Link Between Clonal Hematopoiesis and Stroke in Carotid Stenosis

About a fifth of all ischemic strokes are attributed to embolization of ruptured atherosclerotic plaque from carotid arterial stenosis. But it has been difficult to predict which person with asymptomatic carotid artery stenosis is likely to progress to symptomatic carotid disease and stroke. Now there is evidence linking clonal hematopoiesis, carotid stenosis and stroke. Clonal hematopoiesis is characterised by clonal expansion of hematopoietic stems cells due to aquired somatic leukemogenic driver mutations. Those having these mutations have increased vascular inflammation before it progresses to malignancies and double the risk of ischemic stroke. It has been mentioned that risk due to clonal hematopoiesis is equal in magnitude to conventional risk factors like smoking, hypertension, dyslipidemia and diabetes. Thus clonal hematopoiesis is being described as a novel cardiovascular risk factor [1].

A study published in the Journal of American College of Cardiology assessed the combined effects of clonal hematopoiesis and carotid artery stenosis on cardiovascular mortality [2]. They conducted deep sequencing of selected genomic regions in 968 patients with asymptomatic carotid atherosclerosis detected by duplex sonography. Multivariate analyses indicated that clonal hematopoiesis was significantly associated with increased risk of cardiovascular death. Effect was more in older persons and was independent of inflammatory status as measured by high sensitivity C-reactive protein. Superior risk was found in those with more than 50% carotid stenosis and concomitant clonal hematopoiesis.

Clonal hematopoiesis is a common age related phenomenon in hematopoietic stem cells. The graph of clonal hematopoiesis from the United States of America shows negligible numbers below the age of 30 years and a steady increase after that as age advances, peaking in seventh decade and mild decline after that.

References

1. Natarajan P, Bellomo TR. Clonal Hematopoiesis Among Patients With Asymptomatic Carotid Stenosis Compounds Risk of Cardiovascular Death. J Am Coll Cardiol. 2024 May 7;83(18):1728-1730. doi: 10.1016/j.jacc.2024.03.389. PMID: 38692826.
2. Jäger R, Hoke M, Mayer FJ, Boden S, Englisch C, Ay C, Kralovics R, Binder CJ. Combined Effects of Clonal Hematopoiesis and Carotid Stenosis on Cardiovascular Mortality. J Am Coll Cardiol. 2024 May 7;83(18):1717-1727. doi: 10.1016/j.jacc.2024.02.043. PMID: 38692825.