Clonal Hematopoiesis of Indeterminate Potential and Hypertension: Results from the Women’s Health Initiative

Bernhard Haring (Homburg/Saar)1, A. Aragaki (Washington)2, D. Shimbo (NYC)3, S. Rapp (Winston-Salem)4, C. Eaton (Providence)5, M. LaMonte (New York)6, J. Wactawski-Wende (New York)6, M. Allison (LaJolla)7, A. Shadyab (LaJolla)8, J. Rossouw (Washington)2, E. Whitsel (Chapel Hill)9, N. Franceschini (Chapel Hill)9, C. Kooperberg (Washington)2, P. Desai (New York)10, M. Simon (Detroit)11, M. Böhm (Homburg/Saar)1, P. Natarajan (Boston)12, S. Wassertheil-Smoller (Bronx)13, J. Manson (Boston)14

1Universitätsklinikum des Saarlandes Innere Medizin III - Kardiologie, Angiologie und internistische Intensivmedizin Homburg/Saar, Deutschland; 2Women's Health Initiative Washington, USA; 3Columbia University Irving Medical Center NYC, USA; 4Wake Forest School of Medicine Winston-Salem, USA; 5Brown University Providence, USA; 6University of Buffalo New York, USA; 7University of San Diego LaJolla, USA; 8University of California, San Diego LaJolla, USA; 9University of North Carolina Chapel Hill, USA; 10Weill Cornell Medicine New York, USA; 11Karmanos Cancer Institute Detroit, USA; 12Mass General Heart Center Boston, USA; 13Albert Einstein College of Medicine Bronx, USA; 14Brigham and Women’s Hospital Boston, USA



Clonal Hematopoiesis of Indeterminate Potential (CHIP) has been related to accelerated atherosclerosis.



Whether CHIP carriers have different blood pressure (BP) trajectories and higher risk of hypertension has not been investigated.


Design, Setting and Participants

This analysis included 2,492 postmenopausal women [mean age: 63 years] enrolled in the Women’s Health Initiative, a multicenter longitudinal study on major health issues causing morbidity and mortality in postmenopausal women.


Main Outcomes and Measures

CHIP was identified via deep-coverage whole genome sequencing data. Blood pressure was measured at baseline and then annually thereafter. Incident hypertension was defined in two ways: (a) a new self-report of medication-treated hypertension, and (b) a composite endpoint of self-report of medication-treated hypertension and/or measured blood pressure ≥ 140/90 mmHg during an annual study visit.



Over a mean (standard deviation) follow-up of 5.8 (0.9) years, among 1,517 women initially without hypertension there were 74 of 117 cases of incident hypertension in CHIP and 741 of 1,400 cases in non-CHIP carriers. In multivariable-adjusted analyses, presence of CHIP was associated with a higher risk for incident hypertension, as defined above [(a) HR 1.50; 95% CI 1.04-2.17; p=0.03 and (b) HR, 1.39; 95% CI 1.04-1.84; p=0.02]. In gene-specific analysis, results for the individual mutations TET2 or DMNT3A were not statistically different from the overall result. Among women with hypertension (n= 975), CHIP carrier status was associated with taking 24% more antihypertensive medications [95% CI, 1.10-1.30; p<0.001] compared to non-CHIP carriers.



Among postmenopausal women without hypertension, CHIP carriers had a higher risk of incident hypertension. This risk was similar across major driver mutations. CHIP carriers should be closely followed to mitigate CHIP-associated cardiovascular disease risk.

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