High Resolution Phenotyping in Healthy Humans

January 5, 2016 updated by: John Eisenach, Mayo Clinic

Blood Pressure Variability, Baroreflex Sensitivity, and Cardiovascular Responses to Sympathoexcitation in Healthy Normotensive Humans

Baroreflex sensitivity is integral to blood pressure regulation, and varies among healthy, normotensive individuals. A reduced compensatory ability of baroreflex buffering in patients with carotid denervation results in blood pressure variability and an elevated blood pressure response to mental stress. Furthermore, 24-hour ambulatory blood pressure variability may also be a significant and independent risk determinant of cardiovascular disease. It remains unknown whether the degree of baroreflex sensitivity and ambulatory blood pressure variability are predictive of the pressor response to sympathoexcitatory stress in healthy humans. In this study the investigators propose a comprehensive evaluation of the relationships among the pressor and forearm vasodilator response to sympathoexcitation, ambulatory blood pressure variability, and baroreflex sensitivity in healthy normotensive subjects. Ultimately this study will provide preliminary data and protocol development for large-scale high resolution phenotyping in population-based trials aimed at determining the functional relevance of candidate gene variation in intermediate physiological traits pertinent to the pathogenesis of hypertension and cardiovascular disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Growing evidence suggests an association of environmental stress with the development of hypertension and there is strong evidence in normotensive subjects that a greater pressor response to sympathoexcitatory stress is a harbinger of future hypertension. Pharmacological studies have shown that individuals with HTN have a blunted baroreflex sensitivity, and display a greater increase in blood pressure during administration of an alpha-agonist. Furthermore, exaggerated 24-hour ambulatory blood pressure variability (BPV) is proposed to be a risk factor for the development of cardiovascular disease. Finally, Beta-2 adrenergic receptor-mediated forearm vasodilator responses to mental stress are blunted in Caucasian subjects at increased risk for hypertension, in African Americans, and in mild hypertension. We postulate that a relationship exists between these variables, even in normotensive healthy individuals. We also believe that signs of subclinical metabolic dysfunction exist in healthy individuals and that they may either contribute to or be affected by BPV. There is also evidence the prematurity at birth and low birth weight are associated with hypertension. Finally, arterial stiffness may also be related to blood pressure variability and the pressor response. Therefore the specific aims of this study are:

  1. To examine the relationship between 24-hour ambulatory BPV and baroreflex sensitivity. By measuring the baroreflex control of heart rate during sequential boluses of nitroprusside and phenylephrine, we hypothesize that baroreflex sensitivity will be inversely related to the degree of 24-hour BPV.
  2. To examine the relationship between 24-hour ambulatory BPV and the pressor response to four sympathoexcitatory maneuvers: head-up tilt testing, mental stress, cold pressor test, and isometric handgrip to fatigue. We hypothesize that greater BPV will predict the pressor response to stress.
  3. To examine the relationship between baroreflex sensitivity and the pressor response/forearm vasodilator response to the three sympathoexcitatory maneuvers. We hypothesize that individuals with higher baroreflex sensitivity will have a lower pressor response and a lower forearm vasodilator response to sympathoexcitatory stress.
  4. To draw a venous blood sample for future screening of genetic polymorphisms of interest, which may include nitric oxide synthase (NOS), alpha-adrenergic and beta-adrenergic receptor polymorphisms. We hypothesize that genetic variation in these key regulatory systems might explain some of the differences in baroreflex sensitivity, BPV, the pressor response and forearm vasodilator response to sympathoexcitation.
  5. To examine the relationship between 24-hour ambulatory BPV and the pressor response to sympathoexcitatory maneuvers and insulin resistance, dyslipidemia, and body fat distribution. We hypothesize that greater BPV will be associated with insulin resistance, dyslipidemia, and increase waist-hip ratio.
  6. To examine the relationship between 24-hour ambulatory BPV and arterial stiffness using measurements of pulse wave velocity. We hypothesize that greater BPV will be associated with increased pulse wave velocity, an index of arterial stiffness.
  7. To examine the relationship between 24-hour ambulatory BPV and the pressor response to sympathoexcitatory maneuvers with birth weight and post-conceptual age at birth. We will ask each subject to provide this data based on their birth certificate and/or knowledge of their medical history.

Study Type

Observational

Enrollment (Actual)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Residents of Southeast Minnesota

Description

Inclusion Criteria:

  • Men age 18-40
  • Non-pregnant women age 18-50

Exclusion Criteria:

  • Any medical conditions affecting the cardiovascular system
  • Any prescribed chronic medications (except contraceptives)
  • Extremes of fitness (not totally sedentary, not highly exercise-trained)
  • BMI greater than 28

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
All subjects
All subject participants
Other: Physiological maneuvers
These healthy subjects undergo physiological testing, which includes aortic augmentation index, pulse wave velocity, orthostatic stress, baroreflex sensitivity (modified Oxford protocol), mental stress, cold pressor test, isometric handgrip, heart rate variability, 24-hour ambulatory blood pressure monitoring.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Blood Pressure Response to Sympathoexcitation
Time Frame: On day of study
On day of study

Secondary Outcome Measures

Outcome Measure
Time Frame
Baroreflex Sensitivity
Time Frame: On day of study
On day of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2006

Primary Completion (Actual)

February 1, 2013

Study Completion (Actual)

February 1, 2013

Study Registration Dates

First Submitted

July 20, 2009

First Submitted That Met QC Criteria

July 20, 2009

First Posted (Estimate)

July 22, 2009

Study Record Updates

Last Update Posted (Estimate)

January 6, 2016

Last Update Submitted That Met QC Criteria

January 5, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05-004352
  • R01HL089331 (U.S. NIH Grant/Contract)
  • NS-32352

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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