Combined Effects of Clonal Hematopoiesis and Carotid Stenosis on Cardiovascular Mortality
abstract
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Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
The expansion of hematopoietic stem cells caused by acquired somatic mutations (clonal hematopoiesis [CH]) is a novel cardiovascular risk factor. The prognostic value of CH in patients with carotid atherosclerosis remains to be evaluated.
OBJECTIVES
This study assessed the prognostic significance of CH in patients with atherosclerosis as detected by ultrasound of the carotid artery.
METHODS
We applied deep sequencing of selected genomic regions within the genes DNMT3A, TET2, ASXL1, and JAK2 to screen for CH in 968 prospectively collected patients with asymptomatic carotid atherosclerosis evaluated by duplex sonography.
RESULTS
We detected clonal markers at variant allele frequency ≥2% in 133 (13.7%) of 968 patients (median age 69.2 years), with increasing prevalence at advanced age. Multivariate analyses including age and established cardiovascular risk factors revealed overall presence of CH to be significantly associated with increased risk of cardiovascular death (HR: 1.50; 95% CI: 1.12-2.00; P = 0.007), reflected also at the single gene level. The effect of CH was more pronounced in older patients and independent of the patients' inflammatory status as measured by high-sensitivity C-reactive protein. Simultaneous assessment of CH and degree of carotid stenosis revealed combined effects on cardiovascular mortality, depicted by a superior risk for patients with >50% stenosis and concomitant CH (adjusted HR: 1.60; 95% CI: 1.08-2.38; P = 0.020).
CONCLUSIONS
CH status in combination with the extent of carotid atherosclerosis jointly predict long-term mortality. Determination of CH can provide additional prognostic information in patients with asymptomatic carotid atherosclerosis.
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Additional Info
Combined Effects of Clonal Hematopoiesis and Carotid Stenosis on Cardiovascular Mortality
J Am Coll Cardiol 2024 May 07;83(18)1717-1727, R Jäger, M Hoke, FJ Mayer, S Boden, C Englisch, C Ay, R Kralovics, CJ BinderFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.