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 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.

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.

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.

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.

Dissecting the damage in Northern Greek patients with childhood-onset systemic lupus erythematosus: a retrospective cohort study.

The improved survival of childhood-onset systemic lupus erythematosus (cSLE) has resulted in longer patients' exposure to disease inflammation, medications and/or comorbid diseases, which can all contribute to the development of organ damage. The aim of this study was to assess the evolution of damage accrual in cSLE patients overtime and investigate for predisposing factors. Disease characteristics and treatment in 47 Northern Greek Caucasian cSLE patients were retrospectively reviewed. The Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) was used for damage assessment and the European Consensus Lupus Activity Measurement (ECLAM) to monitor cSLE activity. After a median disease duration of 7.4 years, 17/47 patients (36 %) had developed damage (SDI > 0). The most frequent domains damaged were the ocular (41 %), neuropsychiatric (35 %) and peripheral vascular (35 %) one. Peripheral vascular and neuropsychiatric damage was seen more frequently during the first 5 years of the disease. Longer exposure to azathioprine was associated with higher SDI at the end of follow-up (ß = 0.008 for every additional month of use, p = 0.041). The mean annual flare frequency was associated with a shorter time interval until the development of the first damage (hazard's ratio, HR 2.38 for each unit of increase, p = 0.018), while hydroxychloroquine use was associated with longer time interval (HR 0.19, p = 0.007). The lower rates of damage accrual in this study compared to other cohorts might be due to milder disease phenotype in Greek Caucasian cSLE patients, prompt diagnosis and effective disease control. Damage was noticed early in the disease course, and one-third of patients had an SDI > 0 at study completion. Disease flares and a severe disease course leading to prolonged use of immunosuppressives were significant risk factors, while hydroxychloroquine use was protective against cSLE damage accrual.

Assessing disability in patients with rheumatic diseases: translation, reliability and validity testing of a Greek version of the Stanford Health Assessment Questionnaire (HAQ).

The purpose of this study was to translate into the Greek language the HAQ, validate its psychometric, and also, to assess the degree to which questions in the scale did address common themes, using exploratory factor analysis. HAQ has been translated into Greek (HAQ-GrV), applied to 53 patients with rheumatic pathology and validated as follows: Cronbach's alpha for the estimation of the internal consistency, and the assessment of test-retest reliability, Spearman's rho for the assessment of concurrent validity, and confirmatory factor analysis. The results showed the following: (a) The HAQ-GrV demonstrated very good internal consistency (alpha: 0.90), (b) test-retest scores produced no significant difference (P = 0.07). Spearman's rho ranged from 0.64 to 0.90 for each item. (c) Spearman's rho between HAQ-GrV and HADS was 0.31 (P < 0.05). (d) Factor analysis identified five factors with Eigen values ranging from 1.26 to 6.98, explaining totally 69.4% of the variance.

Post-traumatic stress reactions of children and adolescents exposed to the Athens 1999 earthquake.

This study was undertaken 6-7 months after the 1999 Athens earthquake with the aim of exploring the differences in post-traumatic stress disorder (PTSD), anxiety and depression symptoms between a group of children exposed to earthquake with a group of children not exposed to it, but with both groups potentially exposed to the same levels of post-earthquake adversities. The study included 2037 children, aged 9-17 years, who were assessed with self-completed questionnaires. The directly exposed group (N=1752) had significantly higher anxiety and PTSD scores than the indirectly exposed group (N=284), but no significant group differences were found in depression scores. Girls in both groups reported significantly more PTSD, anxiety and depressive symptoms than boys. Younger children reported significantly more PTSD and anxiety symptoms than the older ones. No significant interactions were found between direct exposure to earthquake, age group and gender. The severity of PTSD symptoms was most strongly predicted by greater perceived threat during the earthquake, whereas depression was most strongly predicted by the level of post-earthquake adversity. The severity of anxiety symptoms was most strongly predicted by female gender. These findings are discussed in relation to the need for screening and intervention following earthquake events.