乌鸦传媒

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Coronary disease doubles with clonal hematopoiesis of indeterminate potential (CHIP) in peripheral blood cells, found researchers who then demonstrated in mice how it drives atherosclerosis via inflammation.

CHIP -- an age-related condition in which mutated hematopoietic stem cells gradually take over -- was associated with 1.9 times the coronary heart disease risk seen in noncarriers (95% CI 1.4-2.7) overall in two cohort studies with an average age of 70.

Among people with MI before age 50, CHIP was found in only 2% but appeared to confer a "profound" risk. Compared with noncarriers in the same age range in two retrospective case-control cohorts, MI risk was fourfold (95% CI 2.4-6.7).

The four most common driver mutations -- in DNMT3A, TET2, ASXL1, and JAK2 genes -- were also individually associated with coronary disease as well as preclinical disease in terms of coronary-artery calcification, Sekar Kathiresan, MD, of the Massachusetts General Hospital in Boston, and colleagues reported in the New England Journal of Medicine.

These findings "provide new insight into how aging can promote atherosclerosis and cardiovascular events," John F. Keaney, Jr., MD, of the University of Massachusetts Medical School in Worcester, noted in an accompanying editorial.

That "indeterminate potential" isn't indeterminate anymore for cardiovascular disease, he concluded.

Mouse model experiments on how this hematologic problem could hurt the coronaries suggested that the associations found in humans may actually be causal, Kathiresan's group noted.

When mice prone to high cholesterol got bone marrow grafts from mice carrying the TET2 mutation, they had larger atherosclerotic lesions in the aortic root and aorta than did mice that had received control bone marrow, indicating that this common CHIP driver accelerated atherosclerosis. And the effect appeared to be because of excess production of interleukin-1β by monocytes.

"Thus, the data ... are consistent with established paradigms that inflammation is an accelerator of atherosclerosis and coronary heart disease," Keaney wrote. "Moreover, their findings should prompt a discourse about studying the use of anti-inflammatory agents in patients with CHIP to limit the most common cause of death in these patients -- cardiovascular disease."

And because about 10% of people age 70 and older have CHIP, it's worth considering whether CHIP impacts other chronic illnesses, like heart failure and type 2 diabetes, too, he suggested.