부산대학교 도서관

Introduction:Psychological stress is a risk factor for major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD). Certain brain regions that control both emotional states and cardiac physiology may play an important mediating role. The ventromedial prefrontal cortex (vmPFC) may be a key brain region that processes stress and regulates immune/autonomic function. Changes in vmPFC activity with emotional stress (reactivity) may be particularly informative of future risk.Hypothesis:High vmPFC stress reactivity is associated with greater stress-induced inflammation, vagal withdrawal, and MACE.Methods:Subjects with stable CAD underwent acute mental stress testing with brain PET imaging with a series of standardized speech/arithmetic stressors. Interleukin-6 (IL-6) levels 90 minutes post-stress and high-frequency heart rate variability (HF-HRV) during stress were also assessed. MACE included composite death, myocardial infarction, heart failure hospitalization and urgent revascularization. We defined high vmPFC reactivity by a difference between stress and control scans greater than the median value.Results:We examined 148 subjects (69% male) with mean age of 62 ? 8 years. After adjustment, higher vmPFC stress reactivity was independently associated with higher IL-6 and lower HF-HRV with stress (Figure 1). During a median follow-up of 3 years, 34 subjects (21.3%) experienced a MACE. After adjustment, high vmPFC stress reactivity was associated with increased risk of MACE (HR=3.7 95% CI= 1.6 ? 8.1). Post-stress IL-6 and HF-HRV during mental stress explained 14% and 30% of the relationship between vmPFC reactivity and MACE, respectively (Figure). In a logistic regression model predicting 3-year MACE, the C-statistic increased from 0.71 (risk factors alone) to 0.76 after adding vmPFC (p=0.03).Conclusion:High vmPFC stress reactivity is associated with MACE and partly mediated by inflammation and vagal withdrawal.