# US 10,945,612 B2 · Assessing endothelial function using a blood pressure cuff

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- Number: US 10,945,612 B2
- Document ID: US10945612B2
- Status: Granted
- Kind: B2
- Application number: 14/678,642
- Filed: 2015-04-03
- Published: 2015-12-17
- Granted: 2021-03-16
- Earliest claimed: 2014-04-03
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Jonathan S. Maltz
- Web page: https://patentgrep.com/patent/US10945612B2

## CPC

- A61B 5/02007: {Evaluating blood vessel condition, e.g. elasticity, compliance}
- A61B 5/02141: {Details of apparatus construction, e.g. pump units or housings therefor, cuff pressurising systems, arrangements of fluid conduits or circuits (A61B5/02233, A61B5/0235 take precedence)}
- A61B 5/0225: the pressure being controlled by electric signals, e.g. derived from Korotkoff sounds
- A61B 5/107: Measuring physical dimensions, e.g. size of the entire body or parts thereof
- A61B 5/6824: {Arm or wrist}
- A61B 5/6828: {Leg}
- A61B 5/7285: {for synchronizing or triggering a physiological measurement or image acquisition with a physiological event or waveform, e.g. an ECG signal}
- A61B 17/1355: {Automated control means therefor}
- A61B 5/7246: {using correlation, e.g. template matching or determination of similarity}
- A61B 17/135: inflatable
- A61B 2017/00123: {and automatic shutdown}
- A61B 2017/00199: {with a console, e.g. a control panel with a display}
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)

## Abstract

Methods and apparatus are provided for assessing endothelial function in a mammal. In certain embodiments the methods involve applying to the artery a substantially constant external pressure that causes the tension in the arterial wall to be reduced, where the pressure is provided via a cuff adjacent to and/or around a region of the mammal's body; determining, over the course of one or more cardiac cycles, changes in pressure in the cuff resulting from cardiac activity of the mammal to establish a baseline value for a parameter related to endothelial function in the mammal; applying a stimulus to the mammal; determining, over the course of one or more cardiac cycles, changes in pressure in the cuff resulting from cardiac activity of the mammal to establish a stimulus-effected value for a parameter related to endothelial function in the mammal; wherein the baseline value is determined from measurements made when the mammal is not substantially effected by the stimulus; and wherein differences in the baseline value and the stimulus-effected value provide a measure of endothelial function in the mammal.

## Claims

### Claim 1

A method of assessing endothelial function in a mammal, said method comprising:
a) applying to an artery an external pressure that causes tension in a wall of said artery to decrease, where said pressure is provided via a cuff adjacent to and/or around a region of the mammal's body, and said external pressure is below the average diastolic pressure for said mammal, and provides a measurement pressure set point;
b) determining, over a course of one or more cardiac cycles, changes in pressure in said cuff resulting from cardiac activity of said mammal, or an artificially induced arterial pulse to determine a baseline value for a parameter related to endothelial function in said mammal;
c) applying a stimulus to said mammal; and
d) determining, over a course of one or more cardiac cycles, changes in pressure in said cuff resulting from cardiac activity of said mammal, or an artificially induced arterial pulse, to determine a stimulus-affected value for a parameter related to endothelial function in said mammal;
wherein said determining of steps (b) and (d) comprises:
i) during a first time interval (T1) maintaining the pressure in said cuff within a first pressure range (ΔP1) around said measurement pressure set point, where said pressure set point is below the average diastolic pressure for said mammal, during a period where tissue compression under the cuff leads to a drop in the mean pressure in said cuff; and
ii) once the mean pressure in said cuff stabilizes, during a second time interval (T2) maintaining the pressure in said cuff within a second pressure range (ΔP2) around said measurement pressure set point, where (ΔP2) is greater than (ΔP1), and determining over a course of one or more cardiac cycles said changes in pressure in said cuff; and
wherein said baseline value is determined from measurements made when said mammal is not substantially affected by said stimulus and differences in said baseline value and said stimulus-affected value provide a measure of endothelial function in said mammal.

### Claim 2 (depends on 1)

The method of claim 1, wherein during said first time interval pressure is applied to said cuff using a control feedback system to adjust a pump or other pressure source and/or a proportional release valve to maintain said desired pressure set point.

### Claim 3 (depends on 1)

The method of claim 1, wherein
during said second time interval adjustment of said pressure is stopped; or
during said second time interval adjustment of said pressure is periodically adjusted using an on-off control system.

### Claim 4 (depends on 1)

The method of claim 1, wherein during said second time interval adjustment of said pressure is periodically adjusted using an on-off control system.

### Claim 5 (depends on 1)

The method of claim 1, wherein said first pressure range (ΔP1) ranges from 1 mm Hg to 6 mm Hg and said second pressure range (ΔP2) ranges from 5 mm Hg up to 15 mm Hg.

### Claim 6 (depends on 1)

The method of claim 1, wherein the duration of said first time interval and/or said second time interval ranges from 1 sec up to 30 min.

### Claim 7 (depends on 1)

The method of claim 1, wherein said determining a baseline value comprises establishing a baseline value for an artificially induced arterial pulse.

### Claim 8 (depends on 7)

The method of claim 7, wherein said determining a stimulus-affected value comprises determining a stimulus-affected value for an artificially induced arterial pulse.

### Claim 9 (depends on 1)

The method of claim 1, wherein said determining a baseline value comprises establishing a baseline value for changes in pressure resulting from cardiac activity of said mammal.

### Claim 10 (depends on 9)

The method of claim 9, wherein said determining a stimulus-affected value comprises establishing a stimulus-affected value for changes in pressure resulting from cardiac activity of said mammal.

### Claim 11 (depends on 1)

The method of claim 1, wherein said external pressure is applied by a pressurized cuff disposed around an arm or leg of said mammal.

### Claim 12 (depends on 1)

The method of claim 1, wherein said external pressure is maintained by a system that monitors and adjusts the pressure in said cuff so that the changes in pressure resulting from said cardiac activity are attenuated by said system by less than 10%.

### Claim 13 (depends on 1)

The method of claim 1, wherein said external pressure is maintained by setting the pressure in said cuff to a value and not altering external pressure applied to said cuff during the measurements of pressure variations due to said cardiac activity.

### Claim 14 (depends on 1)

The method of claim 1, wherein said determining, over the course of one or more cardiac cycles, changes in pressure in said cuff resulting from cardiac activity of said mammal in steps (b) and (d) comprises determining the pressure in said cuff as a function of time.

### Claim 15 (depends on 14)

The method of claim 14, wherein
said determining of step (b) and said determining of step (d) comprises integrating the value of a pressure change over time (calculating the area under a pressure/time curve) for one or for a plurality of cardiac cycles to determine an integrated pressure value; or
said determining of step (b) and said determining of step (d) comprises determining the maximum, or a certain percentile rank of the derivative of the pressure versus time wave form on the rising edge of a pressure pulse for one or for a plurality of cardiac cycles to determine a compliance value.

### Claim 16 (depends on 15)

The method of claim 15, wherein
said integrated pressure value and/or said compliance value is averaged over a plurality of cardiac cycles; or
said integrated pressure value and/or said compliance value is determined for a single cardiac cycle.

### Claim 17 (depends on 15)

The method of claim 15, wherein said integrated pressure value and/or said compliance value is determined for a single cardiac cycle; and
said single cardiac cycle is a cardiac cycle selected for the maximum change in said value in a plurality of cardiac cycles; or
said single cardiac cycle is a cardiac cycle selected for the maximum change in said value between a baseline measurement and a stimulus-affected measurement.

### Claim 18 (depends on 1)

The method of claim 1, wherein applying the stimulus comprises
restricting flow of blood to the limb by occlusion of a blood vessel; or
administering a drug to the patient; or
applying acoustic/mechanical tissue vibration.

### Claim 19

An apparatus for assessment of endothelial function in a mammal comprising:
a measurement cuff adapted to apply an external pressure to an artery in said mammal, where the external pressure is below the average diastolic pressure for said mammal and provides a measurement pressure set point;
a pressure sensor adapted to detect and quantify over one or more cardiac cycles, pressure pulses in said cuff while said pressure is applied;
a controller that is adapted to control a pressure source and a valve to control the pressure in said cuff, wherein said controller is configured to:
i) during a first time interval (T1) maintain the pressure in said cuff within a first pressure range (ΔP1) around said measurement pressure set point, where said pressure set point is below the average diastolic pressure for said mammal, during a period where tissue compression under the cuff leads to a drop in the mean pressure in said cuff; and
ii) once the mean pressure in said cuff stabilizes, during a second time interval (T2) maintain pressure in said cuff within a second pressure range (ΔP2), where (ΔP2) around said measurement pressure set point is greater than (ΔP1), and determine over a course of one or more cardiac cycles said changes in pressure in said cuff; and
a processor adapted to analyze, and/or store, and/or compare values determined from said pressure pulses in at least two measurement rounds.