Epidemiology and Health

Original Articles

Causal association between serum bilirubin and ischemic stroke: multivariable Mendelian randomization: Jong Won Shin, Keum Ji Jung, Mikyung Ryu, Jungeun Kim, Heejin Kimm, Sun Ha Jee; Epidemiol Health. 2024;46:e2024070. Published online August 19, 2024; DOI: https://doi.org/10.4178/epih.e2024070

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Abstract Summary PDF Supplementary Material: Abstract
OBJECTIVES
Previous research has predominantly focused on total bilirubin levels without clearly distinguishing between direct and indirect bilirubin. In this study, the differences between these forms were examined, and their potential causal relationships with ischemic stroke were investigated.
METHODS
Two-sample multivariable Mendelian randomization (MVMR) analysis was employed, extracting summary data on bilirubin from the Korean Cancer Prevention Study-II (n=159,844) and the Korean Genome and Epidemiology Study (n=72,299). Data on ischemic stroke were obtained from BioBank Japan (n=201,800). Colocalization analysis was performed, focusing on the <i>UGT1A1, SLCO1B1</i>, and <i>SLCO1B3</i> genes, which are the primary loci associated with serum bilirubin levels.
RESULTS
Crude 2-sample Mendelian randomization analysis revealed a significant negative association between total bilirubin levels and ischemic stroke. However, in MVMR analyses, only indirect bilirubin demonstrated a significant negative association with ischemic stroke (odds ratio, 0.76; 95% confidence interval, 0.59 to 0.98). Colocalization analysis did not identify a shared causal variant between the 3 genetic loci related to indirect bilirubin and the risk of ischemic stroke.
CONCLUSIONS
Our study establishes a causal association between higher genetically determined levels of serum indirect bilirubin and reduced risk of ischemic stroke in an Asian population. Future research should include more in-depth analysis of shared genetic variants between indirect bilirubin and ischemic stroke.; Summary

Korean summary
이 연구는 혈청 빌리루빈의 세 가지 형태(총, 직접, 간접 빌리루빈)와 허혈성 뇌졸중 간의 인과적 연관성을 다루었습니다. 다변수 멘델리안 무작위 분석(MVMR)을 통해 간접 빌리루빈이 허혈성 뇌졸중 위험을 유의미하게 감소시키는 것으로 나타났습니다. 이 결과는 빌리루빈의 항산화 역할과 허혈성 뇌졸중 간의 상관관계를 심화 이해하는 데 기여합니다.

Key Message
This study investigated the causal associations between three forms of serum bilirubin (total, direct, and indirect) and ischemic stroke. Multivariable Mendelian randomization (MVMR) analysis revealed a significant inverse association between indirect bilirubin and the risk of ischemic stroke. These findings contribute to a deeper understanding of the relationship between bilirubin's antioxidant role and ischemic stroke.

The risk of stroke according to statin medication compliance in older people with chronic periodontitis: an analysis using the Korea National Health Insurance Service-Senior Cohort Database: Seon-Rye Kim, Minkook Son, Yu-Rin Kim; Epidemiol Health. 2022;44:e2022055. Published online July 5, 2022; DOI: https://doi.org/10.4178/epih.e2022055

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3 Web of Science
3 Crossref

Abstract Summary PDF Supplementary Material

Abstract

OBJECTIVES
We investigated the risk of stroke according to statin medication compliance in older people with chronic periodontitis.

METHODS

Chronic periodontitis patients were extracted from the National Health Insurance Service-Senior Cohort Database from 2002 to 2014. Among 255,056 chronic periodontitis patients, 41,412 patients with statin prescriptions for 28 days or more were included. The study population was divided into the top 25% of medication compliance group (TSG) and the lower 25% of medication compliance group (BSG). After 1:1 propensity score matching was performed, the final number of patients in the BSG and TSG was 6,172 each. To analyze the risk of stroke, a Cox proportional hazard model was performed to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) after adjusting for age, sex, income level, hypertension, diabetes, and Charlson comorbidity index.

RESULTS

In the Kaplan-Meier curve, the disease-free probability was prominently lower in the BSG than in the TSG (p for log-rank= 0.001). The HR in the multivariable-adjusted model for stroke occurrence in the TSG compared to the BSG was 0.79 (95% CI, 0.67 to 0.92; p= 0.002). Subgroup analyses showed significant associations between compliance to statin medication and stroke, especially in female, people 85 years or older, and patients with comorbidities.

CONCLUSIONS

Increasing compliance to statins may reduce stroke risk in older adults with chronic periodontitis. Therefore, in order to increase medication compliance among older people with chronic periodontitis, it is necessary for medical staff to make efforts to provide effective medication guidance.

Summary

Korean summary
만성치주질환을 가진 노인에서 스타틴 복용순응도가 낮은 그룹에 비해 높은 그룹이 뇌졸증 발생위험이 낮았다. 특히 여성과 후기 노인 (85세 이상), 동반 질환을 가진 그룹에서 유의한 차이가 있었다. 따라서 스타틴 복용 순응도를 증대시키기 위한 의료진의 노력이 필요할 것이다.

Key Message
The stroke risk of chronic periodontal disease patients was related to statin medication compliance, and the effect of stroke risk was different in women, the elderly, and comorbidities.

Citations

Citations to this article as recorded by

Association between statin compliance and risk of dementia among patients with chronic periodontitis
Yu‐Rin Kim, Minkook Son, Seon‐Rye Kim
Oral Diseases.2024; 30(5): 3440. CrossRef
The association between dental caries, periodontal diseases, and tooth loss with diabetes mellitus among the elderly population
Mohammad-Hossein Heydari, Farshad Sharifi, Shayan Sobhaninejad, Ali Sharifi, Leili Alizadeh, Soheila Darmiani, Shima Bijari, Parvin Parvaie, Soheila Bakhshandeh, Shervan Shoaee, Mohammad-Hossein Khoshnevisan
Journal of Diabetes & Metabolic Disorders.2024; 23(1): 1371. CrossRef
Impact of statin treatment on cardiovascular events in patients with retinal vein occlusion: a nested case-control study in Korea
Joonsang Yoo, Joo Youn Shin, Jimin Jeon, Jinkwon Kim
Epidemiology and Health.2023; 45: e2023035. CrossRef

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