Inflammation: Is It the New Cholesterol?

In scientific circles, the hypothesis that reducing inflammation can lower the risk of heart disease has been gaining ground. Last weekend, that hypothesis may have finally become fact, with far-reaching implications.

At the European Society of Cardiology meetings in Barcelona, the Novartis-sponsored CANTOS trial demonstrated that an anti-inflammation drug (albeit one that is currently reported to be priced at about $200,000 a year) could reduce the risk of the combination of heart attacks, stroke and death from cardiovascular disease in people who had previously had a heart attack and a blood test that indicated the presence of inflammation. And it did so without affecting cholesterol levels.

The effect on patient care will not be immediate, but the study is transformative in moving inflammation into the category of a modifiable risk factor for heart disease.

What is inflammation? The body’s immune system protects us from foreign invaders, like viruses and bacteria.

Inflammation is the body’s response, with the activation of white blood cells and other substances. Most often, that response helps us. In cancer, scientists have been using our own immune systems to target disease.

However, sometimes, our immune systems can actually attack our own body and cause disease; these are called autoimmune diseases, like rheumatoid arthritis.

Now people are looking at inflammation as contributing to the risk of common conditions, like heart disease.

Paul Ridker, the principal investigator of the CANTOS trial and a cardiologist at Harvard, is the leading proponent of this inflammation hypothesis. [Disclosure: Paul is married to my sister (and I want to disclose that) and so I have had a front row seat in these developments over the last two decades.] His work and that of other scientists carefully and methodically laid the groundwork for the idea that giving people treatment that would quiet their immune systems would reduce their risk of heart disease.

As basic scientists were revealing that inflammation played a role in the biology of the causes of heart disease, clinical scientists were showing that blood tests of inflammation could indicate levels of risk.

People who had a more revved-up immune system had a higher risk of heart disease. And this risk was in addition to what was indicated by traditional risk factors like smoking and high cholesterol levels.

They found that statin drugs, which are highly effective in reducing heart disease risk, actually not only lowered cholesterol, but also calmed inflammation.

And so many speculated that the benefit of statins may also derive from what they do to the immune system.

But the question persisted – could an intervention that targeted the immune system without affecting lipid levels reduce heart disease risk? CANTOS used canakinumab, an expensive drug that is approved for use in some autoimmune diseases, like juvenile arthritis. It targets a particular part of the immune system and can reduce inflammation.

In the study of about 10,000 people who were randomized to receive canakinumab or placebo and followed for 4 years, there was a benefit. For every 1000 people treated with canakinumab, there were about 6 fewer deaths from heart attacks, stroke, or heart disease.

There was also a higher risk of an infection causing death.

There was no difference in deaths from any cause (though the study was not designed to detect a difference in overall deaths).

For patients, this trial is not likely to make canakinumab a household name.

 The benefits were modest, there were some risks, and the price tag, at least now, is in the stratosphere.

But make no mistake, this trial heralds the beginning of a new era in cardiology. It signals that the manipulation of the immune system is likely to be another avenue of reducing cardiovascular risk – and there are many possibilities with new drugs and old ones that could be repurposed.

In fact, the NIH has supported Dr. Ridker to investigate the possibility that methotrexate, an old and inexpensive drug with anti-inflammatory effects, could reduce the risk of heart disease – and that trial, theCardiovascular Inflammation Reduction Trial, according to ClinicalTrials.gov is still recruiting.

And there is something more. In an exploratory analysis that ultimately may or may not turn out to be important, the CANTOS investigators reported that lung cancer rates and deaths were much lower in the canakinumab.

Could such drugs reduce the risk of cancer and heart disease? Could an even safer and less expensive drug do the same thing? This trial should open the gates to an abundance of future research.

The idea that inflammation is important in heart disease is not new and is supported by a mountain of science.

But now we may be at the beginning of translating that science into strategies and interventions. Healthy behaviors continue to be the best way to combat heart disease – but it will be nice to have more tools available and to see this potential unfold in the years ahead.

Source        forbes