Patent Application
20080294021
The invention relates to a system and to a method for the management or control of cardiovascular related diseases, in particular hypertension according to the independent patent claims.
It is widely accepted that hypertension and other cardiovascular diseases is one the major problem in health systems of most countries. Hypertension is currently treated in particular by prescribing medication such as alpha-blockers, beta-blockers, calcium channel-blockers, diuretic, angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. However, such medication is often made on a try and error basis. Consequently, many patients are prescribed with unnecessary medication or suffer from side effects.
According to recommendations of the British Hypertension Society there are suggested some combinations for blood pressure lowering drugs following the so called AB/CD rule (see e.g. Gordon T. McInnes, “Lowering blood pressure for cardiovascular risk reduction”, Journal of Hypertension 2005, 23 (suppl 1): S. 3 to S. 8, with reference to Brown et al., “Better blood pressure control: how to combine drugs”, J Hum Hypertens 2003; 17: 81-86). While such a combination of medication may lead to a better and more focused use of medication, there are still drawbacks in context with such suggestions.
In “2003 European Society of Hypertension—European Society of Cardiology Guidelines for the Management of Arterial Hypertension” (Journal of Hypertension 2003, 21: 1011-1053) there are disclosed a variety of different causes of hypertension and of possible combinations of different anti-hypertensive medication. Furthermore, other treatments such as lifestyle change are disclosed.
Samual J. Mann (“Healing Hypertension, A Revolutionary New Approach”, Hypertension Center of the New York Presbyterian Hospital-Cornell Medical Center) has made a differentiation between different organs as driving factors for hypertension, in particular the brain or the kidneys. According to Mann, it would be logical to select drugs this way on the basis of the driving factor of hypertension. However, neither renin measurement nor any other biochemical test can distinguish brain driven from kidney driven hypertension.
It is thus an object of the present invention to overcome the drawbacks of the prior art, in particular to provide a system and a method for the management or control of cardiovascular related diseases such as hypertension which allows to provide an individual diagnosis and an individual suggestion for treatment of a patient in particular in view of hypertension. In particular, the method and the system according to the invention shall help to reduce or avoid medication errors and limit the number of medication prescribed to a particular individual to the maximum extent possible and to reduce side effects and to improve compliance. In particular the method and the system according to the invention provide a proactive and side effect free complementary and alternative method of treatment to the individual, who are in the pre-hypertension stage or medium or low risk level where the drug treatment is not appropriate but/and life style change can not be implemented in short term.
According to Possidente (“The Role of Home Blood Pressure Monitoring in Hypertension Control”, Judy Possidente Kaufman, Journal of Clinical Hypertension 3 (3): 171-173, 2001) home monitoring supports physicians or other health care professionals in caring for patients with hypertension by providing plenty of data. Kaufman sees one major problem in hypertension management in sub optimal adherence to blood pressure lowering medications. In particular, because a majority of hypertensive patients require more than one medication, it is assumed that complex medication regimes contribute to poor treatment adherence. According to Kaufman, an integrated comprehensive approach of hypertension and its management is often lacking.
These and other objects are solved with a system and a method according to the independent patent claims.
The system and the method according to the invention generally are helpful in context with cardiovascular related diseases. In particular, the invention is directed to hypertension. However, the invention is not limited to hypertension but can be equally applied in context with other cardiovascular related diseases. In particular, diabetes, metabolic syndrome or dyslipidaemia may be managed and related measurement values such as glucose, insulin or cholesterol level might be considered. These diseases and symptoms are in close interrelationship in view of their effect on cardiovascular diseases and hypertension. According to the present invention, one major focus is hypertension. However, other indications or symptoms may be taken into consideration.
The system for the management of hypertension of an individual according to the invention comprises a blood pressure measuring device for measuring the blood pressure of the individual. In addition, the system comprises means for detecting the activity of the autonomic nervous system. Autonomic nervous system activity status may be an indication of the root cause for hypertension as will be shown herein after. According to a first embodiment of the invention, the system may comprise a heart rate variability detection means for determining the heart rate variability of the individual. Preferably, the system then comprises a calculation means for determining the autonomic nervous system activity status based on the heart rate variability. The system may also display heart rate variability information without further calculation. In this case, the system nevertheless has means for determination of the autonomic nervous system activity status.
It is known that the heart rate variability is a tool to assess the autonomic function (see e.g. J. P. Singh et al., “Reduced Heart Rate Variability and New-Onset Hypertension, Insights Into Pathogenesis of Hypertension: The Framingham Heart Study, in Hypertension, 1998; 32:293-297).
Heart rate variability (HRV) is a useful noninvasive tool to assess cardiac autonomic function.
HRV has considerable potential to assess the role of autonomic nervous system fluctuations in normal healthy individuals and in patients with various cardiovascular and noncardiovascular disorders. HRV studies should enhance our understanding of physiological phenomena, the actions of medications, and disease mechanisms. (see “Heart Rate Variability: Standards of Measurement, Physiological Interpretation, and Clinical Use”, Circulation 93 (5): 1043).
Therein, different measurement methods for determining heart rate variability are disclosed.
According to an alternative embodiment of the invention, the activity of the autonomic nervous system is determined on the basis of the composition ratio of granulocytes and lymphocytes in leukocytes. This ratio also may be an indication for the autonomic nervous system activity status based on the findings of Toru Abo in “Immunomodulation by the autonomic nervous system”, Recent Res. Devel. Immunology, 4 (2002), page 559-578.
According to the present invention, there is provided a complete system which at the same time allows to acquire blood pressure data of an individual and autonomic nervous system activity status, e.g. by determining heart rate variability data of the individual. If the blood pressure measuring device indicates that the individual suffers or may suffer from hypertension, the calculation means may determine an activity status of the autonomic nervous system on the basis of the heart rate variability or on the basis of a composition ratio of granulocyte and lymphocyte in leukocytes. In particular, an activity status of the sympathetic nervous system or of the parasympathetic nervous system will be determined.
According to a preferred embodiment of the invention, the system further comprises a display for display of the autonomic nervous system activity status or of a composition ratio of granulocytes and lymphocytes in leukocytes. The display of this status allows a doctor or care person to decide whether hypertension rather may be kidney driven or brain driven. Depending on this assessment, a specific prescription for medication may be made. It is, however, also possible not to directly display the autonomic nervous system activity status but to base further calculations on this status and to display further information as will be shown herein after.
According to a preferred embodiment of the invention, the blood pressure measuring device and the heart rate variability determination means are integrated within the same physical device. Such a device allows for very easy measurements. One single device will allow the user or the care person to gather blood pressure data and heart rate variability data as well as to determine the driving factor for possible hypertension.
According to a first embodiment of the invention, the heart rate variability determination means may be adapted to determine heart rate variability of the basis of pressure pulse measurement. This is particularly simple if such a measurement device is integrated with a blood pressure monitor for automatically measuring the blood pressure. Such blood pressure monitors determine pressure pulse data. No further measuring sensors are thus necessary. It is sufficient to provide the blood pressure measuring device with further calculating arrangements for determining the heart rate variability based on pressure pulse data.
Alternatively, it is, however, also possible to include an ECG measuring unit within the heart rate variability determination means. In this case, the heart rate variability determination means are adapted to determine heart rate variability on the basis of an electrocardiogram of the individual.
The system according to the present invention preferably may comprise a user input interface adapted for entry of information relating to at least one risk factor of the individual to suffer from diseases, in particular from cardiovascular diseases or adapted for entry of influencing or driving factors relating to such a disease. Such a system allows to display information in view of an optimum treatment of the patient on the basis of measurements done by the system and of risk factors or driving factors entered into the system. A device allowing entry of such data is e.g. shown in EP 1 297 783 A1.
In particular, the risk factors may be factors selected from the group of age and sex, total cholesterol level, smoking, family history of cardiovascular disease, diabetes, target organ damage or associated clinical conditions. The driving factor also may include information relating to the level of renin, insulin and lipoid profile or genetic test information. Low renin may indicate that the individual rather suffers from salt sensitive hypertension. Especially in combination with the nervous autonomic system activity status, this allows to make a differentiation between brain and kidney driven hypertensive individuals. Other biochemistry data which are relevant in context with cardiovascular diseases may also be entered.
According to a further preferred embodiment of the invention, the blood pressure measuring device is designed for measurement of blood pressure according to a predetermined or predeterminable clinically validated measurement schedule. Such a device has been disclosed in the co-pending application PCT/EP2005/0502739.
Such a clinically validated blood pressure monitor allows for home blood pressure measurement. In view of costs home blood pressure measurements are preferred. Because of the so called white coat effect, home blood pressure measurements with an appropriate tool also lead to more reliable results.
According to the further preferred aspect of the invention, the system may comprise a decision making means. This decision making means may be coupled or adapted to be coupled to the blood pressure measuring device and to the heart rate variability determination means. The decision making means comprises data processing means for determining a risk level for the patient to suffer from a disease and/or for determining the causes for such a potential disease and/or for determining appropriate measures for prevention or treatment of said patient in view of this disease. Such a decision making means makes the system an integrated complete system for making measurements and for giving treatment of medication suggestions.
Such a data processing means is particularly adapted to make medication suggestions based on the entered and/or acquired data. In particular, medication or treatment suggestions may be made based on the finding of the driving factor of hypertension, in particular whether hypertension is brain driven or kidney driven.
The system may comprise display means for display of at least one of short, medium or long term measures in view of treatment of risk factors or a disease.
The decision making means may be a separate device and may be provided with communication interfaces, e.g. wireless communication for communication with the blood pressure measuring device or the heart rate variability determination means. It is, however, also possible to integrate the decision making device in the same physical device as the blood pressure measuring device or the heart rate variability determination means. A separate decision making device has, however, certain advantages: in particular, it is possible to have one decision making device located at the premises of a care person. Patients may make their home measurements and bring their measuring device to the care person where data are exchanged with the decision making device through the communication interface. It is therefore not necessary for each individual using the system according to the present invention to purchase such decision making device.
According to a further preferred aspect of the invention, the system also may comprise follow-up means. Such follow-up means can be in particular means for following compliance of the patient with a specific medication or treatment schedule. Such means for following compliance are known in the art. In combination with the system according to the invention, such follow-up or compliance means are particularly useful.
The method according to the present invention is used for operation of a system for management of hypertension of an individual. In particular, the method is used for operation of a system as disclosed herein above. In a first step, blood pressure data of the individual are acquired. In a further step, the activity of the autonomic nervous system is determined as a activity status. This may be done on the basis of heart rate variability data of the individual. Based on these heart rate variability data, an autonomic nervous system activity status is determined. Alternatively, the autonomic nervous system activity status may also be determined on a composition ratio between granulocytes and lymphocytes in leukocytes of the individual. In a final step, reasons for hypertension are determined, risk levels are stratified and/or appropriate long, medium or short term measures are selected on the basis of the blood pressure data and the autonomic nervous system activity status.
According to a preferred embodiment of the invention, the autonomic nervous system activity status is displayed on a display.
The heart rate variability may be determined on the basis of pressure pulse information measured by a blood pressure monitor or on the basis of electrocardiographic information measured by an ECG device.
According to a further preferred step, information relating to risk factors or driving factors for hypertension may be acquired.
It is further preferred to measure the blood pressure according to a clinically validated measurement schedule.
According to the method, it is possible to determine specific measures to be taken in view of prevention or treatment of hypertension or associated diseases. Such measures may also be displayed.
While this invention has been shown with respect to driving causes for a treatment of hypertension, a similar system and method can be used for treatment of other diseases, in particular for any kind of metabolic syndrome.
The invention will now be explained in more detail with reference to the embodiments and the accompanying drawings which show:
a to 10g: Flow charts for operation of the devices of
a and 13b: A flow chart for operation of the devices according to
a to 16d: Several graphics in relation to determination of heart rate variability and
In a blood pressure pulse display 34 the number of blood pressure pulses considered for determination of the heart rate variability is displayed.
Based on the ratio HF/LF between high frequency and low frequency percentage, an autonomic nervous system activity status is displayed as a bar graph in an activity status display 31.
The operation of the device of
In a next step, heart rate variability measurements are made. Before starting heart rate variability measurement, a plurality of parameters are set. The cuff pressure P will be set at about 80% of the mean arterial pressure MAP which has been previously determined. The measurement time T will be determined in dependence of the heart rate HR. The duration of the measurement shall be such that approximately 256 pulses will be considered. Before start of the heart rate variability measurement, variables Set Time and PulseCount are set to zero.
In the next step, the valve of the cuff is closed and the cuff, which can be placed on the upper arm or on the wrist is inflated to the pressure P which has been previously set to 80% of the mean arterial pressure MAP. As long as there are less than 256 pulses and the time is below the previously set measurement time T, the pulses are detected and pulse intervals PPN are saved. Each time a pulse interval is saved, the variable PulseCount is increased by 1. If no valid pulse is detected, no pulse time intervals are stored and the variable PulseCount is not increased. Sampling of pulses is continued in this case.
As soon as the measurement time T has been reached and the pulse count variable is above 256, the valve of the cuff is opened such as to release pressure. The heart rate variability sampling is completed.
In a next step, a power spectral analysis of the pulse time difference PPN is made. During this analysis, high frequency percentages and low frequency percentages are determined. Determination of the heart rate variability will be explained in more detail with reference to
The pulse to pulse intervals PPN and the autonomic nervous system results ANS subsequently are stored in a memory such as a flash or a EEPROM. The autonomic nervous system results ANS are displayed as a high frequency and a low frequency percentage in the display 33 as shown in
Contrary to the operation of the system of
The preferred number of sampled pulses is 256. However, to prevent too long measurement times, a measurement time will be also set.
Completion of the heart rate variability sampling and determination of autonomic nervous system data ANS is done in the same manner as explained with reference to
In a risk factor display area 35, there will be an indication whether the specific risk factors mentioned above have been confirmed by the user by applying a confirmation button of the user input interface 32.
The display of the device 1 according to
In a driving factor display 36, it is indicated whether hypertension of the individual rather is kidney driven (see
In addition, the system 1 is provided with a decision making means which, on the basis of the determined data determines measures for treatment of prevention against hypertension and cardiovascular diseases. Such measures are displayed in a display area 41. Typical measures might be “begin drug treatment” as shown in
After completion of these measurements, an average of blood pressure readings and an average of the autonomic nervous system status ANS, in particular of the low frequency rate LF, the high frequency rate HF and the ratio LF/HF is calculated. These results are displayed in a subsequent step.
Based on these readings and on the risk factors, the risk level for the individual is stratified according to guidelines as shown in
Thereafter, in a decision loop, the device starts to determine measures to be taken in view of treatment of the patient in the decision making means as will be explained hereinafter with reference to
The decision device 40 is provided with a communication interface 42 for receiving data from the blood pressure measuring device. In the embodiment according to
An operation interface 38 is provided with buttons for operation of the device. In the lower part of
Heart rate variability is determined on the basis of blood pressure pulses as has been disclosed herein above.
Operation of the devices according to the embodiments of
In a further step, autonomic nervous system data ANS are downloaded from the blood pressure measuring device 10 in accordance with the embodiment of
It is, however, also possible to have a separate blood pressure pulse based heart rate variability determination means integrated within decision making device 40.
The averages of the blood pressure readings and the autonomic nervous system activity status will then be determined and displayed on the autonomic nervous system activity status display 31 (see
In the next step, the user or doctor is asked to enter information relating to the risk factors. Risks for the individual to suffer from cardiovascular diseases are then stratified and displayed as a risk level in the risk level display 37 (see
Appropriate measures for treatment/prevention will then be determined in a decision loop which will be explained with reference to
If the individual is found to suffer from hypertension, in a first step lifestyle modifications such as quit smoking, reduce alcohol and coffee intake, reduce risk factors such as high total cholesterol or obesity will be displayed. In a further step, it is checked whether the individual suffers from diabetes or has insulin resistance or dyslipidaemia. This judgement which may be optional is based on risk factors and biochemistry test data entered into the device as explained with reference to the flow chart in
This judgement is based on criteria as outlined in
If no drug treatment shall be started, in a complementary and alternative medicine mode CAM (see
c shows a complementary alternative medicine determination mode. In a first step, it is judged whether the sympathetic nervous system dominates in the individual. If the autonomic nervous system activity status HF/LF as determined and displayed earlier is above 1/1, it is considered that the asympathetic nervous system dominates. The decision device will prompt for an entry of an appropriate treatment by the doctor. According to an alternative embodiment, it is also possible for a doctor to switch between a complementary and alternative medicine mode and a drug treatment mode by manually changing the operation. If the sympathetic nervous system is found to dominate, the patient is considered to suffer from brain driven hypertension. In a next step, as short and medium term actions, natural supplements are prescribed. Such natural supplements typically may be Gamma aminobutyric acid or other appropriate supplements. As long term actions, relaxation programs such as mediation, yoga, Chi Kong, deep breathing or other measures will be prescribed.
If these measures have been effective, regular exercise and proper diet will be suggested to the individual. If these long term actions are not effective, psychotherapy in view of removal of hidden emotions may be prescribed.
The system according to the invention continues to monitor the user's hypertension until hypertension is found to be sufficiently well controlled. Measurements may be repeated, e.g. on a daily basis.
If the sympathetic nervous system does not dominate, the individual is considered to suffer from kidney driven hypertension.
In a further step, biochemical test results, in particular renin level in the blood volume are assessed. Information relating to renin level has been entered as a decision parameter see
Finally, regular exercise and proper diet is suggested in both cases to the patient.
d shows a drug determination mode. Distinction between brain driven, kidney driven and high or low renin driven hypertension is made in a similar manner as described with reference to
For brain driven hypertension, alpha-, beta- or CC-blockers are prescribed as a short term action. Medium term and long term actions prescribed are identical to the actions as disclosed with reference to
If the patient is found to suffer from kidney driven high renin hypertension, medication such as ACEi, AGTR1 or beta-blockers are prescribed. If the individual is considered to suffer from low renin hypertension, diuretics and CCB are prescribed. Medium and long term actions are the same as explained with reference to
If in the judgement step related to diabetes shown in
Typically, insulin resistance will be deemed to be present if fasting glucose is between 110 and 125 mg/dl. Boradline dyslipidaemia is deemed to be present if TC is between 200 and 239 mg/dl, LDL-c is 130 to 159 mg/dl, TG is 150 to 199 mg/dl and HDL is <40 mg/dl. In a further step, it is checked whether the patient suffers from a metabolic syndrome as defined in the NCEP ATPIII 2002 Guidelines.
A doctor or a user can input biochemistry test results relating to risk factors or related biochemistry test data such as fasting blood glucose, TC, TG, LDL, HDL or other results. According to the above mentioned guidelines, a determination if patients suffer from insulin resistance or dyslipideamia may be made in the decision device. The result of this determination may be displayed in the device.
If the patient is found to suffer from the metabolic syndrome, a complementary alternative medicine treatment determination sequence as shown in
If the answer to the judgement is “no”, the complementary alternative medicine routine as shown in
According to the NCEP ATP III 2002 Guidelines typically, diagnostic criteria for the “metabolic syndrome” may be a waist conference of >102 cm (for male) or >88 cm (for female), fasting glucose >110 mg/dl, HDL-C<40 mg/dl (for male) or <50 mg/dl (for female), TG>=150 mg/dl or an arterial pressure >=130/85 mm HG. Typically, metabolic syndrome will be considered to be present if there are more than three risk factors as mentioned above.
f shows typical short and medium term actions and long term actions for treating a patient suffering from insulin resistance or dyslipidaemia with complementary alternative medicine. Typically, as a short and medium term action, natural supplements like Poliocosanol (for dyslipidaemia) or Chromium (for insulin resistance) are prescribed. As a long term action, typically life style change actions will be proposed.
g shows a routine relating to a drug treatment in view of high LDL-C with CHD or high LDL with multiple risk factors. This routine will be applied if LDL-C is above 130 mg/dl with CHD or if LDL is above 160 mg/dl with multiple of the risk factors TG>200 mg/dl, TC>240 mg/dl or HDL-C<40 mg/dl.
As a short term action, medication such as stains, cholestyramine, niaspan, clofribrate or the like are prescribed. As a medium term action, natural supplements such as poliocosanol may be prescribed. As a long term action, appropriate life style changes will be suggested.
Prescriptions determined in accordance with the rules of
A flow chart of operation of the devices of
a shows the heart rate variability power spectrum as e.g. shown in “heart rate variability, standards of measurement, physiological interpretation, and clinical use, circulation 1996/93: 1043-1065”. The HRV power spectrum can be divided into four components based on the frequency range. The ultra low frequency (ULF) is a frequency having a power density number below 0.003 Hz. The very low frequency range (VLF) has a power density number between 0.003 and 0.04 Hz. The low frequency (LF) has a power density number between 0.04 and 0.15 Hz. Such frequency range is mainly generated by sympathetic nervous activity. The high frequency range (HF) corresponds to power density numbers between 0.15 and 0.4 Hz. High frequency is derived from the vagal activity. This activity is modulated by respiration.
Since LF represents mainly sympathetic activity and HF represents vagal activity, the ratio HF/LF is a good indicator of the autonomic nervous balance.
In a further step, abnormal pulses which are deemed to be based on artefacts will be rejected. Methods for artefact determination are known to those skilled in the art.
In a further step as shown in
In a further step power spectral density of HF and LF (see
Such a heart rate variability power spectrum is shown with reference to
HVR thus is basically determined in accordance with the teaching of “heart rate variability, standards of measurement, physiological interpretation, and clinical use, circulation 1996/93: 1043-1065”, which is incorporated by reference into the present application.
The left and the right hand side branch of
Hypertension as a result of these pathways has its roots mainly in psycho stress, hidden stress or physical stress. Such hypertension is rather brain driven. A wrong diet and obesity may furthermore influence these pathways.
The middle branch of
In
If PG is above 54% and below 60% and LY is between 35% and 41% it is deemed that the autonomic nervous system is moderate and that the individual may suffer from kidney driven hypertension.
| Number | Date | Country | Kind |
|---|---|---|---|
| 05110708.4 | Nov 2005 | EP | regional |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP2006/066760 | 9/26/2006 | WO | 00 | 6/6/2008 |
