Association of systemic lupus erythematosus with peripheral arterial disease: a meta-analysis of literature studies

Forte, Francesco; Buonaiuto, Alessio; Calcaterra, Ilenia; Iannuzzo, Gabriella; Ambrosino, Pasquale; Minno, Matteo Nicola Dario Di

doi:10.1093/rheumatology/keaa414

Cited by 8 publications

(5 citation statements)

References 80 publications

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“…Our primary analysis identified ApoB as the major lipoprotein-related trait responsible for both PAD and CAD risk. This finding is consistent with a recent meta-analysis of 22 studies (including 1,892 PAD cases and 30,937 controls) which found significantly higher ApoB levels among PAD cases compared to controls (28). A nested case-control study within the Physicians’ Health Study (PHS) similarly identified baseline ApoB levels (in addition to several other lipid fractions) as a significant predictor of incident PAD (29).…”

Section: Discussionsupporting

confidence: 92%

Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease

Levin

Zuber

Walker

et al. 2021

Preprint

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BackgroundCirculating lipid and lipoprotein levels have consistently been identified as risk factors for atherosclerotic cardiovascular disease (ASCVD), largely on the basis of studies focused on coronary artery disease (CAD). The relative contributions of specific lipoproteins to risk of peripheral artery disease (PAD) have not been well-defined. Here, we leveraged large scale genetic association data to identify genetic proxies for circulating lipoprotein-related traits, and employed Mendelian randomization analyses to investigate their effects on PAD risk.MethodsGenome-wide association study summary statistics for PAD (Veterans Affairs Million Veteran Program, 31,307 cases) and CAD (CARDIoGRAMplusC4D, 60,801 cases) were used in the Mendelian Randomization Bayesian model averaging (MR-BMA) framework to prioritize the most likely causal major lipoprotein and subfraction risk factors for PAD and CAD. Mendelian randomization was used to estimate the effect of apolipoprotein B lowering on PAD risk using gene regions that proxy potential lipid-lowering drug targets. Transcriptome-wide association studies were performed to identify genes relevant to circulating levels of prioritized lipoprotein subfractions.ResultsApoB was identified as the most likely causal lipoprotein-related risk factor for both PAD (marginal inclusion probability 0.86, p = 0.003) and CAD (marginal inclusion probability 0.92, p = 0.005). Genetic proxies for ApoB-lowering medications were associated with reduced risk of both PAD (OR 0.87 per 1 standard deviation decrease in ApoB, 95% CI 0.84 to 0.91, p = 9 × 10−10) and CAD (OR 0.66, 95% CI 0.63 to 0.69, p = 4 × 10−73), with a stronger predicted effect of ApoB-lowering on CAD (ratio of ORs 1.33, 95% CI 1.25 to 1.42, p = 9 × 10−19). Among ApoB-containing subfractions, extra-small VLDL particle concentration (XS.VLDL.P) was identified as the most likely subfraction associated with PAD risk (marginal inclusion probability 0.91, p = 2.3 × 10−4), while large LDL particle concentration (L.LDL.P) was the most likely subfraction associated with CAD risk (marginal inclusion probability 0.95, p = 0.011). Genes associated with XS.VLDL.P and L.LDL.P included canonical ApoB-pathway components, although gene-specific effects varied across the lipoprotein subfractions.ConclusionApoB was prioritized as the major lipoprotein fraction causally responsible for both PAD and CAD risk. However, diverse effects of ApoB-lowering drug targets and ApoB-containing lipoprotein subfractions on ASCVD, and distinct subfraction-associated genes suggest possible biologic differences in the role of lipoproteins in the pathogenesis of PAD and CAD.

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Section: Discussionsupporting

confidence: 92%

Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease

Levin

Zuber

Walker

et al. 2021

Preprint

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“…Peripheral arterial disease is often asymptomatic, and the ankle-brachial index (ABI) is typically used to assess for subclinical disease [51]. The prevalence of PAD in SLE has been reported between 21 and 33% [52][53][54]. SLE patients are four times more likely to have PAD (OR 3.9, 95% CI 1.8-7.9), compared with controls [54].…”

Section: Peripheral Arterial Diseasementioning

confidence: 99%

“…The prevalence of PAD in SLE has been reported between 21 and 33% [52][53][54]. SLE patients are four times more likely to have PAD (OR 3.9, 95% CI 1.8-7.9), compared with controls [54]. A retrospective review of the Taiwan National Health Insurance program data identified a ninefold higher risk of PAD (HR 9.39, 95% CI 7.70-11.5) in SLE patients, compared with controls [32].…”

Section: Peripheral Arterial Diseasementioning

confidence: 99%

Accelerated Atherosclerosis in SLE: Mechanisms, Consequences, and Future Directions

Semalulu¹,

Tselios²

2023

Systemic Lupus Erythematosus - Pathogenesis and Management

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The bimodal mortality rate in systemic lupus erythematosus (SLE) has been well documented, with atherosclerosis identified as a leading cause of late-stage death. Multiple mechanisms are responsible for accelerated atherosclerosis in SLE, ultimately resulting in endothelial dysfunction, arterial stiffness, arterial wall thickening, and plaque formation. This leads to an increased risk of coronary artery disease, cardiovascular events, cerebrovascular accidents, and peripheral arterial disease. SLE patients are not only impacted by traditional risk factors for cardiovascular disease (age, smoking, dyslipidemia, diabetes), but additionally nontraditional risk factors (prolonged corticosteroid use, disease activity and chronic inflammation). Identifying the impact of traditional risk factors and mediating nontraditional risk factors in SLE are vital to reduce morbidity and mortality related to atherosclerosis. SLE-specific screening methods should be established in the routine care of these patients, including the use of validated modified risk scores and imaging modalities. Furthermore, the utility of disease-specific biomarkers and anti-atherosclerotic therapies should be elicited. This chapter will provide an overview of considerations for the mechanisms, impact, and prevention of atherosclerosis in SLE patients.

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“…SLE is a systemic autoimmune disease, characterized by the presence of a wide variety of autoantibodies and multiple organ system involvement [40]. SLE is characterized by a plethora of clinical manifestations, leading to fatal complications and chronic disability requiring tailored rehabilitation strategies [41][42][43][44][45]. Thrombosis substantially contributes to morbidity and mortality in this clinical setting, being related to a complex interaction between traditional thrombotic risk factors, systemic inflammation, and autoimmunity [40].…”

Section: Apl Ppositivity and Systemic Lupus Erythematosusmentioning

confidence: 99%

Risk Assessment and Antithrombotic Strategies in Antiphospholipid Antibody Carriers

et al. 2021

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Antiphospholipid antibodies (aPL) are a cluster of autoantibodies directed against plasma proteins with affinity for membrane phospholipids. The most frequently tested aPL are lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and anti-β2-glycoprotein I antibodies (anti-β2GPI). aPL play a key pathogenic role in the development of the antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by recurrent thrombotic and/or pregnancy complications in patients with persistent aPL. However, aPL positivity is occasionally documented in patients with no previous history of thrombotic or pregnancy morbidity. LA activity, multiple aPL positivity, high-titer aPL, and a concomitant systemic autoimmune disease are recognized risk factors for future thrombotic events in asymptomatic carriers. Moreover, an accelerated atherosclerosis with increased cardiovascular (CV) risk has also been associated with aPL positivity, thus exposing aPL carriers to fatal complications and chronic disability requiring cardiac rehabilitation. Overall, an accurate risk stratification is recommended for aPL-positive subjects in order to prevent both venous and arterial thrombotic complications. In this review, we provide an overview of the main antithrombotic and risk assessment strategies in aPL carriers.

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Association of systemic lupus erythematosus with peripheral arterial disease: a meta-analysis of literature studies

Cited by 8 publications

References 80 publications

Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease

Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease

Accelerated Atherosclerosis in SLE: Mechanisms, Consequences, and Future Directions

Risk Assessment and Antithrombotic Strategies in Antiphospholipid Antibody Carriers

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