Endothelial dysfunction and arterial stiffness in patients with systemic lupus erythematosus: A systematic review and meta-analysis

Mendoza‐Pinto, Claudia; Rojas-Villarraga, Adriana; Molano-González, Nicolas; Garcı́a-Carrasco, Mario; Munguía‐Realpozo, Pamela; Etchegaray‐Morales, Ivet; Morales-Sánchez, Héctor; Berra‐Romani, Roberto; Cervera, Ricard

doi:10.1016/j.atherosclerosis.2020.01.028

Cited by 30 publications

(19 citation statements)

References 80 publications

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“…Enhanced arterial stiffness and impairments in endotheliumdependent vasorelaxation have been described in association with vasculopathy and subclinical atherosclerosis in SLE 20,21 . Consistent with previous studies, the baseline values for various measures of arterial stiffness and impairments in endothelial dysfunction in SLE subjects were higher than the reference values for age-matched controls (Table 1) 22,23 . Patients in the tofacitinib Baseline P values were calculated using the two-sample t tests.…”

Section: Resultssupporting

confidence: 89%

Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus

et al. 2021

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Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In lupus animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled clinical trial of tofacitinib in SLE subjects (ClinicalTrials.gov NCT02535689). In this study, 30 subjects are randomized to tofacitinib (5 mg twice daily) or placebo in 2:1 block. The primary outcome of this study is safety and tolerability of tofacitinib. The secondary outcomes include clinical response and mechanistic studies. The tofacitinib is found to be safe in SLE meeting study’s primary endpoint. We also show that tofacitinib improves cardiometabolic and immunologic parameters associated with the premature atherosclerosis in SLE. Tofacitinib improves high-density lipoprotein cholesterol levels (p = 0.0006, CI 95%: 4.12, 13.32) and particle number (p = 0.0008, CI 95%: 1.58, 5.33); lecithin: cholesterol acyltransferase concentration (p = 0.024, CI 95%: 1.1, −26.5), cholesterol efflux capacity (p = 0.08, CI 95%: −0.01, 0.24), improvements in arterial stiffness and endothelium-dependent vasorelaxation and decrease in type I IFN gene signature, low-density granulocytes and circulating NETs. Some of these improvements are more robust in subjects with STAT4 risk allele.

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Section: Resultssupporting

confidence: 89%

Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus

et al. 2021

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“…Several studies in the general population revealed an association between inflammatory biomarkers and arterial stiffness [6,32,33,34]. However, our cross-sectional study did not show significant differences between individuals with and without autoimmune diseases.…”

Section: Arterial Stiffness and Systemic Inflammationcontrasting

confidence: 90%

“…First, individuals having autoimmune diseases presented with a wide range of severity because they were selected randomly on a population basis [11]. Second, most previous studies used the carotid-femoral pulse wave velocity, the gold standard for assessing regional arterial stiffness, a value usually obtained by tonometry or mechanotransducers [32,33,34]. Since we performed an ultrasound analysis, commonly used to assess local mechanical properties of arterial walls, the measures considered to assess arterial stiffness were carotid distensibility and compliance [35].…”

Section: Arterial Stiffness and Systemic Inflammationmentioning

confidence: 99%

Do individuals with autoimmune disease have increased risk of subclinical carotid atherosclerosis and stiffness?

et al. 2021

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To explore the role of chronic inflammation inherent to autoimmune diseases in the development of subclinical atherosclerosis and arterial stiffness, this study recruited two population-based samples of individuals with and without autoimmune disease (ratio 1:5) matched by age, sex, and education level and with a longstanding (≥6 years) diagnosis of autoimmune disease. Common carotid intima media thickness (IMT) and arterial distensibility and compliance were assessed with carotid ultrasound.Multivariable linear and logistic regression models were adjusted for 10-year cardiovascular risk. In total, 546 individuals with and without autoimmune diseases (91 and 455, respectively) were included. Mean age was 66 years (standard deviation 12), and 240 (43.9%) were women. Arterial stiffness did not differ according to presence of autoimmune diseases. In men, the diagnosis of autoimmune diseases significantly increased common carotid IMT [beta-coefficient (95% confidence interval): 0.058 (0.009; 0.108); p-value=0.022] and the percentage having IMT ≥ percentile 75 [1.012 (0.145; 1.880); p-value=0.022]. Women without autoimmune disease were more likely to have IMT ≥ percentile 75 [-2.181 (-4.214; -0.149); p-value=0.035] but analysis of IMT as a continuous variable did not yield significant results. In conclusion, subclinical carotid atherosclerosis, but not arterial stiffness, was higher in men with autoimmune diseases. Women did not show significant differences in any of these carotid features.Sex was an effect modifier in the association between common carotid IMT values and the diagnosis of autoimmune diseases.

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“…The study suggests the systemic inflammatory processes in SLE can lead to impaired endothelial tissue and arterial stiffness even during the earliest disease phases and in the absence of traditional CVD risk factors [76]. Similarly, a meta-analysis by Mendoza-Pinto et al found decreased flow-mediated dilatation, considered a proxy of general vascular health, and increased pulse wave velocity (a surrogate marker of arterial stiffness) in lupus [77].…”

Section: Sle Plasma Effects On Vascular Endothelium and Plateletsmentioning

confidence: 83%

Understanding Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Toward Better Treatment and Prevention

et al. 2021

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Systemic lupus erythematosus (SLE) carries a significant risk of cardiovascular disease (CVD). The prevalence of premature CVD is especially noteworthy because it occurs in premenopausal women with SLE who would otherwise have very low rates of CVD. While traditional risk factors likely play a role in development of CVD in the setting of SLE, they do not fully explain the excess risk. The pathogenesis of CVD in SLE is not fully understood, but the inflammatory nature of SLE is believed to be a key factor in accelerating atherosclerosis. Systemic inflammation may lead to an abnormal lipid profile with elevated triglycerides, total cholesterol, and low-density lipoprotein cholesterol and dysfunctional high-density lipoprotein cholesterol. Additionally, the inflammatory milieu of SLE plasma promotes endothelial dysfunction and vascular injury, early steps in the progression of atherosclerotic CVD. Despite the overall headway that has been achieved in treating lupus, innovative therapeutics specifically targeting the progression of atherosclerosis within the lupus population are currently lacking. However, there have been advancements in the development of promising modalities for diagnosis of subclinical atherosclerosis and detection of high CVD risk patients. Due to the significant impact of CVD on morbidity and mortality, research addressing prevention and treatment of CVD in SLE needs to be prioritized. This review explores the intricate interplay of SLE-specific properties that contribute to atherosclerosis and CVD within this population, as well as screening methods and possible therapies.

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Endothelial dysfunction and arterial stiffness in patients with systemic lupus erythematosus: A systematic review and meta-analysis

Cited by 30 publications

References 80 publications

Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus

Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus

Do individuals with autoimmune disease have increased risk of subclinical carotid atherosclerosis and stiffness?

Understanding Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Toward Better Treatment and Prevention

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