A Shot for the Heart

Scientists are looking at the possibility of a vaccine for cardiovascular disease.

When it comes to cardiovascular disease, India is either one of the world’s greatest laboratories or killing fields, depending on how you see it. The prevalence rate of this ailment has shot up in the last five decades from 4 per cent to 11 per cent of the population. The World Health Organisation (WHO) predicts that by 2010, 60 per cent of all cardiac patients in the world will be Indians. South Asians are genetically prone to the disease, and should thus greet any new prevention option with enthusiasm. Now there is potential for a new approach at controlling the disease: vaccination.

It is not as if everyone can get vaccinated during childhood and secure lifelong protection from heart disease, although it is not something that can be completely ruled out in the long run. Many scientists the world over are actively pursuing vaccination as a strategy to reduce the risk of heart disease significantly. If all goes well, in four or five years we could see the first vaccine entering the market, and that can decrease certain kinds of cardiovascular risk. “We could start clinical trials for a cardiovascular vaccine in two years,” says Johan Frostegard, a scientist at the Karolinska Institutet in Sweden.

Frostegard and his collaborators at Lund University in Sweden recently discovered a new risk factor for cardiovascular disease: low levels of an antibody against a molecule called phosphorylcholine (PC). These antibodies, called anti-PC, decrease the risk for cardiovascular disease. Some people have large amounts of this antibody, while others do not. Since the discovery is new, people from around the world have not been tested for it. Frostegard knows that Swedes have low levels of the antibody compared to inhabitants of New Guinea who live a traditional life. Cardiovascular disease is rare in such people in New Guinea. Frostegard’s method is to increase anti-PC levels in the blood through vaccination. “A vaccine gives you antibodies you should have had in the first place,” he says.

There have been a few other recent attempts at using vaccination to protect against heart disease. One of them, at the US firm AVANT Immunotherapeutics, uses methods to increase high-density lipoproteins (HDL) in the body. The other strategy, again from Lund University, targets low-density lipoproteins (LDL). Both of these methods are early in their development and have not been tested in clinical trials, and it is not certain if the institutions will try to test them. But both have shown the scientific validity of the vaccination approach at preventing or treating cardiovascular disease.

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Cardiovascular disease is complex and has many causes and risk factors. It is not clear if we have discovered all the risk factors, or even the majority of them. Some major risk factors have been known for a long time. These include high blood pressure and diabetes. Two other risk factors were discovered a few decades ago: high levels of LDL and low levels of HDL. Both are cholesterols, and increasing HDL and reducing LDL — through diet or drugs — are now part of all strategies to control cardiovascular disease.

There are other risk factors like high levels of triglycerides whose precise role is not well known. Of late, medical scientists have discovered other risk factors, an important one being a molecule called C-reactive protein.

Although we know the risk factors, cardiologists and researchers are yet to agree on a strategy to fight them effectively. Diet and exercise are the first part of any strategy, and it is well known that they work in some cases, particularly in controlling diabetes and high blood pressure.

However, controlling cholesterol is not so easy with diet and exercise because 80 per cent of the cholesterol is manufactured in the body itself. HDL clearly goes up with exercise, but it may not be enough for people who have very low levels to start with.

This is why a class of drugs called statins has become very popular among cardiologists and patients. Statins reduce LDL and boost HDL, but are toxic for some patients. In this context, a vaccine that can reduce the risk factors would be a safe alternative. For example, Una Ryan and Charles Ritterhaus of AVANT showed two years ago that a vaccine could help to increase HDL. These scientists had targeted choleteryl ester transfer protein (CETP), an intermediary molecule that plays an important role in the balance of HDL and LDL. The vaccine they developed induces antibodies against CETP and ultimately increases HDL. But after the acquisition of AVANT by another company called Celldex, it is not clear if the scientists will proceed with the vaccine.

The Karolinska scientists, however, plan to go ahead with developing a vaccine against PC. They expect to be ready with it in two years, and clinical trials would take another two or three years, by which time there would be many other cardiovascular vaccines under development. Vaccines help to address a large number of people with the lowest possible risk. Within a decade, they could become the most important strategy against a large number of diseases, let alone cardiovascular disease.

Sources: The Telegraph (Kolkata, India)

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