Amylin serum levels are upregulated in patients with systemic lupus erythematosus.

OBJECTIVES: Amylin is a pancreatic hormone that participates in glucose homeostasis. We aimed to investigate how serum amylin levels are expressed in patients with systemic lupus erythematosus (SLE) compared to matched controls, and their possible relationship to disease-related characteristics, such as activity or damage. METHODS: 144 SLE patients and 96 non-diabetic sex- (female 96% vs. 91%, p=0.43) and age-matched controls (49±11 vs. 51±8 years, p=0.09) were included. Amylin, insulin and C-peptide serum levels, as well as insulin resistance indexes were assessed in both groups. Multivariable regression analysis was performed to compare amylin between groups and to explore its interrelations with SLE features. The analyses were adjusted for glucocorticoids intake and for insulin resistance classic risk factors. RESULTS: Patients with SLE exhibited significant higher serum levels of amylin when compared to controls after multivariable analysis (beta coef. 1.56 [95%CI 1.01-2.11], p=0.000). Moreover, SLE patients not on prednisone (beat coef. 1.54 [95%CI 0.98-2.10] ng/ml, p=0.000) and those on prednisone (beta coef. 1.51 [95%CI 0.96-2.07] ng/ml, p=0.000) disclosed higher amylin serum levels compared to controls in the fully multivariable analysis. Hyperamylinaemia in SLE patients remained significant even adjusting for differences in the insulin resistance and beta cell production rates between patients and controls. The damage produced by the disease and its severity were independently and positively associated with amylin serum levels. CONCLUSIOINS: Amylin is upregulated in SLE patients compared to controls, regardless of the insulin resistance that SLE may present. The damage produced by the disease and its severity independently explains this upregulation.

Impaired HDL cholesterol efflux capacity in systemic lupus erythematosus patients is related to subclinical carotid atherosclerosis.

OBJECTIVES: Lipid profiles appear to be altered in SLE patients due to disease activity and inflammation. Cholesterol efflux capacity (CEC) is the ability of high-density lipoprotein cholesterol to accept cholesterol from macrophages. CEC has been linked to cardiovascular events in the general population and is impaired in SLE patients. The aim of this study was to establish whether CEC is related to subclinical carotid atherosclerosis in SLE patients. METHODS: The present report is of a cross-sectional study that encompassed 418 individuals: 195 SLE patients and 223 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. Carotid intima-media thickness and carotid plaques were evaluated in SLE patients. A multivariable analysis was performed to study the relationship of CEC to SLE-related data, lipid profile and subclinical carotid atherosclerosis. RESULTS: CEC was downregulated in SLE patients [8.1 (4.2) % vs 16.9 (10.4) %, P = 0.004). This occurred independently of traditional cardiovascular risk factors, statin use or other variations in the lipid profile related to the disease. Traditional cardiovascular risk factors, both in patients and controls, and SLE-related data such as activity, severity or damage were not associated with CEC. After multivariable regression analysis including lipid profile-related molecules, CEC was inversely and independently associated with the presence of carotid plaques in SLE patients [odds ratio 0.87 (95% CI: 0.78, 0.97), P = 0.014]. CONCLUSION: CEC is impaired in SLE patients independently of other inflammation-related lipid profile modifications that occur during the disease. CEC is associated with carotid plaques in SLE patients.

Proprotein convertase subtilisin/kexin type 9 in patients with systemic sclerosis.

OBJECTIVES: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation, and which has been linked to cardiovascular risk. The purpose of the present study was to examine whether PCSK9 serum levels are disrupted in patients with systemic sclerosis (SS) compared to controls, and if PCSK9 is related to disease-related data and the subclinical atherosclerosis that occurs in these patients. METHODS: Cross-sectional study that encompassed 146 individuals; 73 patients with SS and 73 age- and sex-matched controls. PCSK9, lipoproteins serum concentrations, and standard lipid profiles were assessed in patients and controls. Carotid intima-media thickness (cIMT) and the presence of carotid plaques were evaluated in SS patients. A multivariable analysis, adjusted for traditional cardiovascular risk factors, was performed to evaluate the differences in PCSK9 between patients and controls, the association of SS-related manifestations with PCSK9 levels, and if PCSK9 was associated with subclinical carotid atherosclerosis in SS patients. RESULTS: After multivariable analysis, PCSK9 was downregulated in SS patients compared to controls (beta coefficient -78 (95%CI -106 - -50) ng/ml, p=0.000) and skin thickness was associated with higher serum levels of PCSK9 (beta coef. 22 (7-37) units, p=0.005). PCSK9 was significantly and positively associated with cIMT (beta coef. 0.65 (0.06-1.24) ng/ml, p=0.031) in SS patients after multivariable adjustment. CONCLUSIONS: PCSK9 serum concentration is downregulated in SS patients compared to controls and is directly associated with disease severity subrogated parameters. PCSK9 was independently related to cIMT in SS patients.

Comparable effects of traditional cardiovascular risk factors on subclinical atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) have an increased premature prevalence of atherosclerosis. We aimed to determine whether there are differences in the prevalence of classic cardiovascular risk factors between SLE and RA. We also analysed the effect of traditional cardiovascular risk factors on the development of subclinical atherosclerosis in both conditions and if some disease-characteristic features are associated with these traditional cardiovascular risk factors. METHODS: This was a cross-sectional study encompassing 602 individuals, 276 SLE and 326 RA patients. Subclinical atherosclerosis (presence of carotid plaques and carotid intima-media thickness [cIMT]) was determined by carotid ultrasonography. A multivariable regression analysis was performed to evaluate whether classic cardiovascular-related risk factors differentially influence subclinical carotid atherosclerosis in SLE compared to RA patients. RESULTS: Age (interaction factor [if] p=0.000), hypertension (if p=0.034), and diabetes (if p=0.037) had a higher effect on cIMT in RA than in SLE subjects. However, these traditional cardiovascular factors did not yield different effects on the presence of carotid plaques in RA and SLE when the univariate interaction was analysed. In addition, no differences were found in the influence of hypertension, diabetes, dyslipidaemia or current smoking on cIMT or carotid plaque after adjusting for demographics, the presence of other traditional cardiovascular factors, and disease-related data. Moreover, the additive effect of several cardiovascular risk factors on the subclinical carotid atherosclerosis did not differ between the two diseases. CONCLUSIONS: The influence of traditional cardiovascular risk factors on cIMT and carotid plaque is similar in RA and SLE.

Insulin resistance in systemic lupus erythematosus patients: contributing factors and relationship with subclinical atherosclerosis.

OBJECTIVES: Insulin resistance (IR) plays a role in the increased cardiovascular risk of systemic lupus erythematosus (SLE) patients. This study aimed to determine the potential association of IR with disease activity, drug exposure and subclinical atherosclerosis in patients with SLE. METHODS: This cross-sectional study encompassed 87 non-diabetic SLE patients and 82 sex-matched controls. Insulin and C-peptide serum levels, IR indexes by homeostatic model assessment (HOMA2) (both insulin-based: HOMA2-IR, and with C-peptide: HOMA2-IR-C-peptide) and lipid profiles were assessed in patients and controls. Activity (SLEDAI), severity (Katz) and damage (SLICC) index scores, as well as carotid intima-media thickness (cIMT) and carotid plaques, were determined in SLE patients. A multivariable regression analysis, adjusted for classic IR related factors, was performed to evaluate the differences in IR indexes between patients and controls and how IR is associated with disease-related characteristics, including carotid ultrasound results, in SLE patients. RESULTS: SLE patients had higher C-peptide serum levels (2.61±1.51 vs. 1.34±0.62 ng/ml, p=0.00) and elevated HOMA2-IRC-peptide index (1.90±1.12 vs. 0.97±0.45, p=0.00) than controls. These differences remained statistically significant after adjusting for classic cardiovascular risk factors and prednisone intake. Traditional IR-related factors, such as body mass index, waist circumference or hypertension, and prednisone intake were significantly associated with HOMA2-IR and HOMA2-IRC-peptide in SLE patients. SLICC damage index was independently associated with HOMA2-IR-C-peptide. The presence of carotid plaques and cIMT values were associated with IR indexes in SLE patients only in the univariate analysis. CONCLUSIONS: C-peptide serum levels are independently up-regulated in SLE patients. Although classic IR factors and prednisone are associated with IR, SLE damage over time also contributes to IR in an independent way.

Impact of Disease Activity on Physical Activity in Patients With Psoriatic Arthritis.

OBJECTIVE: The purpose of this study was to compare physical activity (PA) in a group of patients with psoriatic arthritis (PsA) versus healthy controls and to determine whether the mobility of these patients is affected by disease activity. METHODS: A group of 52 patients with PsA and 53 controls were included in this case-control study. PA was assessed by accelerometry in both groups and additionally with the International Physical Activity Questionnaire (IPAQ) in patients with PsA. Multiple regression analysis was used to compare PA between groups and to determine the relationship between PA and PsA features, including disease activity, as assessed by the 28-joint Disease Activity Score (DAS28) and the Disease Activity Index for Psoriatic Arthritis (DAPSA) score. In a group of 36 patients, a test-retest study was carried out after 6 months. RESULTS: The time engaged in moderate-to-vigorous physical activity (MVPA) per day, as evaluated by accelerometry, and adjusted by confounders, proved similar in patients with PsA and controls. In patients with PsA, disease activity was inversely related to PA as assessed either by IPAQ or accelerometry. When PA was compared in patients with PsA between the 2 visits, a significant difference in the amount of time doing MVPA was found (42 ± 33 versus 30 ± 22 minutes/day; P = 0.004). Interestingly, in the test-retest study, variations in disease activity over time based on DAPSA scores (r = -0.49, P = 0.002) and DAS28 using the C-reactive protein level (r = -0.4, P = 0.017) were inversely correlated with changes in PA, as determined by accelerometry. CONCLUSION: Patients with PsA show levels of PA like healthy controls. In patients with PsA, disease activity and PA are inversely correlated and the evaluation of PA by accelerometry is sensitive to changes in disease activity.

Higher Prevalence and Degree of Insulin Resistance in Patients With Rheumatoid Arthritis Than in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: Since insulin resistance (IR) is highly prevalent in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), we aimed to determine whether differences in IR exist between the two conditions. METHODS: We conducted a cross-sectional study comprising 413 subjects without diabetes (186 with SLE and 227 with RA). Glucose, insulin, and C-peptide serum levels, as well as IR by the homeostatic model assessment (HOMA2) were studied. A multivariable regression analysis was performed to evaluate the differences in IR indexes between patients with SLE and RA, as well as to determine if IR risk factors or disease-related characteristics are differentially associated with IR in both populations. RESULTS: The insulin:C-peptide molar ratio was upregulated in patients with RA compared to patients with SLE (ß 0.009, 95% CI 0.005-0.014, P < 0.001) after multivariable analysis. HOMA2 indexes related to insulin sensitivity (HOMA2-%S) were found to be lower (ß -27, 95% CI -46 to -9, P = 0.004) and ß cell function (HOMA2-%B) showed higher IR indexes (ß 38, 95% CI 23-52, P < 0.001) in RA than in SLE patients after multivariable analysis. Patients with RA more often fulfilled the definition of IR than those with SLE (OR 2.15, 95% CI 1.25-3.69, P = 0.005). The size effect of IR factors on IR indexes was found to be equal in both diseases. CONCLUSION: IR sensitivity is lower and ß cell function is higher in RA than in SLE patients. The fact that traditional IR factors have an equal effect on IR in both SLE and RA supports the contention that these differences are related to the diseases themselves.

HDL cholesterol efflux capacity and lipid profile in patients with systemic sclerosis.

OBJECTIVE: It is well established that patients with systemic sclerosis (SSc) have a disrupted lipid profile and an increased cardiovascular risk. Cholesterol efflux capacity (CEC), the ability of high-density lipoprotein (HDL)-cholesterol to accept cholesterol from macrophages, has been linked to cardiovascular events. The aim of this study was to establish whether CEC and lipid profile were impaired in SSc patients with respect to controls and whether these changes were associated with disease-related data. METHODS: Cross-sectional study encompassed 188 individuals: 73 SSc patients and 115 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. A multivariable analysis was performed to study the differences in CEC between patients and controls, and if SSc-related data could explain such differences. RESULTS: The multivariable analysis adjusted for demographic characteristics, cardiovascular risk factors, and lipid-related molecules showed that total cholesterol (beta coefficient: - 22 [95%CI - 37 to - 7], p = 0.004), triglycerides (beta coefficient: 24 [95%CI 2-47], p = 0.033), lipoprotein A (beta coefficient: 22 [95%CI 2-43], p = 0.033), and CEC (beta coefficient: - 6 [95%CI - 10 to - 2]%,p = 0.002) were significantly different between patients and controls. Skin thickness, as assessed by modified Rodnan skin score, was independently associated with a lower CEC (beta coefficient: - 0.21 [95%CI - 0.37 to - 0.05]%, p = 0.011) after multivariable adjustment. CONCLUSION: SSc patients show an abnormal lipid profile with respect to controls including CEC. Skin thickness is independent and inversely associated with CEC in SSc patients.

Differences in Capacity of High-Density Lipoprotein Cholesterol Efflux Between Patients With Systemic Lupus Erythematosus and Rheumatoid Arthritis.

OBJECTIVE: Cholesterol efflux capacity (CEC) is the ability of high-density lipoprotein (HDL) cholesterol to accept cholesterol from macrophages. Lipid profiles and CEC appear to be altered in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) due to disease activity and inflammation. CEC has been linked to cardiovascular events in the general population and to subclinical atherosclerosis in SLE and RA patients. The aim of this study was to establish whether CEC varies between patients with SLE and those with RA. METHODS: The study encompassed 460 individuals (195 SLE patients and 265 patients with RA). CEC (using an in vitro assay) and concentrations of lipoprotein serum were assessed in both populations. A multivariable regression analysis was performed to study whether CEC differs between SLE patients and RA patients. RESULTS: Comparison of lipid patterns revealed that patients with RA have lower HDL cholesterol and higher apolipoprotein B serum levels than SLE patients. CEC was downregulated in SLE patients compared to patients with RA (ß -12 [95% confidence interval -13, -10], P < 0.001). It occurred independently of traditional cardiovascular risk factors, statin use, disease-related data, and other variations in the lipid profile related to the diseases. CONCLUSION: Patients with RA have a more proatherogenic lipid pattern compared to those with SLE. However, CEC seems to be more damaged in SLE patients than in RA patients.

HDL cholesterol efflux capacity is related to disease activity in psoriatic arthritis patients.

OBJECTIVE: Cholesterol efflux capacity (CEC) is the ability of high-density lipoprotein (HDL) cholesterol to accept cholesterol from macrophages. CEC is linked to cardiovascular events in the general population, and it has been shown to be disrupted in inflammatory states. The aim of this study was to establish whether CEC is impaired in PsA patients and if this could be explained by disease-related features like disease activity. METHODS: Case-control study that encompassed 105 individuals: 52 PsA patients and 53 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. Disease activity in patients with PsA was measured using the Disease Activity Index for Psoriatic Arthritis (DAPSA). Multivariate analysis was performed to study the differences between CEC in patients and controls, and the relation of CEC with PsA activity-related data and lipid profile. RESULTS: Total cholesterol, apolipoprotein A1, and LDL cholesterol serum levels were downregulated in PsA patients. CEC did not differ between controls and patients (17 ± 10 vs. 18 ± 2%, p = 0.15) after adjusting for traditional cardiovascular risk factors or other variations in the lipid profile related to the disease. Traditional cardiovascular risk factors, both in patients and controls, were not related to CEC. After multivariate regression analysis, the DAPSA score was inversely and independently associated with CEC (beta coefficient - 0.75 [95%CI - 1.39-- 0.11] %, p = 0.023). CONCLUSION: CEC is inversely associated with disease activity in PSA patients, reinforcing the role of disease activity as a key factor in the development of accelerated atherosclerosis in these patients.Key Points• Cholesterol efflux capacity is linked to cardiovascular events in the general population.• In patients with psoriatic arthritis, cholesterol efflux capacity is inversely associated with disease activity (beta coefficient - 0.75[95% CI - 1.39-- 0.11] %, p = 0.023).• This finding reinforces the role of disease activity as a key factor in increasing cardiovascular risk in psoriatic arthritis patients.

Proprotein convertase subtilisin/kexin type 9 is related to disease activity and damage in patients with systemic erythematosus lupus.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation and that has been linked to cardiovascular (CV) disease. The purpose of the present study was to examine whether PCSK9 levels are disrupted compared with controls in patients with systemic lupus erythematosus (SLE). We additionally sought to establish whether PCSK9 is related to both the abnormalities in the lipid profile and to the disease activity or damage of patients with SLE. METHODS: We performed a cross-sectional study that encompassed 366 individuals: 195 SLE patients and 171 age-, sex-, and statin intake-matched controls. PCSK9, lipoproteins serum concentrations, and lipid profiles were assessed in patients and controls. A multivariable analysis, adjusted for standard CV risk factors, was performed to evaluate the role of PCSK9 in SLE-related dyslipidemia. RESULTS: Most lipid related-molecules were decreased in patients with SLE compared with controls. This downregulation included PCSK9, with PCSK9 levels being lower in patients than controls in the full multivariable analysis, including the modifications in lipid profiles that the disease itself produces {beta coefficient -73 [95% confidence interval (CI) -91 to -54] ng/ml, p ⩽ 0.001}. Both SLICC and SLEDAI scores were independently and positively related to PCSK9. Patients currently on hydroxychloroquine exhibited decreased levels of PCSK9 compared with those that were not taking hydroxychloroquine [beta coefficient -30 (95% CI -54 to -6) ng/ml, p = 0.015]. CONCLUSION: PCSK9 is downregulated in SLE compared with controls, but SLE patients with higher disease activity and damage exhibited higher PSCK9 serum levels.

Recommendations of the Spanish Rheumatology Society for Primary Antiphospholipid Syndrome. Part I: Diagnosis, Evaluation and Treatment. / Recomendaciones de la Sociedad Española de Reumatología sobre síndrome antifosfolípido primario. Parte I: Diagnóstico, evaluación y tratamiento.

OBJECTIVE: The difficulty in diagnosis and the spectrum of clinical manifestations that can determine the choice of treatment for primary antiphospholipid syndrome (APS) has fostered the development of recommendations by the Spanish Society of Rheumatology (SER), based on the best possible evidence. These recommendations can serve as a reference for rheumatologists and other specialists involved in the management of APS. METHODS: A panel of four rheumatologists, a gynaecologist and a haematologist with expertise in APS was created, previously selected by the SER through an open call or based on professional merits. The stages of the work were: identification of the key areas for drafting the document, analysis and synthesis of the scientific evidence (using the Scottish Intercollegiate Guidelines Network [SIGN] levels of evidence) and formulation of recommendations based on this evidence and formal assessment or reasoned judgement techniques (consensus techniques). RESULTS: 46 recommendations were drawn up, addressing five main areas: diagnosis and evaluation, measurement of primary thromboprophylaxis, treatment for APS or secondary thromboprophylaxis, treatment for obstetric APS and special situations. These recommendations also include the role of novel oral anticoagulants, the problem of recurrences or the key risk factors identified in these subjects. This document reflects the first 21, referring to the areas of: diagnosis, evaluation and treatment of primary APS. The document provides a table of recommendations and treatment algorithms. CONCLUSIONS: An update of the SER recommendations on APS is presented. This document corresponds to partI, related to diagnosis, evaluation and treatment. These recommendations are considered tools for decision-making for clinicians, taking into consideration both the decision of the physician experienced in APS and the patient. A partII has also been prepared, which addresses aspects related to obstetric SAF and special situations.

Disease Damage Influences Cardiovascular Risk Reclassification Based on Carotid Ultrasound in Patients with Systemic Lupus Erythematosus.

OBJECTIVE: Composite scores of cardiovascular (CV) risk factors underestimate the CV risk in patients with systemic lupus erythematosus (SLE). Carotid artery ultrasound (US) was found useful in identifying high CV-risk patients with inflammatory arthritis. We assessed the effect of carotid US assessments on the CV risk stratification of patients with SLE. METHODS: This cross-sectional study included 276 patients with SLE. These indices were measured: lipid profile, Systematic COronary Risk Evaluation (SCORE) risk calculation, and disease activity (SLE Disease Activity Index), severity (Katz), and damage [Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology Damage Index]. Carotid plaques were assessed by US. A multivariable regression analysis, adjusted for classic CV-related factors, was performed to evaluate how risk reclassification was influenced by disease characteristics in patients with SLE. RESULTS: Thirty-six percent of patients had carotid plaques. However, only 6% of them fulfilled the definitions for high or very high risk according to the SCORE risk charts. Following carotid US assessment, 32% of the patients were reclassified as very high risk. Disease duration (OR 1.04, 95% CI 1.00-1.07, p = 0.025) and a SLICC > 0 (OR 2.48 95% CI 1.15-5.34, p = 0.020) were independently associated with a higher risk of reclassification. A predictive model for reclassification included age (cutoff 52 yrs, sensitivity 60%, specificity 86%), disease duration (cutoff 24 yrs, sensitivity 40%, specificity 82%), presence of hypertension, SLICC > 0, waist circumference (cutoff 102 cm, sensitivity 48%, specificity 84%), and C3 (cutoff 127 mg/dl, sensitivity 52%, specificity 92%) and triglyceride (cutoff 140 mg/dl, sensitivity 68%, specificity 79%) serum levels. CONCLUSION: Reclassification into a very high-risk category is frequent after carotid US assessments in patients with SLE. This is independently influenced by disease damage.