Possible Modulation of Vascular Function Measures in Rheumatoid Arthritis by Homocysteine

Alomari, Mahmoud A.; Khabour, Omar F.; Alawneh, Khaldoon; Shammaa, Rania A.

doi:10.1155/2018/8498651

Cited by 5 publications

(21 citation statements)

References 51 publications

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“…In general, HCYS levels above 1.4 mg/L are considered elevated, and CV risk has been shown to increase in a linear fashion for HCYS levels greater than this threshold. 6,40,41 Because patients in both tertile 2 (HCYS reduction of 1.3 mg/L) and tertile 3 (HCYS reduction of 1.1 mg/L) had achieved HCYS reductions of less than 1.4 mg/L, CV risk estimates for these serum tertiles were not statistically significantly different. The lack of doseresponse association for serum folate and CV mortality is consistent with findings in the general population.…”

Section: Discussionmentioning

confidence: 99%

Association of Serum Folate Levels With Cardiovascular Mortality Among Adults With Rheumatoid Arthritis

et al. 2020

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IMPORTANCE Patients with rheumatoid arthritis (RA) are at high risk for cardiovascular (CV) mortality, attributed to chronic inflammation coupled with elevated circulatory homocysteine levels. Increasing the serum folate level reduces homocysteine, but the association of serum folate concentration with CV mortality in patients with RA has not been previously examined. OBJECTIVE To examine the association of serum folate concentration and CV mortality risk among patients with RA. DESIGN, SETTING, AND PARTICIPANTS A cohort study of the third National Health and Nutrition Examination Survey (1988-1994) and 2011 Linked Mortality File was performed. Adults aged 18 years or older with self-reported physician-diagnosed RA were included. Data analysis was performed between April 2019 and June 2019. EXPOSURE Serum folate level. MAIN OUTCOMES AND MEASURES All-cause and CV mortality risk estimated using Cox proportional hazards models, adjusted for the complex survey design and patient characteristics, including demographic characteristics, body mass index, C-reactive protein level, smoking, RA medication use, and comorbid conditions. RESULTS A total of 683 patients with RA (mean [SE] age, 55.9 [1.0] years; 225 [30.2%] men; 478 [87.0%] white) were classified into tertiles based on serum folate levels, as follows: tertile 1, folate levels less than 4.3 ng/mL (n = 239); tertile 2, folate levels 4.3 ng/mL to 8.2 ng/mL (n = 234); and tertile 3, folate levels greater than 8.2 ng/mL (n = 210). During a median (interquartile range) follow-up of 17.4 (10.0-19.4) years, a total of 392 all-cause deaths and 258 CV deaths occurred. Compared with tertile 1, patients in tertile 2 had lower all-cause mortality risk (hazard ratio [HR], 0.63; 95% CI, 0.47-0.85). The risk of CV mortality was lower among patients in tertile 2 (HR, 0.52; 95% CI, 0.30-0.92) and tertile 3 (HR, 0.44; 95% CI, 0.26-0.75) compared with those in tertile 1 (P for trend = .01). Findings for CV mortality were consistent in a sensitivity analysis that estimated 10-year risk; patients in tertile 2 (HR, 0.31; 95% CI, 0.17-0.57) and tertile 3 (HR, 0.39; 95% CI, 0.22-0.69) had lower CV mortality risk compared with those in tertile 1 (P for trend = .04). CONCLUSIONS AND RELEVANCE Among patients with RA, a serum folate level of at least 4.3 ng/mL was associated with lower CV mortality risk. Further research is needed to examine whether a causal relationship exists between serum folate and CV risk among patients with RA.

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Section: Discussionmentioning

confidence: 99%

Association of Serum Folate Levels With Cardiovascular Mortality Among Adults With Rheumatoid Arthritis

et al. 2020

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“…There is a higher prevalence of several traditional risk factors among the RA population. Higher systolic and diastolic blood pressures (SBP/DBP) are seen in RA [3][4][5][6]10,17]. In several studies, higher SBP was associated with higher arterial stiffness [6,[18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…Homocysteine is considered a biomarker of vascular function, but causality is not yet proven. Homocysteine amount is generally higher in RA patients, but some studies showed not constant increase in the homocysteine level among RA patients mostly because of B6 supplements [10]. Adequate intake of B vitamins might prevent homocysteine elevation in RA patients.…”

Section: Homocysteinementioning

confidence: 95%

“…In addition, Inflammatory factors contribute to higher homocysteine levels. Vascular function could be affected by homocysteine, and a hyperinflammatory state intensifies the effect [10].…”

Section: Homocysteinementioning

confidence: 99%

“…Importantly, arterial stiffness occurs only in medium-large vessels. Thus these two parameters could not be used interchangeably, and examination of endothelial function should incorporate morphological and functional appraisal [10].…”

Section: Diagnostic Options and Parametersmentioning

confidence: 99%

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Evaluation of the Risk of Getting Peripheral Artery Disease in Rheumatoid Arthritis and the Selection of Appropriate Diagnostic Methods

Sedrakyan

Fatima

Khatun

et al. 2020

Cureus

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This study aims to review the evidence regarding the association between peripheral artery disease (PAD) and rheumatoid arthritis (RA), as well as influential underlying factors and diagnostic options. Eligible literature was searched in PubMed published up to June 1, 2020, in English. Case studies, case series, reviews, and meta-analyses were excluded. We also excluded non-human studies and those 20 years and older. A total of 44 studies were finally incorporated in the narrative review. The results indicated that compared to controls, RA patients are more prone to PAD. Traditional risk factors, disease-characteristics, vitamin D deficiency, therapy used, and other relevant conditions have a variable effect on overall PAD progression. Studies comparing diagnostic options revealed that vascular function and morphology are connected but are still distinctive processes. In early-stage disease, there are functional alterations in the endothelium that can be controlled by anti-inflammatory medications. Ankle-Brachial Index (ABI) <0.9 might not be quite susceptible to PAD evaluation. Supplemental diagnostic tools could detect vascular disease in the preclinical stage. Most risk factors are adjustable, and the management will have a good impact on vascular health. PAD is mostly subclinical when the therapeutic options have a better impact. Diagnostic modalities should be chosen depending on the features of RA. In addition, multiple diagnostic options increase the accuracy of PAD diagnosis. Future prospective studies with larger populations at different age groups and different disease activity duration are essential to make firm conclusions and better understand the phenomenon of RA and PAD.

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Transsulfuration and folate pathways in rheumatoid arthritis: A systematic review and meta‐analysis

Mangoni,

Zinellu

2024

Eur J Clin Investigation

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BackgroundMetabolomic assessment of the transsulfuration and folic acid biochemical pathways could lead to the identification of promising biomarkers of nitric oxide dysregulation and oxidative stress in rheumatoid arthritis (RA).MethodsWe conducted a systematic review and meta‐analysis of transsulfuration (methionine, homocysteine, and cysteine) and folic acid (folic acid, vitamin B6, and vitamin B12) metabolites in RA patients in remission and healthy controls. Electronic databases were searched from inception to 15 July 2023 for relevant articles. We assessed the risk of bias using the JBI checklist and the certainty of evidence using GRADE.ResultsIn 28 eligible studies, compared to controls, RA patients had significantly higher concentrations of homocysteine (standardized mean difference, SMD = 0.74, 95% CI 0.54–0.93, p < 0.001; low certainty of evidence) and methionine (SMD = 1.00, 95% CI 0.57–1.44, p < 0.001; low certainty) and lower concentrations of vitamin B6 (SMD = −6.62, 95% CI −9.65 to −3.60, p < 0.001; low certainty). By contrast, there were non‐significant between‐group differences in vitamin B12 and folic acid. In meta‐regression and subgroup analysis, there were no associations between the effect size and several study and patient characteristics except for homocysteine (year of publication, C‐reactive protein, triglycerides, and analytical method) and folic acid (biological matrix).ConclusionsThe results of our study suggest that homocysteine, methionine, and vitamin B6 are promising biomarkers to assess nitric oxide dysregulation and oxidative stress in RA. (PROSPERO registration number: CRD42023461081).

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Possible Modulation of Vascular Function Measures in Rheumatoid Arthritis by Homocysteine

Cited by 5 publications

References 51 publications

Association of Serum Folate Levels With Cardiovascular Mortality Among Adults With Rheumatoid Arthritis

Association of Serum Folate Levels With Cardiovascular Mortality Among Adults With Rheumatoid Arthritis

Evaluation of the Risk of Getting Peripheral Artery Disease in Rheumatoid Arthritis and the Selection of Appropriate Diagnostic Methods

Transsulfuration and folate pathways in rheumatoid arthritis: A systematic review and meta‐analysis

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