Immune mechanisms associated with cardiovascular disease in systemic lupus erythematosus: A path to potential biomarkers

Guzmán‐Martínez, Gabriela; Marañón, Concepción

doi:10.3389/fimmu.2022.974826

Cited by 9 publications

(9 citation statements)

References 150 publications

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“…Traditional CVD risk factors including hypertension, dyslipidaemia, insulin resistance, central obesity and smoking are prevalent in IMIDs, 3 but do not solely account for the excess cardiovascular risk. The role of traditional risk factors for CVD may not be directly translatable in IMIDs.…”

Section: Mechanisms Of Increased Atherosclerotic Cvd Risk In Imids In...mentioning

confidence: 99%

Use of coronarycomputed tomography for cardiovascular risk assessment in immune-mediated inflammatory diseases

Peverelli,

Maughan,

Gopalan

et al. 2024

Heart

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Immune-mediated inflammatory diseases (IMIDs) are recognised risk factors for accelerated atherosclerotic cardiovascular disease (CVD), particularly in younger individuals and women who lack traditional CVD risk factors. Reflective of the critical role that inflammation plays in the formation, progression and rupture of atherosclerotic plaques, research into immune mechanisms of CVD has led to the identification of a range of therapeutic targets that are the subject of ongoing clinical trials. Several key inflammatory pathways implicated in the pathogenesis of atherosclerosis are targeted in people with IMIDs. However, cardiovascular risk continues to be systematically underestimated by conventional risk assessment tools in the IMID population, resulting in considerable excess CVD burden and mortality. Hence, there is a pressing need to improve methods for CVD risk-stratification among patients with IMIDs, to better guide the use of statins and other prognostic interventions. CT coronary angiography (CTCA) is the current first-line investigation for diagnosing and assessing the severity of coronary atherosclerosis in many individuals with suspected angina. Whether CTCA is also useful in the general population for reclassifying asymptomatic individuals and improving long-term prognosis remains unknown. However, in the context of IMIDs, it is conceivable that the information provided by CTCA, including state-of-the-art assessments of coronary plaque, could be an important clinical adjunct in this high-risk patient population. This narrative review discusses the current literature about the use of coronary CT for CVD risk-stratification in three of the most common IMIDs including rheumatoid arthritis, psoriasis and systemic lupus erythematosus.

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Section: Mechanisms Of Increased Atherosclerotic Cvd Risk In Imids In...mentioning

confidence: 99%

Use of coronarycomputed tomography for cardiovascular risk assessment in immune-mediated inflammatory diseases

Peverelli,

Maughan,

Gopalan

et al. 2024

Heart

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“…The intricate pathogenesis of SLE involves a complex interplay among genetic predisposition, environmental factors, and dysregulation of the immune system, ultimately leading to the deposition of autoantibodies, widespread inflammation, and tissue damage 2 . Among the myriad complications associated with SLE, cardiovascular disease emerges as a prominent contributor to both morbidity and mortality in affected individuals 3 . Epidemiological studies have revealed a notable increase 2–3 times higher in the incidence of cardiovascular diseases, such as atherosclerosis and myocardial infarction, among SLE patients compared to the general population 4,5 .…”

Section: Introductionmentioning

confidence: 99%

“…2 Among the myriad complications associated with SLE, cardiovascular disease emerges as a prominent contributor to both morbidity and mortality in affected individuals. 3 Epidemiological studies have revealed a notable increase 2-3 times higher in the incidence of cardiovascular diseases, such as atherosclerosis and myocardial infarction, among SLE patients compared to the general population. 4,5 A comprehensive national population-based cohort study conducted by Hermassen et al 6 further illuminated the heightened risk in SLE patients with lupus nephritis.…”

Section: Introductionmentioning

confidence: 99%

Association between genetically proxied PCSK9 inhibition and systemic lupus erythematosus risk: A mendelian randomization study

Ji,

Guo,

Han

et al. 2024

Int J of Rheum Dis

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BackgroundPreclinical and epidemiological studies suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) had a potential effect on the development of SLE, but it was unclear whether a causal relationship exists. We aimed to investigate the association between genetically proxied inhibition of PCSK9 and the risk of SLE using a two‐sample Mendelian randomization (MR) approach.MethodsSingle nucleotide polymorphisms (SNPs) associated with PCSK9 were extracted from pooled data obtained from the Global Lipid Genetics Consortium (GLGC) Genome‐wide Association Study (GWAS) related to LDL‐c levels, which was used as a proxy for PCSK9 inhibition. Pooled statistics for SLE were obtained from an independent GWAS dataset including 5201 SLE patients and 9066 controls. Inverse variance‐weighted random‐effects models were used to examine the association between genetically proxied inhibition of PCSK9 and the risk of SLE. MR‐Egger, weighted median, weighted mode, Simple mode, and co‐location analyses were used as sensitivity analyses to test the robustness of the analyses.ResultsGenetically proxied inhibition of PCSK9 was associated with a reduced risk of SLE (OR = 0.51, 95% CI = 0.34 to 0.77, p = .001). This finding was replicated in an earlier GLGC GWAS analysis (OR = 0.59, 95% CI = 0.40 to 0.87, p = .007). Sensitivity analysis ensured that the results were robust. Co‐localization analysis did not find evidence of shared causal variation between PCSK9 and SLE.ConclusionsThis Mendelian randomization study showed that PCSK9 was associated with SLE pathogenesis, and its inhibition was associated with a reduced risk of SLE. This study has offered a prospective therapeutic avenue for intervening in the progression of SLE by inhibiting PCSK9 levels.

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“…All these cytokines have been shown to be increased in patients with SLE, particularly during the active phases of the disease. 20 The increased rate of apoptosis of endothelial cells is not compensated by repair from the endothelial progenitors as IFN-a (interferon-a) induces dysregulation of these cells. 21 The increased rate of endothelial apoptosis leads to insufficient apoptotic debris clearance from monocytes/macrophages and amplifies the autoimmune inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…It induces the coagulation cascade through the increase in tissue factor (TF) expression and is also related to plaque vulnerability. 20 The complexity of the pathophysiologic basis of atherosclerosis in SLE as well as its clinical impact warrants further investigation aiming to identify biomarkers for its early identification and prevention.…”

Section: Introductionmentioning

confidence: 99%

Managing Cardiovascular Risk in Systemic Lupus Erythematosus: Considerations for the Clinician

Semalulu,

Tago,

Zhao

et al. 2023

ITT

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A significant improvement in the survival of patients with systemic lupus erythematosus (SLE) over recent decades is largely attributed to the impact of disease-modifying therapies on end-organ damage. Thus, cardiovascular disease now represents the leading cause of mortality in SLE. Various disease-specific mechanisms are responsible for advanced atherosclerosis, as they lead to premature endothelial dysfunction, arterial stiffness, arterial wall thickening, and plaque formation. Consequently, in the assessment of cardiovascular risk in SLE, we must not only consider traditional risk factors (ie, age, gender, dyslipidemia) but also the additional role of non-traditional risk factors such as persistent disease activity and prolonged corticosteroid use. Cardiovascular risk assessment incorporates general cardiovascular screening, as existing risk prediction scores underestimate cardiovascular risk in this patient population. There is also an expanding role of imaging modalities in screening. Risk reduction strategies integrate unique considerations for the use of low-dose aspirin and more stringent hypertension targets. Hydroxychloroquine is the only disease-modifying therapy with known cardiovascular benefit in SLE, though this is a promising area of study.

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Immune mechanisms associated with cardiovascular disease in systemic lupus erythematosus: A path to potential biomarkers

Cited by 9 publications

References 150 publications

Use of coronarycomputed tomography for cardiovascular risk assessment in immune-mediated inflammatory diseases

Use of coronarycomputed tomography for cardiovascular risk assessment in immune-mediated inflammatory diseases

Association between genetically proxied PCSK9 inhibition and systemic lupus erythematosus risk: A mendelian randomization study

Managing Cardiovascular Risk in Systemic Lupus Erythematosus: Considerations for the Clinician

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