Dataset Information

Metabolic Modulators in Cardiovascular Complications of Systemic Lupus Erythematosus.

ABSTRACT: Systemic lupus erythematosus (SLE) is a multifactorial disorder with contributions from hormones, genetics, and the environment, predominantly affecting young women. Cardiovascular disease is the primary cause of mortality in SLE, and hypertension is more prevalent among SLE patients. The dysregulation of both innate and adaptive immune cells in SLE, along with their infiltration into kidney and vascular tissues, is a pivotal factor contributing to the cardiovascular complications associated with SLE. The activation, proliferation, and differentiation of CD4+ T cells are intricately governed by cellular metabolism. Numerous metabolic inhibitors have been identified to target critical nodes in T cell metabolism. This review explores the existing evidence and knowledge gaps concerning whether the beneficial effects of metabolic modulators on autoimmunity, hypertension, endothelial dysfunction, and renal injury in lupus result from the restoration of a balanced immune system. The inhibition of glycolysis, mitochondrial metabolism, or mTORC1 has been found to improve endothelial dysfunction and prevent the development of hypertension in mouse models of SLE. Nevertheless, limited information is available regarding the potential vasculo-protective effects of drugs that act on immunometabolism in SLE patients.

SUBMITTER: Minano S

PROVIDER: S-EPMC10741086 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Metabolic Modulators in Cardiovascular Complications of Systemic Lupus Erythematosus.

Miñano Sofía S González-Correa Cristina C Moleón Javier J Duarte Juan J

Biomedicines 20231125 12

Systemic lupus erythematosus (SLE) is a multifactorial disorder with contributions from hormones, genetics, and the environment, predominantly affecting young women. Cardiovascular disease is the primary cause of mortality in SLE, and hypertension is more prevalent among SLE patients. The dysregulation of both innate and adaptive immune cells in SLE, along with their infiltration into kidney and vascular tissues, is a pivotal factor contributing to the cardiovascular complications associated wit ...[more]

PMID: 38137363

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Project description:ImportanceIndividuals with systemic lupus erythematosus (SLE) have an increased risk of pregnancy-related complications. However, data on acute cardiovascular complications during delivery admissions remain limited.ObjectiveTo investigate whether SLE is associated with an increased risk of acute peripartum cardiovascular complications during delivery hospitalization among individuals giving birth.Design, setting, and participantsThis population-based cross-sectional study was conducted with data from the National Inpatient Sample (2004-2019) by using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification (ICD-10-CM) codes to identify delivery hospitalizations among birthing individuals with a diagnosis of SLE. A multivariable logistic regression model was developed to report an adjusted odds ratio (OR) for the association between SLE and acute peripartum cardiovascular complications. Data were analyzed from May 1 through September 1, 2022.ExposureDiagnosed SLE.Main outcomes and measuresPrimary study end points were preeclampsia, peripartum cardiomyopathy, and heart failure. Secondary end points included ischemic and hemorrhagic stroke, pulmonary edema, cardiac arrhythmias, acute kidney injury (AKI), venous thromboembolism (VTE), length of stay, and cost of hospitalization.ResultsA total of 63 115 002 weighted delivery hospitalizations (median [IQR] age, 28 [24-32] years; all were female patients) were identified, of which 77 560 hospitalizations (0.1%) were among individuals with SLE and 63 037 442 hospitalizations (99.9%) were among those without SLE. After adjustment for age, race and ethnicity, comorbidities, insurance, and income level, SLE remained an independent risk factor associated with peripartum cardiovascular complications, including preeclampsia (adjusted OR [aOR], 2.12; 95% CI, 2.07-2.17), peripartum cardiomyopathy (aOR, 4.42; 95% CI, 3.79-5.13), heart failure (aOR, 4.06; 95% CI, 3.61-4.57), cardiac arrhythmias (aOR, 2.06; 95% CI, 1.94-2.21), AKI (aOR, 7.66; 95% CI, 7.06-8.32), stroke (aOR, 4.83; 95% CI, 4.18-5.57), and VTE (aOR, 6.90; 95% CI, 6.11-7.80). For resource use, median (IQR) length of stay (3 [2-4] days vs 2 [2-3] days; P < .001) and cost of hospitalization ($4953 [$3305-$7517] vs $3722 [$2606-$5400]; P < .001) were higher for deliveries among individuals with SLE.Conclusions and relevanceThis study found that SLE was associated with increased risk of complications, including preeclampsia, peripartum cardiomyopathy, heart failure, arrhythmias, AKI, stroke, and VTE during delivery hospitalization and an increased length and cost of hospitalization.

Project description:ImportanceSystemic lupus erythematosus (SLE) predisposes individuals to early cardiovascular (CV) events. While hydroxychloroquine is thought to mitigate CV risk factors, its protective role against CV events, particularly arterial ones, remains to be confirmed.ObjectiveTo evaluate the association between hydroxychloroquine and the risk of myocardial infarction (MI), stroke, and other thromboembolic events (OTEs) in patients with SLE.Design, setting, and participantsThis cohort study using a nested case-control design was conducted within the National French Healthcare Database (SNDS), which represents 99% of the French population, from 2010 to 2020. Participants were the cohort of all patients with SLE recorded in the SNDS. Patients with SLE experiencing CV events during the study period were the case group; those without CV events were controls. The analysis period was from February 2022 to September 2023.ExposuresHydroxychloroquine use within 365 days prior to the index date, defined as current (within 90 days), remote (91-365 days), or no exposure within the previous 365 days.Main outcomes and measuresOutcomes of interest were MI, stroke, and OTE, analyzed individually and as a composite outcome (primary analysis). Controls were matched to patients with CV events by age, sex, time since SLE onset and entry into the SNDS database, index date, prior antithrombotic and CV medication, chronic kidney disease, and hospitalization. Multivariable conditional logistic regression was performed using hydroxychloroquine exposure as the main independent variable.ResultsThe SLE cohort included 52 883 patients (mean [SD] age, 44.23 [16.09] years; 45 255 [86.6%] female; mean [SD] follow-up, 9.01 [2.51] years), including 1981 patients with eligible CV events and 16 892 matched control patients. There were 669 MI events, 916 stroke events, and 696 OTEs in the individual outcome studies. For current exposure to hydroxychloroquine, the adjusted odds were lower for composite CV events (odds ratio [OR], 0.63; 95% CI, 0.57-0.69) as well as for MI (OR, 0.72; 95% CI, 0.60-0.85), stroke (OR, 0.69; 95% CI, 0.60-0.81), and OTEs (OR, 0.58; 95% CI, 0.49-0.69) individually compared with no hydroxychloroquine exposure within 365 days.Conclusions and relevanceIn this nationwide cohort study of patients with SLE, a protective association was found between the current use of hydroxychloroquine and the occurrence of CV events, but not between remote use of hydroxychloroquine and CV outcomes, highlighting the value of continuous hydroxychloroquine treatment in patients with SLE.

Dataset Information

Metabolic Modulators in Cardiovascular Complications of Systemic Lupus Erythematosus.

Publications

Metabolic Modulators in Cardiovascular Complications of Systemic Lupus Erythematosus.

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