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

Columbia University

Status: Completed

Conditions: Endothelial Dysfunction; Emotions

Treatments: Other: Anger Induction; Other: Depressed Mood Induction; Other: Neutral emotion task; Other: Anxiety Induction

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01909895

AAAK4250

1R01HL116470-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 280 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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280 participants in 4 patient groups

Anger induction

Experimental group

Description:

The participant will be asked to undergo a validated anger induction task.

Treatment:

Other: Anger Induction

Depressed Mood Induction

Experimental group

Description:

The participant will be asked to undergo a validated depression/sadness induction task.

Treatment:

Other: Depressed Mood Induction

Anxiety Induction

Experimental group

Description:

The participant will be asked to undergo a validated anxiety induction task.

Treatment:

Other: Anxiety Induction

Neutral emotion task

Other group

Description:

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).

Treatment:

Other: Neutral emotion task