Low-Density Lipoprotein Cholesterol and the Risk of Rheumatoid Arthritis: A Prospective Study in a Chinese Cohort

Q: What are the key findings of this study?

Higher updated LDL-C concentrations (highest vs. lowest tertile) were inversely associated with incident rheumatoid arthritis risk (HR 0.38, 95% CI 0.22-0.64; p-trend < 0.01) in Chinese adults.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Risk of rheumatoid arthritis (n=97411). Intervention: Highest updated LDL-C tertile (≥2.65 mmol/L) vs. Lowest LDL-C tertile (<2.02 mmol/L). Primary outcome: Incident rheumatoid arthritis meeting 2010 ACR/EULAR criteria (HR 0.38, 95% CI 0.22-0.64, p=p-trend < 0.01).

Q: What does this research mean for the field?

Higher updated LDL-C concentrations are inversely associated with the risk of developing rheumatoid arthritis, driven by a decline in LDL-C in the few years immediately preceding diagnosis. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To investigate whether low-density lipoprotein cholesterol (LDL-C) concentration is associated with the risk of developing rheumatoid arthritis (RA) in Chinese adults.

Hannah VanEvery; Wenhao Yang; Jinmei Su; Nancy J. Olsen; Le Bao; Bing Lü; Shouling Wu; Liufu Cui; Xiang Gao

doi:10.3390/nu14061240

March 15, 2022NutrientsOpen Access

Low-Density Lipoprotein Cholesterol and the Risk of Rheumatoid Arthritis: A Prospective Study in a Chinese Cohort

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Key result

Higher LDL-C linked to ~62% lower risk of incident rheumatoid arthritis.

HR 0.38
95% CI 0.22-0.64
P -trend < 0.01
n=97,411

Figures

Why the study?

It was unknown whether low-density lipoprotein cholesterol concentration was associated with the risk of rheumatoid arthritis in Chinese adults.

Are baseline and time-updated LDL-C concentrations associated with the future risk of incident rheumatoid arthritis in Chinese adults not taking lipid-lowering medications?

Key Points

To investigate whether low-density lipoprotein cholesterol (LDL-C) concentration is associated with the risk of developing rheumatoid arthritis (RA) in Chinese adults.
Prospective cohort analysis of 97,411 participants without RA from the Kailuan Study in China (mean age 51.8 years; 19,566 women and 77,845 men) followed between 2006 and 2018.
Participants with complete baseline LDL-C data and no use of lipid-lowering medications at baseline or during follow-up were included.
Multivariable Cox proportional hazards regression calculated hazard ratios (HR) and 95% confidence intervals (CI) across baseline and updated LDL-C tertiles, adjusting for age, sex, BMI, HDL-C, triglycerides, diabetes, hypertension, alcohol, and smoking.
Over follow-up, 97 incident cases of RA occurred; the adjusted HR comparing the highest baseline LDL-C tertile (≥2.65 mmol/L) to the lowest (<2.02 mmol/L) was 0.64 (95% CI: 0.38, 1.09; p-trend = 0.10).
For updated LDL-C measurements closest to diagnosis or follow-up end, the adjusted HR was 0.56 (95% CI: 0.35, 0.90) for the middle tertile and 0.38 (95% CI: 0.22, 0.64; p-trend < 0.01) for the highest tertile compared with the lowest tertile.

Study Design

Type

Cohort (n=97,411)

Structured PICO

Are baseline and time-updated LDL-C concentrations associated with the future risk of incident rheumatoid arthritis in Chinese adults not taking lipid-lowering medications?

P

Population

97,411 Chinese adults (mean age 51.8 years, 20.1% female) free of rheumatoid arthritis and not using lipid-lowering medications at baseline or during 10 years of follow-up.

E

Exposure

Higher baseline and time-updated low-density lipoprotein cholesterol (LDL-C) concentrations (middle tertile: 2.02–2.65 mmol/L; highest tertile: ≥2.65 mmol/L), measured biennially after an overnight fast.

C

Comparator

Lowest LDL-C concentration tertile (<2.02 mmol/L) as the reference group.

O

Outcome

Incident rheumatoid arthritis (RA) over 10 years of follow-up (median time to diagnosis 5.84 years), confirmed by three rheumatologists reviewing medical records according to the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria.hard clinical

Main Result

Hazard Ratio: 0.38 (95% CI 0.22–0.64)

p-value: p-trend < 0.01

Limitations

Limited generalizability as the cohort is predominantly male and Chinese, not representative of diverse races or socioeconomic classes
Potential under-reporting of lipid-lowering medication use
Unmeasured confounding for important RA risk factors such as family history, exposure to silica dust, dietary intake, and exercise
Small number of incident RA cases (n=97) limiting statistical power and detailed subgroup analyses
Smoking assessment did not account for duration or average amount of cigarettes smoked
Limited generalizability because the cohort is majority male and Chinese, not representative of diverse races or socioeconomic classes
Possibility of under-reporting of lipid-lowering medication use
Inability to account for unmeasured RA risk factors including family history, exposure to silica dust, diet, and exercise
Small sample size of incident RA cases (n=97) limiting statistical power and preventing detailed subgroup analyses
Smoking measure did not account for duration or average amount of cigarettes smoked

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Implication

Time-updated high LDL-C is inversely associated with short-term incident rheumatoid arthritis risk due to a decline in LDL-C levels occurring approximately 2 to 2.5 years prior to RA diagnosis, likely reflecting preclinical inflammatory cholesterol catabolism.

Abstract

Objective: This study aimed to investigate whether low-density lipoprotein cholesterol (LDL-C) concentration was associated with the risk of rheumatoid arthritis (RA) in Chinese adults. Methods: The study included the 97,411 participants in the Kailuan Study without RA, with complete baseline LDL-C data, and who did not use lipid-lowering medications at baseline or during follow-up. We used Cox proportional hazards modeling to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of RA according to baseline LDL-C tertiles, adjusting for age, sex, body mass index, HDL-C, triglycerides, diabetes, hypertension, alcohol consumption, and smoking. We also calculated the HR and 95% CI of RA using updated LDL-C measurements prior to the end of follow-up, adjusting for covariates. Results: We identified 97 incident RA cases between 2006 and 2018. After adjusting for potential confounders, updated LDL-C concentration—rather than baseline LDL-C—was inversely associated with RA risk. The adjusted HR of RA was 0.64 (95% CI: 0.38, 1.09; p-trend = 0.10) comparing the two extreme baseline LDL-C tertiles, and 0.38 (95% CI: 0.22, 0.64; p-trend < 0.01) comparing the two extreme tertiles of the updated LDL-C concentrations. Conclusions: In this prospective study, high LDL-C concentrations, when measured closest to RA diagnosis or the end of follow-up, were associated with a low risk of RA. These findings highlight the changes in LDL-C prior to RA diagnosis, and the importance of including lipid analyses into studies of the pathogenesis of RA.

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Cite This Study

VanEvery et al. (2022) conducted a cohort in Risk of rheumatoid arthritis (n=97,411). Highest updated LDL-C tertile (≥2.65 mmol/L) vs. Lowest LDL-C tertile (<2.02 mmol/L) was evaluated on Incident rheumatoid arthritis meeting 2010 ACR/EULAR criteria (HR 0.38, 95% CI 0.22-0.64, p=p-trend < 0.01). Higher updated LDL-C concentrations (highest vs. lowest tertile) were inversely associated with incident rheumatoid arthritis risk (HR 0.38, 95% CI 0.22-0.64; p-trend < 0.01) in Chinese adults.

synapsesocial.com/papers/6a7308b93347cc31859a3490 https://doi.org/10.3390/nu14061240

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Low-Density Lipoprotein Cholesterol and the Risk of Rheumatoid Arthritis: A Prospective Study in a Chinese Cohort

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Low-Density Lipoprotein Cholesterol and the Risk of Rheumatoid Arthritis: A Prospective Study in a Chinese Cohort

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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