Cardiovascular Risk in Systemic Autoimmune Diseases: Epigenetic Mechanisms of Immune Regulatory Functions

López‐Pedrera, Chary; Pérez-Sánchez, C.; Ramos-Casals, Manuel; Santos‐González, Mónica; Rodríguez‐Ariza, Antonio; Cuadrado, M J

doi:10.1155/2012/974648

Cited by 40 publications

(44 citation statements)

References 91 publications

(90 reference statements)

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“…Totally, 8113 IMD patients with previous or coexisting ischemic stroke and 1416 with hemorrhagic stroke were excluded from the study, which in turn instead may underestimate the stroke risk. In fact, our results are within the limit for published cardiovascular disease risk in IMDs like RA [3,5,6,8-12,20] and SLE [3,5,6,8,13-15,19]. Thus, the estimated risks of stroke in IMD patients appear to be fairly valid.…”

Section: Discussionsupporting

confidence: 75%

Risk of subsequent ischemic and hemorrhagic stroke in patients hospitalized for immune-mediated diseases: a nationwide follow-up study from Sweden

et al. 2012

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BackgroundCertain immune-mediated diseases (IMDs) have been associated with increased risk for cardiovascular disorders. The aim of the present study was to examine whether there is an association between 32 different IMDs and first hospitalization for ischemic or hemorrhagic stroke.MethodsAll individuals in Sweden hospitalized with a main diagnosis of IMD (without previous or coexisting stroke), between January 1, 1987 and December 31, 2008 (n = 216,291), were followed for first hospitalization for ischemic or hemorrhagic stroke. The reference population was the total population of Sweden. Adjusted standardized incidence ratios (SIRs) for ischemic and hemorrhagic stroke were calculated.ResultsTotally 20 and 15 of the 32 IMDs studied, respectively, were associated with an increased risk of ischemic and hemorrhagic stroke during the follow-up. The overall risks of ischemic and hemorrhagic stroke during the first year after hospitalization for IMD were 2.02 (95% CI 1.90–2.14) and 2.65 (95% CI 2.27–3.08), respectively. The overall risk of ischemic or hemorrhagic stroke decreased over time, to 1.50 (95% CI 1.46–1.55) and 1.83 (95% CI 1.69–1.98), respectively, after 1–5 years, and 1.29 (95% CI 1.23–1.35) and 1.47 (95% CI 1.31–1.65), respectively, after 10+ years. The risk of hemorrhagic stroke was ≥2 during the first year after hospitalization for seven IMDs: ankylosing spondylitis (SIR = 8.11), immune thrombocytopenic purpura (SIR = 8.60), polymyalgia rheumatica (SIR = 2.06), psoriasis (SIR = 2.88), rheumatoid arthritis (SIR = 3.27), systemic lupus erythematosus (SIR = 8.65), and Wegener´s granulomatosis (SIR = 5.83). The risk of ischemic stroke was ≥2 during the first year after hospitalization for twelve IMDs: Addison’s disease (SIR = 2.71), Crohn´s disease (SIR = 2.15), Grave´s disease (SIR = 2.15), Hashimoto´s thyroiditis (SIR = 2.99), immune thrombocytopenic purpura (SIR = 2.35), multiple sclerosis (SIR = 3.05), polymyositis/dermatomyositis (SIR = 3.46), rheumatic fever (SIR = 3.91), rheumatoid arthritis (SIR = 2.08), Sjögren’s syndrome (SIR = 2.57), systemic lupus erythematosus (SIR = 2.21), and ulcerative colitis (SIR = 2.15).ConclusionsHospitalization for many IMDs is associated with increased risk of ischemic or hemorrhagic stroke. The findings suggest that several IMDs are linked to cerebrovascular disease.

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Section: Discussionsupporting

confidence: 75%

Risk of subsequent ischemic and hemorrhagic stroke in patients hospitalized for immune-mediated diseases: a nationwide follow-up study from Sweden

et al. 2012

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“…Examples include the role of miR-15a-5p in cellular apoptosis (12, 13), miR-24-3p in maintenance of autoreactive B cells (14), miR-125a-5p and miR-223-3p in macrophage cytokine production (15), and miR-26a-5p, miR-146a-5p and miR-155-5p in IL-17 producing T cells (16). Alterations of several of these miRNAs, such as miR-146a-5p and miR-155-5p, have been suggested to also play a role in the development of cardiovascular disease in RA (17). …”

mentioning

confidence: 99%

Utility of Select Plasma MicroRNA for Disease and Cardiovascular Risk Assessment in Patients with Rheumatoid Arthritis

Ormseth¹,

Solus²,

Vickers³

et al. 2015

J Rheumatol

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Objective MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression and serve as potential mediators and markers of disease. Recently, plasma miR-24-3p and miR-125a-5p concentrations were shown to be elevated in rheumatoid arthritis (RA) and useful for RA diagnosis. We assessed the utility of seven candidate plasma miRNAs, selected for biological relevance, for RA diagnosis and use as markers of disease activity and subclinical atherosclerosis in RA. Methods The cross-sectional study included 168 patients with RA and 91 control subjects, of similar age, race and sex. Plasma concentrations of miR-15a-5p, miR-24-3p, miR-26a-5p, miR-125a-5p, miR-146a-5p, miR-155-5p, and miR-223-3p were measured by quantitative PCR. Utility of plasma miRNA concentrations for RA diagnosis was assessed by area under the receiver operating characteristic curve (AUROC). Association between plasma miRNA concentrations and RA disease activity and coronary artery calcium score were assessed by Spearman correlations. Results Plasma concentrations of miR-15a-5p, 24-3p, miR-26a-5p, miR-125a-5p, miR-146a-5p, miR-155-5p, and miR-223-3p were significantly increased in patients with RA. miR-24-3p had the highest AUROC for diagnosis of RA (AUROC=0.725), including among rheumatoid factor negative patients (AUROC=0.772). Among all patients with RA, the combination of miR-24-3p, miR-26a-5p and miR-125a-5p improved the model modestly (AUROC=0.747). miR-155-5p was weakly inversely associated with swollen joint count (P=0.024), but no other miRNAs were associated with disease activity or coronary artery calcium score. Conclusion The combination of miR-24-3p, miR-26a-5p and miR-125a-5p had strongest diagnostic accuracy for RA. Candidate miRNAs had little or no association with RA disease activity or subclinical atherosclerosis.

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“…The pathogenesis of CHD is associated with autoimmune activation, which can enhance atherosclerosis (Onat and Yuksel, 2013;Meurice et al, 2016). Patients suffering from an autoimmune disease, such as systemic lupus erythematosus, rheumatoid arthritis or psoriasis, display an increased CHD risk (Levy et al, 2008;Vizzardi et al, 2010;Lopez-Pedrera et al, 2012). For patients without autoimmune diseases, but established CHD, levels of natural autoantibodies against various endogenous epitopes, such as modified LDL, heat shock proteins have been shown to independently predict CHD outcome (Roux-Lombard et al, 2013;Vuilleumier et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Low Level Antibodies Against Alpha-Tropomyosin Are Associated With Increased Risk of Coronary Heart Disease

et al. 2020

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Objective: Natural autoantibodies have been implicated to play a key role in the pathogenesis of coronary heart disease (CHD) because they augment autoimmune activation. The aim of this study was to identify novel specific autoantibodies of CHD, and analyze the relationship between their levels and CHD risk indicators.Approach and Results: First, clinical data and sera from CHD patients were collected. Then, one protein microarray containing 37 proteins that represent candidate autoantigens was developed. The arrays were used to profile autoantibodies in randomly selected sera from 35 samples (20 CHD patients, and 15 healthy controls). After that, microarray data were analyzed and autoantibodies for CHD were screened out. Then, ELISA detection was conducted to validate the differentiable autoantibodies using larger numbers of serum samples (131 CHD patients, and 131 healthy controls). Finally, the associations of antibodies with CHD risk indicator parameters were assessed. Inter-group comparison by microarray indicated that three CHD novel autoantibodies, including glucose-6-phosphate isomerase (G6PI), alphatropomyosin (TPM1), and heterogeneous nuclear ribonucleoprotein D-like (HnRNPDL), were significantly (P < 0.05) increased when compared with the healthy controls. Moreover, a significant increase of IgG autoantibodies for these three autoantigens was confirmed in CHD patients by ELISA (P < 0.0001). The correction analysis revealed a negative correlation of anti-TPM1 antibody levels and total cholesterol (P = 0.0034), and low-density lipoprotein cholesterol (P = 0.0086), respectively.Conclusion: G6PI, TPM1, and HnRNPDL were CHD natural autoantigens, and serum anti-TPM1 antibody could be used as a potential marker to predict the risk for CHD patients.

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Cardiovascular Risk in Systemic Autoimmune Diseases: Epigenetic Mechanisms of Immune Regulatory Functions

Cited by 40 publications

References 91 publications

Risk of subsequent ischemic and hemorrhagic stroke in patients hospitalized for immune-mediated diseases: a nationwide follow-up study from Sweden

Risk of subsequent ischemic and hemorrhagic stroke in patients hospitalized for immune-mediated diseases: a nationwide follow-up study from Sweden

Utility of Select Plasma MicroRNA for Disease and Cardiovascular Risk Assessment in Patients with Rheumatoid Arthritis

Low Level Antibodies Against Alpha-Tropomyosin Are Associated With Increased Risk of Coronary Heart Disease

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