Potential role of high sensitivity cardiac troponin T in subclinical coronary atherosclerosis in systemic lupus erythematosus patients

Aim of the workTo determine the role of high sensitivity cardiac troponin T (HS cTnT) in subclinical coronary atherosclerosis in SLE patients at an apparent low risk for CVD according to traditional risk factors.Patients and methodsThe presence of subclinical coronary atherosclerosis was assessed by non-contract coronary computerized tomography and calcium score was measured using Agatston score in 30 SLE patients asymptomatic for CVD and 30 age and sex matched apparently healthy controls. SLE disease activity index (SLEDAI) was assessed. Serum HScTnT concentration was measured using enzyme-linked immunosorbent assay (ELISA).ResultsThe mean age of the patients was 33 ± 5.7 years, disease duration of 33.7 ± 22 months and mean SLEDAI 8.1 ± 5.02. The mean HS cTnT level was 12.8 ± 11.3 ng/L (1–36 ng/L). Their Framingham score was 4.8 ± 3.1 (1–12). Framingham score was low in both SLE patients (range 1–12%) and controls (1–9%) (p = 0.12). 11 (36.7%) patients, but none of the controls, had coronary artery calcification (CAC). Serum HScTnT concentration was detectable (>3 ng/L) in 16 (53.3%) patients and 2 (6.7%) control (p < 0.001). Interestingly, it was detectable in all patients with CAC, but in only 26.3% of patients without (p < 0.001). HScTnT significantly correlated with Agatston (r = 0.63, p = 0.04), with erythrocyte sedimentation rate (r = ?0.65, p = 0.03), and with C-reactive protein (r = 0.76, p = 0.03) in SLE patients with CAC.ConclusionSerum HScTnT level is high and associated with CAC in SLE patients who are at an apparently low risk for CVD according to the Framingham risk score. HS cTnT may be a useful biomarker for SLE-associated subclinical atherosclerosis.     

The association between adipokines and stigmata of atherosclerosis in patients with systemic lupus erythematosus

Aim of the workEarly cardiovascular disease is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). The study was designed to assess the relationship between the serum levels of adipokines and atherosclerotic risk factors in SLE patients.Patients and methods56 patients and 31 control were included. Serum levels of leptin, adiponectin, traditional and new risk factors for atherosclerosis including plasma glucose levels, lipid profile, high-sensitivity C-reactive protein (hs-CRP), vascular cell adhesion molecule-1 (VCAM-1) and homocysteine were measured. The intima-media thickness (IMT) of the carotid was measured by ultrasonography. The SLE disease activity index (SLEDAI-2k) was assessed.ResultsThe patients mean age was 30.8 ± 9.9 years, disease duration was 55.7 ± 59.3 months and were 54 (91.5%) females and 5 (8.5%) males. Serum adiponectin levels were significantly lower in patients (3.58 ± 0.4 ng/ml) compared to control (3.9 ± 0.26 ng/ml) (p < 0.001) while leptin levels were comparable. Serum adiponectin levels correlated with triglyceride (r = 0.3, p = 0.003) and high-density lipoprotein (HDL) (r = 0.2, p = 0.04). Serum leptin significantly correlated with the BMI and total cholesterol (r = 0.43, p = 0.002 and r = 0.3, p = 0.04 respectively) as well as with the anti-double stranded deoxyribonucleic acid (anti-dsDNA) (r = 0.28, p = 0.04). There was lack of a meaningful relationship between serum adiponectin and leptin levels and disease duration or risk factors such as hsCRP, VCAM, homocysteine and IMT as well as with the SLEDAI-2k or complement.ConclusionsSerum adiponectin levels inversely correlate with HDL. A significant correlation of leptin with BMI and total cholesterol was found in SLE. None of the two adipokines were associated with atherosclerosis as assessed with the carotid IMT or with the disease activity.     

Hemorheological parameters are related to subclinical atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis patients

Objectives

Rheological characteristics of blood are strongly linked to atherothrombosis in the general population, but its contribution to atherosclerosis in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) is currently unclear. This work examines the relationship between blood rheology, traditional cardiovascular (CV) risk factors, inflammation and subclinical atherosclerosis in SLE and RA.

Methods

Whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte deformability (ED), aggregation (EA) and erythrocyte NO production were measured in 197 patients (96 SLE and 101 RA) and compared to 97 controls, all females without previous CV events. Clinical information was obtained and fasting lipids and acute phase reactants were measured. The relationship between hemorheological parameters, CV risk factors and inflammation was assessed in patients and the impact of these variables on carotid intima-media thickness (cIMT) was evaluated in univariate followed by multivariate regression analyses.

Results

WBV and ED are significantly lower in patients, while EA is elevated as compared with controls. Hemorheological disturbances correlate with CV risk factors and markers of inflammation and are more profound in patients with metabolic syndrome. Multivariable analysis showed that menopause (OR 34.72, 95%CI 4.44–271.77), obesity (OR 4.09, 95%CI 1.00–16.68) and WBV (OR 3.98; 95%CI 1.23–12.83) are positively associated whereas current corticosteroid dose (OR 0.87; 95%CI 0.78–0.98), and erythrocyte NO production (OR 0.16; 95%CI 0.05–0.52) are negatively associated with cIMT.

Conclusion

Disturbed hemorheological parameters in SLE and RA women are related to the presence of CV risk factors and inflammation. WBV and erythrocyte NO are independently associated with the early stages of atherosclerosis.     

Relationship of change in traditional cardiometabolic risk factors to change in coronary artery calcification among individuals with detectable subclinical atherosclerosis: The multi-ethnic study of atherosclerosis

Background/Objectives

Data describing relationships between change in risk factors and coronary artery calcification (CAC) are lacking and could inform optimal cardiovascular disease prevention and treatment strategies. This study aimed to examine how change in traditional cardiometabolic risk factors related to change in CAC among individuals with detectable subclinical atherosclerosis.

Methods

Latent growth modeling was used to examine change in cardiometabolic risk factors (waist circumference, body mass index, systolic and diastolic blood pressure, high- and low-density lipoprotein cholesterol, triglycerides, and glucose) related to change in CAC up to an average 4.9-year follow-up in a multi-ethnic cohort of 3398 asymptomatic individuals (57.8% men) who had detectable CAC (score > 0) at baseline, adjusting for baseline risk factor levels and CAC values, age, gender, race/ethnicity, smoking, family history of CVD, income, and use of antihypertensive, lipid-lowering, and glucose-lowering medications.

Results

Greater declines in blood pressure (systolic and diastolic) and low-density lipoprotein cholesterol at follow-up were each associated with greater CAC progression. The observed inverse associations were attributable to greater CAC progression in participants taking antihypertensive and lipid-lowering drugs who, as expected, had declines in blood pressure and lipid levels, respectively. These inverse associations did not emerge in participants not taking these medications.

Conclusions

Among individuals with subclinical atherosclerosis, the unexpected inverse associations observed between change in blood pressure and lipid levels with CAC progression emphasize the importance of considering medication use, and, when feasible, the severity and duration of disease, in exploring associations between risk factors and CAC change.     

Paediatric-onset systemic lupus erythematosus

Paediatric-onset systemic lupus erythematosus (SLE) is usually more severe than its adult counterpart. In particular, there is a higher incidence of renal and central nervous system involvement. Specific measures to assess disease activity and damage have been implemented. The disease is very rare before the fifth birthday and therefore the onset of an SLE picture in the first years of life should lead to the suspicion of the presence of one of the rare monogenic diseases that causes SLE or of one of those congenital diseases that has been showed to be closely associated with the SLE.     

Infection in systemic lupus erythematosus patients

BackgroundInfection is a leading cause of morbidity, mortality and hospital admission in systemic lupus erythematosus (SLE) patients.Aim of the workTo study infection in SLE patients regarding site of infection, pathogenic organism, hospitalization and/or intensive care unit (ICU) admission.Patients and methodsThis study included 79 patients. SLE disease activity index (SLEDAI-2K) and damage index were evaluated. Detailed information about the site of infection and pathogens were reported.Results71 females and 8 male patients (F:M 8.9:1), with a mean age of 29 ± 9.6 years (17–55 years) and disease duration of 5.9 ± 5.7 years, 55 (69.6%) patients had infection at time of study while 24 (30.4%) did not. The SLEDAI-2 k and damage index were significantly higher in SLE patients with infection (14.2 ± 11.8 and 3.7 ± 3.7) compared to those without infection (5.9 ± 5.03 and 1.8 ± 1.3) (p = 0.03 and p = 0.045 respectively). Those with infection had a shorter disease duration (4.9 ± 5.2 vs 8.3 ± 6.2; p = 0.005), received more cyclophosphamide (56.4% vs 16.7%; p = 0.001), higher erythrocyte sedimentation rate (ESR) (75.5 ± 27.1 vs 35.8 ± 24.7 mm/1^sthr) (p < 0.0001) and consumed complement (C3) (71.1 ± 28.4 vs 97.2 ± 28.2; p < 0.0001). 17/55 (30.9%) had more than one site of infection and 46/55 (83.6%) required hospital admission. 17 (30.9%) of hospitalized patients were transferred to the ICU. The main pathogenic organisms were bacterial (40%), fungal (27.3%), viral (10.9%) and unconfirmed in 21.8%. Chest was the commonest site (40%) followed by the skin (34.4%), oropharynx (25.5%) and urinary tract (20%).ConclusionInfection is an important cause of hospital and ICU admission in SLE patients. Early disease, disease activity and damage, cyclophosphamide, ESR and consumed C3 were associated with infection in SLE.     

Serum resistin,insulin resistance and carotid intima-media thickness as an indication of subclinical atherosclerosis in systemic lupus erythematosus patients

Aim of the workTo evaluate resistin level in systemic lupus erythematosus (SLE) patients and to assess the relationship with insulin resistance, disease characteristics, inflammatory markers and carotid intima-media thickness (CIMT) as a marker of subclinical atherosclerosis.Patients and methodsThirty adult SLE patients and twenty age and sex-matched control were enrolled. All patients were subjected to history taking, clinical examination and assessment of anthropometric measurements. Laboratory investigations included serum resistin, measures of insulin resistance, highly sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR) and lipid profile. Carotid duplex was performed for measurement of CIMT. SLE disease activity index (SLEDAI-2k) and damage index were evaluated.ResultsThe 30 patients were 23 (76.7%) females and 7 (23.3%) males (F:M 3.3:1) with a mean age of 30.9 ± 7.9 years. The disease duration was 4.8 ± 1.8 years. The mean serum resistin in patients was 7.7 ± 2.9 ng/dl and in control was 8.5 ± 5.1 ng/dl (p = 0.8). The ESR and hs-CRP were significantly increased (p < 0.001) and the high-density lipoprotein (HDL) decreased (p < 0.001). The mean CIMT was significantly increased in cases (0.62 ± 0.16 mm) compared to control (0.51 ± 0.11 mm)(p = 0.006). Serum resistin significantly correlated with hs-CRP, HDL and anti-nuclear antibody (p = 0.027, p < 0.001,p = 0.013 respectively). There was no significant correlation between resistin and markers of insulin resistance, SLEDAI-2 k and CIMT.ConclusionResistin expression in the serum of patients with SLE was not significantly higher than controls. Although resistin was correlated with two cardiovascular risk factors (HDL-C, hs-CRP), it did not correlate significantly with insulin resistance, disease activity, damage index and CIMT in SLE patients.     

Dyslipoproteinemia and premature atherosclerosis in pediatric systemic lupus erythematosus

While modern treatments for systemic lupus erythematosus (SLE) have resulted in greatly improved long term outcome in children and adults, complications of atherosclerosis have become a major cause of morbidity and mortality. Although children and adolescents with SLE rarely experience adverse cardiovascular events before adulthood, dyslipoproteinemia and early evidence of premature atherosclerosis is present much earlier. Accelerated atherogenesis in SLE is multifactorial, most likely reflecting vascular, immune, and inflammatory changes along with medication effects. The long term complications of cardiovascular disease in childhood lupus present a particularly important target for intervention because of the potential return on investment by significantly lengthening life and improving quality of life over many decades. An ongoing multi-center, randomized, controlled trial, Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE), testing the efficacy of statins in preventing premature atherosclerosis in children and adolescents with SLE will guide future therapeutic intervention.     

二维超声检测冠心病患者颈动脉粥样硬化病变

对103例经选择性冠状动脉造影的患者作双侧颈动脉超声检查，探讨了颈动脉超声检查的方法学以及颈动脉粥样硬化斑块的好发部位和超声分型，发现颈动脉粥样硬化斑块好发于颈动脉分叉处，以左侧多见，且多为扁平斑；颈动脉粥样硬化与冠状动脉粥样硬化之间有着密切的相关关系，冠状动脉病变支数越多，其颈动脉粥样硬化斑块积分也越高，不同冠状动脉病变组之间有非常显著的差异（P＜0．001）。     

Intercellular adhesion molecules in systemic lupus erythematosus patients with lupus nephritis

Cardiovascular events are markedly increased in systemic lupus erythematosus (SLE), and the mechanism of atherogenesis remains poorly understood. Several methods have been employed to assess endothelial function, among these is the measurement of biomarkers of endothelial activation and dysfunction [intercellular adhesion molecule (ICAM-1)]. It has been reported that such biomarkers play a more important role than traditional risk factors in cardiovascular disease. The objectives of this study were to determine the level of ICAM-1 as markers of endothelial dysfunction in 40 Egyptian patients who have SLE with various degrees of activity and to investigate their relationship to disease activity. Sixty people (40 with SLE and 20 healthy as the control group) were the subject of this study; their clinical disease activity was scored according to the SLE disease activity index (SLEDAI), and serum sampling was obtained for ICAM-1 level assay. Renal biopsy was carried out and examined by light microscopy by a pathologist blinded to the clinical activity. The mean level of ICAM-1 was significantly higher in SLE patients with active disease (826.05 ± 367.1 Pg/ml) compared to those with inactive disease (441.33 ± 225.19 Pg/ml) and the healthy control volunteers (111.5 ± 17.36 Pg/ml). There was a positive correlation between serum ICAM-1 and SLEDAI (r = 0.66). A high concentration of soluble ICAM-1 in SLE patients with nephritis is reported in this paper. Our finding of increased concentrations of ICAM-1 in SLE patients with nephritis underlines the importance of inflammation and endothelial involvement in this disease, but their predictive value in the disease monitoring need to be further studied.     

Early morning neutropenia in a patient with systemic lupus erythematosus

Abstract

An autopsy case of an 11-year-old boy with polyarteritis nodosa is described in which the onset of the disease was associated with the presence of hepatitis B (HB) antigens (Ag) in the cytoplasm and nuclei of hepatocytes as detected by immunohistological methods. Deposits of HBsAg, HBeAg, IgG, IgM, C3, and C1q were demonstrated in systemic vascular lesions. It is considered that the arteritis was due to deposition in the arteries of immune complexes formed by HBAg and HB antibodies.     

Serum tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and leptin as biomarkers of accelerated atherosclerosis in patients with systemic lupus erythematosus and antiphospholipid syndrome

Background

Patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are at increased risk of atherosclerosis, and occurs much earlier compared to the general population even after accounting for traditional risk factors.

Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus

OBJECTIVE: To evaluate traditional and non-traditional risk factors for subclinical atherosclerosis in systemic lupus erythematosus (SLE). METHODS: A prospective cohort of 78 patients with SLE without overt atherosclerotic disease was studied. SLE clinical and laboratory parameters, disease activity and damage, treatment and traditional risk factors for atherosclerosis were evaluated. At baseline (T1) and after five years' follow up (T2), the serum levels of anti-oxidised palmitoyl arachidonoyl phosphocholine (oxPAPC), anti-heat shock protein 65, and anti-beta(2)-glycoprotein I antibodies and C reactive protein were tested. At T2, intima-media thickness (IMT) was measured using duplex carotid sonography. Thickened intima, plaque, mean IMT (m-IMT), and maximum IMT (M-IMT) were assessed. RESULTS: A thickened intima was seen in 22/78 (28%) patients and plaque in 13/78 (17%). M-IMT and m-IMT were (mean (SD)) 0.77 (0.34) mm and 0.55 (0.15) mm, respectively. Patients with carotid abnormalities were significantly older, had higher blood pressure and total serum cholesterol levels, and had taken a higher prednisone cumulative dosage than those without any lesions. The carotid abnormalities were associated with renal disease and ECLAM >2 at T1, and with azathioprine treatment. In multivariate analysis, age and cumulative prednisone dose were associated with carotid abnormalities; age, hypertension, and anti-oxPAPC at T2 were correlated with higher M-IMT and m-IMT. CONCLUSIONS: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose. The role of some traditional risk factors, such as age and hypertension, was also confirmed. The predictive value of the new immunological and inflammatory markers of atherosclerosis seems to be masked by some disease related features.     

Pulmonary involvement in early systemic lupus erythematosus

Aim of the workSLE is an autoimmune disease characterized by a variety of clinical and laboratory abnormalities. It may affect many organs and pulmonary involvement is a common finding in SLE. The purpose of this study was to disclose the pulmonary involvement in early SLE patients not more than 2 years of disease duration using the computed tomography (CT) as well as the pulmonary function tests as ways of pulmonary involvement assessment.Patients and methodsForty-two patients aged 29 ± 12.5 with early SLE not more than 2 years of disease duration were recruited for the study. All patients were assessed clinically for their SLE with BILAG which was utilized for disease activity determination.ResultsNine and half percent of our patients were found to be clinically involved by ILD, where 28.6% have abnormal HRCT finding, 26.2% with abnormal PFT. Variants that were associated with an abnormal forced vital capacity FVC < 80% in a significant manner were: smoking, long disease duration, self-reported pulmonary symptoms (p 0.001), BILAG global score (p 0.006), Anti dsDNA (p 0.001), Antiphospholipid (IgM or IgG) (p 0.01), anti Sm (p 0.002), anti-RNP (p 0.005), HRCT abnormalities (p 0.001), current medication of steroid (any dose) (p 0.005), immunomodulator therapy (p 0.002), and Rituximab therapy (p 0.001).ConclusionsILD occurs as early as in the first 2 years in the course of SLE patients. There was a clear predilection of ILD with certain variables in our cohort of patients.     

Resistin in systemic lupus erythematosus: Relation to lupus nephritis and premature atherosclerosis

BackgroundLupus nephritis (LN) is one of the most severe complications of SLE. SLE patients have a greater risk of developing premature atherosclerosis. Resistin is an adipocyte-secreted peptide. It has pro-inflammatory and atherogenic effects.Aim of the workTo assess the serum levels of resistin in SLE patients and to evaluate it as a marker of nephritis and premature atherosclerosis.Patients and methodsThis study included 50 SLE nonpregnant female adult (mean age 23.1 ± 6.9 years) patients as well as 40 healthy volunteers matched in age and sex as a control group. Serum levels of resistin were assayed using enzyme-linked immunosorbent assay (ELISA). All patients and controls underwent laboratory investigations and carotid duplex. Disease activity was assessed using SLE Disease Activity Index (SLEDAI). Renal biopsy was performed for SLE patients with LN.ResultsThere was a highly statistically significant increase in mean serum resistin levels (14.1 ± 3.88 ng/ml) in patients versus the control group (6.44 ± 1.34 ng/ml) being more obvious in those with LN. Resistin had a significant positive correlation with markers of inflammation, SLEDAI and carotid intima media thickness (CIMT).ConclusionSerum level of resistin may serve as a marker of LN and atherosclerosis in SLE patients. A more aggressive control of the underlying inflammatory process along with the control of traditional risk factors (hypertension and cholesterol) may be beneficial in reducing the risk factors of renal and atherosclerotic involvement in SLE. Therapeutic approaches with drugs that target resistin might be useful in the treatment of SLE.     

Autoantibodies in systemic lupus erythematosus and normal subjects

Summary The presence of various antibodies in serum samples from patients with systemic lupus erythematosus (SLE) and from healthy subjects was investigated by ELISA, using a panel of natural antigens. Fifty-eight serum samples from 58 healthy women and 50 serum samples from 30 patients with active SLE were tested with 9 natural antigens (ds-DNA, actin, tubulin, thyroglobulin, myosin, myoglobin, human transferrin, human interferon a and BSA FV). It was found that the proportion of positive sera from healthy women at a dilution of 1/20 was almost the same as that of lupus sera at a dilution of 1/150 for nearly all antigens, while at a dilution of 1/150 the proportion of positive sera from patients with SLE was significantly higher for nearly all antigens. In lupus sera a high degree of correlation was observed between titers of anti-DNA and titers of the other antibodies. One hundred eighty-eight serum samples from 53 SLE patients, taken during exacerbation and remission of the disease were tested with ds-DNA, actin and tubulin. Antibodies (IgG) to ds-DNA actin and tubulin were found in the majority of serum samples taken during the active phase of the disease. On the other hand, very few serum samples taken during remission were found to be positive. A high degree of correlation was found between the OD of anti-actin/anti-ds-DNA (r=0.769) and anti-tubulin/anti-ds-DNA (r=0.829). In a competitive enzyme immunoassay for DNA, actin, tubulin, myosin and thyroglobulin, a high degree of inhibition was observed with the homologous antigens. Cross inhibition was observed between actin, tubulin and myosin, and to a lesser degree with DNA. These results indicate that normal sera contain low titers of auto and foreign antibodies while active SLE sera react strongly with the same antigens.     

Cardiovascular risk scores and the presence of subclinical coronary artery atherosclerosis in women with systemic lupus erythematosus

The Framingham risk score is widely used to identify patients at increased cardiovascular risk, and women with systemic lupus erythematosus (SLE) have a marked increased prevalence of cardiovascular events. Thus, we examined the hypothesis that cardiovascular risk scores would identify women with SLE who had asymptomatic coronary atherosclerosis. Ninety-three women with SLE and 65 control subjects were studied. The Framingham score and a score for younger populations developed from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study were compared in both groups. Coronary atherosclerosis was ascertained by electron beam computed tomography. There were no significant differences in the median (interquartile range) Framingham [5 (2-10) compared to 7 (0-10), P = 0.88] and PDAY [15 (14-18) compared to 16 (13-18), P = 0.99] scores in patients with SLE and controls, respectively. Coronary atherosclerosis was associated with higher Framingham [12 (3-15) compared to 4 (1-8), P = 0.008] and PDAY [17 (15-19 compared to 15 (12-18), P = 0.03)] scores in patients with SLE; however, 99% of patients were classified as low-risk with a 10-year predicted risk of 1% (<1-3%). Our data indicate that cardiovascular risk scores are not adequate for risk stratification in women with SLE. Measurement of coronary calcification may add information to identify asymptomatic women with lupus who might benefit from aggressive preventive measures.