Kevin Lomangino is the managing editor of HealthNewsReview.org. He tweets as @KLomangino.
Earlier this week, The New York Times introduced the American public to a potential new heart disease risk factor involving mutated stem cells, known as “CHIP” (clonal hematopoiesis of indeterminate potential).
The enthusiastic story by journalist Gina Kolata makes for a fascinating read about some fascinating science. The gist is that in some people, mutated stem cells in bone marrow grow into white blood cells that carry the same mutation. Those white blood cells may eventually contribute to inflammation inside artery-clogging plaques, possibly accelerating the growth of those plaques or making them more prone to rupture. People with CHIP mutations have higher rates of heart disease compared with non-carriers, several studies show.
One thing readers of the story will learn is that CHIP testing — though not yet recommended clinically — is currently available for those trailblazers who are willing to pay several thousand dollars to know their CHIP status.
But there’s another thing readers won’t learn about CHIP: The researcher who discusses the test, and who is the senior author of the New England Journal of Medicine study that sparked the coverage, is listed on a patent related to CHIP and serves as a consultant to a testing company. Many other authors on this study, and sources for the Times story, have similar conflicts of interest.
Along with two of his co-authors, Benjamin Ebert, MD, PhD holds intellectual property rights for a “Method of Identifying and Treating a Person Having a Predisposition to or Afflicted with a Cardiometabolic Disease” that’s based on CHIP. He also receives personal fees and royalties from Genoptix, a testing company to which he has previously reported licensing his intellectual property. A fourth study co-author discloses a patent related to CHIP on testing for bone marrow disorders that has been licensed to Genoptix. Another source for the story who wasn’t an author of the study — David Steensma, MD — also consults for Genoptix.
[Editor’s note: Dr. Ebert wrote to clarify that the consulting relationship with Genoptix that he disclosed with the study has ended, and he no longer receives royalty income from the company for that licensing arrangement. He said that intellectual property related to CHIP for cardiovascular disease has not been licensed.]
These financial interests are properly identified — though somewhat difficult to find — in the supplemental NEJM disclosure forms that accompanied the study the Times reported on. However, none of these financial interests made it into the Times’s coverage of CHIP.
The existence of such commercial relationships shouldn’t diminish the excitement surrounding the science. Experts I reached out to all agreed that this is important and groundbreaking research. Some optimism is warranted.
But is it possible that financial interests might subtly bias the perspective of the CHIP researchers — contributing to an enthusiasm that stretches past what the current evidence can support?
The Times’ role as a journalistic organization is to critically evaluate claims for its readers and seek out alternate views. But its story doesn’t feature anyone who was willing to pump the brakes on CHIP.
It’s pedal to the metal on this story–starting with the brash headline, which claims that CHIP is “emerging as a major cause of heart attacks and stroke, as deadly as high blood pressure or cholesterol.” Another researcher calls CHIP “the most important discovery in cardiology since statins.”
Harold DeMonaco, MS, a visiting scientist at the MIT Sloan School of Management and one of our expert reviewers, said it was too early to be putting CHIP mutations on the same level with blood pressure, cholesterol, or statins.
“Is there an association? Yes. Is CHIP a cause of heart attack and stroke? Perhaps. Much of Kolata’s reporting is on target. Indeed, it is unclear why people without identifiable risk factors have cardiac events and CHIP may be an important factor. Research to date certainly points in that direction both in terms of epidemiology and well as in a mechanism,” he said.
But DeMonaco noted that the accompanying NEJM editorial said the study “supports the hypothesis that CHIP is linked to the clinical events of atherosclerosis and that certain CHIP driver genes are involved in regulating inflammation.” (emphasis added)
A hypothesis is not a certainty, and yet the Times says unequivocally that CHIP “doubled the risk of a heart attack in typical patients — and increased the risk fourfold in those who had heart attacks early in life.”
The NEJM study, by contrast, said CHIP mutations were “associated” with increased risk — reflecting the lack of definitive data showing a cause-and-effect relationship.
Also, DeMonaco said these impressive-sounding relative risks are not as dramatic when viewed in absolute terms. The “fourfold” increase in risk translates to a 2% rate of heart attacks in CHIP carriers compared to <1% in the control group, he said. While a 1% difference may still be meaningful in this group of people under the age of 50, it’s not as substantial as the “fourfold” Times description might suggest to some readers.
Cardiologist Christopher Labos, MD, also a HealthNewsReview.org contributor, pointed out that studies have identified more than 100 genetic mutations associated with heart disease.
Some have stronger associations than others, but none has been shown to be a particularly good predictor on its own. Whether CHIP will provide more useful information than these other genetic variants remains to be seen, Labos said.
“While CHIP may, and probably does play a role in cardiovascular disease formation, people should know that many other genetic variants also play a role, and while they may have a ‘bad gene’ in one part of their DNA, they might have a ‘good gene’ in another part of their DNA,” Labos said. “How these good and bad genes balance out is still being teased out, which means the reality of genetic testing in cardiology is more complicated than a single test.”
He also said that many other promising markers have been proposed to measure cardiovascular risk over the years, and that many have been abandoned because they don’t add information to what we already know.
“For CHIP to be helpful clinically, you either have to show that testing for it changes how you approach the patient’s care, or that you can develop some sort of treatment to reverse the condition and lower somebody’s risk,” he said.
Here’s a summary of why we think this issue is important to address:
It’s good that the Times acknowledges that CHIP testing is not recommended and that there’s nothing people with CHIP mutations can do right now beyond live a healthy lifestyle and control other risk factors.
One day researchers may develop an effective therapy that targets the CHIP mutation, but that prospect is still years away.
“If you have CHIP,” Labos said, “you should stop smoking, eat right, exercise, control your blood pressure, etc. And if you don’t have CHIP you should still do all these things, so it doesn’t lead to any different recommendations.”
Addendum 2/2/18: One of the co-authors on the NEJM study, Siddhartha Jaiswail, MD, PhD, took to Twitter to criticize the Times coverage as overly enthusiastic. (Click the tweet to view the entire thread.) In doing so, he raised many of the same issues that we discussed in this post. Of note, Jaiswal holds an interest in the patent for using CHIP in cardiovascular testing and therapy, suggesting that a conflict of interest need not preclude someone from openly acknowledging the limitations of their research and calling out hype.
— Siddhartha Jaiswal (@jaiswalmdphd) February 1, 2018