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Study of the Effects of Negative Emotions on Endothelial Function (PUME)

This study has been completed.
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Daichi Shimbo, Columbia University
ClinicalTrials.gov Identifier:
NCT01909895
First received: July 25, 2013
Last updated: July 15, 2017
Last verified: July 2017
July 25, 2013
July 15, 2017
August 2013
May 2017   (Final data collection date for primary outcome measure)
  • Endothelium-dependent arterial vasodilation [ Time Frame: baseline ]
  • Circulating EMPs expressing CD62E [ Time Frame: baseline ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: baseline ]
  • Endothelium-dependent arterial vasodilation [ Time Frame: 3 mins after end of mood induction ]
  • Endothelium-dependent arterial vasodilation [ Time Frame: 40 mins after end of mood induction ]
  • Endothelium-dependent arterial vasodilation [ Time Frame: 70 mins after end of mood induction ]
  • Endothelium-dependent arterial vasodilation [ Time Frame: 100 mins after end of mood induction ]
  • Circulating EMPs expressing CD62E [ Time Frame: 3 mins after end of mood induction ]
  • Circulating EMPs expressing CD62E [ Time Frame: 40 mins after end of mood induction ]
  • Circulating EMPs expressing CD62E [ Time Frame: 70 mins after end of mood induction ]
  • Circulating EMPs expressing CD62E [ Time Frame: 100 mins after end of mood induction ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: 3 mins after end of mood induction ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: 40 mins after end of mood induction ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: 70 mins after end of mood induction ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: 100 mins after end of mood induction ]
Same as current
Complete list of historical versions of study NCT01909895 on ClinicalTrials.gov Archive Site
  • Circulating EMPs expressing CD31 [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ]
  • Circulating EMPs expressing CD51 [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ]
  • Self-reported anger, depressed mood, and anxiety [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ]
Same as current
  • Nitric oxide(NO) inhibition [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ]
    Circulating measures of asymmetric dimethylarginine (ADMA) and oxidative stress measures
  • Stress response [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ]
    Circulating measures of catecholamines, cortisol, endothelin-1; blood pressure and heart rate
Same as current
 
Study of the Effects of Negative Emotions on Endothelial Function
Translational Research of Negative Emotions and Acute Endothelial Dysfunction

Study aims and hypotheses are as follows:

Primary Hypotheses:

Compared to the neutral condition, the anger recall task will acutely induce endothelial dysfunction by impairing endothelium-dependent arterial vasodilation (Hypothesis 1a); increasing circulating levels of EC-derived microparticles (EMPs), a marker of EC injury (Hypothesis 1b); and reducing circulating levels of bone marrow-derived endothelial progenitor cells (EPCs), a marker of EC reparative capacity (Hypothesis 1c).

Secondary Hypotheses:

Compared to the neutral condition, the depressed mood and separately the anxiety recall tasks will acutely impair endothelium-dependent arterial vasodilation, increase circulating levels of EMPs, and reduce circulating levels of bone marrow-derived EPCs. There will be a relation of the level of self-reported anger, depressed mood, and anxiety with endothelial dysfunction.

Atherosclerosis-related cardiovascular disease (CVD) events remain the leading causes of morbidity and mortality in industrialized nations. Atherosclerosis is a diffuse disease characterized by the deposition of lipid and other blood-borne material within the arterial wall. Evidence demonstrates that disruption of an arterial atherosclerotic plaque and subsequent thrombus formation is responsible for the onset of CVD events. Cardiovascular research efforts have been directed toward the identification of early underlying factors that initiate this cascade.

It has been known for some time that the experience of negative emotions is associated with an increased risk of incident CVD events, independent of traditional risk factors. Among the best-studied negative emotions is anger. Population-based studies have demonstrated that the experience of anger is a trigger of incident CVD events. The mechanism(s) by which provoked anger acutely affects the pathways that underlie atherosclerosis development and progression remain to be fully characterized.

Endothelial dysfunction is a promising mechanism that may explain the link between anger and incident CVD events. Vascular endothelial cells (ECs) play essential roles in maintaining vascular tone and the integrity of blood vessels. Evidence suggests that endothelial dysfunction is an early pathogenic process underlying atherosclerosis development and CVD event onset. Our preliminary findings show in apparently healthy individuals, an anger recall task acutely induces endothelial dysfunction by impairing endothelium-dependent vasodilation, injuring ECs, and disrupting the molecular processes underlying EC reparative capacity. We have additionally found that this task may induce endogenous nitric oxide (NO) inhibition, which plays a central role in aggravating endothelial dysfunction. Therefore, NO inhibition may partially mediate anger-provoked endothelial dysfunction.

Although the strongest data are on anger-provoked CVD events, there is also some evidence that the experience of other core negative emotions such as depressed mood and anxiety may trigger CVD events. Whether the provocation of depressed mood and anxiety acutely induces endothelial dysfunction and NO inhibition remains to be determined. The overall aim of this study is to primarily examine the acute effects of provoked anger and secondarily depressed mood and anxiety on EC health. We will also explore whether NO inhibition partially mediates the acute effects of anger, depressed mood, and anxiety on endothelial function. Examination of these critical pathways will help identify the biological pathways by which the experience of core negative emotions leads to incident CVD risk.

To address these highly significant research questions, we propose a state-of-the-art, laboratory-based, randomized controlled experiment in which 280 participants will be randomized to one of four experimental conditions: an anger recall task (N=70), a depressed mood recall task (N=70), an anxiety recall task (N=70), and an emotionally neutral condition (N=70).

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Other
  • Emotions
  • Endothelial Dysfunction
  • Other: Anger Induction
    The participant is asked to recall an incident in the recent past during which they became moderately to extremely angry, or is asked to read statements out loud evoking moderate to extreme feelings of anger. The participant is asked to take a few moments to bring the details of the incident to mind and, when ready, to describe the incident in great detail to the experimenter. Participants are asked to describe key elements, such as any dialogue that transpired during the incident, along with other details of the incident, particularly regarding the feelings of that particular emotion experienced at the time. In so doing, the experimenter works to re-elicit the emotions that accompanied the original incident. The duration of the negative emotion induction task is 8 minutes.
  • Other: Depressed Mood Induction
    The participant will be asked to undergo a validated depression/sadness induction task.
  • Other: Anxiety Induction
    The participant will be asked to undergo a validated anxiety induction task.
  • Other: Neutral emotion task
    This is a neutral control task that each of the negation emotion induction tasks will be compared to.
  • Experimental: Anger induction
    The participant will be asked to undergo a validated anger induction task.
    Intervention: Other: Anger Induction
  • Experimental: Depressed Mood Induction
    The participant will be asked to undergo a validated depression/sadness induction task.
    Intervention: Other: Depressed Mood Induction
  • Experimental: Anxiety Induction
    The participant will be asked to undergo a validated anxiety induction task.
    Intervention: Other: Anxiety Induction
  • Neutral emotion task
    The participant will be asked to undergo a validated neutral task (i.e. count aloud by ones, starting with one and ending with 100, over and over, until the task period has ended).
    Intervention: Other: Neutral emotion task
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
280
May 2017
May 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age 18 and over
  • Fluent in English

Exclusion Criteria:

  • History of any chronic medical condition including prevalent CVD and traditional risk factors
  • Active smoking
  • Chronic medication use, including over-the-counter drugs or herbal medications
  • History of psychosis, a mood disorder, or any overt personality disorder
  • Latex allergy
  • Poor peripheral veins with low possibility of getting IV access
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01909895
AAAK4250
1R01HL116470-01 ( U.S. NIH Grant/Contract )
No
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Undecided
Daichi Shimbo, Columbia University
Columbia University
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Daichi Shimbo, MD Columbia University
Columbia University
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP