Modifying Effect of the Interleukin-18 Level on the Association between BDNF Methylation and Long-Term Cardiovascular Outcomes in Patients with Acute Coronary Syndrome

• Published in: International journal of molecular sciences 2022-12, Vol.23 (23), p.15270
• Main Authors: Choi, Wonsuk, Kang, Hee-Ju, Kim, Ju-Wan, Kim, Hee Kyung, Kang, Ho-Cheol, Kim, Sung-Wan, Kim, Jung-Chul, Ahn, Youngkeun, Jeong, Myung Ho, Kim, Jae-Min
• Format: Article
• Language: English
• Subjects: Acute Coronary Syndrome - genetics; Acute coronary syndromes; Brain-derived neurotrophic factor; Cardiovascular System; Clinical outcomes; Cytokines; Epigenetics; Humans; Hypertension; Independent variables; Inflammation; Interleukin 18; Interleukin-18 - genetics; Investigations; Kinases; Methylation; Mortality; Myocardial infarction; Myocardial Infarction - etiology; Percutaneous Coronary Intervention - adverse effects; Risk Factors; Statistical models
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232315270

This study investigated the potential modifying effects of the level of the serum interleukin-18 (IL-18) on the association between methylation status and long-term cardiovascular outcomes in patients with acute coronary syndrome (ACS). Hospitalized ACS patients were recruited sequentially from 2006 to 2012. At baseline, the IL-18 level and methylation status were evaluated in 969 patients who were followed for major adverse cardiac events (MACEs) for 5-12 years, until 2017 or death. The time to first composite or individual MACE was compared between individuals with lower and higher average methylation levels (in the low- and high-IL-18 groups, respectively) using a Cox proportional hazards model. After adjusting for potential covariates, the modifying effects of IL-18 and average methylation levels on the initial composite and individual MACEs were examined. In the high-IL-18 group, but not in the low-IL-18 group, a higher average methylation level was associated with increases in composite MACEs (HR (95% CI) = 2.15 (1.42-3.26)), all-cause mortality (HR (95% CI) = 1.89 (1.11-3.22)), myocardial infarction (HR (95% CI) = 1.98 (1.07-3.67)), and percutaneous coronary intervention (HR (95% CI) = 1.81 (1.01-3.23)), independent of confounding variables. The interaction effect between the IL-18 and average methylation levels on composite MACEs ( = 0.019) and myocardial infarction ( = 0.027) was significant after adjusting for covariates. Analysis of methylation status and IL-18 levels may help identify ACS patients who are most likely to have adverse clinical outcomes.