Imaging technologies are used to screen for colon and breast cancers. Why not heart attack and stroke? That's the early news from the High Risk Plaque (HRP) Initiative, one of the largest studies underway — 6,822 participants — designed to discover and validate tests that will find individuals with vulnerable plaque before they have a heart attack or stroke.

Currently, physicians diagnose patients in danger of heart attack or stroke via risk factors such as high cholesterol, hypertension, smoking, an inactive lifestyle, diabetes and obesity.

"The problem in first heart attacks and strokes is that the vast majority of people are missed — even the day before a heart attack," Pieter Muntendam, MD, president/CEO of BG Medicine (Waltham, Massachusetts) told Medical Device Daily. "There's been tremendous work on risk factors and the Framingham Heart study came up with various markers that were predictive of increased risk of heart attack and stroke. They really work well in the long term, but they fail in the short term."

BG is one of six companies sponsoring the HRP Initiative, along with Humana (Waltham, Massachusetts) to advance the understanding and management of high-risk plaque, which is believed to be the primary underlying cause of heart attacks and strokes. The other companies include Merck (Whitehouse Station, New Jersey), Astra Zeneca (London), Philips (Amsterdam, the Netherlands), Abbott (Abbott Park, Illinois) and Takeda Pharmaceutical Company (Osaka, Japan) (MDD, Feb. 13, 2008).

There are actually four separate studies underway as part of the HRP Initiative. The information about using imaging technologies to diagnose a person at risk for heart attack or stroke comes out of the observational Bioimage study. Enrollment was completed at the end of June and participants underwent an advanced ultrasound examination of arteries in the neck (carotid arteries) and a CT-scan measurement of calcium deposits in the coronary artery. Additionally, participants provided blood samples for future research.

Muntendam said the participants will be followed for three years, or until 600 of them have developed a heart attack or stroke. The study's goal is to determine whether any of the methods and tests used at the time of enrollment are a valid way to identify those people with a higher risk to develop a future heart attack or stroke.

"We have already made some important observations as it pertains to use of 3-D ultrasound," he said. "We have made ultrasound a standard to view the carotid arteries. We decided to pursue a scanning of carotid arteries because you have a beautiful major artery right under the skin that you can characterize and we have found a high proportion of plaque in these arteries. We're finding people who have this build-up of plaque and a degrading-plaque phenomenon. We're looking for disease as opposed to looking at risk factors. We're so excited about the ultrasound finding."

Muntendam's comments about these early findings come from anecdotal cases since the data has not yet been released. He said a series of articles analyzing these early results will be published later this year.

In addition to the imaging aspect of the study, the primary objective HRP Initiative is to develop a simple blood test that would alert physicians to the fact that a person is at risk for heart attack or stroke.

BG Medicine is conducting a study with the Copenhagen Heart Study and Copenhagen General Population Study in conjunction with the HRP Initiative to discover biomarkers that would predict the risk of a first heart attack. This study enrolled 250 people who suffered a first heart attack within four years of entering in the Copenhagen General Population Study. At the time of their entry into the Copenhagen General Population Study, those subjects were free of cardiovascular disease. A total of 500 subjects are matched controls with no cardiovascular disease.

"The primary objective is to develop a simple blood test," Muntendam said. "But it may well be that the blood test alone isn't sufficient and you need an imaging back-up. Ultrasound meets all the criteria for ideal imaging modality.

"Out of the gate we said we wanted to develop a new clinical paradigm," he said. "You can find people in the general population who are ticking time bombs. We always thought it would be a combination of blood test to screen everyone because it's lowest cost and imaging when you have a positive hit."

What's in it for BG Medicine?

"There's no doubt that if we can bring to market a blood test to find people before their first heart attack, it could be the largest proprietary diagnostic on the market," he said.

The HRP Initiative is unique in that the healthy volunteers (age 55-80 for men and 60-80 for women) came from a health benefits company. Participants are from diverse ethnic backgrounds and live in both Chicago and South Florida areas.

"It's the first time there's a collaboration between a health benefits provider and a life sciences company to discover new treatments," he said.

Muntendam said that data which emerge from the HRP Initiative will also likely be valuable in the ever-growing call for comparative effectiveness research.