Integrated backscatter analysis of carotid intima–media complex in patients with systemic lupus erythematosus

A number of studies based on conventional ultrasound scanning (CUS) gave contrasting results about the occurrence of early atherosclerosis in patients with systemic lupus erythematosus (SLE), while no study on early arterial sclerosis in the same patients are available. Recently, information on early arterial sclerosis can be provided by the integrated backscatter (IBS) analysis which reflects the collagen and calcium content within the vascular wall. In order to evaluate if atherosis and/or sclerosis of carotid arteries are early features of SLE, we performed carotid CUS and IBS analysis in 16 SLE patients (15 females; aged 37 ± 10 years), free from clinically evident cardiovascular diseases and cardiovascular risk factors, with the only exception of five patients who had arterial hypertension. The same investigations were performed in 16 sex- and age-matched healthy control subjects. No statistically significant difference was observed either in carotid corrected IBS values or in carotid intima–media thickness (IMT) values between SLE patients and control subjects (−17.9 ± 2.5 dB vs −19.0 ± 1.7 dB, p = 0.14; 0.66 ± 0.08 mm vs 0.62 ± 0.13 mm, p = 0.35, respectively). The little sub-group of hypertensive SLE patients exhibited a significantly higher carotid corrected IBS mean value compared to control subjects (−16.4 ± 3.1 dB vs −19.0 ± 1.7 dB, p = 0.026), while it did not significantly differ in carotid IMT value from control group (0.67 ± 0.09 mm vs 0.62 ± 0.13 mm, respectively; p = 0.86). These findings show that neither atherosis nor sclerosis of carotid arteries are early features of SLE patients free from cardiovascular risk factors. Further studies are needed to clearly demonstrate that early carotid sclerosis affects hypertensive SLE patients.     

Serum salusin-β levels in patients with systemic lupus erythematosus

Clinical Rheumatology - Endothelial dysfunction (ED) has an important role in the pathogenesis of systemic lupus erythematosus (SLE). Studies on other inflammatory diseases show that salusin-β...     

Increased augmentation of central blood pressure is associated with increases in carotid intima–media thickness in type 2 diabetic patients

Aims/hypothesis Type 2 diabetes is associated with a two- to seven-fold increase in cardiovascular morbidity and mortality. The aim of this study was to determine the relationships between intima–media thickness (IMT), an established marker of atherosclerosis, large artery function and other determinants of cardiovascular risk in type 2 diabetic patients.Methods We studied 228 type 2 diabetic patients (75 women, aged 62±2 years [mean±SEM]). Carotid IMT was bilaterally measured using ultrasound technology. Applanation tonometry and pulse wave analysis were used to measure aortic systolic and diastolic blood pressures, central pressure augmentation (AG) and the augmentation index (AIx), a measure of systemic arterial stiffness. Conventional cardiovascular risk factors (lipids, HbA₁c, smoking and diabetes duration) were also assessed.Results Women had higher AG and AIx (p<0.0001), despite comparable systolic BP and heart rate in women and men. In women, AG (r=0.39, p<0.001), age (r=0.32, p<0.01), brachial systolic BP (r=0.34, p<0.01) and aortic systolic BP (r=0.34, p<0.01) correlated with IMT. In men, age (r=0.41, p<0.001), diabetes duration (r=0.25, p<0.01), AG (r=0.22, p<0.01), aortic systolic BP (r=0.21, p<0.01), brachial systolic BP (r=0.21, p<0.01) and body weight (r=0.16, p<0.05) correlated with IMT. In multiple linear regression analyses, AG and aortic systolic BP, but not brachial systolic BP, were age-independent determinants of IMT in men and women. In all patients, increased AG (adjusted for sex, age and heart rate) correlated with longer duration of diabetes, urinary albumin excretion and IMT.Conclusions/interpretation Measures of central systolic pressure correlate with carotid IMT, independently of age and other risk markers.     

Does carotid intima media thickness indicate coronary atherosclerosis?

Increased carotid intima media thickness (IMT) is relatively simple, inexpensive, and reproducible noninvasive marker of global atherosclerotic disease. It is a frequently used experimental tool in epidemiologic studies to identify and follow cardiovascular disease. There is evidence that early detection of atherosclerotic disease processes and subsequent therapeutic interventions significantly alter the natural course of the disease. Several large prospective studies have evaluated the usefulness of ultrasonographic measurement of IMT and have demonstrated its role in predicting future cardiovascular events. This article will focus on the relation between carotid artery IMT and coronary heart disease, and its utility and limitations in predicting cardiovascular events.     

Symptomatic knee osteonecrosis in patients with systemic lupus erythematosus: a case–control study

To explore the associated risk factors of symptomatic knee osteonecrosis (KON) in patients with systemic lupus erythematosus (SLE), we conducted a retrospective case–control study to compare the clinical and laboratory features between SLE patients with and without symptomatic KON matched by age and gender. Univariate and multivariate regression analyses were used to evaluate possible associated risk factors. Twenty (one male, nineteen females) out of 3941 lupus patients were identified as symptomatic KON, which was confirmed by magnetic resonance imaging. The mean age at KON onset was 34.4 (range 12–67) years, and the median course of lupus at KON onset was 72.5 (range 8–123) months. Univariate and multivariate analyses identified that the prevalence of cutaneous vasculitis (OR 5.23; 95 % CI 1.11–24.70), hyperfibrinogenemia (OR 4.75; 95 % CI 1.08–20.85), and elevated IgG levels (OR 6.05; 95 % CI 1.58–23.16) were statistically higher in KON group, and hydroxychloroquine (HCQ) usage was statistically lower in KON group (OR 0.27; 95 % CI 0.07–0.97). Glucocorticoid usage, in terms of maximal dose, duration of treatment, and the percentage of receiving methylprednisolone pulse therapy, did not show statistical difference between the two groups (p > 0.05). Symptomatic KON is a relatively rare complication of SLE. Cutaneous vasculitis, hyperfibrinogenemia, and elevated IgG levels are possible risk factors, whereas HCQ may provide a protective effect. Our results suggest that lupus activity as well as hypercoagulation status may play a role in the pathogenesis of KON in lupus.     

A positive correlation between homocysteine and brachial–ankle pulse wave velocity in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is associated with premature atherothrombotic complications. Hyperhomocysteinemia is considered a cardiovascular risk factor. Increased vascular stiffness may increase cardiovascular mortality. Pulse wave velocity (PWV) is a noninvasive method of analyzing vascular stiffness in the assessment of atherosclerosis. The objective of this study was to identify the relationship between plasma homocysteine levels and brachial–ankle pulse wave velocity (baPWV) measurement in SLE. Plasma homocysteine, baPWV, ankle–brachial index, blood pressure, C3, C4, anticardiolipin antibody (aCL), and anti-double-stranded DNA antibodies were determined in a total of 58 female patients with SLE. The control group comprised 32 age-matched healthy females. In addition, all patients were further classified into subgroups according to the presence of aCL (SLE/aCL+, n=27 vs SLE/aCL−, n=31) to determine the effect of aCL on the tested variables. The mean values for plasma homocysteine and baPWV were 13.19 μmol/l and 1,482 cm/s, respectively. Plasma homocysteine levels were significantly elevated in SLE patients when compared with the healthy controls. SLE patients with aCL had a significantly higher plasma homocysteine level than those without aCL. A significant positive correlation between plasma homocysteine and baPWV was found in patients with SLE (r=0.335, P=0.028, n=58). Plasma homocysteine also significantly correlated with right baPWV in all SLE patients (r=0.371, P=0.014, n=58) and in the SLE/aCL+ group (r=0.523, P=0.031, n=27). These findings indicate a possible link between plasma homocysteine and baPWV in SLE. In conclusion, SLE patients had an increased level of plasma homocysteine, and this phenomenon appeared to be related to vascular stiffness.     

A comparative study of arterial stiffness, flow-mediated vasodilation of the brachial artery, and the thickness of the carotid artery intima–media in patients with systemic autoimmune diseases

Patients with autoimmune diseases may have increased vascular risk leading to higher mortality rates. Novel imaging techniques are necessary for the early assessment and management of these patients. In this study, we compared augmentation index (AIx) and pulse wave velocity (PWV), indicators of arterial stiffness, to brachial arterial flow-mediated vasodilation (FMD) and common carotid artery intima–media thickness (ccIMT), standard indicators of endothelial dysfunction and atherosclerosis, respectively. We wished to assess the vascular status of autoimmune patients by using a novel, cheap, and reproducible technique, the arteriograph. Altogether, 101 patients with systemic autoimmune diseases including primary antiphospholipid syndrome, systemic sclerosis, rheumatoid arthritis, and polymyositis, all having various types of vasculopathies, as well as 36 healthy individuals were investigated. Arterial stiffness was assessed by a TensioClinic arteriograph, a recently validated technique. Brachial arterial FMD and ccIMT were determined using high-resolution ultrasonography. Autoimmune patients exerted impaired FMD (3.7 ± 3.8%), increased ccIMT (0.7 ± 0.2 mm), AIx (1.2 ± 32.2%), and PWV (9.7 ± 2.4 m/s) in comparison to control subjects (FMD = 8.4 ± 4.0%; ccIMT = 0.6 ± 0.1 mm; Aix = −41.1 ± 22.5%; PWV = 8.0 ± 1.5 m/s; p < 0.05). We found a significant negative correlation of FMD with AIx (R = −0.64; p < 0.0001) and PWV (R = −0.37; p = 0.00014). There were significant positive correlations between ccIMT and AIx (R = 0.34; p = 0.0009), ccIMT and PWV (R = 0.44; p < 0.0001), as well as AIx and PWV (R = 0.47; p < 0.0001). AIx, PWV, and ccIMT positively correlated and FMD negatively correlated with the age of the autoimmune patients. Arterial stiffness indicated by increased AIx and PWV may be strongly associated with endothelial dysfunction and overt atherosclerosis in patients with autoimmune diseases. Assessment of arterial stiffness, FMD, and ccIMT are reproducible and reliable noninvasive techniques for the complex assessment of vascular abnormalities in patients at high risk.     

Depression symptoms and the progression of carotid intima–media thickness: A 5-year follow-up study

Objective

Only a few studies have investigated the changes in carotid intima–media thickness (IMT) over time, and uncertainties remain on the underlying mechanisms linking depression and subclinical atherosclerosis. We carried out a prospective cohort study to evaluate whether depression is associated with changes in carotid IMT in subjects with cardiac risk factors but free from coronary heart disease (CHD), and to what extent the atherogenicity of depression can be explained by inflammatory markers and autonomic nervous system dysfunction.

Methods

During baseline and follow-up visits: all participants were asked to provide blood samples and compile a structured questionnaire; trained physicians assessed depression symptoms using Beck Depression Inventory (BDI); altered cardiac autonomic tone was measured using time-domain components of heart rate variability in 24 h Holter recordings; measurements of carotid IMT were carried out using B-mode ultrasound image acquisition. Logistic and linear regression analyses were used to adjust for potential confounders and explore potential mediators.

Results

A total of 381 subjects completed the 5-year follow-up. The mean carotid IMT significantly increased in all subjects but the amount of increase was significantly larger among subjects with depression symptoms: mean IMT increased by 0.16 ± 0.14 mm; 0.31 ± 0.28 mm and 0.61 ± 0.54 mm among the subjects with no, mild and moderate/severe depression, respectively (all p < 0.01). The association between moderate/severe depression and IMT increase remained highly significant even after controlling for all the variables considered, however when both IL-6 and CRP were included in multivariate models the regression coefficient decreased by 42.3%. Some of the inflammation markers and autonomic nervous system dysfunction were also independently correlated with carotid IMT increase.

Conclusion

Depression symptoms are independently associated with an accelerated progression of carotid IMT in subjects with CHD risk factors, and inflammation may substantially modulate the association between depression and carotid IMT progression.     

Neglected spontaneous rupture of the Achilles’ tendon in patients with systemic lupus erythematosus

Abstract

Spontaneous Achilles’ tendon rupture associated with systemic lupus erythematosus (SLE) is rare complication in literature review. We encountered two patients with neglected spontaneous ruptures of Achilles’ tendons who had been on corticosteroid therapy to treat SLE. The ages of these patients were 43 and 49 years, and both were women. One of them was a case of bilateral Achilles’ tendons rerupture. Achilles’ tendons of both patients were reconstructed by surgery because of delay in their diagnosis. Histological section of the both ruptured Achilles’ tendon revealed fibrotic scar tissue and little existence of inflammatory change. We concluded that careful diagnosis, surgical suture, and careful treatment after operation are necessary for Achilles’ tendon rupture in those patients with SLE.     

Carotid and popliteal artery intima–media thickness in patients with poor oral hygiene and the association with acute-phase reactants

Purpose

The aim of this study was to evaluate whether poor oral hygiene is associated with carotid and popliteal arterial intima–media thickness, which is one of the predictors of future progression of sub-clinical atherosclerosis, and high-sensitivity C-reactive protein (hsCRP) and fibrinogen levels.

Methods

A specialised dentist checked the patients and selected 550 patients during periodontal examinations, according to their oral hygiene. The patients had no history of atherosclerotic disease. Carotid and popliteal artery B-mode ultrasonographic examinations and hsCRP and fibrinogen levels were analysed at baseline and after a mean of 6.2 months. The patients were scored on the DMFT index for the number of decayed (D), missing (M), and filled (F) teeth (T). We also used the Silness-Loe plaque index (SLI) to evaluate oral hygiene and dental plaque. The patients were divided into two groups using the DMFT and SLI criteria. Group I had a DMFT index score from 0 to 3 and SLI index score of 0 or 1. Group II had a DMFT index score from 4 to 28 and SLI index score of 2 or 3.

Results

A significant association was observed between dental status, oral hygiene, carotid and popliteal artery intima–media thickness and hsCRP level. Patients with increasing DMFT and SLI scores correlated with increasing carotid artery intima–media thickness.

Conclusions

The results clearly showed that chronic poor oral hygiene and tooth loss are related to sub-clinical atherosclerotic changes in the carotid arteries and may be indicative of future progression of atherosclerosis.     

Neglected spontaneous rupture of the Achilles’ tendon in patients with systemic lupus erythematosus

Spontaneous Achilles' tendon rupture associated with systemic lupus erythematosus (SLE) is rare complication in literature review. We encountered two patients with neglected spontaneous ruptures of Achilles' tendons who had been on corticosteroid therapy to treat SLE. The ages of these patients were 43 and 49 years, and both were women. One of them was a case of bilateral Achilles' tendons rerupture. Achilles' tendons of both patients were reconstructed by surgery because of delay in their diagnosis. Histological section of the both ruptured Achilles' tendon revealed fibrotic scar tissue and little existence of inflammatory change. We concluded that careful diagnosis, surgical suture, and careful treatment after operation are necessary for Achilles' tendon rupture in those patients with SLE.     

Exercise therapy in patients with idiopathic inflammatory myopathies and systemic lupus erythematosus – A systematic literature review

Idiopathic inflammatory myopathies (IIM) and systemic lupus erythematosus (SLE) are inflammatory connective tissue diseases (CTDs) with common features of arthritis, muscle impairment, skin rash, and heart- and lung involvement. Exercise is becoming an important part of the treatment in patients with IIM and SLE; however, there is a need for evidence-based exercise recommendations on patient-relevant outcomes. To evaluate the evidence and to present evidence-based exercise recommendations on patient-relevant outcomes in patients with IIM and SLE. A systematic literature search of five databases was performed at two time points, 2016 going back all years, and an update in 2019. Inclusion criteria: RCTs including exercise, physical activity intervention, and patient-relevant outcomes. Systematic reviews and meta-analysis was also included. Grading of evidence was done according to the GRADE system. Five RCTs and 1 systematic review were identified in patients with IIM and eight RCTs, 6 systematic reviews, and 2 meta-analysis for patients with SLE. Aerobic exercise and resistance training on moderate-high intensity can improve aerobic capacity, muscle impairment, activity limitation, quality of life, and disease activity (limited evidence) in patients with established polymyositis (PM) and dermatomyositis (DM). Moderate-high intensity aerobic exercise can improve aerobic capacity (moderately strong evidence) and improve fatigue and depressive symptoms (limited evidence) without changing disease activity in patients with mild/inactive SLE with low/no organ damage. There is insufficient evidence for effects of exercise in patients with recent onset PM/DM and IBM. Exercise performed in line with American College of Sports Medicine recommendations can improve aerobic capacity, patient-reported outcomes in patients with nonactive PM/DM and mild/inactive SLE. More well-designed studies are needed to increase the scientific evidence. Studies with additional focus on evaluating effects of exercise in patients with higher disease activity, in patients with vital-organ involvement and in patients with IBM are needed.     

Influence of the Mediterranean diet on carotid intima–media thickness in hypercholesterolaemic children: A 12-month intervention study

Background and aimsThe Mediterranean diet has been recognised as having a protective role on the cardiovascular system due to its low lipid and high antioxidant content. Lipid profile and oxidant status represent two important risk factors related to endothelial dysfunction, even at early stages of cardiovascular diseases. The aim of the study was to evaluate the influence of a 12-month Mediterranean diet on the variation of lipid profile and carotid intima–media thickness (cIMT) in pre-pubertal hypercholesterolaemic children.Methods and resultsWe performed a cross-sectional study comparing lipid profile and cIMT in a group of 68 pre-pubertal children (36 with hypercholesterolaemia and 32 controls). In addition, in the hypercholesterolaemic children a 12-month intervention programme with a Mediterranean diet was started to evaluate the variation of lipid profile and cIMT. At baseline, hypercholesterolaemic children showed a significantly higher cIMT (both right and left carotid artery) compared to controls (both p < 0.05). After 12 months of diet intervention, a significant reduction of total cholesterol, LDL-cholesterol and cIMT was documented (all p < 0.05). Furthermore, at the end of follow-up, delta body mass index-Standard Deviation score and delta LDL-cholesterol were significantly and independently related to the changes of cIMT (both p < 0.05).ConclusionThe Mediterranean diet represents a valid approach in the treatment of hypercholesterolaemia even during childhood.     

Are patients with systemic lupus erythematosus at increased risk for Fibromyalgia?

Widespread chronic pain, fatigue, and distress do not represent risk factors for future systemic lupus erythematosus (SLE) or other autoimmune syndromes. On the other hand, SLE seems to be a significant risk factor for fibromyalgia (FM). Up to 47% of SLE patients fulfill FM criteria. SLE patients with concomitant FM are often highly symptomatic and dysfunctional. The presence of FM symptoms in SLE patients, however, does not predict more extensive organ involvement or lupus activity. The high concordance of SLE with FM suggests common mechanisms related to pain and distress in both patient groups. Recent research suggests involvement of N-methyl-D-aspartate (NMDA) and neurokinin receptor systems. Thus, autoimmune activity against these receptor systems in SLE patients could result in pain, cognitive defects, and chronic pain states including FM. Conversely, treatment of SLE-FM patients with inhibitors of NMDA or neurokinin receptors may prevent or alleviate cognitive abnormalities and chronic pain, as well as FM.