Relation betwEen Abdominal Aorta and Carotid Artery Responses to SymPathetic stimulatiON uSing duplEx Ultrasound (RESPONSE)

Abdominal aortic aneurysm (AAA) is a common vascular disease and associated with risk of rupture, but also with a high cardiovascular (CV) event rate. A key difficulty in AAA is predicting these life-threatening complications. Recent studies suggest that the endothelial function of the abdominal aorta might have a correlation with the disease development. A novel, easy to perform, non-invasive test can assess central artery endothelial function (i.e. the carotid artery reactivity (CAR)). The CAR test is based on the cold pressure test (CPT), which induces sympathetic stimulation by placing one hand in cold water. Using duplex ultrasound, central artery blood flow and diameter responses can be examined.

Previous work has demonstrated that the CPT is associated with an increase in abdominal aortic diameter, whilst others found that the carotid and coronary artery diameter also shows dilation. Interestingly, a previous study found a strong correlation between carotid and coronary artery diameter responses to the CPT, whilst these artery responses show independent prognostic value for future cardiovascular events in patients with peripheral arterial disease. Possibly, similarity may be present in central artery reactivity to the CPT. To date, no study examined whether carotid and aorta responses are in agreement during the CPT. Given the potential importance of central artery vasoreactivity for AAA, the CAR-test may have potential in this group, especially given the relative simplicity of measuring the carotid artery.

The aim of this explorative study is to investigate the correlation between the magnitude of the abdominal aorta and the carotid artery diameter and blood flow responses during the sympathetic stimulation (using the cold pressor test) between healthy young, healthy older and individuals with AAA.

Study Overview

• Status: Completed
• Conditions: Abdominal Aortic Aneurysm
• Intervention / Treatment: Diagnostic test: Carotid artery reactivity test (CAR-test)

Detailed Description

The present study is an explorative, observational study, which will include in total 60 participants divided over 3 groups; healthy young adults, healthy older adults and patients with a stable abdominal aortic aneurysm (i.e. 30-50 mm), who are currently under threshold for repair. When participants meet the criteria, they will be informed about the study and they will be asked for their written informed consent, when they are willing to participate. Every participant only need to visit one time, which takes approximately 30 minutes. Participant characteristics will be registered, including traditional risk factors and CV history. Subsequently, the investigators will perform the CAR-test, which takes approximately 15 minutes. Prior to the CAR-test, participants should follow some instructions with regard to food and fluid intake according to a physiological guideline, which can influence this test.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Arnhem, Gelderland, Netherlands
      • Rijnstate Hospital
    • Nijmegen, Gelderland, Netherlands, 6525GA
      • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

1. twenty healthy, young (18-40 years) subjects,
2. twenty older subjects (>60 years) with a small, stable abdominal aortic aneurysm (i.e. AAA diameter of 30-50 mm), and
3. twenty healthy, age-/sex matched with group 2. We aim to include an equal number of male and females in both groups.

Description

Inclusion Criteria:

• Young healthy group: Male or female between the age of 18 and 40 years old;
• Older healthy group: Male or female, which are age-/sex-matched with the AAA patients group;
• AAA patients group: Male or female with an abdominal aortic aneurysm who is still under surveillance, with a diameter between 3.0 and 5.0 cm and at least 18 years old. These patients may participate in the 1-2-3 Trial, which is a similar approved investigation by CMO region Arnhem-Nijmegen with registration number 2019-5216.
• Informed consent form understood and signed;

Exclusion Criteria:

• Psychiatric or other conditions that may interfere with the study;
• Participating in another clinical study, interfering on outcomes;
• With regard to the necessary quality of the ultrasound images, BMI ≥ 30 kg/m2;
• Increased risk for coronary spasms (score Rose-questionnaire ≥2; this questionnaire can be found in the Appendix);
• Known carotid artery disease
• Presence of Raynaud's phenomenon, Marfan syndrome, chronic pain syndrome at upper extremity(s), presence of an AV fistula or shunt, open wounds to the upper extremity(s), and/or scleroderma associated with placing the hand in ice water;
• Recent (<3 months) presence of angina pectoris, myocardial infarction, cerebral infarction, and/or heart failure, or PAD treatment.

• Healthy groups:

  • Systolic blood pressure >140 and/or diastolic blood pressure >90
  • Cardiovascular history
  • Antihypertensive medication

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1. Young healthy group; Male or female between the age of 18 and 40 years old. No presence of systolic blood pressure >140 and/or diastolic blood pressure >90, cardiovascular history or antihypertensive medication	Diagnostic test: Carotid artery reactivity test (CAR-test); The CAR test will be applied to stimulate the sympathetic nervous system. This thermal stimulus is known to elevate blood pressure via sympathetic pathways, so it can be used to study the vascular response to sympathetic activation. The participant will submerge their left hand in a bucket of ice water (approximately 4 degrees celcius) for 3 minutes, which is reported to be sufficient to induce a maximal dilation in the common carotid artery. At baseline and every minute after the hand is submerged in ice water, the blood pressure will be measured to check whether a sympathetic stimulation is achieved. During this test as well the carotid artery as the abdominal aorta will be visualized using ultrasound.
2. Patients with an AAA; Individuals (>60 years) with a small, stable, abdominal aortic aneurysm (i.e. AAA diameter of 30-50 mm)	Diagnostic test: Carotid artery reactivity test (CAR-test); The CAR test will be applied to stimulate the sympathetic nervous system. This thermal stimulus is known to elevate blood pressure via sympathetic pathways, so it can be used to study the vascular response to sympathetic activation. The participant will submerge their left hand in a bucket of ice water (approximately 4 degrees celcius) for 3 minutes, which is reported to be sufficient to induce a maximal dilation in the common carotid artery. At baseline and every minute after the hand is submerged in ice water, the blood pressure will be measured to check whether a sympathetic stimulation is achieved. During this test as well the carotid artery as the abdominal aorta will be visualized using ultrasound.
3. Healthy older group; Healthy age- and sex- matched with group 2 with no presence of systolic blood pressure >140 and/or diastolic blood pressure >90, cardiovascular history or antihypertensive medication	Diagnostic test: Carotid artery reactivity test (CAR-test); The CAR test will be applied to stimulate the sympathetic nervous system. This thermal stimulus is known to elevate blood pressure via sympathetic pathways, so it can be used to study the vascular response to sympathetic activation. The participant will submerge their left hand in a bucket of ice water (approximately 4 degrees celcius) for 3 minutes, which is reported to be sufficient to induce a maximal dilation in the common carotid artery. At baseline and every minute after the hand is submerged in ice water, the blood pressure will be measured to check whether a sympathetic stimulation is achieved. During this test as well the carotid artery as the abdominal aorta will be visualized using ultrasound.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAR-test	Percentage of vasodilation/vasoconstriction to the CAR test at the common carotid artery	Baseline
CAR-test	Percentage of vasodilation/vasoconstriction to the CAR test at the abdominal aorta	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAR-test	Magnitude of the blood flow and perfusion response of the carotid artery	Baseline
CAR-test	Timing of the blood flow and perfusion response of the carotid artery	Baseline
CAR-test	Magnitude of the blood flow and perfusion response of the abdominal aorta	Baseline
CAR-test	Timing of the blood flow and perfusion response of the abdominal aorta	Baseline
CAR-test	Blood pressure response	Baseline
CAR-test	Heart rate response	Baseline
Age	Age	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demographic characteristics	Gender	Baseline
Demographic characteristics	If current smoker	Baseline
Demographic characteristics	Height	Baseline
Demographic characteristics	Weight	Baseline
Demographic characteristics	Medical history	Baseline
Demographic characteristics	Blood pressure	Baseline
Demographic characteristics	Heart rate	Baseline
Medication use	Ask about: Statins	Baseline
Medication use	Ask about: Beta-blockers	Baseline
Medication use	Ask about: Sympathicomimetica	Baseline
Medication use	Ask about: Anti-platelets	Baseline
Medication use	Ask about: Anti-coagulants	Baseline
Medication use	Ask about: Anti-hypertensives (questioned)	Baseline

Collaborators and Investigators

• Sponsor: Rijnstate Hospital
• Collaborators: Radboud University Medical Center
• Investigators: Principal Investigator: Michel Reijnen, MD, prof, Rijnstate Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): October 5, 2020

Study Registration Dates

• First Submitted: July 25, 2019
• First Submitted That Met QC Criteria: July 25, 2019
• First Posted (Actual): July 29, 2019

Study Record Updates

• Last Update Posted (Actual): October 12, 2020
• Last Update Submitted That Met QC Criteria: October 9, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Abdominal aortic aneurysm; Functional response; Carotid artery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Aortic Diseases; Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Abdominal
• Other Study ID Numbers: RESPONSE study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No