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      Cutaneous lupus erythematosus is associated with an increased risk of cardiac and vascular diseases: a large-scale, propensity-matched global retrospective cohort study

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          Summary

          Background

          Autoimmune skin diseases can expedite various systemic sequelae involving other organs. Although limited to the skin, cutaneous lupus erythematosus (CLE) was noted to be associated with thromboembolic diseases. However, small cohort sizes, partially discrepant outcomes, missing data on CLE subtypes, and incomplete risk assessment limits these findings.

          Methods

          The Global Collaborative Network of TriNetX provides access to medical records of more than 120 million patients worldwide. We used TriNetX to elucidate the risk for cardiac and vascular diseases after diagnosis of CLE, and its subtypes chronic discoid (DLE) and subacute cutaneous lupus erythematosus (SCLE). We included 30,315 CLE, 27,427 DLE, and 1613 SCLE patients. We performed propensity-matched cohort studies determining the risk to develop cardiac and vascular diseases (ICD10CM:I00-99) following diagnosis of CLE, DLE, or SCLE. Patients with systemic lupus erythematosus were excluded.

          Findings

          We document that CLE and its subtype DLE but less so SCLE are associated with a higher risk for various cardiac and vascular diseases. This included predominantly thromboembolic events such as pulmonary embolism, cerebral infarction, and acute myocardial infarction, but also peripheral vascular disease and pericarditis. For example, the hazard ratio of arterial embolism and thrombosis was 1.399 (confidence interval: 1.230–1.591, p < 0.0001) following CLE diagnosis. The study is limited by retrospective data collection and reliance on ICD10-disease classification.

          Interpretation

          CLE and its major subtype DLE are associated with an increased risk for the development of a wide range of cardiac and vascular diseases.

          Funding

          This research was funded by doi 10.13039/501100001659, Deutsche Forschungsgemeinschaft; (EXC 2167, CSSL/CS01-2022) and the Excellence-Chair Program of the State of Schleswig-Holstein.

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          Most cited references39

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          General cardiovascular risk profile for use in primary care: the Framingham Heart Study.

          Separate multivariable risk algorithms are commonly used to assess risk of specific atherosclerotic cardiovascular disease (CVD) events, ie, coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. The present report presents a single multivariable risk function that predicts risk of developing all CVD and of its constituents. We used Cox proportional-hazards regression to evaluate the risk of developing a first CVD event in 8491 Framingham study participants (mean age, 49 years; 4522 women) who attended a routine examination between 30 and 74 years of age and were free of CVD. Sex-specific multivariable risk functions ("general CVD" algorithms) were derived that incorporated age, total and high-density lipoprotein cholesterol, systolic blood pressure, treatment for hypertension, smoking, and diabetes status. We assessed the performance of the general CVD algorithms for predicting individual CVD events (coronary heart disease, stroke, peripheral artery disease, or heart failure). Over 12 years of follow-up, 1174 participants (456 women) developed a first CVD event. All traditional risk factors evaluated predicted CVD risk (multivariable-adjusted P<0.0001). The general CVD algorithm demonstrated good discrimination (C statistic, 0.763 [men] and 0.793 [women]) and calibration. Simple adjustments to the general CVD risk algorithms allowed estimation of the risks of each CVD component. Two simple risk scores are presented, 1 based on all traditional risk factors and the other based on non-laboratory-based predictors. A sex-specific multivariable risk factor algorithm can be conveniently used to assess general CVD risk and risk of individual CVD events (coronary, cerebrovascular, and peripheral arterial disease and heart failure). The estimated absolute CVD event rates can be used to quantify risk and to guide preventive care.
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            2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease

            Circulation
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              2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus

              To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). This international initiative had 4 phases: 1) Evaluation of anti-nuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. 2) Criteria reduction by Delphi and nominal group technique (NGT) exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared to previous criteria in a new validation cohort of 1270 subjects. The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared to 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria. These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.
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                Author and article information

                Contributors
                Journal
                eBioMedicine
                EBioMedicine
                eBioMedicine
                Elsevier
                2352-3964
                06 June 2023
                July 2023
                06 June 2023
                : 93
                : 104639
                Affiliations
                [a ]Department of Dermatology, University of Lübeck, Lübeck, Germany
                [b ]Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
                [c ]Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
                [d ]Unit of Dermatology and Skin Research Laboratory, Barch Padeh Medical Center, Poriya, Israel
                [e ]Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lübeck, Germany
                Author notes
                []Corresponding author. Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany. henning.olbrich@ 123456uksh.de
                [f]

                Equal contribution.

                Article
                S2352-3964(23)00204-9 104639
                10.1016/j.ebiom.2023.104639
                10279782
                37285617
                7c96f7ba-7673-4f20-a9b5-b1e5b6adce58
                © 2023 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 12 January 2023
                : 15 May 2023
                : 18 May 2023
                Categories
                Articles

                lupus,cutaneous lupus,cardiovascular disease,pulmonary embolism,myocardial infarction,stroke

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