Cardiorespiratory fitness and age-related arterial stiffness in women with systemic lupus erythematosus.

BACKGROUND: The aim of this study was twofold: (i) to examine the association of cardiorespiratory fitness with arterial stiffness in women with systemic lupus erythematosus; (ii) to assess the potential interaction of cardiorespiratory fitness with age on arterial stiffness in this population. MATERIALS AND METHODS: A total of 49 women with systemic lupus erythematosus (mean age 41.3 [standard deviation 13.8] years) and clinical stability during the previous 6 months were included in the study. Arterial stiffness was assessed through pulse wave velocity (Mobil-O-Graph® 24 hours pulse wave velocity monitor). Cardiorespiratory fitness was estimated with the Siconolfi step test and the 6-minute walk test. RESULTS: Cardiorespiratory fitness was inversely associated with pulse wave velocity in crude analyses (P < .05), although this relationship was attenuated when age and other cardiovascular risk factors were controlled. There was a cardiorespiratory fitness × age interaction effect on pulse wave velocity, regardless of the test used to estimate cardiorespiratory fitness (P < .001 for the Siconolfi step test; P = .005 for the 6-minute walk test), indicating that higher cardiorespiratory fitness was associated with a lower increase in pulse wave velocity per each year increase in age. CONCLUSIONS: The results of this study suggest that cardiorespiratory fitness might attenuate the age-related arterial stiffening in women with systemic lupus erythematosus and might thus contribute to the primary prevention of cardiovascular disease in this population. As the cross-sectional design precludes establishing causal relationships, future clinical trials should confirm or contrast these findings.

Association between perceived level of stress, clinical characteristics and psychopathological symptoms in women with systemic lupus erythematosus.

OBJECTIVES: To evaluate psychopathological status and stress level from a sample with SLE; compare mental functioning and stress levels between women with SLE and healthy women; determine whether disease duration, disease activity, cumulative organ damage and stress have an influence on psychopathological symptoms in SLE patients; and evaluate whether perception of stress is related to SLE severity. METHODS: We conducted a cross-sectional study of 425 participants; 202 women with SLE, with an average age (SD) of 36.61 (10.15), and 223 healthy women, with age-matched controls. The assessment included the clinical characteristics (disease duration, SLE activity, cumulative organ damage, pharmacotherapy), the Symptom Checklist-90-Revised (SCL-90-R) and the Perceived Stress Scale. Descriptive, comparative, univariate and multivariate analysis were performed. RESULTS: SLE patients showed psychopathological alterations in the somatisation, obsessive-compulsive and positive discomfort subscales of SCL-90-R. Women with SLE reported significantly higher scores on the psychopathological dimensions and perceived stress compared to healthy women, except for paranoid ideation. Disease duration, SLE activity, cumulative organ damage, and perceived stress were shown to be significant predictors of psychopathological manifestations, explaining a range, between 20 and 43%, of variance across SCL-90-R dimensions. Moreover, perceived stress was related to SLE activity, after controlling for psychopathological dimensions. CONCLUSIONS: The psychopathological manifestations in SLE appeared to be influenced by perceived stress, disease duration, disease activity and cumulative organ damage. In turn, perceived stress was associated with disease severity. This knowledge may contribute to a more comprehensive perspective of these manifestations in the SLE population in the clinical setting.

Cumulated organ damage is associated with arterial stiffness in women with systemic lupus erythematosus irrespective of renal function.

OBJECTIVES: To determine whether there is an association between cumulated organ damage and arterial stiffness in women with systemic lupus erythematosus (SLE) with normal renal function and without renal damage. METHODS: Eighty-eight SLE women with normal renal function and without renal damage, and 102 sex- and age-matched controls with no history of coronary heart disease or peripheral arterial disease were studied. Cumulated organ damage and arterial stiffness were measured using the SLICC/ACR Damage Index (SDI) and pulse wave velocity (PWV), respectively. Patients were categorised as with (SDI ≥1) or without cumulated organ damage (SDI=0) and bivariate analyses were performed to compare both groups. A multivariate logistic regression was carried out to analyse the independent factors associated with cumulated organ damage. A multiple linear regression analysis was used to investigate the correlation between SDI and PWV, adjusted for appropriate confounders. RESULTS: PWV was significantly higher in patients with respect to controls (p=0.007). Also, patients with SDI ≥1 had significantly higher PWV than those with SDI=0 (p=0.007). In the multivariate analysis, cumulated organ damage was significantly associated with PWV (p=0.006) and obesity (p=0.003). Furthermore, PWV correlated with SDI after adjustment for age, SLE duration, systolic blood pressure, body mass index, renal function, prednisone and homocysteine (r=0.283, p=0.011). Patients with increased PWV were more likely to have organ damage (SDI ≥1) than those with normal PWV (67% vs. 36%, p=0.023). CONCLUSIONS: Cumulated organ damage was found to be independently associated with the arterial stiffness in SLE women without renal involvement.

Identification of a new putative functional IL18 gene variant through an association study in systemic lupus erythematosus.

Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in chronic inflammation and autoimmune disorders. In this study, we aimed to determine the potential role of the IL18 gene in SLE. To define the genetic association of the IL18 and SLE, we have genotyped nine SNPs in an independent set of Spanish cases and controls. The IL18 polymorphisms were genotyped by PCR, using a predeveloped TaqMan allele discrimination assay. Two SNPs were still significant after fine mapping of the IL18 gene. The SNP (rs360719) surviving correction for multiple tests was genotyped in two replication cohorts from Italy and Argentina. After the analysis, a significance with rs360719 C-allele remained across the sets and after the meta-analysis (Pooled OR = 1.37, 95% CI 1.21-1.54, combined P = 3.8E-07, Pc = 1.16E-06). Quantitative real-time PCR was performed to assess IL18 mRNA expression in PBMC from subjects with different IL18 rs360719 genotypes. We tested the effect of the IL18 rs360719 polymorphism on the transcription of IL18 by electrophoretic mobility shift assay and western blot. We found a significant increase in the relative expression of IL18 mRNA in individuals carrying the rs360719 C-risk allele; in addition we show that the polymorphism creates a binding site for the transcriptional factor OCT-1. These findings suggest that the novel IL18 rs360719 variant may play an important role in determining the susceptibility to SLE and it could be a key factor in the expression of the IL18 gene.

Replication of the TNFSF4 (OX40L) promoter region association with systemic lupus erythematosus.

The tumor necrosis factor ligand superfamily member 4 gene (TNFSF4) encodes the OX40 ligand (OX40L), a costimulatory molecule involved in T-cell activation. A recent study demonstrated the association of TNFSF4 haplotypes located in the upstream region with risk for or protection from systemic lupus erythematosus (SLE). To replicate this association, five single nucleotide polymorphisms (SNPs) tagging the previously associated haplotypes and passing the proper quality-control filters were tested in 1312 cases and 1801 controls from Germany, Italy, Spain and Argentina. The association of TNFSF4 with SLE was replicated in all the sets except Spain. There was a unique risk haplotype tagged by the minor alleles of the SNPs rs1234317 (pooled odds ratio (OR)=1.39, P=0.0009) and rs12039904 (pooled OR=1.38, P=0.0012). We did not observe association to a single protective marker (rs844644) or haplotype as the first study reported; instead, we observed different protective haplotypes, all carrying the major alleles of both SNPs rs1234317 and rs12039904. Association analysis conditioning on the haplotypic background confirmed that these two SNPs explain the entire haplotype effect. This first replication study confirms the association of genetic variation in the upstream region of TNFSF4 with susceptibility to SLE.

[Study of blood pressure variability in arterial hypertension and relation with glomerular filtration]. / Estudio de la variabilidad de la presión arterial en pacientes con hipertensión arterial y su relación con el filtrado glomerular.

BACKGROUND AND OBJECTIVE: Besides reducing blood pressure, it is important to think about the blood pressure variability that hypertensive patients may present. Indeed, studies suggest that target organ damage is greater in hypertensive people with high blood pressure variability. The purpose of the present study was to determine the blood pressure variability in patients who had not been treated with antihypertensive medication, as well as its relationship with the glomerular filtration. PATIENTS AND METHOD: We included 702 patients with clinical indication for 24h ambulatory blood pressure monitoring. RESULTS: 43.6% of patients had high variability of the blood pressure. These patients had greater levels of 24-h systolic blood pressure, diurnal and night blood pressure and a lower glomerular filtration. The main factors associated with high blood pressure variability were age, years from diagnosis of arterial hypertension, systolic blood pressure and a glomerular filtration smaller than 60ml/min. CONCLUSIONS: A high variability of blood pressure is frequent among hypertensive patients. Since it is not possible to perform ambulatory blood pressure measurement in all them, we should mainly suspect it in old patients and in those with reduced glomerular filtration.

Primary Sjögren syndrome in Spain: clinical and immunologic expression in 1010 patients.

We conducted the current study to characterize the clinical presentation of primary Sjögren syndrome (SS) in a large cohort of Spanish patients and to determine whether epidemiologic, clinical, and analytical features modulate disease expression. Patients were from the GEMESS Study group, which was formed in 2005 and included 12 Spanish reference centers. By March 2007, the database included 1010 consecutive patients, recruited since 1994, both incident and prevalent cases. The cohort included 937 women and 73 men (ratio, 13:1), with a mean age of 53 years at diagnosis and 59 years at inclusion in the registry. Multivariate analysis showed that male patients had a lower frequency of thyroiditis, Raynaud phenomenon, and antinuclear antibodies. Young-onset patients had a low degree of sicca involvement (xerostomia and parotid enlargement) and a high frequency of immunologic markers (anti-Ro/SS-A and low C4 levels). Patients with disease duration of more than 10 years had a higher prevalence of xerophthalmia, parotid enlargement, lung involvement, and peripheral neuropathy in comparison with incident cases. The subset of patients with anti-Ro/La antibodies had the highest prevalence of most systemic, hematologic, and immunologic alterations (higher frequency of Raynaud phenomenon, altered parotid scintigraphy, positive salivary gland biopsy, peripheral neuropathy, thrombocytopenia, and rheumatoid factor). Hypocomplementemia was associated with a higher frequency of vasculitis and lymphoma, and cryoglobulins with a higher frequency of parotid enlargement, vasculitis, and leukopenia.Epidemiologic, clinical, and analytical features have a significant impact on the clinical presentation of primary SS, influencing the results of the main diagnostic tests, the prevalence and diversity of extraglandular involvement, and the frequency of the main immunologic markers. Primary SS should be considered as a systemic autoimmune disease that can express in many guises beyond sicca involvement.

Alterations in episodic memory in patients with systemic lupus erythematosus.

The purpose of this paper was to examine memory performance in patients with SLE by studying the overall deterioration in memory, analyzing the differences and frequency of impairment in the variables from the visual and verbal memory tests, and studying the alterations in the memory. This study included 59 patients with a diagnosis of systemic lupus erythematosus (SLE) and 18 with a diagnosis of chronic discoid lupus (CDL), who were administered the Spanish complutense verbal learning test (TAVEC) and the Rey complex figure test (RCFT). Statistically significant differences were detected between the two groups on the immediate visual recall and delayed visual recall variables, with the mean of the SLE group being lower than that of the CDL group. The difference between the frequency of verbal and visual impairment could be explained by various factors, one of which would be a lateralization of memory impairment.

Potentially inappropriate prescribing according to STOPP-2 criteria among patients discharged from Internal Medicine: prevalence, involved drugs and economic cost.

AIM: This study aims to determine the prevalence of potentially inappropriate prescribing (PIP) among patients discharged from Internal Medicine, the drugs and factors associated and economic cost of PIP. METHODS: This retrospective cross-sectional, single-center study included participants aged ≥65 years consecutively discharged from the Internal Medicine Unit in a tertiary hospital of Southern Spain. PIP was defined by the Screening Tool for Older Persons Prescriptions (STOPP-2) criteria version 2 (2015 update). The association of PIP with chronic conditions was analyzed using multilevel logistic regression model. Data on economic cost associated to PIP were determined according to the computerized prescribing database of Andalusia ("Receta XXI"). RESULTS: Out of the 275 patients studied, a total of 249 PIPs were detected in 114 (41.5%) patients of whom 79 (28.7%) had one or two STOPP-2 criteria and 35 (12.7%) 3 or more criteria. The most involved drugs were benzodiazepines (45.5%); antithrombotics (14.5%), including anticoagulants or antiplatelets, and opioids (11.4%). The multivariate logistic regression analysis identified polypharmacy (OR=11.00; 95% CI 1.41-85.52) and extreme polypharmacy (OR=26.25; 95% CI 3.34-206.07) as independent risk factors for PIP. The mean cost of PIP was €18.75±4.24 per patient and month. Opioids accounted for the highest percentage expenditure of PIP (39.02%), followed by inhaled bronchodilator drugs (30.30%), antithrombotics (12.20%) and benzodiazepines (7.92%). CONCLUSIONS: PIP is frequent among patients discharged from Internal Medicine. The number of prescribed drugs was independently associated to PIP and benzodiazepines were the most involved drugs. PIP was associated to a significant economic cost.

Effect of ethnicity on clinical presentation and risk of antiphospholipid syndrome in Roma and Caucasian patients with systemic lupus erythematosus: a multicenter cross-sectional study.

AIM: To determine if there are ethnic differences in the prevalence of antiphospholipid syndrome (APS), clinical presentation and autoantibody profile between Roma and Caucasian patients with systemic lupus erythematosus (SLE). METHOD: A cross-sectional study was conducted including data from Roma and Caucasian SLE patients consecutively attending six hospitals in Spain. Socio-demographic characteristics, prevalence of APS, clinical and analytical features of SLE and APS were compared between ethnic groups. RESULTS: Data from 52 Roma and 98 Caucasian SLE patients were included. Roma SLE patients had a higher risk (odds ratio 2.56, 95% CI 1.02-6.39) and prevalence of APS (28.8% vs. 13.3%, P = 0.027). Furthermore, Roma SLE patients had a statistically significant higher prevalence of abortions (23.5% vs. 10.2%, P = 0.049). In relation to other APS diagnostic criteria, Roma SLE patients had a non-statistically significant higher prevalence of fetal deaths (14.3% vs. 5.1%, P = 0.106) and thrombotic events (21.1% vs. 12.2%, P = 0.160). In relation to SLE clinical features, Roma patients had a significantly higher prevalence of arthritis (75% vs. 57.1%, P = 0.034) and non-significant higher prevalence of serositis (44.2% vs. 29.6%, P = 0.104), discoid lesions (11.5% vs. 5.1%, P = 0.191), oral ulcers (46.1% vs. 34.7%, P = 0.218) and livedo reticularis (21.1% vs. 15.3%, P = 0.374). No statistically significant differences were found in the Systemic Lupus International Collaborating Clinics Damage Index or the autoimmune serological profile. CONCLUSION: Prevalence and risk of APS were significantly higher in Roma SLE patients. Furthermore, Roma patients had a significantly higher prevalence of abortions and a non-significant higher prevalence of fetal deaths and thrombotic events.

MYO9B gene polymorphisms are associated with autoimmune diseases in Spanish population.

The aim of the study was to test MYO9B gene polymorphisms for association with three autoimmune diseases, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and celiac disease (CD), in a Spanish population. We analyzed three SNPs (rs2305767, rs1457092, and rs2305764) in a case-control cohort composed of 349 SLE patients, 356 RA patients, 90 CD patients, and 345 healthy controls. All three SNPs showed a consistent increased frequency of the A allele in SLE, RA, and CD patients compared with healthy controls. An association was observed between CD and rs2305764 (p=0.01, OR=2.3), between SLE and rs1457092 (p=0.002, OR=1.4), and between RA and rs1457092 (p=0.02, OR=1.3). The three autoimmune diseases combined showed significant association with rs1457092 and rs2305764 and with the AAA haplotype (p haplotype=0.005, OR=1.3). Our data demonstrate consistent association with the A allele and AAA haplotype of three SNPs in the MYO9B gene, which were previously reported to be associated with CD in the Dutch population. This suggests that genetic variation in MYO9B is associated with CD, SLE, and RA and that MYO9B is a general risk factor for autoimmunity.

[Effect of olmesartan medoxomil on arterial stiffness in patients with essential hypertension]. / Efecto del olmesartán medoxomilo en la rigidez de las grandes arterias en pacientes con hipertensión arterial esencial.

BACKGROUND AND OBJECTIVE: Arterial stiffness is one of the early lesions of the arteries in patients with cardiovascular risk factors. Pulse wave velocity (PWV) is one form of measurement of arterial stiffness. The renin-angiotensin system seems to be involved in the inflammatory mechanisms that take place at level of the vascular wall. The aim of this study is to investigate the effect of olmesartan (angiotensin II type 1 receptor antagonist) in the arterial stiffness, measuring the PWV. Another secondary objective is to determine the antihypertensive efficacy with ambulatory blood pressure monitoring (ABPM). PATIENTS AND METHOD: Seventy-one patients with mild-to-moderate essential hypertension were consecutively included. Clinical blood pressure (CBP), ABPM and PWV, automatized measurement between the carotid and femoral arteries using the Complior device (Colson, Paris, France), were determined in a baseline and after 16 weeks of treatment with 10-40 mg of olmesartan. RESULTS: Sixty-four patients completed the study. The mean (standard deviation) age was 48.31 (9.69) years and 44.9% were men. A significant reduction of the PWV was observed. The basal PWV was 10.50 (1.87) m/s and after treatment was 9.26 (1.84) m/s (p < 0.0001). We found only a positive correlation between the decline of PWV and diastolic blood pressure (BP). We could not find such correlation with systolic BP. The reduction degree was higher in the youngest patients where BP decrease was less evident. The BP decreased in a significant way (p < 0.0001) doing so in CBP and in the periods of 24 h, diurnal and nocturnal. CONCLUSIONS: Olmesartan has shown effective to decrease the arterial stiffness, mainly in young patients. This effect seems to be independent of the decrease of the systolic BP. Olmesartan reduces effectively the BP during the 24 h.

Association study of genetic variants of pro-inflammatory chemokine and cytokine genes in systemic lupus erythematosus.

BACKGROUND: Several lines of evidence suggest that chemokines and cytokines play an important role in the inflammatory development and progression of systemic lupus erythematosus. The aim of this study was to evaluate the relevance of functional genetic variations of RANTES, IL-8, IL-1alpha, and MCP-1 for systemic lupus erythematosus. METHODS: The study was conducted on 500 SLE patients and 481 ethnically matched healthy controls. Genotyping of polymorphisms in the RANTES, IL-8, IL-1alpha, and MCP-1 genes were performed using a real-time polymerase chain reaction (PCR) system with pre-developed TaqMan allelic discrimination assay. RESULTS: No significant differences between SLE patients and healthy controls were observed when comparing genotype, allele or haplotype frequencies of the RANTES, IL-8, IL-1alpha, and MCP-1 polymorphisms. In addition, no evidence for association with clinical sub-features of SLE was found. CONCLUSION: These results suggest that the tested functional variation of RANTES, IL-8, IL-1alpha, and MCP-1 genes do not confer a relevant role in the susceptibility or severity of SLE in the Spanish population.

Relationship between QT Interval Length and Arterial Stiffness in Systemic Lupus Erythematosus (SLE): A Cross-Sectional Case-Control Study.

INTRODUCTION AND OBJECTIVES: The QT interval on the electrocardiogram has been shown to be longer in patients with systemic lupus erythematosus (SLE) compared to that of the general population. The clinical significance of this finding is unknown. The aim of this study was to assess the relationship between QT interval and subclinical atherosclerosis, measured by carotid-femoral pulse-wave velocity. MATERIAL AND METHODS: 93 patients with SLE and 109 healthy women with similar basal characteristics were studied. All patients underwent a 12- lead electrocardiogram, and corrected QT interval (QTc) was measured using the Bazett's formula. The presence of atherosclerosis was evaluated by carotid-femoral pulse-wave velocity. RESULTS: Clinical basal characteristics were similar in both groups. QTc interval was 415 ± 21.4 milliseconds in all patients, and 407 ± 19.1 milliseconds in the control group (p = 0.007). There was a positive correlation between QTc interval and carotid-femoral pulse-wave velocity (r = 0.235; p = 0.02) in patients with SLE. This association was independent of hypertension and age in a multivariate analysis. CONCLUSION: QTc interval measured by electrocardiogram is prolonged in SLE patients; it is related to subclinical atherosclerosis, measured by carotid-femoral pulse-wave velocity. This measure may help stratify risk in routine clinical practice and select the patients that might benefit from a more aggressive therapy in the prevention of cardiovascular events.