Cardiovascular Disease In SLE Research Articles

Towards an understanding of the biopsychosocial determinants of CVD in SLE: a scoping review

ObjectiveSystemic lupus erythematosus (SLE) is a chronic autoimmune condition with significant physical, mental, psychosocial and economic impacts. A main driver of SLE morbidity and mortality is cardiovascular disease (CVD). Both...

Disease duration, age at diagnosis and organ damage are important factors for cardiovascular disease in SLE.

ObjectiveTo report the incidence rate ratios (IRR) of acute myocardial infarctions (AMI) and cerebrovascular events (CVE) in incident SLE cases from a defined population. To study the risk factors for cardiovascular events in all patients with SLE at our unit.MethodsPatients with SLE diagnosed from 1981 to 2006 were followed through to 2016. IRRs of AMI and CVE were calculated. The AMI and CVE incidence patterns for patients with SLE were studied in relation to hypertension, smoking, renal dysfunction, anticardiolipin (aCL) antibodies at diagnosis, disease duration and organ damage before an event.Results262 patients with SLE were included in the study; of these 175 were from the defined population. Overall, 37 AMI and 44 CVE were recorded. An increased IRR of 3 for AMI was found (p<0.001). Smoking, hypertension and reduced renal function were risk factors for AMI. An increased IRR of 3.3 for ischaemic CVE was found for women (p<0.001). Hypertension and aCL were risk factors for CVE. Organ damage before events was increased.ConclusionsCardiovascular events are increased in SLE and are associated with hypertension, smoking and increased damage rate.

P173 Progression of subclinical cardiovascular disease in SLE: a five year follow up study

Abstract Background Patients with SLE have 5-10-fold increased risk of developing CVD compared to age and sex-matched controls. The average age of developing a first CVD event in patients with SLE is only 49. In this study we aimed to describe the rate and determinants of carotid plaque progression in a cohort of SLE patients who were asymptomatic of CVD at baseline. Methods We carried out vascular ultrasound studies of 100 patients with SLE asymptomatic of CVD at baseline. Sixty-nine patients were rescanned over a median of 5 years of follow up. Ninety-four percent who were re-scanned were women and the mean overall age was 46 years (SD 11). Clinical and CVD risk was assessed at baseline and follow up. The same protocol for assessment at baseline using B-mode Doppler ultrasound to measure intimal media thickness and plaque was used at follow up to assess progression. We also assessed total plaque area (TPA), a more sensitive measure of plaque, and echolucency expressed as gray scale median (GSM) which is linked to plaque lipid content. Results Of the 100 patients with a baseline scan, 69 patients had a second scan at a median of 5 years follow up. New plaque developed in 9% and 26% had an increase in plaque number. The mean overall IMT (0.111 vs 0.064, p &amp;lt; 0.01) and common carotid IMT (0.065 vs 0.055, p &amp;lt; 0.01) were significantly raised in plaque vs non-plaque patients. In a multi -variable analysis CIMT at follow-up was independently associated with age (beta 0.415, p &amp;lt; 0.001) and diastolic blood pressure (beta 0.285, p &amp;lt; 0.021). Independent predictors of plaque at follow-up scan on multi-variable analysis were age at scan&amp;gt;52 years (OR 10.41, CI 2.66-40.80) and systolic BP &amp;gt; 133 (OR 5.26, CI 1.396 - 19.862). In contrast, total cholesterol was negatively correlated with TPA (beta = -1.167, p = 0.002) and with GSM (beta = -0.513, p = 0.012). Conclusion Amongst these 69 patients, 26% had increased plaque and none had decreased plaque over a median of five years follow-up. Measurement of novel ultrasound variables such as TPA and echolucency may identify more modifiable risk factors that can be used to improve CVD outcomes in patients with SLE. Disclosures J. Bakshi: None. M. Griffin: None. S. Croca: None. F. Farhina: None. D. Isenberg: None. A. Nicolaides: None. A. Rahman: None.

E089 Cardiovascular disease in SLE: what do patients think about using diet as a therapeutic?

E089 Cardiovascular disease in SLE: what do patients think about using diet as a therapeutic?

Editorial introductions

Current Opinion in Rheumatology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Rheumatology is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS William J. McCuneWilliam J. McCuneDr McCune is a graduate of Harvard College and the University of Cincinnati Medical School, USA. Following residency at the University of Michigan and fellowship at Brigham and Women's Hospital, USA, he joined the faculty of the University of Michigan, USA, where he is the Michael and Marcia Klein Professor of Rheumatic Diseases and Director of the Lupus Program. Dr McCune has devoted much of his research career to systemic lupus. He reported the clinical and immunologic effects of monthly bolus cyclophosphamide for severe lupus using methods that were subsequently adopted as standard treatment for lupus nephritis. He has since focused on improving the efficacy and safety of immunosuppressive therapy, including the use of leuprolide for ovarian protection in women receiving cyclophosphamide. His work in medical imaging helped establish the importance of MRI in neurological complications of lupus and rheumatoid arthritis, and he was the first to describe ultrasound imaging of articular cartilage. His current interests include the pathogenesis of cardiovascular disease in SLE, advanced MRI in SLE, and detailed population-based epidemiologic studies of the SLE in southeastern Michigan. Jon T. GilesJon T. GilesDr Giles's research interests are centered primarily within the inflammatory arthritides. His current projects center around understanding the inflammatory and non-inflammatory determinants of body composition abnormalities in rheumatoid arthritis and psoriatic arthritis, and their subsequent effects on health outcomes. Other current and past research involves the investigation of accelerated atherosclerosis and myocardial dysfunction in rheumatoid arthritis patients, understanding the determinants of rheumatoid arthritis-associated interstitial lung disease, and exploring the musculoskeletal side-effects of a class of medications used to suppress estrogen in women with certain forms of breast cancer. He is the recipient of grant support from the National Institutes of Health, the Arthritis Foundation, the Rheumatology Research Foundation, the Marianne Legato Foundation, and the Arthritis National Research Foundation.

Serum LTB4, HODE13 and PLA2G7 as biomarkers of cardiovascular disease in SLE

Abstract Background Cardiovascular complications are the most serious ones associated with lupus, and are thought to be caused by inflammation which results from autoimmunity. This study uses a metabolomic screen to identify metabolites that are elevated in SLE patients with and without CVD. Four of metabolites elevated in the initial screen have been selected for validation by ELISA. Methods 27 serum samples (10 healthy controls, 8 with SLE and plaque progression, 9 with SLE and no plaque progression) were screened for elevated metabolites. Four of the most significantly elevated metabolites were selected for validation in another cohort of 85 serum samples (25 healthy controls, 53 with lupus nephritis, 7 with both lupus nephritis and cardiovascular disease). Results Metabolomic screening of the initial cohort demonstrated that several lipoxygenase metabolites (and HODE 13) were elevated in SLE patients who developed CVD compared to other SLE patients (p &amp;lt; .05) and healthy controls (p &amp;lt; .05). Based on this, LOX15, LTB4, and PLA2G7 (as well as HODE13) were selected for ELISA validation. Serum PLA2G7 correlated positively with number and increase of atherosclerotic plaques, as well as smoking history (p&amp;lt;.05 and &amp;lt;.01, respectively). LTB4 correlated positively with coronary artery disease (p&amp;lt;.05) and HODE13 correlated positively with hypertension and SLEDAI (p&amp;lt;.05). Conclusions Serum LTB4, HODE13 and PLA2G7 exhibit potential as biomarkers distinguishing between SLE patients who are or are not at risk of developing cardiovascular complications. Longitudinal studies are in progress to assess the clinical utility of these novel markers.

Editorial introductions

Current Opinion in Rheumatology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Rheumatology is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS W. Joseph McCuneW. Joseph McCuneDr Joseph McCune is a graduate of Harvard College, and the University of Cincinnati Medical School, USA. Following residency at the University of Michigan, USA, and fellowship Brigham and Women's Hospital, USA, he joined the faculty of the University of Michigan, where he is the Michael and Marcia Klein Professor of Rheumatic Diseases and Director of the Lupus Program. Dr McCune has devoted much of his research career to systemic lupus. He reported the clinical and immunologic effects of monthly bolus cyclophosphamide for severe lupus using methods that were subsequently adopted as standard treatment for lupus nephritis and has since focused on improving the efficacy and safety of immunosuppressive therapy, including the use of leuprolide for ovarian protection in women receiving cyclophosphamide. His work in medical imaging helped establish the importance of MRI in neurological complications of lupus and rheumatoid arthritis, and he was the first to describe ultrasound imaging of articular cartilage. Current interests include the pathogenesis of cardiovascular disease in SLE, advanced MRI in SLE, and detailed population-based epidemiologic studies of the SLE in southeastern Michigan. Jon T. GilesJon T. GilesDr Giles's research interests are centered primarily within the inflammatory arthritides. Current projects center around understanding the inflammatory and non-inflammatory determinants of body composition abnormalities in rheumatoid arthritis and psoriatic arthritis, and their subsequent effects on health outcomes. Other current and past research involve the investigation of accelerated atherosclerosis and myocardial dysfunction in rheumatoid arthritis patients, understanding the determinants of rheumatoid arthritis-associated interstitial lung disease, and exploring the musculoskeletal side-effects of a class of medications used to suppress estrogen in women with certain forms of breast cancer. He is the recipient of grant support from the National Institutes of Health, the Arthritis Foundation, the Rheumatology Research Foundation, the Marianne Legato Foundation, and the Arthritis National Research Foundation.

Decreased platelet size is associated with platelet activation and anti-phospholipid syndrome in systemic lupus erythematosus.

. SLE is an autoimmune disease with increased cardiovascular morbidity and platelet activation. In the general population, increased platelet size predicts platelet reactivity and cardiovascular disease. The aim of this study was to investigate whether platelet size related to platelet activation and cardiovascular disease in SLE. . Fresh blood samples from SLE patients ( n = 148), healthy volunteers ( n = 79) and disease controls ( n = 40) were analysed for platelet size and activation by flow cytometry, ELISA and cell count. Associations to manifest cardiovascular disease, venous thrombosis and APS were adjusted for traditional cardiovascular risk factors using logistic regression analysis. . SLE patients had decreased platelet size as compared with healthy controls ( P = 0.003). In SLE, decreased platelet size was related to increased platelet activation, in particular microparticle formation ( P < 0.0001, r = -0.46) and release of serotonin from dense granules ( P < 0.001, r = 0.57). SLE patients with aCL had decreased platelet size ( P = 0.02) and aCL decreased platelet size in vitro ( P = 0.007). In contrast to the general population, increased platelet size was not associated with cardiovascular disease. Instead, decreased platelet size was associated with secondary APS, even after adjusting for traditional cardiovascular risk factors ( P = 0.01, odds ratio 3.58). . Platelet size is decreased in SLE patients and associated with microparticle formation and APS. Future studies are needed to determine the underlying mechanism(s) as well as the potential predictive value of small platelets for disease complications in SLE.

Editorial introductions

Editorial introductions

THU0027 Cardiovascular Risk Profile in Systemic Lupus Erythematosus

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune inflammatory disease characterized by the presence of a plethora of autoantibodies and immune complex formation. Virtually every system and organ can be affected...

SAT0016 Correlation of Carotid Intimal Plaque in SLE with Non-Traditional Serum Biomarkers

BackgroundLupus patients have a strikingly increased risk of premature atherosclerosis and fatal cardiovascular events. This predisposition is neither fully accounted for by traditional cardiovascular (CV) risk factors nor SLE disease...

Increased serum levels of S100A8/A9 and S100A12 are associated with cardiovascular disease in patients with inactive systemic lupus erythematosus

Patients with SLE have an increased morbidity and mortality from cardiovascular disease (CVD). The reason for this is not entirely understood, but is believed to be partly related to the long-lasting inflammatory process seen in SLE. The aim of the present study was to investigate whether there is an association between CVD and serum levels of the proinflammatory proteins S100A8/A9 and S100A12 in SLE. Serum levels of S100A8/A9 and S100A12 were measured with ELISA in 237 SLE patients with clinically inactive disease and without infections, as well as in 100 healthy individuals. Cardiovascular manifestations were defined according to the SLICC/ACR Damage Index (SLICC/ACR-DI). Serum levels of S100A8/A9 were elevated in our inactive SLE patients as compared with healthy individuals (P < 0.0001), which was not seen for S100A12 (P = 0.12). SLE patients with a history of CVD had increased serum levels of both S100A8/A9 and S100A12 compared with patients with no CVD or venous thromboembolism (P = 0.003 and P = 0.006, respectively). The presence of organ damage according to SLICC/ACR-DI was associated with an increase in both S100A8/A9 and S100A12 serum levels (P = 0.001 and P = 0.006, respectively). Elevated serum levels of S100A8/A9 and S100A12 may be used as an indicator of severe disease and CVD in SLE, suggesting that SLE patients with elevated serum S100A8/A9 and S100A12 concentrations may benefit from more intense cardiovascular primary preventive strategies and possibly also from more intense and early immunosuppressive treatment.

SP0185 The Metabolic Syndrome in SLE

The increased cardiovascular burden in patients with SLE is now well recognised and represents a significant cause of mortality and morbidity in these conditions. Recent studies continue to highlight the...

Telomere length in patients with systemic lupus erythematosus and its associations with carotid plaque

To evaluate telomere length (TL) between patients with SLE and healthy controls and to test if TL is associated with carotid plaque. A pilot study of 154 patients with SLE and 152 controls was performed from the SOLVABLE (Study of Lupus Vascular and Bone Long-Term Endpoints) cohort. Demographic and cardiovascular disease (CVD) factors were collected at baseline. The presence or absence of plaque was evaluated by B-mode US. Genomic DNA was isolated from whole peripheral blood. TL was quantified using real-time quantitative PCR. SLE women had a short TL compared with healthy controls (4.57 vs 5.44 kb, P = 0.03). SLE women showed shorter TL than controls across all age groups: <35 years (4.38 vs 6.37 kb), 35-44 years (4.52 vs 5.30 kb), 45-54 years (4.77 vs 5.68 kb) and ≥55 years (4.60 vs 4.71 kb). Among patients with SLE and carotid plaque there was a trend towards shorter TL at a younger age and it was significantly lower in the 35- to 44-year age group when compared with controls (P = 0.025). Multiple logistic regression analysis indicated a risk of carotid plaque with older age [odds ratio (OR) 1.09; 95% CI 1.06, 1.12] but not with TL (OR 1.05; 95% CI 0.97, 1.13). SLE women had significantly shorter TL than controls. SLE women trended towards shorter TL at a younger age. When carotid plaque was identified, the younger SLE women had shorter TL. Only older age but not shorter TL was independently associated with carotid plaque. Additional studies are needed to confirm if TL is a novel biomarker for cardiovascular disease in SLE.

Natural antibodies against phosphorylcholine as potential protective factors in SLE

We have recently reported that natural antibodies against phosphorylcholine (anti-PC) have atheroprotective properties. Here we compare anti-PC with other autoantibodies in SLE patients with and without cardiovascular disease (CVD). Twenty-six women (52 +/- 8.2 yrs) with SLE and a history of CVD (SLE cases) were compared with 26 age-matched women with SLE without CVD (SLE controls) and 26 age-matched population-based control women (controls). PC was conjugated with BSA (PC-BSA) or keyhole-limpet haemocyanin (PC-KLH). Anti-PC and antibodies against phosphatidylserine (anti-PS) and BSA (anti-BSA) were studied by ELISA. Anti-PC-IgG were extracted from intravenous immunoglobulin (IVIG). Activation of endothelial cells by platelet-activating factor (PAF) was studied with FACScan. IgG anti-PC-BSA and anti-PC-KLH were decreased among SLE-cases and SLE-controls as compared with controls (P < 0.005 and P < 0.05), respectively. SLE cases were more prevalent in the lowest 25th percentile of anti-PC-IgM (and IgG) as compared with controls (P < 0.05) but anti-PC-IgM levels did not differ significantly between groups. Among SLE controls, anti-PC-BSA were associated negatively with organ damage (SLICC) and disease activity (SLEDAI) (P < 0.05). Among SLE cases, anti-PC-BSA and anti-PC-KLH were associated negatively with SLICC (P = 0.021; P = 0.010) and anti-PC-BSA was negatively associated with SLEDAI (P < 0.039). Anti-PS-IgG and anti-BSA-IgG were raised among SLE cases as compared with other groups (P < 0.05) and did not cross-react with anti-PC. Anti-PC-IgG could be extracted from IVIG and inhibited PAF-induced expression of adhesion molecules. Low levels of anti-PC could be of importance in SLE. Anti-BSA and anti-PS and low levels of anti-PC could contribute to development of CVD in SLE.

The A-1087IL-10 allele is associated with cardiovascular disease in SLE

The risk of cardiovascular disease (CVD) in SLE patients is very high. It is therefore surprising that IL-10 has been discussed both as pathogenic in SLE and as an atheroprotective cytokine. In contrast, TNF is believed to be atherogenic and we recently reported that raised activity in the TNF-system is implicated in SLE-related CVD. Twenty-six (aged 52 ± 8 years) female patients with SLE and a history of CVD (myocardial infarction, angina, stroke or claudication) were compared with 26 age-matched SLE patients without CVD (SLE controls) or 26 age-matched population controls. The −1087IL-10 gene polymorphism was determined by PCR with restriction endonuclease mapping. Serum IL-10 and TNF-levels were determined by ELISA. The A allele frequency of −1087IL-10 gene in SLE/CVD was higher than in SLE controls (0.62 versus 0.42, p < 0.05). Ten (38%) of 26 SLE/CVD exhibited IL-10 AA genotype compared with five (19%) of 26 SLE controls. Serum IL-10 and TNF-levels were raised in SLE/CVD compared with SLE controls or population controls ( p < 0.001). Furthermore, in SLE/CVD, a significantly reduced IL-10:TNF ratio was observed in patients with IL-10 AA genotype compared with AG or GG genotype (0.56 versus 0.77 versus 1.24, p < 0.05). In SLE controls and population controls, individuals with IL-10 GG genotype tended to have higher IL-10:TNF ratio. In conclusion, the A-1087IL-10 allele which has been reported to cause a lower capacity for IL-10 production could contribute to CVD in SLE. Furthermore, the IL-10 AA genotype is associated with reduced ratio of atheroprotective to atherogenic cytokines in SLE patients with CVD.