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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Columbia University
Sponsor:
Information provided by (Responsible Party):
Daichi Shimbo, Columbia University
ClinicalTrials.gov Identifier:
NCT01909895
First received: July 25, 2013
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

The experience of negative emotions is associated with an increased risk of incident atherosclerosis-related cardiovascular disease (CVD) events, independent of traditional risk factors. The strongest data supporting this relation is with provoked anger. There is also some evidence that becoming acutely depressed or anxious are also triggers of incident CVD. The underlying putative mechanisms are poorly understood. Vascular endothelial cells (ECs) play an essential role in maintaining vascular tone and the integrity of blood vessels. Evidence suggests that dysfunction of the endothelium is an early pathogenic process underlying atherosclerosis development and CVD event onset. The aims of this study are to primarily examine the acute effects of provoked anger and secondarily depressed mood and anxiety on EC health. Examination of these critical pathways will help determine whether endothelial dysfunction is a biological mechanism linking the experience of core negative emotions and incident CVD risk. In this application, a state-of-the-art, laboratory-based, randomized controlled experiment is proposed that will test whether provoked anger, depressed mood and anxiety will induce endothelial dysfunction in humans. We hypothesize that compared to an emotionally neutral condition, an anger recall task will impair endothelium-dependent vasodilation, injure ECs, and reduce EC reparative capacity. We will also examine whether a depressed mood and anxiety induction task will similarly induce endothelial dysfunction, as well as whether levels of provoked self-reported anger, depressed mood, and anxiety are associated with the degree of endothelial dysfunction. Finally, given that endogenous nitric oxide (NO) inhibition plays a central role in exacerbating endothelial dysfunction, we will explore whether NO inhibition partially mediates the acute adverse effects of provoked anger, depressed mood, and anxiety on endothelial function. In the United States, atherosclerosis-related CVD events remain the leading cause of morbidity and mortality. Further, anger, depressed mood, and anxiety are negative emotions commonly experienced by adults in the general population on a day-to-day basis. Therefore, evaluation of these hypotheses is timely and highly significant, as it will help identify a putative biological pathway linking the experience of core negative emotions to CVD incidence, for a large number of individuals who are at increased risk for CVD events.


Condition Intervention
Emotions
Endothelial Dysfunction
Other: Anger Induction
Other: Depressed Mood Induction
Other: Anxiety Induction
Other: Neutral emotion task

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Official Title: Translational Research of Negative Emotions and Acute Endothelial Dysfunction

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Endothelium-dependent arterial vasodilation [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Circulating EMPs expressing CD62E [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • Endothelium-dependent arterial vasodilation [ Time Frame: 3 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Endothelium-dependent arterial vasodilation [ Time Frame: 40 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Endothelium-dependent arterial vasodilation [ Time Frame: 70 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Endothelium-dependent arterial vasodilation [ Time Frame: 100 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating EMPs expressing CD62E [ Time Frame: 3 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating EMPs expressing CD62E [ Time Frame: 40 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating EMPs expressing CD62E [ Time Frame: 70 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating EMPs expressing CD62E [ Time Frame: 100 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: 3 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: 40 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: 70 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating early EPCs (KDR+, CD34+, CD133+ cells) [ Time Frame: 100 mins after end of mood induction ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Circulating EMPs expressing CD31 [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Circulating EMPs expressing CD51 [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ] [ Designated as safety issue: No ]
  • Self-reported anger, depressed mood, and anxiety [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Nitric oxide(NO) inhibition [ Time Frame: baseline; 3 mins, 40 mins, 70 mins, 100 mins after end of mood induction ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Circulating measures of catecholamines, cortisol, endothelin-1; blood pressure and heart rate


Estimated Enrollment: 280
Study Start Date: August 2013
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anger induction
The participant will be asked to undergo a validated anger induction task.
Other: Anger Induction
The participant will be asked to undergo a validated anger induction task.
Experimental: Depressed Mood Induction
The participant will be asked to undergo a validated depression/sadness induction task.
Other: Depressed Mood Induction
The participant will be asked to undergo a validated depression/sadness induction task.
Experimental: Anxiety Induction
The participant will be asked to undergo a validated anxiety induction task.
Other: Anxiety Induction
The participant will be asked to undergo a validated anxiety induction task.
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).
Other: Neutral emotion task
This is a neutral control task that each of the negation emotion induction tasks will be compared to.

  Hide Detailed Description

Detailed Description:

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). Our specific 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01909895

Contacts
Contact: Daichi Shimbo, MD 212-342-4490 ds2231@columbia.edu

Locations
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Principal Investigator: Daichi Shimbo, MD         
Sub-Investigator: Matthew Burg, PhD         
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Daichi Shimbo, MD Columbia University
  More Information

No publications provided

Responsible Party: Daichi Shimbo, Associate Professor of Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT01909895     History of Changes
Other Study ID Numbers: AAAK4250
Study First Received: July 25, 2013
Last Updated: February 27, 2014
Health Authority: United States: Institutional Review Board

ClinicalTrials.gov processed this record on September 18, 2014