at rest, a 3-minute sustained IHG, and a sustained IHG to exhaustion with arterial occlusion. Changes in muscle oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), microvascular red blood cell content (tHb), and mVO2 were measured using near-infrared spectroscopy. Force output was recorded. RESULTS: During occlusion, the O2Hb decline did not differ between BRJnitrate and BRJplacebo (magnitude: -30.3 ± 1.6 vs. -31.1 ± 1.5 ΔµΜ; slope: -0.107 ± 0.007 vs. -0.111 ± 0.007 µΜ second-1). During reperfusion, all microvascular reactivity indices were not altered after BRJnitrate (e.g., O2Hbslope: 1.584 ± 0.093 vs. 1.556 ± 0.072 µΜ second-1). During the second and third minute of IHG, O2Hb and tHb were higher in BRJnitrate versus BRJplacebo (p < 0.05), and force output was higher during the third minute (10.8 ± 0.7 vs. 9.5 ± 1.2 kg; p < 0.05); HHb did not differ between trials. In IHG with arterial occlusion, BRJnitrate prolonged the time to fatigue (94.1 ± 5.8 vs. 80.1 ± 3.3 seconds; p < 0.01), with no effects on O2Hb decline (O2Hbslope: -0.226 ± 0.015 vs. -0.230 ± 0.026 µΜ s-1) and mVO2 (14.1 ± 1.0 vs. 14.3 ± 1.6 µmol l-1 minute-1). CONCLUSION: Acute BRJ ingestion in moderately trained individuals (i) did not alter in vivo skeletal muscle microvascular reactivity (index of microvascular function at rest) and basal oxidative efficiency, (ii) increased muscle oxygenation during IHG (possibly via enhanced O2 delivery), and (iii) provided ergogenic benefits during sustained IHG with no effects on muscle oxidative efficiency. The ergogenic effects of BRJ appeared independent of its tissue perfusion benefits.

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.

Impairments in microvascular function and skeletal muscle oxygenation in women with gestational diabetes mellitus: links to cardiovascular disease risk factors.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is a risk factor for the development of endothelial dysfunction and cardiovascular disease. However, in vivo microvascular endothelial function in GDM has not been investigated. This study aimed to examine, using near-infrared spectroscopy (NIRS), whether: (1) there are differences in microvascular reactivity and skeletal muscle oxygen consumption (m[Formula: see text]) at rest and during exercise between GDM and uncomplicated pregnancies; and (2) there is an association of NIRS indices with macrovascular function and cardiovascular disease risk factors. METHODS: Twenty-nine pregnant women (13 with GDM and 16 women with uncomplicated pregnancy, 28 ± 2 gestational weeks) underwent arterial stiffness (pulse wave velocity [PWV]) and 24 h ambulatory BP (24 h BP) evaluation. NIRS continuously monitored, non-invasively, changes in muscle oxygenated and deoxygenated haemoglobin and tissue O2 saturation index (TSI, %) during arterial occlusion/reperfusion and intermittent handgrip exercise. m[Formula: see text] and vascular reactivity indices were calculated. RESULTS: During occlusion and reperfusion, women with GDM exhibited slower TSI response (occlusion slope: -0.06 ± 0.02 vs -0.10 ± 0.04, in GDM and controls, respectively; reperfusion slope: 0.65 ± 0.26 vs 1.05 ± 0.41, respectively), lower m[Formula: see text] (1.3 ± 1.2 vs 3.8 ± 2.3 µmol l-1 min-1) and blunted hyperaemia (ΔTSI 6.8 ± 2.9 vs 9.5 ± 3.4) compared with controls (p < 0.01). Despite similar handgrip strength in the GDM and control groups (29.1 ± 8.1 vs 26.2 ± 10.4 kg, respectively), during repeated forearm contractions, women with GDM presented a blunted TSI response (6.5 ± 3.9 vs 19.2 ± 10.9; p < 0.01) and a reduced capacity to maintain the predetermined handgrip (23.4 ± 2.9 vs 27.4 ± 3.8%, p < 0.05). NIRS indices correlated with PWV, 24 h BP and blood glucose concentration earlier in pregnancy (r = 0.40-0.60; p < 0.05). CONCLUSIONS/INTERPRETATION: Women with GDM exhibited a characteristic blunted TSI curve, showing alterations in muscle oxygenation and microvascular responsiveness compared with women with uncomplicated pregnancies. These alterations were manifested during exercise and possibly contribute to the reduced exercise tolerance in GDM. NIRS indices correlated with macrovascular indices (arterial stiffness) and 24 h BP.

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.

Clinical Significance of Endothelial Dysfunction in Essential Hypertension.

The endothelium is recognized as a major determinant of vascular physiology and pathophysiology. Over the last few decades, a plethora of studies have implicated endothelial dysfunction in the progression of atherosclerosis and the subclinical target organ damage observed in essential hypertension. However, the clinical significance of diagnosing endothelial dysfunction in patients with essential hypertension remains under investigation. Although a number of vascular and non-vascular markers of endothelial dysfunction have been proposed, there is an ongoing quest for a marker in the clinical setting that is optimal, inexpensive, and reproducible. In addition, endothelial dysfunction emerges as a promising therapeutic target of agents that are readily available in clinical practice. In this context, a better understanding of its role in essential hypertension becomes of great importance. Here, we aim to investigate the clinical significance of endothelial dysfunction in essential hypertension by accumulating novel data on (a) early diagnosis using robust markers with prognostic value in cardiovascular risk prediction, (b) the association of endothelial dysfunction with subclinical vascular organ damage, and (c) potential therapeutic targets.

Capillary rarefaction as an index for the microvascular assessment of hypertensive patients.

Arterial hypertension represents a leading cause of cardiovascular mortality and morbidity worldwide through its detrimental effects on target organs. Therefore, the early identification and appropriate management of high-risk patients emerges as extremely important. Given that the microvasculature is subject to a series of morphological and functional changes under the continuous effect of high blood pressure, research over the last years has gradually moved toward the identification of specific microcirculatory alterations that may serve as early prognostic markers of cardiovascular risk. Dermal capillaries represent an "open window" for the in vivo study of human microcirculation that has been long used mainly for the study of rheumatic diseases. However, capillaroscopy has been relatively understudied and only recently applied in the field of hypertension. Capillaroscopy represents a forthcoming promising estimate of the microvascular status in hypertensive patients, with capillary rarefaction representing the most typical finding. The present review aims at summarizing available evidence and the main findings, as well as the premises and promises, of capillary rarefaction as a tool for evaluating patients with hypertension.