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Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation that, if left untreated, can cause joint destruction and physical impairments. The inflammatory process is systematic, and it is associated with increased morbidity and mortality. Over the last years, mortality presents a decreasing trend; still, there is a hig...
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... blood circulation relies on their association with proteins. These proteins are called lipoproteins and are complex particles consisting of a central core that contains cholesterol esters and TGs. They are surrounded by a shell consisting of free cholesterol, phospholipids, and apolipoproteins, which facilitate lipoprotein formation and function (Fig. 1). Lipoproteins are classified according to their size, lipid composition, and apolipoproteins. There are several classes: chylomicrons and chylomicron remnants, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL)and lipoprotein-a (Lp-a). Chylomicron ...
Citations
... However, the "lipid paradox theory" phenomenon has been observed in patients with active RA and other inflammatory disorders, revealing a qualitative U-shaped relationship, where individuals with the lowest LDL-C levels have a higher cardiovascular risk than those with moderate ones. An extensive review of the literature [13] revealed studies suggesting that the lipid paradox arises from the inflammatory process, particularly from an increase in cholesterol degradation. Proinflammatory cytokines such as TNF-alpha and IL-6 stimulate the upregulation of LDLR and SRB1 receptors on hepatocytes, leading to increased LDL uptake by the liver and cholesterol secretion into the bile, resulting in reduced circulating LDL levels. ...
This point of view explores the safety concerns of Janus kinase inhibitors (JAK-Is), used in treating rheumatoid arthritis (RA) and other rheumatologic conditions. Increasing evidence shows that JAK-Is may elevate the risk of venous thromboembolism (VTE), especially pulmonary embolism. This fact has prompted the European Medicines Agency to advise cautious use of these drugs in patients over 65, smokers, and those at risk of cardiovascular issues or cancer. The paper analyses the evidence on the association between VTE risk and RA and whether different JAK-Is pose different risks. It also probes the link between VTE, lipids, and JAK inhibition, noting that JAK-Is can alter HDL and LDL levels. On the other hand, some evidence indicates that tighter LDL-cholesterol control could mitigate VTE risk, particularly pulmonary embolism. Moreover, data from trials show little attention to treating this main cardiovascular and VTE risk factor in rheumatological patients. Although the lipid paradox theory emphasizes the U-shaped relationship between LDL cholesterol and cardiovascular risk in patients with RA, uncontrolled levels of clinically relevant LDL cholesterol remain closely linked to cardiovascular and VTE risk. In conclusion, high-potency statins could help to manage the increased cardiovascular and VTE risk concomitant to JAK-Is treatment in rheumatologic patients without depriving them of the best therapeutic choice and, in addition, reducing the inherent risk associated with the disease.
... The patients with low blood lipid levels are much more susceptible to cardiovascular diseases, whereas well-preserved lipids reserve usually promises better prognosis and milder disease severity. [8][9][10] Until now, this mystery is still unresolved, which imposes obvious negative impact on introducing metabolism intervention-based anti-rheumatic regimens. ...
Background
Rheumatoid arthritis (RA) patients are prone to developing different metabolic complications. Traditional Chinese Medicine attributes this uncertainty to varied syndrome types.
Methods and Results
We retrospectively analyzed some serological indicators of active RA patients and healthy individuals. Randomly selected RA patients were divided into three groups according to NAMPT and SIRT1 expression levels in white blood cells (WBCs). Their disease severity and metabolic status were compared. Representative blood samples were subjected to a UPLC-MS/MS-based metabolomics analysis. Different human WBCs were treated with oleic acid and palmitic acid in vitro. The results indicated that blood glucose and lipid levels were decreased in RA patients, but their decrease was not in accordance with disease severity. Nutrients in the patients highly expressing SIRT1 were well preserved, with the lowest levels of RF and β-CTX and the highest levels of adiponectin and resistin. Most of them exhibited cold symptoms. When SIRT1 deficiency was obvious, lipid depletion became evident, irrespective of expression levels of NAMPT. Simultaneous high-expression of SIRT1 and NAMPT coincided with the increase in production of lactic acid and the prevalence of hot symptoms. Despite the low levels of IL-6, joint injuries were severe. The corresponding WBCs were especially sensitive to fatty acids anti-inflammatory treatments. The levels of CCL27, CCL11, CCL5, AKP, CRP and ESR were similar among all the groups.
Conclusion
NAMPT overexpression is a risk factor for joint injuries and nutrient depletion in RA. Supplementation with lipids would exert beneficial effects on these RA patients. Its aftermath would cause even severe inflammation. Contrarily, SIRT1 up-regulation restrains inflammation and lipid depletion.
... This difference is not surprising because, in case of systemic inflammation, total cholesterol and LDL cholesterol have been reported to be decreased in RA. This is the lipid paradox in RA [23]. It could mean that HOA patients have a high level of LDL cholesterol. ...
It is clear that there is an increased cardiovascular (CV) risk in rheumatoid arthritis (RA) as a result of systemic inflammation. Hand osteoarthritis (HOA) patients, also have an increased CV risk, but the causes are still debated. Our objective was to compare CV risk factors and risk scores between HOA and RA patients. Thirty-five HOA patients were matched by age (< 3 years) and sex to 35 RA patients in a case–control study. We compared their CV risk profiles and their risk of occurrence of CV events at 10 years using the risk equations SCORE1, SCORE2, and QRISK3. There was a significant increase in SCORE1, SCORE2, but not in QRISK3 in the RA group compared to the HOA group, provided that the multiplication coefficient for RA was applied. This increase was found to no longer be significant for SCORE1 when RA patients have low disease activity (DAS28 ≤ 3.2; n = 8). There was no difference between groups in the frequency of metabolic syndrome, blood pressure, abdominal circumference, body mass index, uricemia, triglyceridemia, HDL cholesterolemia, or pain intensity. Conversely, HOA patients had higher LDL cholesterol and fasting blood glucose levels, in the main analysis and in the subgroup of moderate/high RA activity patients (DAS28 > 3.2; n = 26). We found a higher CV risk in RA compared to HOA patients with moderate/high disease activity. The increased CV risk reported in OA remains to be confirmed in HOA, but these patients appear to have a pro-atherogenic lipid and glycemic profile.
... Lipoproteins are complex entities composed of cholesterol ester and TGs (16). The outer layer of these particles is composed of phospholipids, apolipoproteins, and unbound cholesterol, which aid in the formation and operation of lipids (17). High visceral adipose tissue has been linked to metabolic syndrome, hypertension, and increased fasting glucose in RA patients (18). ...
Background: Rheumatoid arthritis A systemic autoimmune disease causes polyarthritis and organ damage. Insulin resistance is associated with inflammatory indicators. Glycated hemoglobin (HbA1c), a biomarker for continuous glucose monitoring, and 1,5-ahydroglucitol are found in the blood in high but consistent amounts under normal conditions. Disease-modifying anti-rheumatic drugs raise lipid levels. The aim of study was to evaluate whether or not there is a relationship between rheumatoid arthritis and diabetes mellitus, using many immunological and biochemical criteria. Methods: Current research on rheumatoid arthritis and diabetes mellitus was conducted at Al-Nasriyah Education Hospital with one hundred blood samples collected from patients. Divided into four groups, this study employed immunological (1,5-anhydroglucitol) and biochemical (random blood sugar, total triglyceride, and total cholesterol) data. Result: In the current study, the control group had more 1,5-anhydroglucitol than the patients. significant increases in random blood sugar, triglyceride, total cholesterol, and HbA1c in patients with only diabetes and patients with both diseases, as well as a significant difference between rheumatoid patients and controls. Conclusion: Patients with type 2 diabetes mellitus who have low 1,5-ahydroglucrtol levels may be strong predictors of diabetes mellitus. Rheumatoid arthritis patients may have an effect on lipid profiles, HbA1c percentages, and 1,5-ahydroglucrtol levels, which should be evaluated throughout the illness.
... Clonal T cell expansion results in increased prevalence of preclinical atherosclerosis predisposing RA patients to CVD risk. 10,13 There is also a significant association between C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels with atherosclerosis increasing the risk of myocardial infarction and stroke in RA. 14,15 The presence of either rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibodies (ACPAs) is associated with increased CVD and mortality on its own, even in patients who present without articular symptoms. 14 This may be due to the genetic contribution of the HLA-DRB1 shared epitope that is restricted to autoantibody-positive RA and is associated with a higher cardiovascular mortality rate. ...
Rheumatoid arthritis (RA) is a systemic inflammatory disorder that characteristically affects the joints. RA has extra-articular manifestations that can impact multiple organ systems including the heart, lungs, eyes, skin, and brain. Cardiovascular involvement is a leading cause of mortality in RA. Cardiovascular manifestations of RA include accelerated atherosclerosis, heart failure, pericarditis, myocarditis, endocarditis, rheumatoid nodules, and amyloidosis. Inflammation is an important mediator of endothelial dysfunction and is a key driver of cardiovascular risk and complications in patients with RA. Prompt identification of cardiac pathologies in patients with RA is essential for appropriate management and treatment. Choosing the most appropriate treatment regimen is based on individual patient factors. In this article, we provide a comprehensive review of the epidemiology, pathophysiology, clinical manifestations, diagnosis, and medical management of cardiovascular manifestations of RA. We also discuss the relationship between anti-rheumatic medications, specifically non-steroidal anti-inflammatory drugs, corticosteroids, methotrexate, statins, tumor necrosis factor inhibitors, interleukin-6 inhibitors, Janus kinase inhibitors, and cardiovascular disease.
... An increase in atherogenic indices, including LDL/HDL-C and AIP correlated with a higher risk of CVD [9]. Although AIP is more preferable atherosclerotic biochemical parameter, TC/HDL-C, and LDL/HDL-C play a key role in CVD risk assessment compared with their measurement [10][11][12]. According to EULAR report, estimation of AIP is a good biochemical marker to assess and manage the risk of CVD in RA patients [7]. ...
... An increase in atherogenic indices, including LDL/HDL-C and AIP correlated with a higher risk of CVD [9]. Although AIP is more preferable atherosclerotic biochemical parameter, TC/HDL-C, and LDL/HDL-C play a key role in CVD risk assessment compared with their measurement [10][11][12]. According to EULAR report, estimation of AIP is a good biochemical marker to assess and manage the risk of CVD in RA patients [7]. ...
Background:
Rheumatoid arthritis (RA) is an autoimmune systemic chronic inflammatory disorder, which is characterized by joint stiffness, damage, and destruction of bone. In RA patients, the risk of cardiovascular disease is increased by 2-3 folds as compared to the general population. The major burden of RA is the development of cardiovascular diseases, including congestive heart failure, stroke, and myocardial infarction.
Objectives:
Assessment of the association of atherogenic indices with C-reactive protein to evaluate CVD risk was one of the purposes of this study. In addition, the association of atherogenic indices with elevated levels of cardiovascular risk factors (LDL-C and TG) was another aim of this study.
Methods:
The preferred study design for this study was a hospital based comparative cross-sectional study method. Data were cleaned, coded, and entered into Epi Data version 4.6 software, and exported to SPSS version 20 for further analysis of atherogenic indices, C-reactive protein, and risk factors. The comparison of atherogenic indices and other variables among the case and control groups was estimated by the independent t-test statistical analysis method. All variables with a p-value less than 0.2 during binary linear regression analysis were selected for multinomial logistic regression analysis. The association of atherogenic indices with C-reactive protein and risk factors was computed using multiple logistic regressions. The data were presented using tables and figures for clarification of the study.
Results:
The levels of atherogenic indices were computed for both RA patients and the control group. The values of atherogenic indices were significantly associated with cardiovascular risk factor (CRP ≥ 2mg/L). Atherogenic index of plasma (AIP) and TC/HDL-C ratio had a statistically significant association with an elevated levels of triglycerides (P<0.01). The TC/HDL-Cratio value of the patient had 2.38 folds more likely to have an elevated low density lipoprotein level. In addition, AIP of RA patients had 57.51 and 23.65 folds more to have elevated low density lipoprotein and triglycerides respectively.
Conclusions:
The result of this study showed that TC/HDL-C, LDL/HDL-C ratio values, and atherogenic index of plasma had a statistically significant association with elevated level of low density lipoprotein and triglycerides. In addition to this, they have a statistically significant association with the level of C-reactive protein. There was a highly significant statistical association between atherogenic indices, elevated low density lipoprotein, and triglycerides values. Therefore, the result of this finding confirmed that atherogenic indices have a potential role in the prediction and management of CVD risk in RA patients.
... Decreased rather that increased cholesterol levels are commonly reported in inflammatory diseases such as RA, SLE and JDM [26,31,34], including long-term JDM [35]. A lipid lowering effect from pro-inflammatory cytokines is a potential explanation for the lower levels of cholesterol in rheumatic patients [36]. Still, this dyslipidemic profile constitutes-similarly to a high lipid profile in non-rheumatic patients-a risk of developing metabolic syndrome, cardiovascular disease, and eventually heart failure [34,36]. ...
... A lipid lowering effect from pro-inflammatory cytokines is a potential explanation for the lower levels of cholesterol in rheumatic patients [36]. Still, this dyslipidemic profile constitutes-similarly to a high lipid profile in non-rheumatic patients-a risk of developing metabolic syndrome, cardiovascular disease, and eventually heart failure [34,36]. ...
Objectives
Primary aims were to compare adipose tissue distribution in adult patients with juvenile-onset dermatomyositis (JDM), with matched controls. Secondary aims were to explore how adipose tissue distribution is associated with cardio-metabolic status (cardiac dysfunction and metabolic syndrome) in patients.
Methods
Thirty-nine JDM patients (all aged ≥18 y, mean age 31.7 y and 51% female) were examined mean 22.7 y (SD 8.9 y) after disease onset and compared with 39 age/sex-matched controls. In patients, disease activity and lipodystrophy were assessed by validated tools and use of prednisolone noted. In all participants, dual-energy X-ray absorptiometry (DXA) and echocardiography were used to measure visceral adipose tissue (VAT)(g) and cardiac function, respectively. Risk factors for metabolic syndrome were measured and associations with adipose tissue distribution explored. For primary and secondary aims respectively, p-values ≤ 0.05 and ≤ 0.01 were considered significant.
Results
Patients exhibited a 2.4-fold increase in VAT, and reduced HDL-cholesterol values compared with controls (p-values ≤ 0.05). Metabolic syndrome was found in 25.7% of the patients and none of the controls. Cardiac dysfunction (systolic and/or diastolic) was found in 23.7% of patients and 8.1% of controls (p= 0.07). In patients, VAT levels were correlated with age, disease duration and occurrence of metabolic syndrome and cardiac dysfunction. Occurrence of lipodystrophy (p= 0.02) and male sex (p= 0.04) tended to be independently associated with cardiac dysfunction.
Conclusion
Adults with JDM showed more central adiposity and cardio-metabolic alterations than controls. Further, VAT was found increased with disease duration, which was associated with development of cardio-metabolic syndrome.
... As far as hypercholesterolemia and BMI are concerned, we did not find any association with the insurgence of new CV events. It is well known that in inflammatory arthritis the so called "lipid paradox" 26 , modifying the composition of lipids, during inflammation, impairs the predictive role of BMI and lipids profile on CVD. although this paradox has been largely studied in RA, it is a matter of debate if the systemic inflammatory process, observed in the other inflammatory joint diseases, may induce similar effects 27 . ...
An accurate prediction of cardiovascular (CV) risk in patients with Axial Spondyloarthritis (axSpA) is a strong unmet need, as CV risk algorithms poorly perform in these subjects. The aim of this study was to establish whether the persistence of high C-reactive protein (CRP) and high disease activity may be considered predictive factors of CVD in axSpA. 295 patients without personal history of CVD, were consecutively enrolled in this study. To evaluate the relationship between CV events occurrence (fatal and non-fatal) and the persistence of increased CRP levels, ASDAS (Ankylosing Spondylitis Disease Activity Score) > 2.1, and BASDAI (Bath Ankylosing Spondylitis Disease Activity) > 4 during the follow-up, univariable and multivariable Cox Proportional Hazard Models have been performed. During follow-up (we analyzed 10-years retrospective data), 23 patients had a CV event. Multivariable Cox Proportional Hazard Models showed a strong association between CV event and the persistency of increased CRP levels (namely, percentage of visits in which CRP levels were increased) (HR = 1.03; 95%CI 1.015–1.045; p < 0.001), of ASDAS > 2.1 (HR = 1.014, 95%CI 1.000–1.028, p = 0.047), and of BASDAI > 4 (HR 1.019, 95%CI 1.006–1.033, p = 0.006) during follow-up, after adjustment for age, sex, and diabetes. This study suggests that persistence of increased CRP levels and high disease activity may be considered biomarkers to identify those axSpA patients at higher risk of CVD. Innovative axSpA-specific CV risk score, including these variables, have to be developed.
... Traditionally, the lipid paradox in RA has been tentatively explained as the effect of systemic inflammation on lipid metabolism [34]. However, other mechanisms might be involved in LDL-C reduction, as supported by our findings. ...
Objective
To compare coronary plaque burden, proatherogenic cytokines, oxidized low-density lipoprotein (oxLDL), anti-oxLDL antibodies, lipoprotein(a)-cholesterol, and their relationships in patients with rheumatoid arthritis with low-density lipoprotein cholesterol (LDL-C)<1.8 mmol/L versus ≥1.8 mmol/L. Also, to study differences in inflammation and proprotein convertase subtilisin/kexin type-9 (PCSK9), which impacts LDL clearance, in patients with low versus high LDL-C.
Methods
Computed tomography angiography evaluated coronary plaque (noncalcified, partially calcified, fully calcified, and high-risk plaque) in 150 patients from a single-center observational cohort. Ox-LDL, anti-oxLDL IgG, lipoprotein(a)-cholesterol, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6, tumor necrosis factor-α (TNF-α) and PCSK9 were measured. Analyses adjusted for Framingham general cardiovascular risk score, statin use, and high-density lipoprotein cholesterol.
Results
Patients with LDL-C<1.8 mmol/L versus ≥1.8 mmol/L demonstrated: 1) higher likelihood of per-segment plaque (adjusted-OR = 1.67 [95%CI = 1.10–2.55], p = 0.017) and high-risk plaque presence (adjusted-OR 2.78 [95%CI = 1.06–7.29], p = 0.038); 2) greater anti-oxLDL titers (p = 0.020), which positively associated with TNF-α and likelihood of noncalcified, partially calcified and high-risk plaque presence only in patients with LDL-C<1.8 mmol/L (all p-for-interaction≤0.046); 3) increased lipoprotein(a)-cholesterol content (10.33% [8.11–12.54] versus 6.68% [6.10–7.25], p < 0.001), which positively associated with oxLDL (p < 0.001) and anti-oxLDL (p = 0.036); 4) higher interleukin-6 and PCSK9. No differences in CRP, ESR, or oxLDL were observed.
Conclusion
RA patients with LDL-C<1.8 mmol/L had more coronary plaque, higher anti-oxLDL titers and anti-oxLDL associated with plaque only in this group. It is possible the observed paradoxical association of low LDL-C with greater atherosclerosis may be related to higher production of the oxidation-prone lipoprotein(a)-cholesterol and anti-oxLDL antibodies, resulting in increased vascular LDL uptake and plaque formation.
