Association Between Lipid Profile and Risk of Incident Systemic Sclerosis: A Nationwide Population-Based Study

Abstract

Background and Aims

Lipid metabolism is altered in systemic sclerosis (SSc), mediating activation of immune cells and fibroblasts. However, it is unclear whether altered lipid profile is associated with a risk of developing SSc. We aimed to assess the association between lipid profile and risk of incident SSc.

Methods

From a Korean nationwide database, individuals without SSc who underwent national health check-ups in 2009 were selected and followed-up through 2019. Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride were measured on the health check-up date in 2009. Individuals who developed SSc during follow-up were identified. Multivariable Cox models were performed to estimate the risk of incident SSc according to TC, HDL-C, LDL-C, and triglyceride levels, respectively.

Results

Of the 9,894,996 individuals selected, 1355 individuals developed SSc during a mean follow-up of 9.2 years (incidence rate=1.49 per 100,000 person-years). Levels of TC (adjusted hazard ratio [aHR] 0.959, 95% confidence interval [CI] 0.945–0.974), HDL-C (aHR 0.968, 95% CI 0.950–0.987), LDL-C (aHR 0.968, 95% CI 0.952–0.983) were inversely associated with the risk of incident SSc, whereas no significant association was observed between levels of triglyceride (aHR 1.004, 95% CI 0.998–1.011) and risk of incident SSc.

Conclusion

Serum levels of TC, HDL-C, and LDL-C were inversely associated with the risk of incident SSc. Our findings provide new insights that altered lipid profile could be considered a non-causal biomarker associated with incident SSc, which could help early diagnosis. The underlying mechanism for this association needs further studies.

Plain Language Summary

Lipid metabolism is altered in patients with systemic sclerosis (SSc), mediating activation of immune cells and fibroblasts. In this large population-based cohort study, we found that levels of TC, HDL-C, and LDL-C were inversely associated with the risk of incident SSc. Our findings suggest that levels of TC, HDL-C, and LDL-C could be considered in detecting individuals at high risk of incident SSc.

Keywords:

• systemic sclerosis
• risk factor
• total cholesterol
• high-density lipoprotein cholesterol
• low-density lipoprotein cholesterol

Abbreviations

SSc, Systemic sclerosis; TC, Total cholesterol; HDL-C, High-density lipoprotein cholesterol; LDL-C, Low-density lipoprotein cholesterol; NHIS, National Health Insurance Service; ICD-10, International Classification of Diseases-10th Revision; RID, Rare intractable disease; IRB, Institutional Review Board; BP, Blood pressure; CKD, Chronic kidney disease; GFR, Glomerular filtration rate; HRs, Hazard ratios; CIs, Confidence intervals; BMI, Body mass index; RA, Rheumatoid arthritis; IBD, Inflammatory bowel diseases.

Data Sharing Statement

All data generated or analyzed during this study are included in this article. All data except the results cannot be shared publicly due to the policy of the national health authorities.

Ethics and Consent Statement

This study was approved by the Institutional Review Board (IRB) of Gangnam Severance Hospital (IRB No: 3-2022-0338). Owing to the retrospective nature of this study and the anonymized patient data, the requirement for informed consent was waived and approved by the IRB of Gangnam Severance Hospital. This study complied with the ethical standards in the 1964 Declaration of Helsinki. All data accessed complied with relevant data protection and privacy regulations.

Acknowledgment

The authors thank MID (Medical Illustration & Design) for providing excellent support with medical illustration. The abstract of this paper was presented at the EULAR 2023 European Congress of Rheumatology as a poster presentation with interim findings. The poster’s abstract was published in ‘Poster Abstracts’ in Annals of the Rheumatic Diseases: http://dx.doi.org/10.1136/annrheumdis-2023-eular.2532.

Disclosure

The authors declare that there is no conflict of interest in relation to this article.

Additional information

Funding

This work was supported by the research fund of the Rheumatology Research Foundation (RRF-2022-02).