Key result
Higher BDNF methylation linked to ~45% greater MACE risk in ACS, mitigated by escitalopram.
Why the study?
BDNF methylation has been extensively investigated in depression but not in cardiac diseases, leaving its association with MACE, inflammation, and depression comorbidity unknown in ACS.
Is BDNF methylation associated with MACE in patients with ACS, and does escitalopram treatment modify this risk?
RCT (n=969)
Double-blind
Is BDNF methylation associated with MACE in patients with ACS, and does escitalopram treatment modify this risk?
Hazard Ratio: 1.45 (95% CI 1.17–1.78)
Higher BDNF methylation is associated with worse long-term prognosis in ACS patients, but this risk may be mitigated by escitalopram treatment in those with comorbid depression.
Higher BDNF methylation signals elevated MACE risk in ACS; escitalopram may offset this in depressed patients, meriting targeted trials.
AIMS: Brain-derived neurotrophic factor (BDNF) plays important roles in angiogenesis, inflammation, and neuronal plasticity. BDNF methylation has been extensively investigated in depression, but not in cardiac diseases. We asked whether BDNF methylation status is associated with a major adverse cardiac event (MACE), inflammation, and the association with depression comorbidity and its treatment in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: A cross-sectional baseline study and nested 24 week double-blind escitalopram placebo-controlled trial (ClinicalTrial.gov identifier NCT00419471) were performed from 2006 to 2012, with 5-12 year follow-up for MACE. Patients with recent ACS (969 total) were divided into four groups according to depression comorbidity at baseline and treatment allocation: 591, absent depression; 127, depression on escitalopram; 128, depression on placebo; 123, depression on care as usual (CAU). BDNF methylation was measured in leucocyte DNA, and multiple demographic and clinical characteristics including interleukin 6 were evaluated as covariates at baseline. The primary outcome, time to first MACE (a composite of all-cause mortality, myocardial infarction and percutaneous coronary intervention), was investigated using Cox regression models after adjustment for covariates. Interleukin 6 level was significantly higher in patients with higher BDNF methylation values. Higher BDNF methylation was associated with increased MACE independent of confounding factors [HR (95% CI) = 1.45 (1.17-1.78)]. This association was significant in patients without depression [HR (95% CI) = 1.39 (1.01-1.90)] and depressive patients on placebo [HR (95% CI) = 1.72 (1.02-3.02)] or CAU [HR (95% CI) = 1.53 (1.01-2.61)], but not in those treated with escitalopram [HR (95% CI) = 1.00 (0.51-1.95)]. CONCLUSION: BDNF methylation was significantly associated with prognosis of ACS. Escitalopram may mitigate the deleterious effect of higher BDNF methylation in depressive patients with ACS. Further research is needed to elucidate the mechanistics and to assess the generalisability of these findings.
No takes yet. Share an insight, caveat, or question.
Kim et al. (2019) conducted an RCT in acute coronary syndrome (n=969). Higher BDNF methylation vs. Lower BDNF methylation was evaluated on time to first MACE (a composite of all-cause mortality, myocardial infarction and percutaneous coronary intervention) (HR 1.45, 95% CI 1.17-1.78). Higher BDNF methylation was associated with increased MACE in patients with acute coronary syndrome (HR 1.45; 95% CI 1.17-1.78), though this risk was mitigated in those treated with escitalopram.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: