José Mario Sabio

Many studies have shown that patients with autoimmune disease present a hypoactive hypothalamic‐pituitary‐adrenal (HPA) axis, but the results are controversial. Our objective was to study differences in stress response axis activity between patients with autoimmune disease and healthy people. The study sample consisted of 97 women divided into four groups: 37 healthy women (HW), 21 with systemic lupus erythematosus (SLE), 21 with Sjögren's syndrome (SS), and 18 with systemic sclerosis (SSc). After being exposed to a stress task, participants' skin conductance and salivary cortisol levels were measured in order to assess their response to psychological stress. Diurnal cortisol concentrations were assessed by measuring salivary cortisol in samples collected five times over one day. In addition, self‐administered questionnaires were used to assess psychological variables. A time × group interaction effect was found (p = 0.003) in salivary cortisol secretion in response to stressful challenge. The healthy group presented normal activation, the SS and SLE groups showed no activation, and the SSc group presented a similar activation pattern to the HW group, except at the time of recovery. Total cortisol production (AUCg) was higher in the SSc group than in the HW group (p = 0.001). Differences were also observed in the cortisol AUCg collected over one day between healthy women and patients with SLE (p = 0.004) as well as with SSc (p = 0.001): women with SLE and SSc presented higher total hormone production than healthy women. Patients with autoimmune disease present a different HPA axis response, which may contribute to the harmful effects of stress in these diseases.

Cardiovascular disease is one of the main causes of death in patients with systemic lupus erythematosus (SLE). On the other hand, sclerostin is a reliable and early biomarker of vascular calcification. This study aimed to estimate the association between sclerostin and two markers of cardiovascular risk, carotid atherosclerotic plaque (CP) and carotid-femoral pulse wave velocity (PWV), in women with SLE. The presence of CP (determined by carotid artery ultrasound) and PWV were measured in 68 women with SLE and preserved renal function. None of the participants had a history of cardiovascular disease. Serum levels of sclerostin were determined using the ELISA method. Other factors associated with increased cardiovascular risk were also measured. The association between sclerostin, CP and PWV was assessed using Receiver Operating Characteristic (ROC) curves and multivariate regression models. The area under the ROC curve was 0.785 (95% confidence interval [CI] 0.662–0.871) for CP and 0.834 (95% CI 0.729–0.916) for dichotomized PWV. After adjusting for other cardiovascular risk factors, it was found that a 10-units increase in sclerostin values was associated with a 44% increase in the odds of CP (95% CI 1–105), but no adjusted association was observed between sclerostin and PWV. Predictive models included age (for both outcomes), hypertension, Framingham risk score and C-reactive protein (for PWV), but not sclerostin. Sclerostin is associated with the presence of CP in women with SLE. Further research should confirm its possible role as a biomarker of cardiovascular risk in these patients.

Cardiovascular disease (CVD) is a main cause of death in patients with systemic lupus erythematous (SLE). Algorithms for cardiovascular risk stratification in general population underestimate the risk for CVD in SLE. Our study aimed to determine whether serum high-sensitivity cardiac troponin I (hs-cTnI) might help to identify SLE patients with subclinical atherosclerosis. Arterial stiffness was assessed measuring the carotid-femoral pulse wave velocity (PWV) in 68 SLE women with a normal or almost normal kidney function and in 71 controls of similar characteristics. None of the participants had a history of an overt CVD. Serum hs-cTnI level was measured using the chemiluminescence method. Factors associated with an increased PWV (iPWV) were identified and multivariate analysis was performed. When detectable, patients tended to have had higher hs-cTnI levels than controls [2.9 (2.3–4.0) vs 2.4 (2.2–4.1); p = 0.098] and were more likely to have detectable hs-cTnI [50% vs 28%, odds ratio (OR) 7.0; 95% confidence interval (CI) 0.008–0.013]. Also, patients with iPWV were more likely to have detectable hs-cTnI than those with normal PWV (OR 6.4; 95% CI 0.019–0.026). In the multivariate analysis, the age at SLE diagnosis (OR 1.24; 95% CI 1.04–1.48), systolic blood pressure (OR 1.28; 95% CI 1.10–1.48) and detectable hs-cTnI level (OR 2.04; 95% CI 1.18–3.50) were independently associated with an iPWV. The negative predictive value of having an iPWV with undetectable hs-cTnI levels was 88%. Hs-cTnI may be a useful biomarker for the identification of SLE patients with iPWV as a surrogated marker of subclinical atherosclerosis. Specifically targeted prospective studies are needed to confirm this hypothesis.

LER & CER: letter to Editor Rheumatology; Authors: A. Rosales-Castillo, J.M. Sabio

This study aimed to examine the association of relative handgrip strength (rHGS) with cardiometabolic disease risk factors in women with systemic lupus erythematosus (SLE). Methods: Seventy-seven women with SLE (mean age 43.2, SD 13.8) and clinical stability during the previous six months were included. Handgrip strength was assessed with a digital dynamometer and rHGS was defined as absolute handgrip strength (aHGS) divided by body mass index (BMI). We measured blood pressure, markers of lipid and glucose metabolism, inflammation (high sensitivity C-reactive protein [hs-CRP]), arterial stiffness (pulse wave velocity [PWV]), and renal function. A clustered cardiometabolic risk index (z-score) was computed. Results: Pearson′s bivariate correlations revealed that higher rHGS was associated with lower systolic blood pressure (SBP), triglycerides, hs-CRP, PWV, and lower clustered cardiometabolic risk (r_range = from −0.43 to −0.23; all p < 0.05). Multivariable linear regression analyses adjusted for age, disease activity (SLEDAI), and accrual damage (SDI) confirmed these results (all p < 0.05) except for triglycerides. Conclusions: The findings suggest that higher rHGS is significantly associated with lower cardiometabolic risk in women with SLE.

Abnormal heart rate variability (HRV) has been observed in patients with systemic lupus erythematosus (SLE). In a combined cross-sectional and interventional study approach, we investigated the association of HRV with inflammation and oxidative stress markers, patient-reported outcomes, and the effect of 12 weeks of aerobic exercise in HRV. Fifty-five women with SLE (mean age 43.5 ± 14.0 years) were assigned to either aerobic exercise (n = 26) or usual care (n = 29) in a non-randomized trial. HRV was assessed using a heart rate monitor during 10 min, inflammatory and oxidative stress markers were obtained, psychological stress (Perceived Stress Scale), sleep quality (Pittsburg Sleep Quality Index), fatigue (Multidimensional Fatigue Inventory), depressive symptoms (Beck Depression Inventory), and quality of life (36-item Short-Form Health Survey) were also assessed. Low frequency to high frequency power (LFHF) ratio was associated with physical fatigue (p = 0.019). Sample entropy was inversely associated with high-sensitivity C-reactive protein (p = 0.014) and myeloperoxidase (p = 0.007). There were no significant between-group differences in the changes in HRV derived parameters after the exercise intervention. High-sensitivity C-reactive protein and myeloperoxidase were negatively related to sample entropy and physical fatigue was positively related to LFHF ratio. However, an exercise intervention of 12 weeks of aerobic training did not produce any changes in HRV derived parameters in women with SLE in comparison to a control group.

Objectives: This study analyzed sleep quality in fibromyalgia (FM) and systemic lupus erythematosus (SLE) and explored its relationship with other clinical and psychological manifestations. Methods: 20 women with FM, 19 women with SLE and 22 healthy women participated in the study. Subjective sleep quality, fatigue, pain, depression and anxiety were evaluated with self-reports, and objective sleep measures were obtained with actigraphy. Comparisons were analyzed with Chi-square, Kruskal-Wallis H and Mann-Whitney U tests. Relationships between measurements were analyzed with Spearman correlation coefficients. Results: Subjective sleep quality was altered in the FM and SLE groups compared to the control group (15.53 ± 3.27, 8.47 ± 3.20, 4.91 ± 2.79, p < 0.05, respectively). FM and SLE patients reported higher levels of pain (22.65 ± 9.87, 10.21 ± 9.93, 2.30 ± 3.096, p < 0.05), fatigue (4.67 ± 0.37, 3.59 ± 3.04, 2.33 ± 0.59, p < 0.05) and depressive symptoms (9.90 ± 3.78, 4.53 ± 3.04, 4.17 ± 3.95, p < 0.05) than controls, respectively. Worse subjective quality of sleep was associated with higher pain intensity and more depressive symptoms in FM and SLE. Actigraphy measures showed that FM patients spent more time in bed than subjects in the remaining groups. Conclusions: Sleep deterioration is related to more pain and depressive symptoms in FM and SLE. Addressing sleep disturbances may improve not only sleep quality but also depressive symptoms and pain.

Objective Blood pressure (BP) physiologically declines more than 10% at night. Subjects who do not experience this drop are classified as non-dippers. They have a higher risk of cardiovascular diseases (CVD). Vitamin D deficiency and non-dipper pattern have been associated in the general population. Patients with systemic lupus erythematosus (SLE) are more likely to have vitamin D deficiency, a non-dipper pattern and CVD. We aimed to evaluate a possible relationship between vitamin D deficiency and non-dipper pattern in patients with SLE. Methods Using 24-hour ambulatory BP monitoring, 77 women with SLE were divided into dippers and non-dippers. 25-hydroxyvitamin D (25(OH) D) levels were compared between both groups. A multivariate analysis was used to determine which variables were independently associated with non-dipper pattern. Results 62% of patients were non-dippers. They had lower levels of 25(OH) D than dippers (19.4 +/- 8.9 vs. 25.9 +/- 10.1 ng/ml, p=0.005). Patients with lower 25(OH) D levels were more likely to be non-dippers (OR 3.7, 95% CI 1.2-11.4; p=0.025). The nocturnal decline of mean BP correlated with levels of 25(OH) D (r=0.227, p=0.047). Night-time systolic, diastolic and mean BP inversely correlated with the levels of 25(OH) D (r=-0.274, p=0.016; r=-0.238, p=0.037, and r=-0.260, p=0.022, respectively), but only night-time systolic BP remained significant after adjustment for age and body mass index (r=-0.228, p=0.049). 25(OH) D levels and the use of mycophenolate were found to be independently associated with non-dipper pattern in SLE patients. Conclusion Vitamin D deficiency may contribute to the development of a non-dipper pattern in patients with SLE.

Background and objectives: Higher physical fitness is associated with a more favorable weight and body composition in the general population, although this association has not been studied in patients with systemic lupus erythematosus (SLE). The aim of the present study was to examine the association of different components of physical fitness with body composition in women with SLE with mild disease activity. Materials and Methods: This cross-sectional study included 77 women with SLE (43.2 ± 13.8 years old) and clinical stability during the previous 6 months. Body composition (including body mass index (BMI), fat mass index (FMI), waist circumference, waist-to-height ratio and waist-to-hip ratio) was assessed using a stadiometer, an anthropometric tape, and a bioimpedance device. Physical fitness included cardiorespiratory fitness (Siconolfi step test and 6 min walk test), muscular strength (handgrip strength test as upper body measure and 30 s chair stand as lower body measure), and flexibility (back-scratch test). Participants with a fitness level equal or above the median of the study sample were categorized as “fit” and those below the median were categorized as “unfit”. Linear regression assessed the association of physical fitness with body composition parameters. Results: Cardiorespiratory fitness and upper body muscular strength were negatively associated with BMI, FMI, waist circumference, and waist-to-height ratio (all, p < 0.05). Lower body muscular strength and flexibility were negatively related to FMI, waist circumference, waist-to-height ratio, and waist-to-hip ratio (all, p < 0.05). These relationships were still significant after controlling for age, disease duration, accrual damage, and SLE activity. Overall, fit patients presented significantly lower values in all body composition parameters compared to unfit patients (all, p < 0.05). Conclusions: The main findings of the present study suggest that physical fitness is inversely associated with body composition in women with SLE. Given the cross-sectional nature of this study, future clinical trials should study the causal pathways underlying these relationships.