Key result
Higher NR3C1 methylation predicted a worse long-term prognosis of acute coronary syndrome only in the presence of depressive disorder (HR 1.98), demonstrating a significant synergistic effect.
Why the study?
High NR3C1 methylation is associated with depression and cardiovascular risk, but whether it impacts long-term ACS prognosis considering early-phase depression and cardiovascular status was unknown.
Does NR3C1 hypermethylation combined with depressive disorder predict worse long-term prognosis in patients with recent acute coronary syndrome?
Cohort (n=969)
No
Does NR3C1 hypermethylation combined with depressive disorder predict worse long-term prognosis in patients with recent acute coronary syndrome?
Hazard Ratio: 1.25 (95% CI 1.01–1.55)
Absolute Event Rate: 44.7% vs 34.3%
p-value: p=<0.05
NR3C1 methylation status combined with a diagnosis of depressive disorder may serve as a prognostic biomarker for long-term cardiac outcomes in patients with acute coronary syndrome.
NR3C1 methylation with depression may worsen ACS prognosis; hypothesis-generating for epigenetic risk stratification.
High levels of methylation in the GR gene (nuclear receptor subfamily 3, group C, member 1; NR3C1) have been associated with depression and cardiovascular risk. This study aimed to investigate whether NR3C1 methylation status was associated with the long-term prognosis of acute coronary syndrome (ACS) considering depression and cardiovascular status at the early phase of ACS. A total of 969 patients with recent ACS were recruited at a tertiary university hospital in Korea. Baseline evaluations were made from 2007 to 2012, including DSM-IV depressive disorder, NR3C1 methylation, and various demographic and clinical characteristics such as cardiovascular risk markers. Over a 5~12 year follow-up after the index ACS, time to major adverse cardiac event (MACE) was investigated using Cox regression models. Higher NR3C1 methylation status was associated with depression and several cardiovascular risk markers at baseline. NR3C1 hypermethylation predicted worse long-term prognosis of ACS only in the presence of depressive disorder with significant synergistic interaction terms and independent of potential confounding factors. Synergistic effects of depressive disorder and NR3C1 hypermethylation on long-term cardiac outcomes in ACS were found. NR3C1 methylation status represents a candidate prognostic biomarker for ACS in combination with a diagnosis of depressive disorder. Further research is needed to ascertain the generalisability of these findings.
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Kang et al. (2020) conducted a cohort in Acute coronary syndrome (n=969). Higher NR3C1 methylation vs. Lower NR3C1 methylation was evaluated on Major adverse cardiac event (MACE), a composite of all-cause mortality, myocardial infarction, and percutaneous coronary intervention (HR 1.25, 95% CI 1.01-1.55, p=<0.05). Higher NR3C1 methylation predicted a worse long-term prognosis of acute coronary syndrome only in the presence of depressive disorder (HR 1.98), demonstrating a significant synergistic effect.
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