Coronary artery disease: best prevented

One of Steven Nissen’s speciality interests is intravascular ultrasound (IVUS). He developed the methodology for application of IVUS in the assessment of the progression and regression of coronary atherosclerosis. “We believed that atherosclerosis was primarily a disease of the vessel wall rather than the flow channel. In the late 1980s, it became technically feasible to miniaturize ultrasound equipment. So a group of people, myself included, worked with industry to develop the technology to put ultrasound on a tiny catheter, which would then be inserted into the coronary arteries and make pictures of the wall of the artery at 30 frames per second in full motion. It proved to be a very enlightening procedure as we began to develop its application,” remembers Nissen. IVUS soon started to deliver its potential. The first human studies were conducted in 1989. “By 1992, we were taking some very good images, learning what those images meant in the process.”

IVUS has enabled advances in clinical research by providing a more thorough perspective and better understanding than angiography, the more traditional method. “Angiography just shows the flow channel,” says Nissen and adds: “What you really want to know is about the plaque in the vessel wall. What makes IVUS different is that it provides very detailed pictures of the atherosclerotic plaque within the vessel wall, which is simply not seen by angiography.”

However, there are also major disadvantages: IVUS is quite invasive. “For an angiogram, you can simply inject dye in the ostium of the vessel or pacify the coronaries. With IVUS, you have to insert the catheter down the coronary. In fact, because there are several coronaries to study, it’s really not practical to IVUS every coronary artery. You can only IVUS selectively to look at the spots you are interested in examining,” says Nissen. As a result IVUS is not used very often in the direct patient care environment. Instead, it mostly serves to study therapies to alter the regression and progression of coronary disease by slowing it down. Nissen: “I see IVUS much more as a research tool than as a tool for clinical care, where angiography is still the gold standard.”

The “fire prevention” business

Today, IVUS is a mature technology. “The thing that’s hot right now is the analysis of IVUS using radiofrequency information, that is using the raw signals to look at not just the size and location of plaques, but their composition,” says Nissen. Once fully developed, the technology has the potential for cardiologists to be able to characterize the morphology of the plaques in the coronaries. “This could enable us to identify the risk of individual plaques to rupture and cause heart attacks. And so the idea then is to look at composition and not just size,” explains Nissen. Progress, however, is slow and the procedure is still quite invasive.

What about minimally-invasive methods? In diagnostics, Nissen believes, CT angiography is developing quickly as a way to see the coronaries and, potentially, the wall of the vessel without having to insert a catheter into the heart. “It’s still got a long way to go but it is developing very rapidly. Beyond that, there has been a lot of progress with magnetic resonance imaging. This technique can see the flow channel, the lumen, as well as the vessel wall,” says Nissen.

No doubt there will be technological improvements aimed at making diagnostic and treatment procedures less stressful for patients with coronary artery disease. However, with ever growing numbers of those patients, where does Nissen see the future? “Prevention is where the action is. We are moving towards developing more powerful drugs designed to actually prevent or even reverse the accumulation of these plaques in the coronary arteries. Ultimately, what we would like to do is move away from the paradigm of being firemen to being in the fire prevention business, that is to prevent the disease in the first place.” To achieve this, Nissen’s focus is on working on drugs which raise high-density lipoprotein (HDL), the good cholesterol. “We lost an opportunity when Pfizer’s drug torcetrapib, supposed to raise HDL, failed. But there are other drugs in development that will work out eventually,” hopes Nissen.

This, unfortunately, will still not solve the problem of coronary artery disease, the leading cause of death in the US in both men and women, because it hits different strata of society unequally. A study by the National Center for Health Statistics shows that poverty is inversely associated with heart disease, including coronary heart disease, hypertension and stroke. “Poverty,” Nissen agrees, “is big a problem. We have a very unequal distribution of wealth in the US. Poor people tend to have poor diets and poor living conditions and the stress associated with this increases the risk of heart disease. But health care disparities also play a big role, because poor people get poor healthcare.”

Universal health coverage

This, Nissen believes, is a problem particular to the US: “If you are privately insured, you get superb care, if you are not insured, you get virtually no care. 46 million people who are not insured get poor quality of care with very poor outcomes,” stresses Nissen and criticizes: “This is a problem that our country has failed to adequately address over many decades.” He believes that a good safety net for people living below the federal poverty level does not exist, which clearly affects his declared goal of prevention. “We are not doing a good job with prevention. There are people, for example in minority communities, that have hypertension and high cholesterol but they are not getting treated. When they finally find out that they have heart disease it’s really much too late. The need for primary prevention as one of the strategies to deal with healthcare disparities is very important,” stresses Nissen.

In the coming years, there is a lot of momentum to address the problem. Nissen: “There has been a lot of discussion about universal health coverage. There are proposals now by states such as California and Massachusetts.” Almost in disbelief, he adds: “Even the Bush administration is coming up with some proposals for enhancing accessibility of health insurance for more Americans.” This leaves Nissen certain that universal health coverage will come: “It has to come! Right now the US is 46th in the world in life expectancy, just ahead of Albania. Our infant mortality rate is about 50 percent higher than in most European countries and that is unacceptable for a contemporary society in a wealthy country such as the US.”

Nissen: “Dr Steven Nissen is Chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic and President of the American College of Cardiology, the professional society that represents America’s cardiologists.”

Nissen: “Ultimately, what we would like to do is move away from the paradigm of being firemen to being in the fire prevention business, that is to prevent the disease in the first place.”

Nissen: “We have a very poor distribution of healthcare, such that if you are privately insured, you get superb care, if you are not insured, you get virtually no care.”