Machine learning-based cardiovascular risk prediction in systemic lupus erythematosus: development and internal validation of a prognostic model.

CARDIOVASCULAR RISK STATUS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: COMPARISON OF FRAMINGHAM, ACC/AHA, AND QRISK3 SCORES

Antiphospholipid antibodies are associated with subclinical cardiac impairment in patients with SLE

Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with 'normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions.

<h3>Background:</h3> Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE).¹ Patients with SLE have a 2- to 10-fold higher risk of ischemic heart disease and stroke compared with the general population. An interrelationship between immunological, disease-related, and traditional cardiovascular risk factors contributes to CVD pathogenesis. <h3>CVD Risk Assessment:</h3> Early recognition and management of CVD risk factors is important for the prevention of CVD events. For the assessment of CVD risk, generic clinical prediction scores have been used. Evidence has shown that Framingham score underestimates CVD risk in SLE, while limited data are available about the performance of the Systematic COronary Risk Evaluation (SCORE). The modified Framingham,² and the modified SCORE, multiplied by 2 and 1.5, respectively have been developed, and the most recent version of the QRISK prediction score (QRISK3) included weights for SLE. The SLE Cardiovascular Risk Equation³ was recently developed including both traditional and disease-related CVD risk factors (SLEDAI, lupus anticoagulant, C3) and was found to have higher estimated risks than the ACS/AHA risk equation. Several vascular imaging markers (e.g. intima-media thickness, carotid and femoral atherosclerotic plaques) and circulating biomarkers have been evaluated for CVD risk stratification. Vascular ultrasound studies showed a 2- to 3-fold increased risk for asymptomatic plaque presence in patients with SLE compared to healthy controls, and a comparable risk to other high-cardiovascular risk disorders such as rheumatoid arthritis and diabetes mellitus.⁴ Markers of arterial stiffness or endothelial dysfunction such as the pulse wave velocity and flow-mediated dilation, respectively, have been also more impaired in SLE than in the general population in some studies. <h3>CVD Risk Management:</h3> According to the recent ‘EULAR recommendations for cardiovascular risk management in Rheumatic and Musculoskeletal Diseases including Systemic Lupus Erythematosus and Antiphospholipid Syndrome’,⁵ a blood pressure target of &lt;130/80 mm Hg should be considered in patients with SLE. Use of ACE inhibitors or angiotensin receptor blockers is recommended for patients with lupus nephritis with urine protein-to-creatinine ratio &gt;500 mg/g or arterial hypertension. Patients with SLE may be candidates for preventative strategies as in the general population, including low-dose aspirin, based on their individual cardiovascular risk profile. Regarding lipid control, recommendations used in the general population should be followed. Evidence from several observational studies has shown a lower risk of CVD events in patients treated with hydroxychloroquine versus those not treated. EULAR recommendations stated that treatment with hydroxychloroquine (which is recommended for all SLE patients) should be considered to also reduce the risk of cardiovascular events.⁵ Accordingly, the lowest possible glucocorticoid dose is recommended to minimise any potential cardiovascular harm. No specific immunosuppressives can be recommended for lowering the risk of cardiovascular events. In conclusion, CVD burden in SLE is high. Increasing of awareness of CVD risk in patients with SLE, regular screening and control of modifiable CVD risk factors, as well as patient education and lifestyle modifications, are crucial for CVD prevention and management in these patients. <h3>References</h3> Tektonidou MG, <i>et al</i>. Trends in hospitalizations due to acute coronary syndromes and stroke in patients with systemic lupus erythematosus, 1996 to 2012. <i>Arthritis Rheumatol</i> 2016;<b>68</b>:2680–2685. Urowitz MB, <i>et al</i>. Modified Framingham risk factor score for systemic lupus erythematosus. <i>J Rheumatol</i> 2016;<b>43</b>:875–879. Petri MA, <i>et al</i>. Development of a systemic lupus erythematosus cardiovascular risk equation. <i>Lupus Sci Med</i> 2019;<b>6</b>:e000346. Tektonidou MG, <i>et al.</i> Subclinical atherosclerosis in systemic lupus erythematosus: comparable risk with diabetes mellitus and rheumatoid arthritis. <i>Autoimmun Rev</i> 2017 Mar;<b>16</b>(3):308–312. Drosos GC, <i>et al.</i> EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. <i>Ann Rheum Dis</i> 2022 Feb 2:annrheumdis-2021-221733. <h3>Learning Objectives</h3> Describe the need for regular screening and control of modifiable CVD risk factors in patients with SLE Explain the importance of increasing awareness of CVD risk in patients with SLE, for improving patient outcomes Discuss the potential impact of paient education and lifestyle modification for the prevention of CVD in patients with SLE

Nonstandard and adjunctive medical therapies for systemic lupus erythematosus

Based on strong research evidence and consensus, the most common disease manifestations at diagnosis of pSLE are constitutional symptoms, arthritis, and malar rash. Based on some research evidence and consensus, patients with pSLE tend to have major organ system involvement (renal/central nervous system) and a greater disease burden compared with adults. Despite these findings, mortality is low. Based on some research evidence and consensus, the diagnosis of pSLE is unlikely if the ANA is negative, and most patients with SLE have a positive ANA at a titer ≥1:160. Based on strong research evidence, both MMF and cyclophosphamide can be used for induction therapy in class III and IV lupus nephritis. Based on strong research evidence, patients with SLE and anticardiolipin antibodies or LA have a two and six times greater risk of venous thrombosis, respectively, compared with patients with SLE without antiphospholipid antibodies. Based on strong research evidence, patients with pSLE have a higher risk for subclinical atherosclerosis when there is weight-adjusted prednisone use, azathioprine use, increasing age, male gender, high BMI, abnormal creatinine clearance, and elevated lipoprotein(a) levels.

AB0599 Antiphospholipid Antibodies, Antiphospholipid Syndrome and Thromboses in Patients with Systemic Lupus Erythematosus

Background Both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients are associated with an increased and premature prevalence of atherosclerosis. This has been characteristically attributed to the inflammation present in both diseases Objectives To analyze the differences in the role of traditional cardiovascular risk factors in the subclinical atherosclerosis between the two diseases. Methods Cross-sectional study encompassing 602 subjects, 276 SLE and 326 RA patients. Carotid plaques were assessed by ultrasonography. A multivariable regression analysis was performed to evaluate if classic cardiovascular-related risk factors influence differentially on subclinical carotid atherosclerosis in SLE compared to RA patients. Results Traditional cardiovascular risk factors were found to be prevalent in RA and SLE patients. Age (interaction factor p=0.000), hypertension (interaction factor p=0.034), and diabetes (interaction factor p=0.037) were found to have a higher effect on cIMT in RA patients compared to SLE subjects. No differences between RA and SLE were discovered in the effect of traditional cardiovascular factors over the presence of carotid plaque when univariate interaction was performed. After final adjustment for demographics, the presence of others traditional cardiovascular factors, and disease related data, no differences were found in the influence of hypertension, diabetes, dyslipidemia or current smoking over cIMT or the presence of carotid plaque. Moreover, the effect of the addition of various cardiovascular risk factors on the subclinical carotid atherosclerosis did not differ between both diseases. Conclusion The influence of traditional cardiovascular risk factors (hypertension, diabetes, dyslipemia and smoking) over cIMT and carotid plaque is equal in RA and SLE. No interaction was found between traditional cardiovascular risk factors and disease related data in the effect of the former on subclinical atherosclerosis. Disclosure of Interests Hiurma Sanchez-Perez: None declared, Juan Carlos Quevedo-Abeledo: None declared, Inigo Rua-Figueroa: None declared, Beatriz Tejera-Segura: None declared, Vanessa Hernandez-Hernandez: None declared, Antonia de Vera-Gonzalez: None declared, Alejandra Delgado-Gonzalez: None declared, Raquel Lopez-Mejias: None declared, Soledad Ojeda Grant/research support from: AMGEN, Speakers bureau: AMGEN, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Ivan Ferraz-Amaro: None declared

BackgroundAutoimmune Rheumatic Diseases (ARDs) occur with a high risk of atherosclerosis development. The macrophages are at the same time a part of the inflammatory response, and also tightly linked to...

An Exploration of the Reproductive Health Concerns in Women with Systemic Lupus Erythematosus

ObjectiveTo develop recommendations for cardiovascular risk (CVR) management in gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome...

Prevalence and target attainment of traditional cardiovascular risk factors in patients with systemic lupus erythematosus: a cross-sectional study including 3401 individuals from 24 countries

Riesgo cardiovascular en el lupus eritematoso sistémico: factores implicados y métodos para su valoración

PV078 / #557Poster Topic:AS11 - Epidemiology and Public HealthBackground/PurposeLittle is known about acute care utilization in patients with antiphospholipid antibodies (aPL) or antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). This study focuses on hospitalizations, intensive care unit (ICU) admissions and emergency department (ED) visits, in patients with APS and/or SLE, both 1 year prior to and after diagnosis with SLE or identification of positive aPLs, compared to a control population in Alberta, Canada.MethodsPatients from our observational aPL/APS and SLE registries were included. Patients had persistently positive aPL (medium positive [40-80 GPU] or high positive [80-160 GPU] anticardiolipin or anti-beta-2 glycoprotein 1 or a positive lupus anticoagulant test, measured at least 12 weeks apart) and/or fulfilled ACR or SLICC SLE classification criteria. Patients diagnosed with APS met revised Sapporo Criteria. The index date was defined as the date that persistently positive aPL were first identified or that SLE classification criteria were met, whichever came first. If the index date was prior to 2002, the date of registry enrollment was used instead, as administrative data was not available. Acute care utilization 1 year prior to and after the index date (between April 1st 2007 and March 31st 2024) was determined. Data were sourced from several Albertan health-related databases, including the Discharge Abstract Database, National Ambulatory Care Reporting System, and Alberta Provincial Registry, linking participants via their Alberta Personal Health Number. Acute care utilization was compared to age- and sex-matched controls, matched to cases 5:1, excluding any individuals with results for aPLs, ANA, ENA or anti dsDNA or those with any practitioner claim codes or inpatient/outpatient ICD codes for SLE or APS. Controls were assigned the index date of their matched case.Results466 patients participated, aPL positive only (n=7), APS only (n=19), SLE only (n=339), SLE and aPL positive (n=55), and SLE and APS (n=46) (Table 1). A total of 1,857,127 potential control candidates were identified, from which 2,330 controls were randomly selected. One year prior to the index date, the proportion of participants with inpatient hospitalizations were as follows: APS only (5.56%), SLE only (10.07%), SLE and aPL positive (4.17%), SLE and APS (14.63%), and control (3.79%), with no hospitalizations recorded among the aPL-positive only group. Patients who had SLE and APS experienced the highest ED visit rate (36.59%). The lowest ED visit rate was observed in the control group (11.84%) (Table 2). One year after the index date, the highest hospitalization rates were observed in patients with SLE and APS (44.44%) and APS (42.11%) groups, while the control group had the lowest rate (3.81%). SLE and APS participants had the longest average hospital length of stay (18.45 days). ICU admissions were rare, peaking at 5.26% in the APS group. ED visits were most frequent in SLE and APS (66.67%) and APS (52.63%) groups, compared to 12.25% in controls (Table 2).Table 1:Baseline characteristics at index date*Table 2Acute care utilization one year prior to, and one year after index date*ConclusionsPatients with APS and/or SLE have a high number of hospitalizations and ED presentations compared to a control population, both 1 year prior to and after the first identification of positive aPLs or diagnosis of SLE.

Роль процессов воспаления и активации тромбоцитов в развитии атеросклероза у больных системной красной волчанкой