Cardiovascular risk in persons at risk of developing rheumatoid arthritis

Chiang

et al. 2023

IJMS

Rheumatoid arthritis (RA), a chronic inflammatory disease, carries a significant burden of atherosclerotic cardiovascular diseases (ASCVD). With their heterogeneous composition, high-density lipoprotein (HDL) particles have varied athero-protective properties, and some may even increase ASCVD risk. In this prospective and cross-sectional study, we aimed to examine the relationship between HDL sizes/metabolites and inflammation in RA. Using 1H-NMR-based lipid/metabolomics, differential HDL-related metabolites were identified between RA patients and healthy control (HC) subjects and between RA patients with and without anti-citrullinated peptide antibodies (ACPA). The correlation between the discriminative HDL-related metabolites and C-reactive protein (CRP) was evaluated in RA patients. RA patients demonstrated higher particle number, lipids, cholesterol, cholesterol ester, free cholesterol, and phospholipids in large/very large-sized HDLs. ACPA-positive patients had higher L-HDL-C and L-HDL-CE but lower small-/medium-sized HDL-TG levels than ACPA-negative patients. An inverse correlation was found between CRP levels and small-sized HDLs. Janus kinase inhibitor treatment was associated with increased serum small-sized HDL-related metabolites and decreased CRP levels. We are the first to reveal the significant associations between RA inflammation and HDL sizes/metabolites. A potential link between ACPA positivity and changes in serum levels of HDL-related metabolites was also observed in RA patients.

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Sizes and Composition of HDL-Cholesterol Are Significantly Associated with Inflammation in Rheumatoid Arthritis Patients

Chiang

et al. 2023

IJMS

“…In a retrospective study, 79 patients who later developed RA had higher TC and lower HDL cholesterol levels than those in controls ( 35 ). However, a 10-year cohort study found that lipid changes commenced prior to RA diagnosis ( 36 ). In another retrospective study, RA patients displayed lower mean TC (by 10%) and LDL (by 17%) but no significant difference in HDL levels when compared with those in non-RA controls in the 5 years preceding diagnosis ( 34 ), revealing that dyslipidemia and RA might have a similar pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Causal relationships between rheumatism and dyslipidemia: A two-sample Mendelian randomization study

Zhang

Cai²,

Liang³

et al. 2022

Front. Endocrinol.

BackgroundDyslipidemia is often observed in rheumatic diseases, such as ankylosing spondylitis (AS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE), yet it remains to be detected whether rheumatic diseases have a causal effect on dyslipidemia.MethodsSignificant (P < 5 × 10-8) and independent (r2 < 0.1) single-nucleotide polymorphisms in genome-wide association studies were selected as instrumental variables to conduct Mendelian randomization (MR) analysis. Inverse variance weighted, weighted median, and MR–Egger regression were adopted for the causal inference. Subsequently, sensitivity analysis was conducted to assess the stability and reliability of MR.ResultsThe MR results revealed positive causal relationships of AS with total cholesterol (TC) (β = 0.089, 95% CI = 0.050 to 0.128, P = 6.07 × 10-6), low-density lipoprotein (LDL) (β = 0.087, 95% CI = 0.047 to 0.127, P = 1.91 × 10-5), and high-density lipoprotein (HDL) (β = 0.043, 95% CI = 0.001 to 0.074, P = 0.009). There was no causal effect of RA on TC (β = 0.008, 95% CI = 4.86 × 10-4 to 0.017, P = 0.064), LDL (β = 6.4 × 10-4, 95% CI = -0.008 to 0.007, P = 0.871), or HDL (β = 0.005, 95% CI = -0.003 to 0.013, P = 0.200). Additionally, SLE had negative causal links for TC (β = -0.025, 95% CI = -0.036 to -0.015, P = 4.42 × 10-6), LDL (β = -0.015, 95% CI = -0.025 to -0.005, P = 0.003), and HDL (β = -0.013, 95% CI = -0.021 to -0.004, P = 0.004). The results were stable and reliable.ConclusionThis study suggested positive causal effects of AS on TC, LDL, and HDL and negative causal effects of SLE on these cholesterol levels, which could provide much help for the pathogenesis and treatment of rheumatic disease patients with dyslipidemia.

“…Cardiovascular disease (CVD) is a major extra-articular manifestation and comorbidity in RA, increasing morbidity and premature CVDrelated mortality [3,4]. Except for the traditional cardiovascular risk factors, like diabetes, hypertension, and hyperlipidemia, the severity of in ammation in RA patients would also increase the risk of CVD [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Prevalence and Risk Factors of Electrocardiogram Abnormalities in Patients with Rheumatoid Arthritis: A Machine Learning Study with Follow-Up Data

Guo

et al. 2021

Preprint

BACKGROUNDElectrocardiogram (ECG) abnormalities could predict some subsequent cardiovascular events. Cardiac involvement is a major extra-articular manifestation in rheumatoid arthritis (RA). We aimed to determine the prevalence of three major ECG abnormalities in RA patients, discover the associated ECG abnormalities associated with machine learning (ML) approaches, and then examine these preselected factors in the follow-up patients with traditional Cox regression.METHODSConsecutive RA patients' records were retrieved from the hospital database; about one-third of patients had follow-up data. Abnormal ECGs with clinical significance were grouped into non-specific ST-segment/T-wave changes, QT interval prolongation, and QRS-T angle increase. Machine learning approaches assessed the associated factors of these abnormalities. The top-important factors selected by the most optimal ML would be used to construct Cox regression models.RESULTSTwo hundred twenty-six patients were enrolled for the first step cross-sectional study. Non-specific ST-T changes (27%) were the most prevalent abnormalities among patients with abnormal ECGs. Random forest models had the best performance in the discovery of associated factors for three outcomes. Cox regression validated that rheumatoid factor and low-density lipoprotein were common risk factors within those three abnormalities. Hypertension, ESR, and serum immunoglobulin G were influential factors for non-specific ST-T changes, prolonged QT interval, and increased QRS-T angle specifically.CONCLUSIONSNon-specific ST-T changes were the most common abnormalities seen in ECGs of RA patients. Our finding suggests that rheumatoid factor, LDL, hypertension, and inflammatory indicators are important risk factors for these ECG abnormalities.