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.

Skin microvascular function, as assessed with laser speckle contrast imaging, is impaired in untreated essential and masked hypertension.

Skin microcirculation has been proposed as a model of generalized microvascular function. Laser speckle contrast imaging (LSCI) is a novel, noninvasive method to assess skin microvascular function (SMF). To date, SMF data in hypertension are conflicting, and no study with LSCI exists. In addition, the application of LSCI in masked hypertension is scarce. We assessed SMF with LSCI coupled with postocclusive reactive hyperemia (PORH) in patients with newly diagnosed untreated essential hypertension (UHT) and masked hypertension (MH) compared to healthy normotensive (NT) individuals. We enrolled consecutive UHT and MH patients and NT individuals matched for age, sex, body mass index, and smoking status. All participants underwent SMF assessment by LSCI coupled with PORH (PeriCam PSI system, Perimed, Sweden). Correlation analyses were performed between SMF and common cardiovascular risk factors and BP parameters. In total, 70 UHT patients, 20 MH patients and 40 NT individuals were enrolled. UHT and MH patients exhibited significantly impaired SMF compared to NT individuals (UHT patients: base-to-peak flux (p < 0.001)), PORH amplitude (p < 0.001); MH patients: base-to-peak flux (p = 0.013), PORH amplitude (p = 0.022). MH patients did not differ compared to UHT patients. SMF was negatively associated with office, ambulatory and central BP. SMF was negatively associated with blood lipids and smoking. Hypertensive status was the single most important predictor of SMF. UHT and MH patients exhibit impaired SMF compared to NT individuals. MH patients did not differ compared to UHT patients. SMF is negatively associated with BP and cardiovascular risk factors. LSCI could be implemented as a useful tool to investigate SMF in hypertension.

Hypertension in rheumatic diseases: prevalence, awareness, treatment, and control rates according to current hypertension guidelines.

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.

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.

Vascular acrosyndromes in young adult population. Definition of clinical symptoms and connections to joint hypermobility.

OBJECTIVES: Clinical recognition of vascular acrosyndromes is often challenging. The term Raynaud's phenomenon (RP) is commonly overused to describe any form of cold-related disorder. This study aims to formally evaluate peripheral vascular symptoms affecting the population, aged ≤ 40 years, and identify any correlations to joint hypermobility (JH). PATIENTS AND METHODS: Fifty patients (31 males, 19 females) with vasomotor symptoms enrolled in this five-year prospective observational study. Clinical examination by a rheumatologist and a vascular surgeon was performed along with cardiology, echocardiographic and Doppler evaluation. Patients underwent blood cell count, biochemistry, thyroid and selectively immunologic testing. Twenty-four (48%) of them performed nailfold capillaroscopy. The SPSS for Windows, v.17.0, Chicago, USA, was used for the statistical analyses. RESULTS: Twenty-eight patients (56%) presented with erythromelalgia (EM), 6 (12%) with acrocyanosis (AC) and 9 (18%) as a combination of the above disorder. RP diagnosed in five (10%) while two patients (4%) presented as a mix of EM-RP. There was no correlation with abnormal laboratory tests. Increased incidence of JH was found in EM and AC patients. Among those who were tested with nailfold capillaroscopy, 75% had abnormalities ranged from mild to autoimmune-like diseases. CONCLUSIONS: Erythromelalgia is the commonest functional vasculopathy in young population followed by acrocyanosis and a combination of these conditions. Joint hypermobility is markedly increased, indicating that dysautonomy may be considered the causative factor following a trigger event. Overall, RP was observed in 14% of patients. Clinical recognition of these disorders avoids unnecessary investigation. Key Points • Vascular acrosyndromes in young adults are commonly functional disorders resembling vascular algodystrophy induced by thermic stress. • Dysautonomy of joint hypermobility is the co-factor influencing the appearance of the vascular disorders. • Raynaud's phenomenon accounts to approximately 14% of vascular acrosyndromes presented in the young adult population.

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.

Association of galectin-3 with markers of myocardial function, atherosclerosis, and vascular fibrosis in patients with rheumatoid arthritis.

BACKGROUND: Galectin-3 has emerged as a promising novel biomarker of cardiovascular fibrosis in patients with cardiovascular diseases. HYPOTHESIS: We investigated whether galectin-3 correlates with markers of vascular fibrosis, subclinical atherosclerosis, and cardiac function in patients with rheumatoid arthritis (RA), a disease accompanied by high cardiovascular risk. METHODS: RA and non-RA individuals underwent applanation tonometry, carotid ultrasound, and impedance cardiography, to obtain markers of arterial stiffness, subclinical atherosclerosis, and myocardial function, respectively. Cardiovascular risk was estimated from the Framingham Heart Study. Serum levels of galectin-3 were determined by enzyme-linked immunosorbent assay. RESULTS: Galectin-3 was elevated in RA patients (n = 85) compared to controls (n = 39), but this difference was no longer significant after adjustment for the presence of cardiovascular comorbidities. In the univariate analysis, galectin-3 significantly correlated with markers of vascular stiffness (including pulse wave velocity, central blood pressure, central and peripheral pulse pressure, and total arterial compliance); atherosclerosis (carotid intima-media thickness); myocardial blood flow (cardiac output, stroke volume) and contractibility (acceleration and velocity index); systemic vascular resistance, and estimated cardiovascular risk. Multivariate analysis models revealed an independent association between galectin-3 and both cardiac output (ß = -0.274, P = 0.039), as well as systemic vascular resistance (ß = 0.266, P = 0.039). CONCLUSIONS: In a relatively well-controlled cohort of RA patients with low-grade systemic inflammation and long-standing disease, serum galectin-3 might be useful as a marker of cardiac function and cardiovascular fibrosis.

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.

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.

Association of nocturnal blood pressure patterns with inflammation and central and peripheral estimates of vascular health in rheumatoid arthritis.

Predictors of adverse cardiovascular outcomes include elevated nighttime systolic blood pressure (SBP) and a non-dipping pattern. We investigated whether these factors correlate with systemic inflammation, cardiovascular risk, and markers of central and peripheral vascular damage in rheumatoid arthritis (RA), a disease characterized by excess cardiovascular risk. Twenty-four-hour ambulatory blood pressure monitoring was applied in patients and controls. Vascular assessments included measurement of arterial stiffness (pulse wave velocity) and carotid atherosclerosis (carotid intima-media thickness). Peripheral vascular resistance was estimated from impedance cardiography. Cardiovascular risk was calculated from the Framingham Heart Study. RA patients exhibited a higher prevalence of non-dipping pattern, elevated nighttime SBP and blunted dipping, compared to controls without cardiovascular comorbidities. Among RA patients, dipping levels correlated with arterial stiffness, and nighttime SBP with all vascular markers and cardiovascular risk. After adjustment for inflammation, the above associations with vascular measures were no longer significant. Plain categorization to dippers and non-dippers did not reveal any differences regarding inflammation, vascular measurements, and cardiovascular risk. However, the combination of a non-dipping profile with high nighttime SBP was accompanied by significantly higher levels of arterial stiffness and cardiovascular risk, compared to non-dippers with normal nighttime SBP; these parameters were similar between the latter group and dippers. Inflammation appears to mediate the observed associations of nighttime SBP and dipping levels with markers of subclinical vascular damage in RA patients. In these patients, the combination of a non-dipping profile with elevated nighttime SBP is accompanied by prominent subclinical vascular impairment and confers the highest cardiovascular risk.

Association of Urinary Sodium Excretion with Vascular Damage: A Local Kidney Effect, Rather Than a Marker of Generalized Vascular Impairment.

Evidence suggests that increased salt consumption induces blood pressure- (BP) mediated organ damage, yet it remains unclear whether it reflects a generalized micro- and macrovascular malfunction independent of BP. We studied 197 newly diagnosed and never-treated individuals with hypertension, intermediate hypertensive phenotypes, and normal BP, classified by use of 24-hour ambulatory BP monitoring. Sodium excretion and microalbuminuria were estimated in 24-hour urine samples, dermal capillary density was estimated from capillaroscopy, and arterial stiffness was estimated with pulse wave velocity (PWV) and augmentation index (AIx). Sodium excretion correlated with microalbuminuria (p<0.001) and 24-hour and day- and nighttime systolic BP, but not with office blood pressure, arterial stiffness, or capillary density. In the multivariate analysis, the association with microalbuminuria was maintained (p=0.007). In a population free from the long-standing effects of hypertension, increased salt intake appears to be associated with early signs of vascular kidney damage, rather than a diffuse micro- and macrovascular impairment.

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.

Subendocardial viability ratio in patients with rheumatoid arthritis: comparison with healthy controls and identification of prognostic factors.

Cardiac involvement is common in rheumatoid arthritis. Subendocardial viability ratio (SEVR) is a non-invasive measure of microvascular coronary perfusion, yet it remains unclear whether it is affected in rheumatoid arthritis patients. We additionally sought predictors of SEVR in rheumatoid arthritis among a wide range of disease-related parameters, cardiac and hemodynamic factors, and markers of atherosclerosis, arteriosclerosis, and endothelial dysfunction. SEVR was estimated in rheumatoid arthritis patients and healthy controls by applanation tonometry, which was also used to evaluate arterial stiffness (pulse wave velocity and augmentation index). In the rheumatoid arthritis group, carotid intima-media thickness (cIMT) was additionally estimated by ultrasound, cardiac and hemodynamic parameters by impedance cardiography, and endothelial dysfunction by measurement of asymmetric dimethylarginine (ADMA). In a total of 122 participants, SEVR was lower among 91 patients with rheumatoid arthritis compared to 31 controls (141.4 ± 21.9 vs 153.1 ± 18.7%, p = 0.009) and remained so among 29 rheumatoid arthritis patients without hypertension, diabetes, or cardiovascular diseases, compared to the control group (139.7 ± 21.7 vs 153.1 ± 18.7%, p = 0.013). SEVR did not significantly correlate with arterial stiffness, cIMT, ADMA, or disease-related parameters. Multivariate analysis revealed gender (p = 0.007), blood pressure (p = 0.028), heart rate (p = 0.025), cholesterol levels (p = 0.008), cardiac index (p < 0.001) and left ventricular ejection time (p = 0.004) as independent predictors of SEVR among patients with rheumatoid arthritis. Patients with rheumatoid arthritis exhibit lower values of SEVR compared to healthy individuals. Cardiac and hemodynamic parameters, rather than functional indices of endothelial and macrovascular dysfunction, may be useful as predictors of myocardial perfusion in rheumatoid arthritis.

Safety profile of repeated rituximab cycles in unselected rheumatoid arthritis patients: a long-term, prospective real-life study.

OBJECTIVES: To evaluate the long-term safety of rituximab (RTX) in rheumatoid arthritis (RA) patients in daily clinical practice. METHODS: This was a multicentre (17 Greek Rheumatology sites), prospective, long-term, pharmacovigilance study of patients with moderate to severe RA and an inadequate response or intolerance to ≥1 anti-tumour necrosis factor (TNF) agents. Adverse events (AEs) were recorded and collected prospectively every 2-6 months. RESULTS: 234 patients (mean age: 59±12.5, 79.5% women, mean DAS28: 5.35±1.32) were included and followed for 27.7 months (median). The overall AEs, serious AE (SAEs) and serious infection (SIEs) rate were 48.36, 6.68 and 2.53/100 patient-years, respectively. Three cases of hepatitis B virus (HBV) reactivation were recorded (two in chronic and one in past HBV infection). Withdrawals due to AEs (5.6%) occurred more frequently during the first cycles of RTX therapy while repeated RTX cycles were not associated with an increased risk of AEs. There were 3 deaths with an incidence rate of 0.69/100 patient-years. Age ≥65 years was associated with a higher incidence rate ratio of AEs and SAEs as compared to <65 years (1.53, p=0.002 and 2.88, p=0.005, respectively). Drug retention rate during 434.28 patient-years of follow-up was 57.3%. Factors associated with drug discontinuation by multivariate analysis included age, baseline swollen joint count and no use of concomitant methotrexate therapy. CONCLUSIONS: Long-term RTX therapy in a real-life RA cohort, did not reveal any new safety issues. Advanced age was associated with increased risk of AEs and premature drug discontinuation.

Impaired metabolic profile is a predictor of capillary rarefaction in a population of hypertensive and normotensive individuals.

Capillary rarefaction is typically encountered in essential hypertension, yet identification of factors interfering with this phenomenon remains substantially underinvestigated. We examined whether components of metabolic profile (dyslipidemia, insulin resistance), inflammatory (high-sensitivity C-reactive protein, high-sensitivity C-reactive protein), and angiogenic (vascular endothelial growth factor) factors are implicated in this phenomenon in a population of newly diagnosed, never-treated hypertensive patients and normotensive controls. Nailfold capillary density was estimated with nailfold capillaroscopy using specifically designed software. A total of 159 individuals, 93 hypertensives, and 66 normotensives were included. Nailfold capillary density was lower among hypertensives compared to normotensives (146.4 ± 31.0 vs. 155.4 ± 26.9, respectively; P = .047). In the total population, capillary density significantly correlated with high-density lipoprotein (HDL) (r = 0.232; P = .003), HDL/low-density lipoprotein ratio (r = 0.175; P = .025), age (r = 0.236; P = .003), but neither with vascular endothelial growth factor or high-sensitivity C-reactive protein. An inverse association was found with body mass index (r = -0.174; P = .029), insulin levels (r = -0.200; P = .018), and homeostasis model assessment-insulin resistance (r = -0.223; P = .009). In the separate analysis for the hypertensive population, sex (P = .014) and homeostasis model assessment-insulin resistance (P = .011) were identified as significant predictors of capillary rarefaction after adjustment for other factors. On the contrary, only HDL levels (P = .036) predicted capillary density in the multiple regression model for the normotensive population. Different aspects of impaired metabolic profile, that is, insulin resistance and low HDL levels, but not angiogenic or inflammatory markers, appear to be independently associated with capillary rarefaction in hypertensive and normotensive individuals.

Depression, anxiety, and quality of life in a large cohort of patients with rheumatic diseases: common, yet undertreated.

A growing amount of literature has explored mainly the role of depression (and/or anxiety) in patients with rheumatic disorders. We aimed at determining the prevalence of depression, anxiety, and their association with quality of life among patients attending a rheumatology clinic, focusing on data regarding concomitant psychiatric treatment. Depression, anxiety, and quality of life were assessed using the Zung Self-Rating Depression Scale, the Hamilton Anxiety Scale, and the Health Assessment Questionnaire, respectively. Overall, 514 rheumatologic patients were studied. Depression and anxiety were documented in 21.8 and 30.8 % of the population, respectively, and correlated significantly with quality of life. Only 13.4 % of patients with depressive symptoms and 12.1 % of patients with anxiety symptoms were receiving antidepressant or antianxiety medication. Given the wide therapeutic armamentarium available nowadays for the management of depression and anxiety, an increased awareness among physicians dealing with rheumatologic patients is warranted in order to integrate detection and effective treatment of anxiety and depression into the routine clinical practice. Special attention should be paid to female patients, patients with longer disease duration, and/or those with established disability.

Predictors of impaired quality of life in patients with rheumatic diseases.

Quality of life (QoL) is a complex outcome and rheumatologic patients typically exhibit several comorbidities with a negative impact. In this study, we analyzed with respect to QoL for the first time a wide range of physical and psychological factors, including individual, clinical and disease-related parameters, mental health disorders, sexual dysfunction, and cardiovascular comorbidities among consecutive rheumatologic patients. QoL was evaluated using the EuroQol 5D (EQ-5D) utility index. The Health Assessment Questionnaire (HAQ) Disability Index, and the HAQ Pain Visual Analogue Scale were used as measures of physical disability and arthritis-related pain, respectively. The Hamilton Anxiety Scale and Zung Self-Rating Depression Scale, the International Index of Erectile Function and the Female Sexual Functioning Index were completed by all patients. In total, 360 patients were included, 301 females and 59 males. In the univariate analysis, pain, physical disability (p < 0.001 for both), disease duration (p = 0.014), anxiety and depression (p < 0.001 for both), as well as sexual dysfunction (p = 0.001 for females, p = 0.042 for males), correlated with QoL. Female sex (p < 0.001), advanced age (p = 0.029), lower educational level (p = 0.005), and cardiovascular factors (hypertension, dyslipidemia, diabetes, lack of systemic exercise) also appeared to negatively affect QoL. However, in the multiple regression model, only anxiety, pain, physical disability (p < 0.001 for all), and disease duration (p = 0.019) remained significant predictors of QoL. The emotional side and the disease-related physiological mode of rheumatic diseases appear as major independent correlates of QoL among rheumatologic patients, who may thus benefit the most from combined supportive psychological and pain-relieving interventions.