Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov:90:294-302.
doi: 10.1016/j.bbi.2020.09.001. Epub 2020 Sep 8.

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

Samaah Sullivan  1 , An Young  2 , Muhammad Hammadah  3 , Bruno B Lima  2 , Oleksiy Levantsevych  2 , Yi-An Ko  4 , Brad D Pearce  5 , Amit J Shah  6 , Jeong Hwan Kim  3 , Kasra Moazzami  2 , Emily G Driggers  7 , Ammer Haffar  5 , Laura Ward  4 , Isaias Herring  8 , Allison Hankus  5 , Tené T Lewis  5 , Puja K Mehta  3 , J Douglas Bremner  9 , Paolo Raggi  10 , Arshed Quyyumi  3 , Viola Vaccarino  2
Affiliations

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

Samaah Sullivan et al. Brain Behav Immun. 2020 Nov.

Abstract

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.

Keywords: Cardiovascular events; Inflammation; Inflammatory response; Mental stress; Women.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.. Forest Plot of Fine & Gray’s Proportional Sub-Distribution Hazard Ratios for each standard deviation increase in IL-6, MCP-1, and MMP-9 Response to Stress and Major Adverse Cardiovascular Events.
Estimates are from fully adjusted model (model 5).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ackerman KD, Martino M, Heyman R, Moyna NM, & Rabin BS, 1998. Stressor-induced alteration of cytokine production in multiple sclerosis patients and controls. Psychosom Med, 60(4), 484–491. - PubMed
    1. Almuwaqqat Z, Sullivan S, Hammadah M, Lima BB, Shah AJ, Abdelhadi N, Fang S, Wilmot K, Al Mheid I, Bremner JD, Garcia E, Nye JA, Elon L, Li L, O’Neal WT, Raggi P, Quyyumi AA, & Vaccarino V, 2019. Sex-Specific Association Between Coronary Artery Disease Severity and Myocardial Ischemia Induced by Mental Stress. Psychosom Med, 81(1), 57–66. doi:10.1097/PSY.0000000000000636. - DOI - PMC - PubMed
    1. Aukrust P, Ueland T, Muller F, Andreassen AK, Nordoy I, Aas H, Kjekshus J, Simonsen S, Froland SS, & Gullestad L, 1998. Elevated circulating levels of C-C chemokines in patients with congestive heart failure. Circulation, 97(12), 1136–1143. - PubMed
    1. Bairey Merz CN, Shaw LJ, Reis SE, Bittner V, Kelsey SF, Olson M, Johnson BD, Pepine CJ, Mankad S, Sharaf BL, Rogers WJ, Pohost GM, Lerman A, Quyyumi AA, Sopko G, & Investigators, Wise, 2006. Insights from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. J Am Coll Cardiol, 47(3 Suppl), S21–29. doi:10.1016/j.jacc.2004.12.084. - DOI - PubMed
    1. Bangasser DA, & Valentino RJ, 2012. Sex differences in molecular and cellular substrates of stress. Cell Mol Neurobiol, 32(5), 709–723. doi:10.1007/s10571-012-9824-4. - DOI - PMC - PubMed

Publication types