Hypertension and Injury

Hypertension, Endothelial Microparticle Release, and Endothelial Function: Role of Pressure, Shear, and Stretch

Membrane microparticles are submicron fragments of membrane vesicles shed from various cell types. Circulating endothelial microparticles have been proposed as markers of endothelial injury. However, which mechanical forces contribute to their release is not clear.

Study Overview

• Status: Completed
• Conditions: Arterial Hypertension; CAD

Detailed Description

In a first series subjects (50% hypertensives) with and without arterial hypertension and no Coronary Artery Disease (CAD) (n=50) will be recruited. MP subpopulations will be discriminated by flow cytometry according to the expression of established surface antigens including CD31+/41-, CD144+, and CD62e+. Besides office and ambulatory 24h blood pressure measurements, pulse wave analysis will be performed to determine central blood pressure, augmentation index (AIX), and pulse wave velocity. Endothelial function (Flow-mediated dilation, FMD), arterial pulsatile stretch (fractional diameter changes, FDC), and wall-shear-stress (WSS) will be measured in the same segment of the brachial artery (BA) by ultrasound. In a second series, the investigators will take measurements in subjects with hypertensive crises (SBP>180 mmHg) (n=20) before and after 4h and normalization of arterial BP by urapidil. In a third series, the investigators will take measurement in subjects with stable CAD (n=10) before and after transfemoral coronary diagnostic angiography.

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Duesseldorf, NRW, Germany, 40225
      • Division of Cardiology, Pulmonology and Vascular Medicine Duesseldorf,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Patients with or without arterial hypertension

Description

Inclusion Criteria:

• male subjects with or without arterial hypertension, hypertensive crises, stable CAD
• written informed consent

Exclusion Criteria:

• subjects with manifest peripheral artery, or cerebrovascular disease, acute inflammation (CRP>0.6 mg/dl), malignancies, arrhythmias

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
male subjects with arterial hypertension; Measurements will be taken at baseline.
male subjects without arterial hypertension and no CAD; Measurements will be taken at baseline.
male subjects with hypertensive crises; Measurements will be taken before and after 4 hours and normalization of arterial blood pressure by urapidil.
male subjects with stable CAD; Measurements will be taken before and after transfemoral coronary diagnostic angiography.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
endothelial function	endothelial function measured by flow-mediated dilation (FMD) for Subgroup 1 and 2	Baseline
Changes in endothelial function	endothelial function measured by flow-mediated dilation (FMD) for Subgroup 3	Baseline and after 4 hours
Changes in endothelial function	endothelial function measured by flow-mediated dilation (FMD) for Subgroup 4 before and after transfemoral coronary diagnostic angiography	Baseline and 4 hours after procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microparticle	Microparticles (CD31+/41-, CD144+, and CD62e+) will be discriminated by flow cytometry for Subgroup 1 and 2	Baseline
Changes in Microparticle	Microparticles (CD31+/41-, CD144+, and CD62e+) will be discriminated by flow cytometry for Subgroup 3	Baseline and after 4 hours
Changes Microparticle	Microparticles (CD31+/41-, CD144+, and CD62e+) will be discriminated by flow cytometry for Subgroup 4 before and after transfemoral coronary diagnostic angiography	Baseline and 4 hours after procedure
Wall Shear Stress	measured by ultrasound in brachial artery for Subgroup 1 and 2	Baseline
Changes in Wall Shear Stress	measured by ultrasound in brachial artery for Subgroup 3	Baseline and 4 hours
Changes in Wall Shear Stress	measured by ultrasound in brachial artery for Subgroup 4 before and after transfemoral coronary diagnostic angiography	Baseline and 4 hours after procedure
changes in fractional diameter (FDC)	measured by ultrasound in brachial artery for Subgroup 1 and 2	Baseline
changes in fractional diameter (FDC)	measured by ultrasound in brachial artery for Subgroup 3	Baseline and after 4 hours
Changes in fractional diameter (FDC)	measured by ultrasound in brachial artery for Subgroup 4 before and after transfemoral coronary diagnostic angiography	Baseline and 4 hours after procedure
pulse wave velocity	measured for Subgroup 1 and 2	Baseline
Changes in pulse wave velocity	measured for Subgroup 3	Baseline and after 4 hours
Changes in pulse wave velocity	measured for Subgroup 4 before and after transfemoral coronary diagnostic angiography	Baseline and 4 hours after procedure
augmentation index	measured for Subgroup 1 and 2	baseline
Changes in augmentation index	measured for Subgroup 3	Baseline and after 4 hours
Changes in augmentation index	measured for Subgroup 4 before and after transfemoral coronary diagnostic angiography	Baseline and 4 hours after procedure

Collaborators and Investigators

• Sponsor: Klinik für Kardiologie, Pneumologie und Angiologie
• Investigators: Principal Investigator: Roberto Sansone, MD, Division of Cardiology, Pulmonary Disease and Vascular Medicine

Publications and helpful links

General Publications

• Sansone R, Baaken M, Horn P, Schuler D, Westenfeld R, Amabile N, Kelm M, Heiss C. Release of endothelial microparticles in patients with arterial hypertension, hypertensive emergencies and catheter-related injury. Atherosclerosis. 2018 Jun;273:67-74. doi: 10.1016/j.atherosclerosis.2018.04.012. Epub 2018 Apr 12.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (ACTUAL): November 1, 2017
• Study Completion (ACTUAL): November 1, 2017

Study Registration Dates

• First Submitted: May 11, 2016
• First Submitted That Met QC Criteria: June 9, 2016
• First Posted (ESTIMATE): June 10, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 9, 2017
• Last Update Submitted That Met QC Criteria: November 8, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: arterial hypertension; endothelial function; microparticle
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: Hypertension and Injury; 12-011 (OTHER: CTSU)