Abstract
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.
Highlights
High levels of methylation in the glucocorticoid receptors (GRs) gene have been associated with depression and cardiovascular risk
We aimed to investigate whether NR3C1 methylation status was correlated with known cardiovascular markers at the early phase of acute coronary syndrome (ACS), and whether it was associated with the long-term prognosis of ACS considering the negative impact of depression on these outcomes
The principal findings from this cohort study were that higher NR3C1 methylation status was correlated with several cardiovascular risk markers at the early phase of ACS and predicted worse long-term prognosis
Summary
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. Our study group found that higher DNA methylation of NR3C1 was independently associated with depressive disorder at the early phase of ACS13 Based on these findings, it can be postulated that NR3C1 methylation status may be associated with cardiac prognosis of ACS independently of or interactively with depression. We aimed to investigate whether NR3C1 methylation status was correlated with known cardiovascular markers at the early phase of ACS, and whether it was associated with the long-term prognosis of ACS considering the negative impact of depression on these outcomes
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