Cardiovascular Consequences of Autoimmune Rheumatic Diseases

: The increased risk of cardiovascular disease (CVD) among patients with autoimmune rheumatic diseases such as rheumatoid arthritis, spondyloarthritis and systemic lupus erythematosus has been extensively documented. Sub-clinical atherosclerosis can be assessed using various non-invasive imaging techniques. However, the mechanisms underlying the higher risk of atherosclerotic CVD in patients with autoimmune rheumatic diseases are not fully known, although they seem to include chronic low-grade systemic inflammation leading to prolonged endothelial activation, accompanied by a pro-thrombotic/pro-coagulant and autoantibody state. Furthermore, sub-clinical atherosclerosis is also influenced by other traditional risk factors for CVD. Including the individual components of the metabolic syndrome (MetS: obesity, impaired glucose metabolism, dyslipidemia and high blood pressure), the degree of which is higher in these patients than in controls. The aim of this narrative review is to discuss the CV manifestations and risk factors involved in the increased risk of CVD among patients with autoimmune rheumatic diseases.

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Adipokines, Metabolic Syndrome and Rheumatic Diseases

Journal of Immunology Research ◽

10.1155/2014/343746 ◽

2014 ◽

Vol 2014 ◽

pp. 1-14 ◽

Cited By ~ 75

Author(s):

Vanessa Abella ◽

Morena Scotece ◽

Javier Conde ◽

Verónica López ◽

Verónica Lazzaro ◽

...

Keyword(s):

Metabolic Syndrome ◽

Cardiovascular Risk ◽

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Vascular Function ◽

Central Obesity ◽

Cvd Risk ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Cardiometabolic Disorders

The metabolic syndrome (MetS) is a cluster of cardiometabolic disorders that result from the increasing prevalence of obesity. The major components of MetS include insulin resistance, central obesity, dyslipidemia, and hypertension. MetS identifies the central obesity with increased risk for cardiovascular diseases (CVDs) and type-2 diabetes mellitus (T2DM). Patients with rheumatic diseases, such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis, have increased prevalence of CVDs. Moreover, CVD risk is increased when obesity is present in these patients. However, traditional cardiovascular risk factors do not completely explain the enhanced cardiovascular risk in this population. Thus, MetS and the altered secretion patterns of proinflammatory adipokines present in obesity could be the link between CVDs and rheumatic diseases. Furthermore, adipokines have been linked to the pathogenesis of MetS and its comorbidities through their effects on vascular function and inflammation. In the present paper, we review recent evidence of the role played by adipokines in the modulation of MetS in the general population, and in patients with rheumatic diseases.

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The Effect of Statin Use on Mortality in Systemic Autoimmune Rheumatic Diseases

The Journal of Rheumatology ◽

10.3899/jrheum.171389 ◽

2018 ◽

Vol 45 (12) ◽

pp. 1689-1695 ◽

Cited By ~ 7

Author(s):

April M. Jorge ◽

Na Lu ◽

Sarah F. Keller ◽

Sharan K. Rai ◽

Yuqing Zhang ◽

...

Keyword(s):

General Population ◽

Propensity Score ◽

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Antineutrophil Cytoplasmic Antibodies ◽

Autoimmune Rheumatic Diseases ◽

Premature Cardiovascular Disease ◽

Increased Risk ◽

All Cause Mortality ◽

Statin Use

Objective.Systemic autoimmune rheumatic diseases (SARD) are associated with an increased risk of premature cardiovascular disease (CVD) and all-cause mortality. We examined the potential survival benefit of statin use among patients with SARD in a general population setting.Methods.We conducted an incident user cohort study using a UK general population database. Our population included patients with a SARD as determined by Read code diagnoses of systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, dermatomyositis, polymyositis, mixed connective tissue disease, Behçet disease, or antineutrophil cytoplasmic antibodies-associated vasculitis between January 1, 2000, and December 31, 2014. We compared propensity score–matched cohorts of statin initiators and noninitiators within 1-year cohort accrual blocks to account for potential confounders, including disease duration, body mass index, lifestyle factors, comorbidities, and medication use.Results.Of 2305 statin initiators, 298 died during the followup period (mean 5.1 yrs), whereas among 2305 propensity score–matched noninitiators, 338 died during the followup period (mean 4.8 yrs). This corresponded to mortality rates of 25.4/1000 and 30.3/1000 person-years, respectively. Statin initiation was associated with reduced all-cause mortality (HR 0.84, 95% CI 0.72–0.98). When we compared the unmatched cohorts, the statin initiators (n = 2863) showed increased mortality (HR 1.85, 95% CI 1.58–2.16) compared with noninitiators (n = 2863 randomly selected within 1-year cohort accrual blocks) because of confounding by indication.Conclusion.In this general population–based study, statin initiation was shown to reduce overall mortality in patients with SARD after adjusting for relevant determinates of CVD risk.

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Factors Associated with Incident Severe Pulmonary Arterial Hypertension in Systemic Autoimmune Rheumatic Diseases: a Nationwide Study

Rheumatology ◽

10.1093/rheumatology/keab118 ◽

2021 ◽

Author(s):

Hsin-Hua Chen ◽

Ching-Heng Lin ◽

Tsu-Yi Hsieh ◽

Der-Yuan Chen ◽

Jia-Ching Ying ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Conditional Logistic Regression ◽

Factors Associated ◽

Autoimmune Rheumatic Diseases ◽

Increased Risk ◽

Pulmonary Arterial ◽

Severe Pulmonary Arterial Hypertension

Abstract Objectives To assess the association of severe pulmonary arterial hypertension (PAH) with particulate matter <2.5 μm (PM2.5) and clinical data in patients with systemic autoimmune rheumatic diseases (SARDs). Methods We used the 2003–2017 nationwide data in Taiwan to identify patients with SARDs, including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, dermatomyositis/polymyositis and primary Sjögren’s syndrome. We identified 479 cases with severe PAH and selected controls matched (1:4) for age, sex, and index-year. We used conditional logistic regression analysis to determine factors associated with risks for severe PAH shown as odds ratios (ORs) with 95% confidence intervals (CIs). Results We found that severe PAH was highly associated with interstitial lung disease (OR, 8.57; 95% CI, 5.52–13.32), congestive heart failure (OR, 7.62; 95% CI, 5.02–11.55), valvular heart disease (OR, 3.34; 95% CI, 2.03–5.50) and slightly associated with thyroid diseases (OR, 1.88; 95% CI, 1.18–3.00), but not the level of exposure to PM2.5. Increased risk for PAH was found in patients receiving corticosteroid (prednisolone equivalent dosage, mg/day, OR, 1.03; 95% CI, 1.01–1.05), biologics (OR, 2.18; 95% CI, 1.15–4.12) as well as immunosuppressants, including cyclosporin (OR, 2.17; 95% CI, 1.31–3.59), azathioprine (OR, 1.96; 95% CI, 1.48–2.61), cyclophosphamide (OR, 2.01; 95% CI, 1.30–3.11) and mycophenolate mofetil/mycophenolic acid (OR, 2.42; 95% CI, 1.37–4.27), and those with the highest level of insured amount (reference, lowest level; OR, 0.53; 95% CI, 0.34–0.83). Conclusion The population-based study identified risks for severe PAH in patients with SARDs, and these findings provide evidence for PAH risk stratification in patients with SARDs.

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Risk of malignancy in patients with rheumatic disorders

Hong Kong Bulletin on Rheumatic Diseases ◽

10.1515/hkbrd-2016-0008 ◽

2016 ◽

Vol 16 (2) ◽

pp. 38-41

Author(s):

Victor Tak-lung Wong ◽

Weng-nga Lao

Keyword(s):

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Disease Burden ◽

Immunosuppressive Agents ◽

Biologic Therapies ◽

Inflammatory Myositis ◽

Autoimmune Rheumatic Diseases ◽

Increased Risk ◽

Risk Of Malignancy

Abstract Patients with autoimmune rheumatic diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren’s syndrome (SS), and inflammatory myositis are at increased risk of developing malignancies. Treatment of these conditions, including disease-modifying anti-rheumatic drugs (DMARDs) and biologic therapies, are also associated with increased risk of malignancies.Cancer adds to the disease burden in these patients, affecting their quality of life and life expectancy. The decision in choosing immunosuppressive agents in these rheumatic diseases should take into account the disease severity, expectation for disease control, comorbidities, as well asthe side effects including risks of cancer. This article does not include the risk of malignancy in patients with the idiopathic inflammatory myopathies, which are well-recognized paraneoplastic conditions.

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Cardiovascular complications in patients with rheumatic diseases.

Clinical Medicine (Russian Journal) ◽

10.18821/0023-2149-2018-96-5-411-418 ◽

2018 ◽

Vol 96 (5) ◽

pp. 411-418

Author(s):

A. V. Arshinov ◽

V. I. Emanuilov ◽

I. G. Maslova

Keyword(s):

Risk Factors ◽

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Cardiovascular Complications ◽

Systemic Lupus ◽

Increased Risk ◽

Male Sex ◽

Traditional Risk Factors ◽

Vascular Accidents ◽

Large Vessels

In the recent years, there are more and more reports stating an increased risk of atherosclerosis and cardiovascular complications in patients with rheumatic diseases. It should be noted that the development of atherosclerosis in this category of patients occurs much earlier than in the general population. Indeed, many rheumatic diseases are associated with an increased risk of developing of cardiovascular diseases and death from vascular accidents, including RA, systemic lupus erythematosus, ankylosing spondylitis, gout, psoriatic arthritis, vasculitis of the middle and large vessels. There are reports of an increased risk of cardiovascular disease in patients with systemic scleroderma. It is significant that rheumatic diseases and coronary heart disease combine common pathophysiological mechanisms - systemic and chronic inflammation. At the same time, traditional risk factors such as hypertension, old age, smoking, hypercholesterolemia, obesity and male sex can not fully explain the mechanism of accelerated development of atherosclerosis in patients with rheumatic diseases. The presence of specific risk factors, such as the duration of the course of treatment, glucocorticosteroids administration, the presence of an increased concentration of inflammatory mediators and autoimmune mechanisms create conditions for the acceleration of atherosclerosis in this group of patients. Coordination of efforts of rheumatologists and cardiologists in studying the mechanisms of accelerated development of atherosclerosis in patients with rheumatic diseases will allow to develop adequate methods for timely diagnosis and prevention of cardiovascular complications in patients with this widespread pathology.

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TNF-α -308 G>A and IL10 -1082A>G polymorphisms as potential risk factors for lymphoproliferative disorders in autoimmune rheumatic diseases

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-019-0043-0 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Manal Y. Tayel ◽

Aida Nazir ◽

Ibtessam M. Abdelhamid ◽

Myriam A. S. Helmy ◽

Nadia E. Zaki ◽

...

Keyword(s):

Risk Factors ◽

Rheumatic Diseases ◽

Lymphoproliferative Disorders ◽

Group Iii ◽

Autoimmune Rheumatic Diseases ◽

Group I ◽

Tnf Α ◽

Ifn Γ ◽

Tgf Β1 ◽

Distribution Frequency

Abstract Background Chronic inflammation with sustained unregulated immune stimulation in autoimmune rheumatic diseases (ARD) may be a risk factor for developing lymphoproliferative disorders (LPD). Markers of ARD activity as high erythrocyte sedimentation rate or erosive joint diseases and the development of B-symptoms were accounted as risk factors for LPD development. We investigated the association of five inflammatory cytokine genes single nucleotide polymorphisms (SNPs): TNF-α -308G>A; TGF-β1 gene codon 10 T>C and 25 G>C; IL-10 promoter SNPs -1082 A>G, -819T>C, and -592A>C; IL-6 -174G>C; and IFN-γ 874 T>A with the risk of LPD development in ARD patients. The study was conducted on 70 patients divided into group I, 25 ARD patients diagnosed as RA (n = 15) and SLE (n = 10) and with no history of malignancy; group II, 25 patients diagnosed with LPD and had no ARD; and group III, 20 patients diagnosed with both diseases: ARD and LPD. Cytokine genotyping was analyzed by PCR-sequence-specific primer (PCR-SSP). Results ARD+LPD patients had significantly higher frequency of TNF-α -308A allele and AA+AG genotype (high TNF-α producers) and IL-10 -1082A allele and AA genotype (low IL-10 producers) than ARD patients (p = 0.003, p = 0.024, p = 0.003, p = 0.03, respectively) with a significantly increased risk of LPD development in ARD patients expressing the corresponding alleles and genotypes. No significant differences were detected in the distribution frequency of either TGF-β1, IL-6, or IFN-γ SNPs between groups I and III or any of the studied SNPs between groups II and III. The distribution frequency of IL-10 ATA haplotype was significantly increased in group III as compared to group I (p = 0.037). Conclusion The significantly increased frequency of the high-TNF-α- and low-IL-10-producing alleles and genotypes in ARD patients may participate in the provision of a proinflammatory milieu that eventually increases the risk of LPD development.

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Vascular Inflammation and Dysfunction in Lupus-Prone Mice-IL-6 as Mediator of Disease Initiation

International Journal of Molecular Sciences ◽

10.3390/ijms22052291 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2291

Author(s):

Paul Marczynski ◽

Myriam Meineck ◽

Ning Xia ◽

Huige Li ◽

Daniel Kraus ◽

...

Keyword(s):

Risk Factors ◽

Lupus Erythematosus ◽

Vascular Dysfunction ◽

Vascular Inflammation ◽

Intima Media Thickness ◽

Leukocytic Infiltration ◽

Increased Risk ◽

Altered Immune Status ◽

Inflammatory Autoimmune Disease ◽

Excellent Tool

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and patients are under an increased risk for cardiovascular (CV) events and mortality. The increased CV risk for patients with SLE seems to be caused by a premature and accelerated atherosclerosis, attributable to lupus-specific risk factors (i.e., increased systemic inflammation, altered immune status), apart from traditional CV risk factors. To date, there is no established experimental model to explore the pathogenesis of this increased CV risk in SLE patients. Methods: Here we investigated whether MRL-Faslpr mice, which develop an SLE-like phenotype, may serve as a model to study lupus-mediated vascular disease. Therefore, MRL-Faslpr, MRL-++, and previously generated Il6−/− MRL-Faslpr mice were used to evaluate vascular changes and possible mechanisms of vascular dysfunction and damage. Results: Contrary to MRL-++ control mice, lupus-prone MRL-Faslpr mice exhibited a pronounced vascular and perivascular leukocytic infiltration in various organs; expression of pro-inflammatory cytokines in the aorta and kidney was augmented; and intima-media thickness of the aorta was increased. IL-6 deficiency reversed these changes and restored aortic relaxation. Conclusion: Our findings demonstrate that the MRL-Faslpr mouse model is an excellent tool to investigate vascular damage in SLE mice. Moreover, IL-6 promotes vascular inflammation and damage and could potentially be a therapeutic target for the treatment of accelerated arteriosclerosis in SLE.

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Association of Particulate Matter with Autoimmune Rheumatic Diseases among Adults in South Korea

Rheumatology ◽

10.1093/rheumatology/keab127 ◽

2021 ◽

Author(s):

Jun Seok Park ◽

Seulggie Choi ◽

Kyuwoong Kim ◽

Jooyoung Chang ◽

Sung Min Kim ◽

...

Keyword(s):

Particulate Matter ◽

Adverse Effects ◽

South Korea ◽

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Cox Regression ◽

Statistical Significance ◽

Cox Regression Analysis ◽

Autoimmune Rheumatic Diseases ◽

Quartile Group

Abstract Objective The primary objective is to investigate adverse effects of ambient particulate matter (PM) in various size on the incidence of prevalent autoimmune rheumatic diseases (AIRDs): Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), and Systemic Lupus Erythematosus (SLE). Methods We investigated 230,034 participants in three metropolitan cities of South Korea from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). Starting from January 2010, subjects were followed up until the first event of prevalent AIRDs, death, or December 2013. 2008-2009 respective averages of PM2.5 (< 2.5μm) and PMcoarse (2.5μm to 10μm) were linked with participants’ administrative district codes. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis in one- and two-pollutant model. Results Adjusted for age, sex, region, and household income in two-pollutant model, RA incidence was positively associated with 10μg/m³ increment of PM2.5 (aHR = 1.74, 95% CI: 1.06-2.86), but not with PMcoarse (aHR = 1.27, 95% CI: 0.87-1.85). In one-pollutant model, an elevated incidence rate of RA was slightly attenuated (PM2.5 aHR = 1.61, 95% CI: 0.99-2.61; PMcoarse aHR = 1.13, 95% CI: 0.80-1.61), with marginal statistical significance of PM2.5. RA incidence was also higher in 4th quartile group of PM2.5 compared to 1st quartile group (aHR = 1.83, 95% CI: 1.07-3.11). No adverse effects of PM were found on AS or SLE in one- and two-pollutant models. Conclusion Important components of PM10 associated with RA incidence were fine fractions (PM2.5), while no positive association was found between PM and AS or SLE.

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Primary CNS tumors in adults and environmental factors: an update

Health Risk Analysis ◽

10.21668/health.risk/2020.3.21 ◽

2020 ◽

pp. 176-181

Author(s):

S.G. Berntsson ◽

Keyword(s):

Risk Factors ◽

Brain Tumor ◽

Mobile Phone ◽

Meta Analysis ◽

Cns Tumors ◽

Acoustic Neurinoma ◽

Low Grade ◽

Mobile Phone Use ◽

Increased Risk

The incidence of adult primary brain tumors is increasing in some European countries. High-dose ionizing irradiation, rare genetic syndromes, and genetic predisposition in 5 % of families are a few established environmental risk factors for brain tumor. Mobile phone use that causes near brain exposure to radiofrequency electromagnetic waves and thus creates risks of CNS tumors has been the focus of many studies. Nine meta-analyses were available on this subject. The Interphone multi-center case-control study is the largest one to date; it included 2.708 glioma and 2.409 meningioma cases and matched controls in 13 countries. Studies exploring metals (cadmium, lead), pesticides, outdoor pollution, virus, and risk of glioma created by exposure to them were reviewed. Interphone study did not show increased risk of glioma or meningioma in mobile-phone users. One recent meta-analysis in 2017 found that prolonged exposure i.e.,> 10 years of all phone types was associated with increased risk of ipsilateral CNS tumor locations. In another meta-analysis, long-term use of mobile-phones was found to be a risk factor for low-grade glioma. In case of all durations regarding mobile phone use and both sides of the head, the results of pooling data were more discordant. A large prospective study in 2014 showed that long term use vs never use increased risks of acoustic neurinoma (10+ years: RR = 2.46, 95 % CI = 1.07–5.64, P = 0.03), but not of glioma or meningioma. Studies of other risk factors showed no/weak/contradictory association with brain tumor risk. In the absence of robust and consistent evidence, a causal relation between radiofrequency exposure and CNS tumors was not found. Large prospective studies of this kind regarding a disease with low incidence require a high number of participants and a long follow-up period.

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Persistent confirmed low-grade dysplasia in Barrett's esophagus is a risk factor for progression to high-grade dysplasia and adenocarcinoma in a US Veterans cohort

Diseases of the Esophagus ◽

10.1093/dote/doz061 ◽

2019 ◽

Cited By ~ 2

Author(s):

K Y Song ◽

A J Henn ◽

A A Gravely ◽

H Mesa ◽

S Sultan ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Independent Risk Factor ◽

High Grade Dysplasia ◽

Low Grade ◽

High Grade ◽

Increased Risk ◽

Low Grade Dysplasia

SUMMARY Patients with Barrett's esophagus (BE) and low-grade dysplasia (LGD) are at increased risk of esophageal adenocarcinoma (EAC), although many regress to nondysplastic BE. This has significant clinical importance for patients being considered for endoscopic eradication therapy. Our aim is to determine the risk for progression in patients with confirmed persistent LGD. We performed a single-center retrospective cohort study of patients with BE and confirmed LGD between 2006 and 2016. Confirmed LGD was defined as LGD diagnosed by consensus conference with an expert GI pathologist or review by an expert GI pathologist and persistence as LGD present on subsequent endoscopic biopsy. The primary outcome was the incidence rate of HGD (high-grade dysplasia)/EAC. Secondary outcomes included risk factors for dysplastic progression. Risk factors for progression were assessed using univariate and multivariate analysis with logistic regression. Of 69 patients (mean age 65.2 years) with confirmed LGD were included. In total, 16 of 69 patients (23.2%) with LGD developed HGD/EAC during a median follow-up of 3.74 years (IQR, 1.24–5.45). For persistent confirmed LGD, the rate was 6.44 (95% confidence interval (CI), 2.61–13.40) compared to 2.61 cases per 100 patient-years (95% CI, 0.83–6.30) for nonpersistent LGD. Persistent LGD was found in only 29% of patients. Persistent LGD was an independent risk factor for the development of HGD/EAC (OR 4.18; [95% CI, 1.03–17.1]). Persistent confirmed LGD, present in only 1/3 of patients, was an independent risk factor for the development of HGD/EAC. Persistence LGD may be useful in decision making regarding the management of BE.

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