It’s been one of the vexing questions in medicine: Why is it that most people who have heart attacks or strokes have few or no conventional risk factors?
These are patients with normal levels of cholesterol and blood pressure, no history of smoking or diabetes, and no family history of cardiovascular disease. Why aren’t they spared?
To some researchers, this hidden risk is the dark matter of cardiology: an invisible but omnipresent force that lands tens of thousands of patients in the hospital each year. But now scientists may have gotten a glimpse of part of it.
They have learned that a bizarre accumulation of mutated stem cells in bone marrow increases a person’s risk of dying within a decade, usually from a heart attack or stroke, by 40 or 50 percent. They named the condition with medical jargon: clonal hematopoiesis of indeterminate potential.
CHIP has emerged as a risk for heart attack and stroke that is as powerful as high LDL or high blood pressure but it acts independently of them. And CHIP is not uncommon.
The condition becomes more likely with age. Up to 20 percent of people in their 60s have it, and perhaps 50 percent of those in their 80s.
“It is beginning to appear that there are only two types of people in the world: those that exhibit clonal hematopoiesis and those that are going to develop clonal hematopoiesis,” said Kenneth Walsh, who directs the hematovascular biology center at the University of Virginia School of Medicine.
The growing evidence has taken heart researchers aback. Dr. Peter Libby, a cardiologist at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, calls CHIP the most important discovery in cardiology since statins.
“I’m turning part of my lab to work on this full time,” Dr. Libby said. “It’s really exciting.”
The mutations are acquired, not inherited — most likely by bad luck or exposure to toxins like cigarette smoke. But there is little that patients can do. (...)
Dr. Benjamin Ebert, chair of medical oncology a the Dana-Farber Cancer Institute, was the first to see the link. He turned for help to Dr. Sekar Kathiresan, a cardiologist and genetics researcher at the Massachusetts General Hospital and the Broad Institute, who had genetic data from four more large studies.
They confirmed 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.
But how might mutated white blood cells cause heart disease? One clue intrigued scientists.
Artery-obstructing plaque is filled with white blood cells, smoldering with inflammation and subject to rupture. Perhaps mutated white cells were causing atherosclerosis or accelerating its development.
In separate studies, Dr. Ebert and Dr. Walsh gave mice a bone-marrow transplant containing stem cells with a CHIP mutation, along with stem cells that were not mutated. Mutated blood cells began proliferating in the mice, and they developed rapidly growing plaques that were burning with inflammation.
“For decades people have worked on inflammation as a cause of atherosclerosis,” Dr. Ebert said. “But it was not clear what initiated the inflammation.”
Now there is a possible explanation — and, Dr. Ebert said, it raises the possibility that CHIP may be involved in other inflammatory diseases, like arthritis.
These are patients with normal levels of cholesterol and blood pressure, no history of smoking or diabetes, and no family history of cardiovascular disease. Why aren’t they spared?
To some researchers, this hidden risk is the dark matter of cardiology: an invisible but omnipresent force that lands tens of thousands of patients in the hospital each year. But now scientists may have gotten a glimpse of part of it.
They have learned that a bizarre accumulation of mutated stem cells in bone marrow increases a person’s risk of dying within a decade, usually from a heart attack or stroke, by 40 or 50 percent. They named the condition with medical jargon: clonal hematopoiesis of indeterminate potential.CHIP has emerged as a risk for heart attack and stroke that is as powerful as high LDL or high blood pressure but it acts independently of them. And CHIP is not uncommon.
The condition becomes more likely with age. Up to 20 percent of people in their 60s have it, and perhaps 50 percent of those in their 80s.
“It is beginning to appear that there are only two types of people in the world: those that exhibit clonal hematopoiesis and those that are going to develop clonal hematopoiesis,” said Kenneth Walsh, who directs the hematovascular biology center at the University of Virginia School of Medicine.
The growing evidence has taken heart researchers aback. Dr. Peter Libby, a cardiologist at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, calls CHIP the most important discovery in cardiology since statins.
“I’m turning part of my lab to work on this full time,” Dr. Libby said. “It’s really exciting.”
The mutations are acquired, not inherited — most likely by bad luck or exposure to toxins like cigarette smoke. But there is little that patients can do. (...)
Dr. Benjamin Ebert, chair of medical oncology a the Dana-Farber Cancer Institute, was the first to see the link. He turned for help to Dr. Sekar Kathiresan, a cardiologist and genetics researcher at the Massachusetts General Hospital and the Broad Institute, who had genetic data from four more large studies.
They confirmed 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.
But how might mutated white blood cells cause heart disease? One clue intrigued scientists.
Artery-obstructing plaque is filled with white blood cells, smoldering with inflammation and subject to rupture. Perhaps mutated white cells were causing atherosclerosis or accelerating its development.
In separate studies, Dr. Ebert and Dr. Walsh gave mice a bone-marrow transplant containing stem cells with a CHIP mutation, along with stem cells that were not mutated. Mutated blood cells began proliferating in the mice, and they developed rapidly growing plaques that were burning with inflammation.
“For decades people have worked on inflammation as a cause of atherosclerosis,” Dr. Ebert said. “But it was not clear what initiated the inflammation.”
Now there is a possible explanation — and, Dr. Ebert said, it raises the possibility that CHIP may be involved in other inflammatory diseases, like arthritis.
by Gina Kolata, NY Times | Read more:
Image: SPL/Science Source
