June 30, 2010 ( Updated July 1, 2010 ) (Oslo, Norway)— A new individual participant meta-analysis showing that pulse-wave velocity (PWV)--a simple measure of arterial stiffness--is an independent predictor of cardiovascular events over and above existing risk factors was presented during a hotline session at the recent European Society of Hypertension (ESH) European Meeting on Hypertension 2010, by Dr Carmel McEniery (University of Cambridge, UK). The results should help better identify higher-risk populations that may benefit from more aggressive management, she says.

Dr Carmel McEniery

McEniery explained to heartwire that there has been a surge of interest in PWV in the past few years and an explosion of data showing that "this fairly simple measure of aortic stiffness does have predictive value for cardiovascular mortality. The measurement tells us how stiff your large arteries are, and the stiffer they are, the more likely you are to have a cardiovascular event."

But recent outcomes studies on this subject have been small and covered a diverse range of patient groups, she says. This meta-analysis is the first to include all of the studies on this subject and to have access to raw data, enabling individual patient-level analyses.

What Is PWV and How Can It Be Used?

PWV is measured by devices that use either probes or cuffs to noninvasively track the speed of blood flow in meters per second, she explained. One measurement is taken at the carotid artery and one at the femoral artery, and the difference between the two--calculated by the device--is the current gold standard measure of aortic stiffness. The slower the PWV, the better: "It means your arteries are nice and elastic and distensible," McEniery said.

Recommendations to measure PWV were included in the recent ESH hypertension guidelines, she says, noting that the technology is already being widely employed as a measure in hypertension and vascular-medicine clinics in tertiary centers across Europe and Australasia. This has been aided by the increasing availability of a number of simple-to-use, noninvasive commercial devices to assess this parameter, she says. But the US "has been slower to adopt this approach," she notes.

Moving PWV measurement into primary care "will be the next big step; it has not happened yet," she says. Asked by heartwire how knowing PWV would change the management of patients, she admitted that it remains to be shown that reducing arterial stiffness specifically will have a benefit on outcomes.

But knowing PWV is high might help doctors make decisions on whether or how aggressively to treat intermediate-risk patients in particular, she said. A number of large studies are now ongoing to examine whether PWV does provide additional benefit in terms of risk stratification, "because that is where it will be most useful," she said.

Around a 20% Increase in Risk for One-SD Higher PWV

McEniery said there has been one recent meta-analysis of studies of PWV, published this year in the Journal of the American College of Cardiology [1], which confirmed that it is predictive for total CV events and mortality. However, it was limited by the fact the authors did not have access to raw data, and it did not include all the known studies, she noted.

In her group's review, on behalf of the PWV Collaborative Group, they obtained data from 12 studies (including three unpublished) in a total of 15 220 subjects with 1779 combined events.

What was striking, she said, "was the similarity in PWV values across the studies," seven of which were European, three from the Far East, one from Australasia, and one from the US.

After adjusting for conventional risk factors--age, sex, systolic BP, cholesterol, HDL, smoking, and antihypertensive medications--they showed that the hazard ratios for a one-standard-deviation (SD) change in PWV were 1.19 for CHD, 1.25 for stroke, 1.27 for CV events, and 1.18 for all-cause mortality, all of which were statistically significant.

When the results were stratified by age, they showed that the predictive effect of PWV was strongest in those younger than 50 years of age, she noted, although the relationship between PWV and events was still significant for those over 50.

"While it was previously thought that arterial stiffness was a surrogate marker, it's becoming clear it is a pathological process that drives a number of nonatherosclerotic cardiovascular diseases, such as white-matter lesions in the brain, and also has adverse effects on the large arteries themselves," McEniery told the meeting.

The next step, she says, will be to look at these same data to determine how much PWV adds to conventional screening, independent of other cardiovascular risk factors.

New Focus on Arterial Stiffness and Vascular Aging

Asked to comment on the findings, Dr Peter Nilsson (University Hospital, Malmö, Sweden) told heartwire these new data on PWV are important.

Dr Peter Nilsson

"With aging comes stiffness, comes BP elevation, comes pulse-pressure increase," he said, noting that pulse pressure (the difference between systolic and diastolic measures) is a crude measure of vascular aging, but it is one that can easily be employed by GPs. However, he also believes that the increasing availability of new and cheaper devices to measure PWV will eventually mean that primary-care clinics will utilize this technology.

He notes, however, that the use of PWV as a routine tool for patient evaluation has been hampered by the absence of reference values. But a paper published June 7, 2010 in the European Heart Journal [2] is the first to establish these, based on a large European population, he noted.

"The bottom line is that 10 years ago, people were focusing on BP; now we are focusing on arterial stiffness and vascular aging and that leads to the concept of vascular protection," he added.

And Nilsson noted that new research showing that blood-pressure variability may be a much more important indicator of risk than mean BP is also an important part of the mix, as many are citing arterial stiffness as a possible cause of high variability in BP.

McEniery agrees that arterial stiffness "is a plausible mechanism for BP variability, particularly in older individuals. Their stiffer arteries may have lost that ability to buffer short-term changes in BP," she noted.

McEniery has no financial disclosures. Nilsson does not have any financial relationships with any companies marketing devices that measure PWV. He consults for a number of companies involved in manufacturing drugs for hypertension and diabetes; has lectured for Merck, Pfizer, Novartis, GlaxoSmithKline, Lilly, Boehringer Ingelheim, and AstraZeneca; and has sat on advisory boards for Merck, Novartis, GlaxoSmithKline, and AstraZeneca.