The association of inflammatory response to a mental stress task and major depressive disorder amongst patients who experienced a myocardial infarction Open Access

Rizzieri, Ashley (Spring 2018)

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Background: Major Depressive Disorder (MDD) is prevalent amongst MI patients and is associated with approximately a twofold increase in adverse events. Different inflammatory responses to stress in MI patients with MDD may contribute to worse adverse outcomes. The purpose of this study was to examine inflammatory responses to a mental stress test according to MDD status. Additionally, we explored this association stratified by sex. 

Methods A secondary analysis of the Myocardial Infarction and Mental Stress 2 (MIMS2) study was performed, using data from 271 patients < 61 years of age hospitalized for MI in the previous 8 months. Participants were categorized into three groups: no history of MDD (n=175), previous MDD (n=52) and current (past month) MDD (n=44). Participants underwent a mental stress task within the parent study and inflammatory responses for Interleukin-6 (IL-6), C-Reactive Protein (CRP), Monocyte Chemoattractant Protein-1 (MCP1), Matrix Metalloproteinase- 9 (MMP9), and Vascular Endothelial Growth Factors (VEGF) were measured. We used mixed models to assess difference in inflammatory biomarker concentrations in response to mental stress (defined as the change in levels comparing post-stress values to pre-stress values) amongst the varying levels of MDD. Differences between women and men were assessed by estimating sex-stratified models and testing the interaction by sex in a model of all participants. 

Results: IL-6 significantly increased from pre- to post- mental stress task (p<.0001) for all categories of MDD, but IL-6 responses to the mental stress task did not significantly differ across the categories of MDD. Furthermore, responses of CRP, MCP1, MMP9 and VEGF did not significantly differ across all three categories of MDD. Although women had higher levels of IL-6 than men throughout the mental stress task, the change in IL-6 means for all MDD categories did not significantly differ between men and women. 

Conclusions: We found no significant association between MDD status and inflammatory changes in response to acute stress amongst MI patients. Further studies should explore other potential biological mechanisms that may explain the adverse prognosis associated with depression post-MI. 

Table of Contents

Chapter 1 Introduction 1

Research objectives                 2

Chapter 2 Literature Review    3

Global Burden of Cardiovascular Disease                  3

National Burden of Coronary Heart Disease (CHD) / Myocardial Infarction (MI)    3

National Burden of MDD       5

The Link Between MDD and MI        6

Why Study Sex Differences Within the Link Between MDD and MI            7

Inflammatory Markers may Partially Explain the Link Between Depression and MI 8

Inflammation and CHD           8

Depression and Inflammation             10

Inflammation, Depression and CHD   10

Aims of the Current Project    12

Aim 1. To compare the inflammatory response to acute mental stress in MI patients with and without depression    12

Aim 2.  To compare the inflammatory response to acute mental stress in MI patients with and without depression stratified by sex.            12

Global Health Implications of the Results from Current Study           13

Chapter 3 Methods      15

Parent Study Design   15

Study Design and Participants 15

Variables for this Study          17

Statistical Analysis      18

Chapter 4 Results        20

Study Sample and Baseline Characteristics     20

Hemodynamic Responses to Stress    20

Inflammation Marker Distribution during Mental Stress Testing        20

Sex Differences in Inflammatory Response    21

Chapter 5 Discussion  23

Limitations of the Current Study         26

Chapter 6 Conclusion  27


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