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 status.
"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 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.
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 current pulse wave analysis systems allow 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 worried.
Now in his 70s and quite healthy, he reflected that "Medicine, at that time, really had nothing for me. I had to re-think everything. I knew I couldn't rely just on pharmaceuticals."
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, boosts endothelial nitric oxide release. Many researchers and clinicians believe that when used properly, arginine improves vascular health and reduces CV risk. It 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 exploring 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 for 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.
Conventional treatment of cardiovascular disease—a complex multi-system disorder—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." 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): 1213–1225).
"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 Sphygmocor 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 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 had 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).
Because pulse wave analysis is noninvasive, it is an excellent office-based tool for tracking patients' response to treatment over time. In Dr. Prendergast's clinic, 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 simplified for home use. "We're not there yet, but we're working on it!"