Sex differences in the inflammatory response to stress and risk of adverse cardiovascular outcomes among patients with coronary heart disease

Samaah Sullivan, An Young, Muhammad Hammadah, Bruno B. Lima, Oleksiy Levantsevych, Yi An Ko, Brad D. Pearce, Amit J. Shah, Jeong Hwan Kim, Kasra Moazzami, Emily G. Driggers, Ammer Haffar, Laura Ward, Isaias Herring, Allison Hankus, Tené T. Lewis, Puja K. Mehta, J. Douglas Bremner, Paolo Raggi, Arshed QuyyumiViola Vaccarino

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Stress may contribute to progression of coronary heart disease (CHD) through inflammation, especially among women. Thus, we sought to examine whether increased inflammatory response to stress among patients with CHD is associated with a greater risk of cardiovascular events and whether this risk is higher in women. We examined inflammatory biomarkers known to increase with mental stress (speech task), including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and matrix metallopeptidase-9 (MMP-9) among 562 patients with stable CHD. Inflammatory response, the difference between post-stress and resting values, was examined as a predictor of major adverse cardiovascular events (MACE) using subdistribution hazards models for competing risks adjusting for demographics, cardiovascular risk factors, and medications. MACE was defined as a composite endpoint of cardiovascular death, myocardial infarction, unstable angina with revascularization, and heart failure. All biomarkers were standardized. The mean age was 63 years (range 34–79) and 24% were women. During a median follow-up of 3 years, 71 patients experienced MACE. Overall, there was no significant association between inflammatory response to stress and risk of MACE, but there were sex-based interactions for IL-6 (p = 0.001) and MCP-1 (p = 0.01). The risk of MACE increased 56% (HR: 1.56; 95% CI: 1.21, 2.01; p = 0.001) and 30% (HR: 1.30; 95% 1.09, 1.55; p = 0.004) for each standard deviation increase in IL-6 and MCP-1 response to mental stress for women, respectively, while there was no association among men. Increased inflammation in response to stress is associated with future adverse cardiovascular outcomes among women with CHD.

Original languageEnglish (US)
Pages (from-to)294-302
Number of pages9
JournalBrain, Behavior, and Immunity
StatePublished - Nov 2020
Externally publishedYes


  • Cardiovascular events
  • Inflammation
  • Inflammatory response
  • Mental stress
  • Women

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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