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Changes in proteinuria and the associated risks of ischemic heart disease, acute myocardial infarction, and angina pectoris in Korean population
Sung Keun Park, Ju Young Jung, Min-Ho Kim, Chang-Mo Oh, Eunhee Ha, Eun Hye Yang, Hyo Choon Lee, Soonsu Shin, Woo Yeon Hwang, Sangho Lee, So Youn Shin, Jae-Hong Ryoo
Epidemiol Health. 2023;45:e2023088.   Published online September 30, 2023
DOI: https://doi.org/10.4178/epih.e2023088
  • 2,668 View
  • 158 Download
AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
OBJECTIVES
Proteinuria is widely used to predict cardiovascular risk. However, there is insufficient evidence to predict how changes in proteinuria may affect the incidence of cardiovascular disease.
METHODS
The study included 265,236 Korean adults who underwent health checkups in 2003-2004 and 2007-2008. They were categorized into 4 groups based on changes in proteinuria (negative: negative → negative; resolved: proteinuria ≥1+ → negative; incident: negative → proteinuria ≥1+; persistent: proteinuria ≥1+ → proteinuria ≥1+). We conducted 6 years of follow-up to identify the risks of developing ischemic heart disease (IHD), acute myocardial infarction (AMI), and angina pectoris according to changes in proteinuria. A multivariate Cox proportional-hazards model was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident IHD, AMI, and angina pectoris.
RESULTS
The IHD risk (expressed as HR [95% CI]) was the highest for persistent proteinuria, followed in descending order by incident and resolved proteinuria, compared with negative proteinuria (negative: reference, resolved: 1.211 [95% CI, 1.104 to 1.329], incident: 1.288 [95% CI, 1.184 to 1.400], and persistent: 1.578 [95% CI, 1.324 to 1.881]). The same pattern was associated with AMI (negative: reference, resolved: 1.401 [95% CI, 1.048 to 1.872], incident: 1.606 [95% CI, 1.268 to 2.035], and persistent: 2.069 [95% CI, 1.281 to 3.342]) and angina pectoris (negative: reference, resolved: 1.184 [95% CI, 1.065 to 1.316], incident: 1.275 [95% CI, 1.160 to 1.401], and persistent: 1.554 [95% CI, 1.272 to 1.899]).
CONCLUSIONS
Experiencing proteinuria increased the risks of IHD, AMI, and angina pectoris even after proteinuria resolved.
Summary
Korean summary
- 본 연구의 목적은 요 시험지 검사를 통해 확인된 단백뇨의 3-5년간의 변화 수준에 따른 허혈성 심질환, 급성 심근 경색, 협심증의 발생 위험을 평가하는 것이다. - 지속적으로 단백뇨가 음성인 집단에 (negative proteinuria) 비해서, 단백뇨가 있었다 사라진 집단 (resolved proteinuria), 새로이 단백뇨가 생긴 집단 (incident proteinuria), 지속적으로 단백뇨가 존재하는 집단 (persistent proteinuria)은 유의하게 증가한 허혈성 심질환, 급성 심근 경색, 협심증의 발생 위험을 나타내었다. - 이러한 결과는 단백뇨가 일단 발생한 사람은, 나중에 사라지더라도, 관상 동맥 질환에 대한 위험이 높으며, 이에 대한 관리와 주의가 필요하다는 것을 시사한다.
Key Message
- The present study was to evaluate the risk of incident ischemic heart disease, acute myocardial infarction, and angina pectoris according to changes in urine dipstick proteinuria over 3-5 years. - Compared with persistently negative proteinuria (negative → negative), resolved proteinuria (positive → negative), incident proteinuria (negative → positive), and persistent proteinuria (positive → positive) had the increased risk of ischemic heart disease, acute myocardial infarction, and angina pectoris. - These results suggest that once manifested proteinuria lead to the increased risk of coronary artery disease, regardless of changes in proteinuria.
Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study
Christina Jeon, Ji-Young Lee, Sun Ju Lee, Keum Ji Jung, Heejin Kimm, Sun Ha Jee
Epidemiol Health. 2019;41:e2019034.   Published online July 12, 2019
DOI: https://doi.org/10.4178/epih.e2019034
  • 12,174 View
  • 287 Download
  • 10 Web of Science
  • 10 Crossref
AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
OBJECTIVES
Bilirubin is an endogenous antioxidant that protects cells against oxidative stress. Increased plasma levels of bilirubin have been associated with a reduced risk of ischemic heart disease (IHD) in previous studies. Nonetheless, whether those associations reflect a true protective effect of bilirubin on IHD, rather than confounding or reverse causation, remains unknown. Therefore, we applied two-sample Mendelian randomization to evaluate the causal association between bilirubin levels and IHD risk in a Korean population.
METHODS
A total of 5 genetic variants—TRPM8 (rs10490012), USP40 (rs12993249), ATG16L1 (rs2119503), SLCO1B1 (rs4149014), and SLCO1B3 (rs73233620)—were selected as genetic instruments for serum bilirubin levels using a communitybased cohort, the Korean Genome and Epidemiology Study, comprising 33,598 subjects. We then evaluated their impact on IHD using the Korean Cancer Prevention Study-II cohort.
RESULTS
Among the 5 instrumental variables that showed significant associations with serum bilirubin levels, rs12993249 (USP40) showed the most significant association (p<2.36×10-105). However, we found no significant association between serum bilirubin levels and IHD. Sensitivity analyses demonstrated a consistent association, suggesting that our observations were robust.
CONCLUSIONS
Using two-sample Mendelian randomization, we found no association between serum bilirubin levels and IHD. Further studies that confirm the observed interactions among other ethnicities are warranted.
Summary
Korean summary
이 연구는 대규모 한국인 코호트를 이용하여, 빌리루빈과 허혈성 심장질환의 인과성을 규명한 연구결과이다. 특히 두 가지 자료를 이용한 멘델리안 무작위배정 연구방법을 적용하여, 한국인을 대상으로 빌리루빈과 허혈성 심장질환의 인과성을 처음으로 규명한 점이 큰 시사점을 가진다.

Citations

Citations to this article as recorded by  
  • Association of Different Total Bilirubin Levels with Prognosis of Peritoneal Dialysis-Associated Peritonitis
    Yujian He, Jingjing Zhu, Fei Xiao, Qingyun Luo, Pengpeng Wang, Xu Wang, Yan He, Zibo Xiong
    Medicina.2023; 59(10): 1837.     CrossRef
  • Novel prognostic score based on the preoperative total bilirubin-albumin ratio and fibrinogen-albumin ratio in ampullary adenocarcinoma
    Xiao-Jie Zhang, He Fei, Chong-Yuan Sun, Ze-Feng Li, Zheng Li, Chun-Guang Guo, Dong-Bing Zhao
    World Journal of Gastrointestinal Surgery.2023; 15(10): 2247.     CrossRef
  • The Nonlinear Relationship Between Total Bilirubin and Coronary Heart Disease: A Dose-Response Meta-Analysis
    Chaoxiu Li, Wenying Wu, Yumeng Song, Shuang Xu, Xiaomei Wu
    Frontiers in Cardiovascular Medicine.2022;[Epub]     CrossRef
  • Another Reason to Cut Down on Alcohol?
    Hyeon Chang Kim
    Korean Circulation Journal.2022; 52(3): 231.     CrossRef
  • Serum bilirubin and kidney function: a Mendelian randomization study
    Sehoon Park, Soojin Lee, Yaerim Kim, Yeonhee Lee, Min Woo Kang, Kwangsoo Kim, Yong Chul Kim, Seung Seok Han, Hajeong Lee, Jung Pyo Lee, Kwon Wook Joo, Chun Soo Lim, Yon Su Kim, Dong Ki Kim
    Clinical Kidney Journal.2022; 15(9): 1755.     CrossRef
  • Heme Oxygenase-1 and Blood Bilirubin Are Gradually Activated by Oral D-Glyceric Acid
    O. Petteri Hirvonen, Maarit Lehti, Heikki Kyröläinen, Heikki Kainulainen
    Antioxidants.2022; 11(12): 2319.     CrossRef
  • Exploring the causal pathway from bilirubin to CVD and diabetes in the UK biobank cohort study: Observational findings and Mendelian randomization studies
    Lei Hou, Hongkai Li, Shucheng Si, Yuanyuan Yu, Xiaoru Sun, Xinhui Liu, Ran Yan, Yifan Yu, Chuan Wang, Fan Yang, Qing Wang, Fuzhong Xue
    Atherosclerosis.2021; 320: 112.     CrossRef
  • The causal association of bilirubin with cardiovascular disease: Are there still any questions?
    Claudia Lamina, Florian Kronenberg
    Atherosclerosis.2021; 320: 92.     CrossRef
  • Association between Alcohol Consumption and Serum Cortisol Levels: a Mendelian Randomization Study
    Jung-Ho Yang, Sun-Seog Kweon, Young-Hoon Lee, Seong-Woo Choi, So-Yeon Ryu, Hae-Sung Nam, Kyeong-Soo Park, Hye-Yeon Kim, Min-Ho Shin
    Journal of Korean Medical Science.2021;[Epub]     CrossRef
  • SLCO1B1 Variants and The Risk of Antituberculosis Drug-induced Hepatotoxicity: A Systematic Review and Meta-analysis
    Min Zhu, Xinyu Chen, Zhuolu Hao, Yiwen He, Bing Han, Shaowen Tang
    Pharmacogenomics.2009; 24(18): 931.     CrossRef
Review
Stress and Cardiovascular Disease.
Byung Yeol Chun
Korean J Epidemiol. 2002;24(2):131-136.
  • 5,371 View
  • 19 Download
AbstractAbstract PDF
Abstract
Stress is a newly recognized risk factor that appears to contribute to all recognized mechanisms underlying cardiac events, specifically, by clustering of traditional cardiovascular risk factors, endothelial dysfunction, myocardial ischemia, plaque rupture, thrombosis, and malignant arrhythmia. And it is necessary to study on the role of stress in the causation of developing cardiovascular disease by a direct hormonal effect on heart or an indirect behavioral change. A better understanding of the behavioral and physiologic associations between psychological stress and cardiovascular disease will assist researchers in developing effective approaches for reducing or reversing the damaging effects of stress and may lead to further reductions of CVD morbidity and mortality in Korea.
Summary

Epidemiol Health : Epidemiology and Health