Disease Activity, Oxidized-LDL Fraction and Anti-Oxidized LDL Antibodies Influence Cardiovascular Risk in Rheumatoid Arthritis

Nowak, Beata; Madej, Marta; Łuczak, Anna; Małecki, Rafał; Wiland, Piotr

doi:10.17219/acem/29847

Cited by 32 publications

(33 citation statements)

References 29 publications

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“…DAS28‐ESR was significantly correlated with atherosclerosis in RA. Previous studies on non‐Japanese patients with RA have reported similar results …”

Section: Discussionsupporting

confidence: 78%

“…A similar report concluded that in RA with continued low disease activity, the plaque score was more sensitive than the mean IMT in predicting the development of atherosclerosis or CVD . Other previous studies have reported that disease activity correlated positively with atherosclerosis or CVD . Thickened cIMT as well as plaque formation is related to inflammation.…”

Section: Discussionmentioning

confidence: 75%

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Evaluation of risk factors for atherosclerosis using carotid ultrasonography in Japanese patients with rheumatoid arthritis

et al. 2019

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Aim: Previous studies have reported that patients with rheumatoid arthritis (RA) have a higher risk of developing cardiovascular disease (CVD) than the general population.A major cause of CVD is atherosclerosis, which can be evaluated with carotid ultrasonography (US). As far as we know, there have been no large-scale carotid artery US studies in Japanese patients with RA. The aim of this study was to identify the risk factors for atherosclerosis in Japanese patients with RA. Methods:The study subjects underwent physical examinations, laboratory tests and US examination, and answered a questionnaire about their lifestyle. Carotid US was performed to measure the maximum carotid intima media thickness (max cIMT) and to detect plaques.Results: Atherosclerosis was detected in 238 patients (52%). Age, hypertension, and total/high-density lipoprotein cholesterol ratio were positively related to max cIMT. Presence of plaques was related to age, Disease Activity Score of 28 jointserythrocyte sedimentation rate (DAS28-ESR), smoking, and any biological treatment.DAS28-ESR correlated positively not with cIMT but with the development of plaques in our patients with low disease activity (average DAS28-ESR of 2.7). Conclusion:Disease Activity Score of 28 joints-erythrocyte sedimentation rate was related to the size and number of plaques, whereas only traditional risk factors were related to max cIMT. This indicated that the inflammatory conditions of RA could affect the formation of atherosclerotic plaques. For the management of CVD in patients with RA, it may be important to control not only traditional risk factors, but also RA disease activity.

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“…DAS28‐ESR was significantly correlated with atherosclerosis in RA. Previous studies on non‐Japanese patients with RA have reported similar results …”

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 75%

Evaluation of risk factors for atherosclerosis using carotid ultrasonography in Japanese patients with rheumatoid arthritis

et al. 2019

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“…On one hand, LDL‐C levels decrease as a consequence of increased LDLR expression, which however fosters the intracellular accumulation of cholesterol (Ruan et al , ; Ye et al , ) and might induce inflammasome activation. On the other hand, circulating LDL have an increased susceptibility to oxidation (Frostegard et al , ; Garcia‐Gomez et al , ), which explain the increased plasma levels of OxLDL in patients with chronic inflammatory disease (Ahmad et al , ; Nowak et al , ). OxLDL are more atherogenic, can amplify the inflammatory response but can also favour the accumulation of cholesterol in lysosomes, which results in increased cellular toxicity by favouring lysosome disruption, because of the presence of cholesterol crystals (Roma et al , ).…”

Section: Introductionmentioning

confidence: 99%

Vascular inflammation and low‐density lipoproteins: is cholesterol the link? A lesson from the clinical trials

Catapano

Pirillo

Norata

2017

British J Pharmacology

118

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For long time, the role of LDL and inflammation in the pathogenesis of atherosclerosis have been studied independently from each other and only more recently a common platform has been suggested. Accumulation of excess cholesterol due to the presence of increased circulating LDL promotes endothelium dysfunction and activation, which is associated with increased production of pro-inflammatory cytokines, overexpression of adhesion molecules, chemokines and C-reactive protein (CRP), increased generation of reactive oxygen species and reduction of nitric oxide levels and bioavailability. All these processes favour the progressive infiltration of inflammatory cells within the arterial wall where cholesterol accumulates, both extracellularly and intracellularly, and promotes vascular inflammation. According to this, lipid-lowering therapies should improve inflammation and, indeed, statins decrease circulating inflammatory markers such as CRP and improve endothelial function and plaque burden. Pleiotropic activities have been proposed to explain this effect. However, mendelian randomization studies ruled out a direct role for CRP on coronary artery disease and studies with other lipid lowering drugs, such as ezetimibe showed that the beneficial effect of LDL-cholesterol-lowering therapies on systemic inflammatory status, as monitored by changes in CRP plasma levels, could be achieved, independently of the mechanism of action, only in patients presenting with baseline inflamed conditions. These observations strengthen the direct link between cholesterol and inflammation and indicate that decreasing LDL levels is one of the key goals for improving cardiovascular outcome. LINKED ARTICLESThis article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/ 10.1111/bcp.v82.4/issuetoc Abbreviations CAD, coronary artery disease; CETP, cholesteryl ester transfer protein; CHD, coronary heart disease; CRP, C-reactive protein; CV, cardiovascular; FMD, flow-mediated dilatation; HMG-CoA, 3-hydroxy-3-methylglutaryl-CoA; hs-CRP, highsensitivity CRP; IVUS, intravascular ultrasound; LDL-C, LDL-cholesterol; LDLR, LDL receptor; Lp(a), lipoprotein(a); NLRP3, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3; OxLDL, oxidized LDL; PAV, percent atheroma volume; PCSK9, proprotein convertase subtilisin/kexin type 9; SNP, single nucleotide polymorphism; TG, triglycerides; VLDL, very low density lipoprotein IntroductionInflammation and hypercholesterolemia are linked in a vicious cycle in which the excess of cholesterol that accumulates in the arterial wall induces an inflammatory response that, in turn, accelerates cholesterol deposition and amplifies inflammation.The role of LDL and inflammation in the pathogenesis of atherosclerosis have been, for a long time, studied independently from each other and only more recently a...

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“…Inflammation is marked and sustained in RA, with persistent plasma CRP levels clearly above the threshold of high‐sensitivity CRP, which is commonly assessed in non‐selected populations. In RA, inflammatory biomarkers were associated with increased CAC in nondiabetic women and with the carotid intima‐media thickness measurements . Disease activity scores were also associated with the occurrence of CV events in RA …”

Section: Discussionmentioning

confidence: 95%

“…In RA, inflammatory biomarkers were associated with increased CAC in nondiabetic women 51 and with the carotid intima-media thickness measurements. 52 Disease activity scores were also associated with the occurrence of CV events in RA. 53,54 Our results reinforce the hypothesis that a non-controlled inflammatory state may promote coronary disease and calcification and the consequent CV risk.…”

Section: Ccs and Disease Activity Parametersmentioning

confidence: 99%

Coronary artery calcium score in female rheumatoid arthritis patients: Associations with apolipoproteins and disease biomarkers

et al. 2019

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Aims and methods In rheumatoid arthritis (RA), cardiovascular (CV) comorbidities are a major cause of mortality. Coronary Calcium Score (CCS) assessed by computed tomography has been associated with RA prognosis. In this work, we aimed to assess CCS in female RA patients and determine CCS association with different clinical, laboratory and imaging disease parameters. Results We evaluated 60 female patients, with a mean age of 53.6 ± 10.4 years, a mean Disease Activity Score of 28 joints (DAS28) (4v) and Health Assessment Questionnaire (HAQ) of 4.542 ± 1.317 and 1.488 ± 0.631, respectively, and a disease duration of 14.7 ± 10.3 years. Mean CCS value was 35.192 ± 117.786. CCS > 10 was significantly associated with CV risk factors (age: odds ratio [OR] = 1.120; P = .002, body mass index [BMI] ≥ 25 kg/m2: OR = 0.271; P = .025, high‐density lipoprotein [HDL]: OR = 0.011; P = .025, low‐density lipoprotein/ HDL ratio: OR = 2.084; P = .030, apolipoprotein A1 [ApoA1]: OR = 0.965; P = .014, apolipoprotein B/ApoA1 [ApoB/ApoA1] ratio: OR = 59.834; P = .011, homocysteine: OR = 1.287; P = .045, diabetes: OR = 10.400; P = .043, and anti‐diabetic therapy: OR = 10.667, P = .041), disease parameters (C‐reactive protein [CRP]: OR = 1.038; P = .046, DAS[4v]: OR = 1.900; P = .009, DAS28[4v; CRP]: OR = 1.700; P = .019, DAS[3v]: OR = 1.947; P = .010, DAS28[3v; CRP]: OR = 1.696; P = .022, HAQ: OR = 3.299; P = .023, erosion score: OR = 1.015; P = .012, and total modified Sharp/van der Heijde Score: OR = 1.008; P = .035), biomarkers (osteoprotegerin: OR = 1.505; P = .022), and bone mineral density (femoral: OR = 0.005; P = .018, lumbar spine: OR = 0.001; P = .002, left hand: OR = 7.9 × 10−9; P = .005, and osteoporosis: OR = 6.628; P = .007). After adjustment for age and BMI, significant associations were maintained with ApoA1, ApoB/ApoA1 ratio, homocysteine, CRP, DAS(4v), DAS(4v; CRP), DAS(3v) and DAS(3v; CRP). A sensitivity analysis undertaken after excluding the 6 diabetics yielded similar results. Conclusions Our work reinforces the hypothesis that in RA, CCS may be a useful tool in CV risk assessment, particularly valuable in poorer controlled patients with certain lipoprotein profiles.

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Disease Activity, Oxidized-LDL Fraction and Anti-Oxidized LDL Antibodies Influence Cardiovascular Risk in Rheumatoid Arthritis

Cited by 32 publications

References 29 publications

Evaluation of risk factors for atherosclerosis using carotid ultrasonography in Japanese patients with rheumatoid arthritis

Evaluation of risk factors for atherosclerosis using carotid ultrasonography in Japanese patients with rheumatoid arthritis

Vascular inflammation and low‐density lipoproteins: is cholesterol the link? A lesson from the clinical trials

Coronary artery calcium score in female rheumatoid arthritis patients: Associations with apolipoproteins and disease biomarkers

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