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Archive for the ‘BPro (by HealthStats): A Cardio Pulse Wave Analyzer’ Category

Device ‘could revolutionise blood pressure monitoring’

Posted by admin On February - 21 - 2011

(This article appeared originally 2-20-11 at this link http://www.bbc.co.uk/news/health-12518633)

 

A device which can be worn like a watch could revolutionise the way blood pressure is monitored in the next few years, scientists say.

Researchers at the University of Leicester and in Singapore have developed a device to measure pressure in the largest artery in the body.

Evidence shows it gives a much more accurate reading than the arm cuff.

The technology is funded by the Department of Health and backed by Health Secretary Andrew Lansley.

It works by a sensor in the watch recording the pulse wave of the artery, which is then fed into a computer together with a traditional blood pressure reading from a cuff.

“This is a great example of how research breakthroughs and innovation can make a real difference to patients’ lives” Quote Andrew Lansley Health Secretary

Scientists are then able to read the pressure close to the heart, from the aorta.

Professor Bryan Williams, from the University of Leicester’s department of cardiovascular sciences at Glenfield Hospital, said: “The aorta is millimetres away from the heart and close to the brain and we have always known that pressure here is a bit lower than in the arm.

“Unless we measure the pressure in the aorta we are not getting an appreciation of the risks or benefits of treatment.”

He said the device would “change the way blood pressure has been monitored for more than a century” and he expected the technology to be used in specialist centres soon, before being “used much more widely” within five years.

“The beauty of all of this is that it is difficult to argue against the proposition that the pressure near to your heart and brain is likely to be more relevant to your risk of stroke and heart disease than the pressure in your arm,” he said.

But it was important to ensure the new device was as small as possible to encourage clinicians and patients to use it, he added.

The research work was funded by the Department of Health’s National Institute for Health Research (NIHR).

The NIHR invested £3.4m, with a further £2.2m of funding coming from the Department of Health, to establish a Biomedical Research Unit at Glenfield Hospital in Leicester.

The university collaborated with the Singapore-based medical device company HealthSTATS International.

Dr Choon Meng Ting, chairman of HealthSTATS, said: “This study has resulted in a very significant translational impact worldwide as it will empower doctors and their patients to monitor their central aortic systolic pressure easily, even in their homes and modify the course of treatment for blood pressure-related ailments.”

Mr Lansley said the device was “a great example of how research breakthroughs and innovation can make a real difference to patients’ lives”.

Judy O’Sullivan, senior cardiac nurse at the British Heart Foundation, said previous research had shown that measuring pressure close to the heart was a better indicator of the effectiveness of treatment for high blood pressure than the standard method.

“However, further research is needed before we can be certain of its superiority in the doctor’s surgery,” she said.

Dr. Joe talks about the BPro (by HealthStats), its accuracy, output readings and blood pressure.

Too many patients get invasive heart tests

Posted by admin On March - 17 - 2010

(Taken from article on MSNBC.com. Original article with graphics found by clicking HERE.)

Study suggests excess angiograms, which carry stroke, heart attack risk

 
NEW YORK – A troublingly high number of U.S. patients who are given angiograms to check for heart disease turn out not to have a significant problem, according to the latest study to suggest Americans get an excess of medical tests.

The researchers said the findings suggest doctors must do better in determining which patients should be subjected to the cost and risks of an angiogram. The test carries a small but real risk — less than 1 percent — of causing a stroke or heart attack, and also entails radiation exposure.

“We can do better. There is no doubt in my mind,” said Dr. Ralph Brindis of the University of California, San Francisco , one of the study’s authors.

 

Every year in the United States, more than a million people get an angiogram, in which a thin tube is inserted in the arm or groin and threaded up to the heart to check for blocked arteries that could lead to a heart attack. Dye is injected through the tube to make blockages show up on X-rays.

‘We fear doing too little’
Angiograms are often given to patients who might be having a heart attack or have symptoms that suggest a serious blockage. They are also sometimes done on people who may have some less clear-cut symptoms, like shortness of breath, or no symptoms but some risky traits like high cholesterol and an abnormal result on another heart test. This group accounts for about 20 to 30 percent of angiogram cases.

In the study, nearly two-thirds of the patients in this second group were found to have no serious blockages.

The researchers could not establish why so few proved to have heart disease. But Dr. Harlan Krumholz, a Yale cardiologist and health-outcomes researcher unconnected to the study, said he thinks the problem arises because doctors are afraid of missing something, and also getting sued.

“We fear doing too little,” he said. “I think that we developed a culture where people feel that doing more and knowing more is always the proper course. What that does is sometimes lead us to overuse.”

Researchers said more study is needed to sort out how to better select patients for an angiogram. For now, experts suggest patients in the category studied by the researchers question their doctors about the need for the test and the risks and alternatives.

Who really needs the exam?
To decide whether someone needs an angiogram, a doctor assesses a patient’s medical status and symptoms, and usually tries a noninvasive test, such as an ultrasound of the heart or having the patient run on a treadmill. It is this gatekeeper process that needs improvement, researchers suggested in Thursday’s issue of the New England Journal of Medicine.

They sifted through records of nearly 2 million angiograms performed at 663 U.S. hospitals between 2004 and April 2008. The data came from a registry kept by the American College of Cardiology, which sponsored the study.

The researchers focused on about 400,000 patients who raised doctors’ suspicions but had no known heart disease and weren’t getting emergency heart treatment.

In those people, the test revealed no significant artery blockages 62 percent of the time. That doesn’t mean all those tests were unnecessary, but the rate is high enough to suggest doctors could do a better job of choosing who really needs the exam, researchers said.

The researchers suggested doctors should be less willing to order an angiogram for symptom-free patients, a group that made up 30 percent of the study sample.

Beyond that, further study might help doctors better gauge heart disease risk from a patient’s symptoms and characteristics like age and history of other diseases, said lead author Dr. Manesh Patel of Duke University .

Doctors could also use more research to help them choose the right noninvasive test, which might reduce the need for angiograms, he said.

Choices now include the treadmill test, injecting a radioactive solution to trace blood flow within the heart, doing an ultrasound to watch the walls of the heart moving, and doing a specialized CT scan that has recently shown promise.

 “We still haven’t figured out, in all honesty, the best way of applying these technologies,” Brindis said.

In fact, one of the study’s co-authors — Dr. Pamela Douglas of Duke — just received a $32.5 million federal grant, the largest ever for heart imaging, to compare various heart imaging tests and see which ones do the most to prevent heart attacks, deaths and hospitalization.

Experts praised Patel’s study.

Some previous reports have found similar results, but the new study is so huge “we can now feel comfortable these aren’t isolated findings, this is for real,” said Dr. Michael Lauer, director of the division of cardiovascular sciences at the National Heart, Lung and Blood Institute.

Taken from MSNBC.com at http://www.msnbc.msn.com/id/35802585/ns/health-heart_health/

(You may want to bookmark this page for easy future reference)

BPro (by HealthStats): A Cardio Pulse Wave Analyzer – science and research

Below are a number of scientific research articles on Cardio Pulse Wave analysis technology. Although it is only a sample of the vast amount of research, it will give you some a good idea of what research is available.

Pulse wave analysis: from the basic sciences to clinical applications

Is there any additional prognostic value of central blood pressure wave forms beyond peripheral blood pressure?

Pulse wave analysis and arterial stiffness.

Noninvasive measurements of central arterial pressure and distensibility by arterial applanation tonometry with a generalized transfer function: implications for nursing.

Arterial stiffness and stroke in hypertension: therapeutic implications for stroke prevention.

Antihypertensive therapy and wave reflections

Analyzing the radial pulse waveform: narrowing the gap between blood pressure and outcomes.

Assessment of outcomes other than systolic and diastolic blood pressure: pulse pressure, arterial stiffness and heart rate.

Systolic blood pressure, pulse pressure and arterial stiffness as cardiovascular risk factors.

Central arterial pressure and arterial pressure pulse: new views entering the second century after Korotkov.

Pulse wave analysis and pulse wave velocity: a review of blood pressure interpretation 100 years after Korotkov.

Mechanical principles. Arterial stiffness and wave reflection.

Arterial pressure waveforms in hypertension.

Pulse wave analysis.

Aortic pulse wave velocity: an independent marker of cardiovascular risk.

Arterial stiffness and cardiovascular outcome.

The indirect assessment of arterial compliance in hypertension patients by tonometric sphygmography

Measurement of pulse wave “augmentation index (AI) “and its clinical application

Arterial stiffness and wave reflection in hypertension: pathophysiologic and therapeutic implications.

Pulse wave analysis in the assessment of patients with left ventricular assist device.

Large-artery stiffness, hypertension and cardiovascular risk in older patients.

Effect of antihypertensive agents on arterial stiffness as evaluated by pulse wave velocity: clinical implications

Mechanisms, pathophysiology, and therapy of arterial stiffness.

Arterial elasticity in cardiovascular disease: focus on hypertension, metabolic syndrome and diabetes.

Pulse Wave Velocity Is an Independent Predictor of the Longitudinal Increase in Systolic Blood Pressure and of Incident Hypertension in the Baltimore Longitudinal Study of Aging

Noninvasive assessment of arterial stiffness and risk of atherosclerotic events.

Clinical value of the study of stiffness of arterial wall. Part I

Arterial hemodynamics and pulse wave propagation

Arterial compliance (stiffness) as a marker of subclinical atherosclerosis

Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease.

Influence of arterial pulse and reflected waves on blood pressure and cardiac function.

Clinical measurement of arterial stiffness obtained from noninvasive pressure waveforms.

Effects of arterial stiffness, pulse wave velocity, and wave reflections on the central aortic pressure waveform.

(You might want to bookmark this page so it is easy for your to find in the future.)

BPro (by HealthStats): A Cardio Pulse Wave Analyzer – medical device information

When you go to the following link below it will take you to the governments FDA site that has the document showing the registration of the BPro (which is the BPro and A-Pulse software (by HealthStats) as found in this document): A Cardio Pulse Wave Analyzer  as a class II medical device. Please click on the link below to find this document:

http://www.accessdata.fda.gov/cdrh_docs/pdf7/K072593.pdf

Pulsology Rediscovered (Cardio Pulse Wave)

Posted by admin On March - 12 - 2010

Pulsology Rediscovered

Commentary on the Conduit Artery Function Evaluation (CAFE) Study

(Full original article with notations, references and links found here: http://www.circ.ahajournals.org/cgi/content/full/113/9/1162)

Suzanne Oparil, MD; Joseph L. Izzo, Jr, MD

From the Vascular Biology and Hypertension Program (S.O.), Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, and Erie County Medical Center and the Division of Clinical Pharmacology (J.L.I.), Department of Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY.

Correspondence to Suzanne Oparil, MD, Vascular Biology and Hypertension Program, University of Alabama at Birmingham, 703 19th St S, ZRB 1034, Birmingham, AL 35294-0007.

Nearly everything that modern practicing clinicians know about hypertension and its treatment is based on simple noninvasive measurement of brachial artery blood pressure. As the study by Williams and colleagues1 illustrates, however, additional knowledge of pulse-wave characteristics may be important in the future to fully assess optimal cardiovascular drug therapy.

The study of pulse-wave characteristics is far older than the study of absolute pressure values, dating back thousands of years to the Chinese masters who used their fingertips and their powers of observation to associate “hardening of the pulse” with adverse outcomes in people who ingested too much salt. These qualitative observations were less well developed in Western medicine, but as early as the 1870s, the sphygmocardiogram was developed as a reproduction of a peripheral pulse wave on a rotating drum via a tonometer attached to a levered stylus.1a Morrell and other early investigators were clearly able to differentiate the effects of nitrovasodilators from digitalis using this early equipment, but interpretations remained largely qualitative. Within a few decades, the development of sphygmomanometry by Korotkovand Riva-Rocci allowed quantitation of brachial cuff blood pressures, and the more descriptive methods largely disappeared.

Article p 1213

Indeed, brachial cuff blood pressure has become an enduring clinical variable. Actuarial data from the life insurance industry and subsequent prospective observational data have clearly shown that hypertension, or elevated cuff blood pressure, is closely related to many forms of cardiovascular disease.2–4 Most recently, a very large meta-analysis by the Prospective Studies Collaborators that involved almost 1 million persons enrolled in 61 prospective observational studies demonstrated a log-linear relationship between cuff systolic or diastolic blood pressure and mortality due to ischemic heart disease or stroke in middle-aged and elderly adults who did not have overt vascular disease at the beginning of the observation period.5

Abundant clinical trial data indicate that lowering cuff blood pressure with antihypertensive drugs effectively reduces the risk of a variety of cardiovascular outcomes, including cardiovascular death, as well as total mortality.6–10 Regarding the benefits of individual drug classes, a meta-analysis of data by the Blood Pressure Lowering Treatment Trialists’ Collaboration from randomized, controlled trials did not show significant differences in total major cardiovascular events among regimens based on angiotensin-converting enzyme inhibitors, calcium antagonists, diuretics, or ß-blockers, as long as similar cuff blood pressure reductions were achieved, although there were some differences in cause-specific outcomes.10 When specifically tested in randomized trials, however, ß-blockers have fallen short of other therapies in preventing hypertensive complications. The Losartan Intervention For Endpoint reduction (LIFE)11 and the Anglo-Scandinavian Cardiovascular Outcomes (ASCOT)12 trials compared active treatments based on an angiotensin receptor blocker (losartan with or without a diuretic) or a calcium antagonist (amlodipine with or without perindopril) with treatment based on a ß-blocker (atenolol). Brachial cuff blood pressure differences between the treatment arms in LIFE and ASCOT were very small and were judged by the investigators to be insufficient to explain the large treatment-related differences in outcomes, which favored the other drugs over the ß-blocker. However, the editorial accompanying the ASCOT main results publication attributes the benefits of amlodipine-based treatment to superior cuff blood pressure reduction,13 whereas others, including the main investigators of the ASCOT trial, have adduced effects beyond blood pressure lowering to explain the results.14

In this issue, Williams et al1 describe results of the Conduit Artery Function Evaluation (CAFE) study, a substudy of the ASCOT trial, which compared the effects of the ASCOT blood pressure-lowering regimens on central aortic pressure and hemodynamics in more than 2000 patients in 5 ASCOT centers. The CAFE study, using radial applanation tonometry and pulse-wave analysis to calculate derived central blood pressures using the Sphygmacor system, describes a subtle but important difference in arterial pulses in hypertensive patients treated with ß-blockers compared with those taking calcium antagonists. The central finding of the CAFE study is that ß-blockers do not lower central systolic pressure as much as calcium antagonists, an observation that is predictable based on the relative inability of ß-blockers to reduce the magnitude of the reflection (augmentation) wave. This observation is similar to that of Morgan and colleagues,15 who used a 5-way crossover study to determine that only ß-blockers (compared with thiazides, angiotensin-converting enzyme inhibitors, and calcium antagonists) increased the placebo-subtracted magnitude of the reflected wave. Compared with ß-blockers, calcium antagonists and other vasodilators are thus more effective in reducing central systolic pressure, cardiac afterload, and left ventricular mass.16 The results from the CAFE study parallel those of the LIFE trial, in which angiotensin receptor blocker-based therapy was more effective than ß-blocker-based therapy in reducing left ventricular hypertrophy and its consequences.11

The present application of “pulsology” to clinical trials would no doubt please the Chinese masters and the sphygmocardiologists. With ß-blocker-based therapy, as with aging or hypertension in general, the arterial pulse taken at the wrist is more “sustained,” because of a larger reflected wave in late systole. The absence of “pulsology” in Western medical curricula probably contributes to the skepticism of many physicians, along with the ongoing debate over the validity of the techniques currently used.

Although technical questions remain problematic in interpretation of the CAFE results, the overall conclusions drawn by the investigators are reasonably conservative. Radial tonometry, without question, produces a high-fidelity pulse contour that is identical to high-frequency catheter-based data. It easily can be shown that the radial or brachial systolic pulse contour in aging is essentially a “sustained” systolic pulse composed of an increased first peak followed by a secondary shoulder peak (due to wave reflection) that is generally lower.17 In contrast, the central systolic contour in aging or hypertension is composed of a lower first peak followed by a higher second systolic peak (augmentation pressure). It has been proposed that a generalized transfer function can be applied to a radial tonogram to yield a derived central pulse waveform18; this technique has been well validated to estimate peak central systolic blood pressure.19 Although there is ongoing debate over whether the transfer function can be applied to interindividual comparisons,20 in the CAFE study, each individual was compared with his/her own baseline, so the data are probably valid. Other alternative explanations for the differences between treatment arms in CAFE also exist, including differences in 24-hour blood pressure control or other “tissue” mechanisms yet to be described.

What is the overall value of the CAFE study? At the very least, it opens our eyes to alternative explanations beyond the reach of conventional sphygmomanometry. In the context of clinical trials, radial tonometry adds to our knowledge of the pharmacodynamic effects of vasoactive drugs. Present findings have importance in describing why some classes of antihypertensive agents yield better profiles of target-organ protection than others. For example, the observation that ß-blockers do not reduce central systolic pressure as much as most other antihypertensive drug classes may account for the finding from meta-analyses of antihypertensive trials that ß-blocker-based treatment is no better than placebo for prevention of cardiovascular disease.21,22 This has led many authorities to recommend that ß-blockers not be prescribed as first-line treatment for hypertensive treatment patients in the absence of compelling indications (heart failure, post myocardial infarction, high coronary heart disease risk, angina) for their use. Whether radial tonometry should be performed routinely in individual patients as a diagnostic or therapeutic indicator, however, remains a matter of considerable debate. At present, the technique is probably not quite ready for “prime time” in routine clinical practice.

Full original article with notations, references and links found here: http://www.circ.ahajournals.org/cgi/content/full/113/9/1162

BPro (by HealtStats): The Cardio Pulse Wave Analyzer – Introduction

Great video to introduce doctors and health care professionals to the Bpro (BPro and A-Pulse software by HealthStats): A Cardio Pulse Wave Analyzer. The CEO, Dr. Ting of HealthStats the manufacturer of the BPro, gives a brief explanation of the device.

Cardio Pulse Wave Analysis (CPWA) uses the BPro device and A-PULSE CASP software (by HealthStats). This is the state-of-the-art equipment, technology and software (Manufactured by HealthStats). Now learn what the measurements mean. This is somewhat technical so bear with me.

A-PULSE CASP is a revolutionary product patented by HealthSTATS International Pte Ltd. It is able to measure accurately the Central Aortic Systolic Pressure (CASP), which is the blood pressure at the root of the aorta. It is the only device which can be used in common clinical setting. CASP has been shown in many recent studies as an important determinant for strokes and CVS events. It has been validated via invasive study and achieved an accuracy (co-relation) R= 0.9917 independently. A-PULSE CASP is FDA and CE MDD approved. It is also being used in large drug trials by Pharmaceutical companies.

What is arterial pulse waveform?

When the left ventricle ejects blood into the aorta in systole, the perturbation generates a wave that initially travels through the arteries from the heart towards the arterial tree.

Pulse waveform has 2 components.
1) Forward travelling wave when the left ventricle contracts and
2) Reflected wave returning back from the peripheral.

Diagrammatic Representation of a Radial Arterial Pulse Wave

 

What is CASP (Central Aortic Systolic Pressure)?
This is the blood pressure at the root of the aorta or the largest artery in the body, as the blood is being pumped out of the heart. This pressure is called Central Aortic Systolic Pressure or CASP. CASP has been shown to be an important factor in the relation to strokes and cardiovascular events, more so than the brachial pressure, or the pressure at the arm commonly.

 

How to measure CASP?

Invasive method

This is direct measurement and has been considered as the most accurate method. To perform the measurement, a catheter must be inserted into the aortic root from brachial or femoral artery, which is obviously an invasive method and could result in complications (Fig. 1). This invasive method of measuring CASP is not available in clinical setting. However, A-PULSE CASP can be used in clinic and the accuracy has been validated against this invasive method, the result is R= 0.9917 (co-relation). (What this means, for those of you who are like me and don’t quite get the point, is the CPW is 99.17% as accurate as the cathater method!)

Fig. 1 Direct measurement of CAP using catheter

Non-invasive method

HealthSTATS (HS) invented a device named BPro which is able to capture radial pressure waveforms. Furthermore, HS developed a proprietary formula to derive central aortic systolic pressure (CASP) from the calibrated radial pressure waveform (Fig. 2).

Fig. 2 Non-invasive measurement of CASP using the Cardio Pulse Wave Analyzer (which is the combination of HealthSTATS BPro device and A-PULSE software)

What is augmentation index?

The difference between the second and first systolic peaks expressed as a percentage of the pulse pressure.

What is the arterial compliance?

The ability of an artery to increase the volume in response to a given increase in blood pressure is called compliance.

What is pulse wave velocity?

PWV is the speed at which the pressure waveform travels (wave propagation) along the aorta and large arteries, during each cardiac cycle.

What is applanation tonometry?

The principle of applanation tonometry is that the force acting on the plunger is proportional to the pressure in the artery when where the artery surface is flattened.

Editorial comment: The present system used to take this measurement is a device manufactured by HealthStats located in Singapore. They provide an officially FDA registered device that has been field proven and clinically verified.

(CARDIOVASCULAR HEALTH)
Digital Pulse Wave Analysis Offers Non-
Invasive Early Heart Risk Assessment

By August West
Contributing Writer

Central Aortic Systolic Pressure (CASP) is one of the most powerful early predictors of cardiovascular risk. New digital pulse wave analysis technology is putting this valuable test in the hands of prevention-focused primary care doctors.

Safe and non-invasive, pulse wave analysis applies the principles of sonar to assess the pliability of the vascular tree, including the major central vessels as well as the small peripheral vessels. Central aortic vascular compliance, or lack thereof, is a key indicator of vascular health or lack thereof.

“This is a really great test for people who are seemingly without symptoms, but who are about to have lots of disease,” explained J. Joseph Prendergast, MD, director of the Endocrine Metabolic Medical Center, Palo Alto, CA. Dr. Prendergast is among the pioneers of pulse wave analysis, particularly as it applies to the prevention of heart disease among people with diabetes.

He noted that diabetics tend to show a pattern of atherosclerosis distinct from what one typically sees in non-diabetic CVD. “Diabetics get more long artery atherosclerosis, whereas in non-diabetics, you tend to see the plaque only in smaller branches, and at the points where the vessels branch off.” Pulse wave analysis opens a window into the condition of the long vessels.

Measuring the Bounce

Arterial pulse wave analysis has been available as a research tool for about ten years, and has just begun to enter clinical practice. In essence, it measures reflection of pulse waves off the walls of the aorta and the peripheral vessels. As the pulse travels down the aortic trunk, it hits smaller arteries and is reflected back. This bounce-back wave runs headlong into the oncoming pressure wave from the subsequent heartbeat, augmenting pressure on the vessel walls.

The general principle is that higher pulse reflection scores indicate stiffer, more plaque-bound vessels, and therefore greater imminent risk of cardiovascular events. “It’s like dropping a ping-pong ball on a carpeted floor versus a hard marble floor. The harder surface will give a stronger bounce, while the carpet will absorb the force.”

Dr. Prendergast said state-of-the-art technology allows assessment of, “all sorts of reflections and pressure subtleties.” But from a practical viewpoint, you really only need to look at two key measures: the central aortic pulse (CASP) reflection, which shows the flexibility of the aorta and, by extension, the major vessels, and the pulse reflection in the small arteries. “The small vessels can tell you about metabolic syndrome. But the bigger vessels tell you about imminent cardiovascular risk.”

In a certain sense, pulse wave analysis is a modern elaboration of the ancient art of pulse diagnosis developed thousands of years ago, and still used by practitioners of traditional Chinese and traditional Indian medicine. TCM and Ayurvedic practitioners will spend considerable time evaluating the pulses, sensing in them subtle indicators of health or disease.

The new pulse wave technology is based on a similar premise that the health of the vasculature, indicated by its degree of elasticity, is a key indicator of overall physical health. Pulse wave analysis quantifies the signals and opens up vast new dimensions of study in this domain.

“I Had to Re-Think Everything”

Dr. Prendergast’s interest in this field grew out of his effort to meet his own health challenges. Back in the 1970s, at the age of 37, he was diagnosed with advanced atherosclerosis, though he was asymptomatic and had fairly normal serum cholesterol. Given that his father had a stroke at age 42, he became very concerned.

Faced with a serious health threat, he realized the limitations of his medical knowledge. “Medicine, at that time, really had nothing for me. I had to re-think everything. I knew I couldn’t rely just on pharmaceuticals,” said Dr. Prendergast, who today is in his 70s and very healthy.

A friend and colleague, Victor Dzau, MD, now chancellor for health affairs at Duke University, introduced Dr. Prendergast to L-arginine, an amino acid which, when taken supplementally, can increase endothelial nitric oxide release. Many researchers and clinicians believe that when used properly, arginine improves vascular health and reduces CV risk. Arginine quickly became a cornerstone not only in Dr. Prendergast’s own personal heart health regimen, but also in his treatment protocols for patients at risk.

He began looking at pulse wave analysis after meeting Stanford University researchers who were the emerging technology to detect early signs of Alzheimer’s disease, diabetes and CVD. He saw in it the potential to be a useful guide in determining who really needs arginine therapy. He is currently consulting with CardioGrade, LLC (www.cardiograde.com), a California company focused on bringing this emerging technology into wider clinical use.

Looking Upstream

Conventional treatment of cardiovascular disease, a complex multi-system aggregation of dysfunction, is often guided by fairly simplistic measurements: serum LDL, HDL and Triglyceride levels, and blood pressure as measured by sphygmomanometer cuff readings at the brachial artery.

Dr. Prendergast sees brachial artery pressure measurement as convenient but primitive. Over-reliance on it is one reason that anti-hypertensive therapy often fails to prevent life-threatening CV events. “When you put the cuff on someone’s arm, all you’re really looking at is the download pressure back into the hands. All it really tells you is the condition of the vessels in the wrist. You need to go upstream into the central vessels.” He added that many drugs will lower brachial pressure but not reduce risk.

Pulse wave devices also take readings from the wrist, but there is no arterial occlusion as with a standard pressure cuff. “The wave forms of the pulse tell you what’s going on in the aorta and the other vessels,” he said. It gives a very different type of information than standard BP measurements.

The discrepancy between the brachial arteries and the central aortic trunk was underscored in the Conduit Artery Function Evaluation (CAFÉ) study. Researchers compared beta-blockers plus diuretics versus calcium-channel blockers in hypertensive, high-risk people, and found that while both treatments gave similar and significant reductions in standard brachial artery pressure, the central aortic systolic and pulse pressures were substantially lower in patients on calcium-channel blockers (Williams B, et al. Circulation. 2006; 113(6): 1213-25).

“You can get similar pressures in the arm but very different pressures in the central arteries, depending on what the drugs do to the wave reflections,” explained Bryan Williams, MD, of the University of Leicester, UK, who led the CAFÉ study. “Beta blockers and diuretics, which we use very commonly, while they lower blood pressure and reduce risk, are less effective…in preventing the reflected wave from coming back at the wrong time. You get a slightly higher central pressure with those drugs than you do with amlodipine and perindopril.”

Dr. Williams had high praise for pulse wave analysis, which in the CAFÉ trial was done with the Spygmocor system (www.atcormedical.com). “I think this type of technology is going to be increasingly used in clinical trials because it gives us information that we haven’t had before. It can be easily used and can produce very effective results.”

A Surge of Research

Pulse wave analysis has attracted vigorous research interest of late, with well over 50 studies published just in the last 6 months.

Investigators at Fukuoka University Hospital, Japan showed a strong correlation between aortic augmentation index, a type of pulse wave measurement, and severity of atheromatous plaques in a cohort of 96 patients with paroxysmal atrial fibrillation. High augmentation scores correlated with age, plasma LDL, aortic stiffness scores, and other risk indicators, leading the researchers to conclude that this represents, “a novel tool for determining the severity of central aortic atheromatous lesions.” (Sako H, et al. Circ J. 2009; Apr 16; Epub ahead of print).

Augmentation index and central aortic pressure also correlates with smoking, according to researchers at Dokkyo Medical University, Japan. They looked at 443 otherwise healthy normotensive men, and found that the augmentation index was markedly higher in current smokers compared with never- and former- smokers. Central systolic pressure was higher in current and former smokers compared with lifelong non-smokers. Interestingly, brachial systolic pressure was not significantly different among these groups (Minami J, et al. Am J Hypertens. 2009; Mar 26, epub ahead of print).

The good news is that most aortic pressure risk indicators will normalize when people quit smoking. A multicenter Portuguese study looking at pulse wave patterns in 71 long-term heavy smokers showed that after 6 months, those who quit showed significant reductions in peripheral systolic pressure, augmentation index, pulse wave velocity and other risk indicators compared with the men who continued smoking (Polonia J, et al. Blood Press Monit. 2009; 14 (2): 69-75)

Dr. Prendergast noted that because pulse wave analysis is noninvasive, it is an excellent office-based tool for tracking patients’ response to treatment over time. In his clinic, the therapy revolves around diet and lifestyle change, as well as intensive use of nutraceuticals like L-arginine, vitamin D, resveratrol, and others. “People still need to change their diets. You cannot totally over-ride a bad diet with arginine or any other supplements,” he said.

Currently, digital pulse wave analysis systems cost roughly $10,000, said Dr. Prendergast. But he expects the prices to come down as the technology improves and gains in popularity. Ultimately, he hopes to see the systems streamlined and simplified to the point where they can be used by patients at home. “We’re not there yet, but we’re working on it!”

END

Digital Pulse Wave Analysis Offers Non-
Invasive Early Heart Risk Assessment
Central Aortic Systolic Pressure (CASP) is one of the most powerful early predictors of cardiovascular risk. New digital pulse wave analysis technology is putting this valuable test in the hands of preventive primary care doctors.
Vol. 10, No. 2 Summer 2009

Editorial comment: The present system used to take this measurement is a device manufactured by HealthStats out of Singapore. They provide an officially FDA registered device that has been field proven and clinically verified.

Measurement of Ambulatory Central Aortic Pressure in Clinical Trials using the BPro™ Device (by HealthStats).

 

Bryan Williams MD FRCP FAHA

 Professor of Medicine

Department of Cardiovascular Sciences

University of Leicester School of Medicine, United Kingdom.

August 2008

 

Introduction:


Blood pressure (BP) plays a key role in the development of cardiovascular disease. Conventionally, BP is measured using a sphygmomanometer (manual or automated) over the brachial artery in the “office setting”. This has remained the “gold standard” for BP measurement in clinical trials. Infrequent isolated BP readings in a seated position in an office setting are unlikely to be comprehensive in assessing the full impact of cardiovascular interventions, particularly BP-lowering drugs therapies in clinical trials. Consequently, more recently,  ambulatory BP monitoring (ABPM) has increasingly been incorporated into trials as sub-studies. Traditionally, ABPM also uses a cuff device to measure BP over the brachial artery at pre-set intervals throughout the day and night. The assumption with all of these measurements is that the pressure being measured over the brachial artery is representative of the pressure in the central circulation, i.e. the aorta. Whilst this assumption be reasonable for the trial population as a whole,  it is not accurate and for individual patients, in whom there may be marked differences in their central pressure, especially their systolic pressure, despite similar brachial pressures. Moreover, this differential relationship between brachial and central aortic systolic pressure (CASP) may be further modified by the effects of drug therapy. These observations are important because they suggest that brachial BP measurements are not always providing an accurate representation of central pressures in individual patients, or the potential effects of BP-lowering drugs on their central pressures.

 

Why is central aortic pressure different from brachial BP?

Whilst diastolic pressure is largely unchanged across the main arteries, i.e. from aorta-to-brachial, systolic pressure (and thus pulse pressure) differs markedly. This is due to pressure amplification as the pressure waves moves from the heart to the periphery. Thus, systolic pressures are higher at the periphery than they are centrally. This difference can be very substantial, amounting to 30mmHg or more in younger, healthy individuals. The differences between central aortic systolic pressure and brachial systolic pressure diminish with age but the two pressures are rarely ever the same. The diminution in pressure amplification from aorta-brachial with ageing reflects deterioration in the performance of large conduit arteries, especially the aorta with ageing and disease. This is mainly due to a loss of the aorta’s elastic properties due to fragmentation of elastin and its replacement by in-elastic collagen. This is further compounded by two processes; i) post-translational modification of the collagen by the accumulation of advanced glycation end-products, a process that it accelerated in people with diabetes; and ii) vascular wall calcification. The resultant stiffening of the aorta  adversely effects the characteristic impedance of the aorta thereby increasing left ventricular work and increasing pulse wave velocity (PWV). In westernised societies, PWV typically doubles from age 20yrs to 80 yrs.  This increase in PWV is of major importance because it results in faster forward wave propagation after systole and earlier pulse wave reflection from distal reflection sites. This earlier pulse wave reflection means that the reflected wave returns earlier, towards the end of systole (rather predominantly in diastole in healthy people) and leads to augmentation of central aortic pressure, further increasing left ventricular work.  The augmentation of central systolic pressure diminishes the normal differential between central aortic and brachial systolic BP (figure 1). Importantly, these dramatic changes in pulse wave morphology and central aortic systolic pressure cannot be appreciated by the simple measurement of brachial BP.

 

Controversy over the mechanism accounting for the increased central aortic systolic pressure with ageing and disease;

There has been much debate about the aforementioned mechanism accounting for the elevation of the central aortic systolic pressure with ageing. Some have suggested it is less dependent on wave reflection and more dependent on the increased  characteristic impedance of the stiffened proximal aorta, for which the increased PWV is a surrogate. Others have argued that the aforementioned changes to wave reflection and enhanced systolic augmentation are more important. Whilst this debate is of academic interest, it should not distract from the unanimous agreement that central aortic systolic and pulse pressures rise relative to brachial pressures with age and are likely to be a major a factor accounting for increased risk of cardiovascular morbidity and mortality with ageing.

 

Central Aortic Systolic and Pulse Pressures and Cardiovascular Disease Risk;

Evidence is now emerging to support the view that this sinister but unmeasured relentless rise in central aortic systolic and pulse pressure is a key driver of target organ damage, cardiac dysfunction and enhanced risk of heart disease and stroke with ageing.  Moreover, this change is enhanced in those at risk of developing early aortic damage, notably, those with i) hypertension, ii) diabetes, and iii) renal impairment, and especially severe in those with a combination of all three. Recent data suggesting that central aortic systolic and pulse pressure might be better predictors of clinical outcome than brachial BP is consistent with this hypothesis. Furthermore, modulation of the relationship between brachial and central pressures might be an important protective action of cardiovascular drugs as highlighted by the CAFE study but has been otherwise been poorly studied. It is indeed remarkable that the main read-out for the action of BP-lowering drugs in clinical trials has been the measurement of seated brachial BP! It is even more remarkable when one considers that the various drugs evaluated often have different mechanisms of action and the potential to influence the relationship between brachial and central aortic pressures in different directions and by different orders of magnitude. In this regard, brachial BP has never been and will never be an adequate surrogate for the differential actions of drug therapies on the circulation.

 

Based on these observations, it seems very likely that the measurement of central aortic pressure would provide a more accurate read-out of the effects of drug therapies on the circulation, and more importantly, on target organ damage and clinical outcomes.

 

The Non-invasive Measurement of Central Aortic Pressures from Radial Pulse Wave Analysis:

To be practical for routine clinical use and for use in clinical trials, central pressure has to be measured simply, accurately and non-invasively. Experience in clinical trials thus far has been limited; i) largely by a lack of suitable technology, ii) compounded by a lack of appreciation of the potential importance of central aortic pressures, iii) poor recognition of the differential effects of drugs on central pressures, and iv) a general assumption/complacency that traditional brachial BP measurements tell us all we need to know.  Where central aortic pressures have been assessed non-invasively, this has mainly been done by the technique of pulse wave analysis. This is performed by applying a tonometer to the skin overlying the radial artery to record a radial wave-form in a patient seated and at rest. This radial wave form can then be calibrated by imputing the readings from the brachial BP (measured contemporaneously in the same arm using a standard validated BP device) to generate a pressure-wave form (the assumption being that the pressures in the brachial artery are little different from those at the radial artery). The Sphygmocor™ device (used in the CAFE study) uses this approach. In this application, the radial pressure wave-form is then transformed to generate a central aortic pressure wave form using a validated generalised transfer function. The central aortic pressures are then derived from the central aortic pressure wave form.  This approach can be used to derive central aortic pressures and other central hemodynamic indices at routine clinical trial visits. However, this is still only recording a static seated pressure reading and provides no information about the ambulatory profile of central pressure. This latter point is important because fluctuations and variability in central aortic systolic pressures are greatest when the patient is ambulant. Moreover, such variability is likely to be even greater in those with stiffer conduit arteries and higher pressures. Thus, seated central aortic  pressure readings  are likely to greatly underestimate the effect of drug therapies on ambulant central aortic pressures.   

 

The BPro™ Watch:

The BPro™ device is different to other devices for measuring ambulatory BP and ambulatory central aortic pressure. It has a high fidelity tonometer incorporated into a watch strap. The watch is worn with the tonometer positioned and fixed over the radial artery (figure 2). The tonometer samples the radial wave-form in up to 96 x 10 second blocks of time, over 24hrs. When the watch is first placed onto the patient, the radial wave-form is calibrated to the brachial BP, measured conventionally using a standard validated electronic BP monitor. This calibration then allows the radial wave form to be transformed into a pressure wave form, providing measurements, equivalent to brachial blood pressure every time the radial wave form is sampled . Thus, the pressure wave form recorded from the radial pulse wave, by virtue of its calibration to the brachial pressure, is now recording ambulatory brachial BP. Thus the BPro™ device can be used as an unobtrusive device to measure 24hr ambulatory BP, calibrated to the brachial pressure measured in clinical trial conditions. The BPro™ is comfortable to wear and the patient simply wears it as a wrist watch for 24hrs. Thereafter, the watch is connected to a computer to down-load the wave form data. The BPro™ has been validated against the AAMI and ESH protocols and passed both validations. It carries a CE mark and is approved for clinical use by the FDA.

 

 

Measurement of Ambulatory Central Aortic Systolic Pressure (CASP) using BPro™:

Unlike conventional BP monitoring devices, the BPro™ records pressure wave forms calcibrated to the brachial BP. Thus, in addition to using the waveforms to measure brachial BP, it seemed feasible to utilise this abundant wave-form data to  derive central aortic systolic pressure (hereafter terms CASP) from the pressure wave forms records. The basis of the “generalised transfer function” used by the Sphygmocor™ device to generate a central aortic wave-from and derive central pressure indices was unpublished and thus unknown to us. We thus considered a novel approach to develop a new method to derive central aortic pressures from the radial artery pressure wave form. We used an “n-point forward moving average” (NpMA) method and experimented with a number of sampling frequencies. We applied the NpMA method to  the wave forms recorded by BPro™  (where n  = ¼ sampling rate of the tonometer)to derive the maximum value from the wave-form array, which we hypothesised should equate to CASP. To further evaluate this novel approach, we utilised the radial wave forms from the CAFE study data base. These wave-forms had been captured with the Sphygmocor™ device and we wanted to determine whether application of the NpMA method to the radial wave-forms would generate similar CASP measurements to those generated by the Sphygmocor™ device for the CAFE study.  We used our NpMA method in a vlinded study of 5,366 brachial pressure calibrated radial wave-forms from the CAFE study. We derived CASP using this method and then compared the CASP result using the NpMA method with the central pressure data derived from the Sphygmocor™ generalised transfer function (figure 3). The correlation was r2=0.993. This confirmed the applicability of the NpMA method to derive CASP directly from the radial pressure wave form.

 

 

In-vivo Validation of BPro™ NpMA method to derive central aortic systolic pressure (CASP):

We then went on to undertake a direct in-vivo validation of this approach in humans in collaboration with Dr. Peter Yan at the Gleneagles medical Centre in Singapore. 20 patients undergoing routine cardiac catheterisation provided their informed consent to participate in this study. At the end of their diagnostic cardiac catheterisation, the central aortic pressures were recorded at the aortic root using a Millar’s SPC-454D tonometer (Millar’s instruments, Texas U.S.A). Simultaneously, the patients were wearing a BPro™ watch calibrated to their brachial BP measured using a conventional (MC3100) automatic BP monitor. The BPro™ provided real-time derivation of the CASP from the calibrated radial pressure wave-form using the NpMA method. This was compared with the simultaneous real-time direct in-vivo aortic measurement of CASP using the Millar’s tonometer.  The correlation between the BPro™ readings of CASP and the direct measurement of aortic CASP was R2=0.9835, r=0.9917 (Figure 4) .

 

 

These two validation steps for the NpMA method to derive CASP, i.e. i) cross validation with the CAFE data set, and ii) direct in-vivo measurement of central pressure in humans, confirms that the BPro™ device can be used to record both; i) the brachial ambulatory BP (as the radial wave form is calibrated to the brachial pressure) and ii) ambulatory central aortic systolic pressure or CASP.

 

Thus, with the BPro™ technology we now have the potential to make the first detailed recordings of ambulatory central aortic pressures. In addition, because the BPro™ records 96 x 10 second blocks of wave forms per 24hrs, there is also the potential to obtain data on heart rate changes and to detect paroxysmal arrhythmias.  Moreover, there is the potential to perform further off-line processing of the wave form data to determine the effects of disease and therapeutic intervention on a wide range of wave form characteristics.

 

Implications for Clinical Trials:

There is an urgent need to learn more about the effects of BP-lowering drugs and other cardiovascular interventions on hemodynamics from two perspectives; i) their impact on BP in an ambulatory setting, rather than just a static isolated clinic setting, and ii) their impact on central aortic pressures. It is likely that both parameters will be seen to be more important than conventional office brachial BP measurements as a predictor of target organ damage and clinical outcomes. It is also likely that potentially beneficial effects of drug interventions on these parameters, by virtue of both their mechanism of action and their duration of action, are being overlooked.

 

Implications for Specific Trials Settings:

Patients with diabetes / diabetic nephropathy: Patients with diabetes have accelerated ageing of their aorta, with enhanced stiffening. This process is accentuated in patients with co-existing renal disease who form the highest risk group. In addition, these patients also have disturbances to their circadian rythms such that nocturnal pressures are higher and BP variability is greater.  Furthermore, aortic stiffening means that the resulting wider fluctuations in pressure and higher central aortic pulse pressures are likely to be transmitted deeper into the circulation – this allied to the impaired blood flow autoregulation of these patients makes them especially vulnerable to small vessel injury. It is conceivable that much of the beneficial effects of ACE-inhibition, ARBs and Direct Renin inhibition on renal, cardiovascular and heart failure outcomes in these patients relate to favourable effects central aortic systolic pressures over 24hrs – effects that are not fully appreciated by simple measurement of clinic BP at the end of the dose interval.

 

Patients with Hypertension: Hypertension accelerates aortic ageing and predisposes to higher central aortic pressures relative to brachial pressures, greater BP variability and potentially higher nocturnal central pressures. As indicated above, we have already shown in the CAFE study that different types of BP-lowering treatment can influence central pressures in different ways. The prospect of incorporating ambulatory central aortic pressure measurements into major clinical outcomes trials in hypertensive patients is very exciting and would provide important and novel data relating central pressures to intermediate and hard clinical outcomes and drug effects on pressures and these outcomes.

 

Patients with Atherosclerosis: There have been many recent studies of patients using intravascular ultrasound (IVUS) to quantify coronary atheroma progression and regression. It seems likely that the pressure modifying effects of drugs could have a major impact on the evolution of atheroma. It is also logical to assume that pressure in the central aorta, rather than pressure in the brachial artery is more relevant to this process. Thus, it would be very interesting to define the impact  of drug related changes in central aortic pressure (both absolute changes and qualitative circadian rhythm changes) with regard to the evolution of atheroma.  

 

Patients with Heart failure: Ventricular:vascular coupling is a key determinant of systolic and diastolic function. We spend much time studying the heart as a pump but too little time considering the huge importance of the aorta as the conduit. Pulse wave characteristics are potentially very important in heart failure but have been poorly studied.  The impact of acute or chronic heart failure on central aortic pressure profiles over 24hrs, the impact of drug therapies on these parameters, and their impact on outcomes, has never been established. The recent data showing impressive falls in plasma NT-proBNP in patients with heart failure receiving direct renin inhibition is consistent with a significant beneficial effect of the intervention on central aortic pressures and improved ventricular:vascular coupling.  

 

Conclusions:

Technology is now available that has the potential to provide much added value to ongoing clinical trials by providing the first detailed recordings of ambulatory central aortic pressures and a repository of arterial pulse wave form data that could be further analysed for other key indicators of large artery function and the impact of specific drug therapies. The standard clinic brachial BP reading has provided an important but crude read-out of the impact of drug therapies on the arterial circulation and pressures. There is a clear need to move to the next level to better appreciate the mechanism of action of modern drug interventions and  inform the development of even more effective drug interventions in the future.