Clonal Hematopoiesis of Indeterminate Potential Increases the Risk of Stroke
A cell is a bag of molecules, all constantly slamming into each other at high speed. Damage to intricate structures such as the packaged DNA of the cell nucleus occurs all time. Most of it is fixed immediately by the highly efficient DNA repair machinery, but a tiny fraction slips through to produce mutations in the sequences describing proteins. In general, even this mutational damage is mostly harmless, except when it hits exactly the right gene to produce a cancerous cell. The damage usually occurs in regions of DNA not used in that cell, or in genes that are used but are not all that important to cell function, or it occurs in a cell that has only a few replications left before reaching the Hayflick limit, and thus any consequences are quite limited.
However, some mutational damage occurs in stem cell and progenitor cell populations, and this ensures that a mutation spreads throughout a tissue over time, present in every daughter somatic cell produced by the mutated stem cell. A layered spread of mutations throughout a tissue, occurring slowly over time as damage accrues in stem cells, is called somatic mosaicism. Researchers consider that this likely contributes to aging by spreading dysfunction, but connecting specific harms to the specific presence of somatic mosaicism has proven challenging.
The one form of somatic mosaicism for which researchers are finding connections is clonal hematopoiesis of indeterminate potential (CHIP), mosaicism in the populations of immune cells generated in the bone marrow. The immune system is influential on health, declines with age, and it seems plausible that one might see widespread effects resulting from significant mutational change in a sizable fraction of circulating immune cells. Today's open access paper is one of a number of examples in which CHIP correlates with unfavorable outcomes, likely because it is giving rise to greater inflammatory behavior in the aged immune system.
Clonal hematopoiesis of indeterminate potential (CHIP), which has recently been shown to be an age-related phenomenon, is associated with cardiovascular diseases, including atherosclerosis and stroke. This study focused on the association between CHIP and short- and long-term stroke recurrence in patients with acute ischemic stroke and intracranial atherosclerotic stenosis (ICAS).
This study included 4,699 patients with acute ischemic stroke based on data from the Third China National Stroke Registry (CNSR-III), a nationwide prospective hospital-based registry. The ICAS assessment followed the criteria established by the Warfarin-Aspirin Symptomatic Intracranial Disease Study and Brain Imaging. Atherosclerosis Scores (AS) were used to assess the atherosclerosis burden, as determined by the number and severity of steno-occlusions in the intracranial arteries. The primary outcome was stroke recurrence three months and one year after the event.
Among the 4,699 patients, 3,181 were female, and the median age was 63.0 years. We found that CHIP significantly increased the risk of stroke recurrence at the 1-year follow-up in patients with ICAS (adjusted hazard ratio [HR] 2.71). Our results revealed that CHIP might have a significant impact on the long-term risk of recurrent stroke, particularly in patients with a higher atherosclerotic burden.