The Role of the Immune and Inflammatory Systems in Hypertension

A Study of the Roles of the Immune and Inflammatory Systems in Hypertension

To define the cytokine and cellular immune signature of primary hypertension. Cross sectional clinical/laboratory study.

Study Overview

• Status: Recruiting
• Conditions: Vascular Diseases; Inflammation; Hypertension
• Intervention / Treatment: Other: None involved

Detailed Description

Experimental data show the presence of immune and inflammatory systems dysregulation in hypertension. Understanding of the inflammatory and immune nature of hypertension is currently based on studies in rodent models of hypertension, but is supported by human epidemiological and genome wide association studies (GWAS) studies. It is now essential to identify key checkpoints and inflammatory mechanism(s) involved in human hypertension in comprehensive and sufficiently powered studies, which will then be able to guide subsequent in-depth hypothesis-driven mechanistic studies. This approach may provide the basis for future randomized clinical trials (RCTs).

To define the relationships and predictive value of the immune signature of hypertension and clinical phenotypes of hypertension :

• Predictive value of immune signature for blood pressure parameters measured by ambulatory blood pressure measurements (ABPM)
• Predictive value of immune signature for endothelial function assessed by Endo-PAT2000 and flow mediated dilatation (FMD) both complementary non-invasive techniques.
• Predictive value of immune signature for vascular stiffness and central pressure assessed by SphygmoCor
• Predictive value of immune signature for renal function parameters
• Predictive value of immune signature for cognitive function. To define genetic determinants of immune signature of hypertension.

• Study Type: Observational
• Enrollment (Anticipated): 160

Contacts and Locations

• Study Contact: Name: Eleanor Murray, MBChB; Phone Number: 0141 232 7600; Email: cams-ins-inflammatension@glasgow.ac.uk
• Study Contact Backup: Name: Tomasz Guzik, Prof; Email: tomasz.guzik@glasgow.ac.uk

Study Locations

• United Kingdom
  • City Of Glasgow
    • Glasgow, City Of Glasgow, United Kingdom, G51 4LB
      • Recruiting
      • Clinical Research Facility
      • Contact: tomasz guzik; Phone Number: 0141 3307590; Email: cams-ins-inflammatension@glasgow.ac.uk
      • Contact: Joanne Flynn; Phone Number: 0141 232 7600; Email: joanne.flynn@ggc.scot.nhs.uk
      • Principal Investigator: eleanor c murray

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Otherwise fit and healthy individuals with hypertension who are treatment naive.

Description

Inclusion Criteria:

• Age between 18-55 years
• Cases: Office blood pressure ≥140 and ≥90
• Controls: Office blood pressure <140 and <90 and age, sex and BMI matching to cases

Exclusion Criteria:

• Age >55 years old;
• Secondary hypertension (including e.g. adrenal tumours, pheochromocytoma, renal artery stenosis; thyroid disease)
• Acute inflammatory disorders incl. flu, rhinitis, sinusitis etc. within 3 weeks;
• hospitalization within the past 3 months;
• Life expectancy of < 3 years;
• History of alcohol/substance abuse
• Inflammatory conditions e.g. Allergic disorders; chronic infections, COPD, tuberculosis; hepatitis B or C; pneumonitis, bronchiectasis; pericardial or pleural effusion, ascites; liver disease;
• Chronic inflammatory/autoimmune conditions such (e.g. SLE, rheumatoid arthritis, ulcerative colitis/Crohn's disease; non-basal cell malignancy or myelo- or lymphoproliferative disease within the past 5 years; known HIV+; Immunizations (3 months); pulmonary hypertension;
• Pregnancy, nursing;
• History of symptomatic coronary artery disease (events) or heart failure;
• BMI>40,
• diabetes/glucose intolerance (fasting glucose, HbA1; testing, glucose challenge where indicated);
• Known albuminuria/microalbuminuria;
• GFR<60mL/min/1.73m2.
• Any chronic concurrent treatment: Use of systemic or local steroids/immunosuppressive agents (within 6 months) of the inclusion; Current (within past 3 months) use of anti-hypertensive medication;
• Major depressive illness or other psychiatric conditions.
• Participants who decline participation in the study or who are unable to provide informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group; 80 with hypertension, defined on office BP readings and confirmed with ambulatory blood pressure monitoring. Clinical and laboratory assessment. NO intervention.	Other: None involved; NO intervention
Control; 80 WITHOUT hypertension, defined on office BP readings and confirmed with ambulatory blood pressure monitoring. Clinical and laboratory assessment. NO intervention.	Other: None involved; NO intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cellular immune signature of primary hypertension: flow cytometry quantification of peripheral blood monocyte subtypes	measuring expression of B cells markers, T cell markers, and DC cell markers	rolling analysis until total number recruited or end of study period (June 2021)
demographics: blood pressure	systolic and diastolic; office and ambulatory; in mmHG	rolling analysis until total number recruited or end of study period (June 2021)
demographics: BMI	in kg/m^2; calculated from height in meters and weight in kg	rolling analysis until total number recruited or end of study period (June 2021)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endo-PAT2000 "hyperaemia index"	As a measure of endothelial function: measuring Peripheral Arterial Tone (PAT) signal changes to a reactive hyperemia challenge. The PAT signal is a measure of the digital pulsatile volume. The expected response is of a post occlusion increase of the PAT signal amplitude. PAT score is provided automatically by the system's software and is basically the ratio between the post- to pre- occlusion average signal size, corrected for systemic changes and baseline level. changes	until total number recruited or end of study period (June 2021)
flow mediated dilatation (FMD) (percent)	as a measure of endothelial function	until total number recruited or end of study period (June 2021)
carotid intimal media thickness (mm)	measure of vascular stiffness and central pressure	until total number recruited or end of study period (June 2021)
assessed by SphygmoCor (meters/second)	measure of vascular stiffness and central pressure	until total number recruited or end of study period (June 2021)
serum Creatinine (mMol/L)	measure of renal function	until total number recruited or end of study period (June 2021)
"International Physical Activity Questionnaire" (score)	Questionnaire measures of physical activity. From hours of sedentary time, mild/moderate/vigorous activity over a week, it then calculates METs/week.	until end of study period (June 2021)
Interheart Diet Questionnaire score	Questionnaire measures of health and activity. Based on known risk factors ie smoking diabetes, family history, dietary factors. Used as a validated measure of cardiovascular risk; score from 0 (minimal risk) to 48 (high risk)	until end of study period (June 2021)

Collaborators and Investigators

• Sponsor: University of Glasgow
• Collaborators: European Research Council

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2019
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: April 30, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (Actual): July 11, 2019

Study Record Updates

• Last Update Posted (Actual): May 14, 2021
• Last Update Submitted That Met QC Criteria: May 12, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: hypertension; endothelial dysfunction; blood pressure; inflammation; immune dysfunction
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Hypertension; Vascular Diseases; Inflammation
• Other Study ID Numbers: 300798-01

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