Birth Weight Is Associated With Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Outcomes in Adulthood.
J Am Heart Assoc
; 12(13): e030220, 2023 07 04.
Article
em En
| MEDLINE
| ID: mdl-37345823
ABSTRACT
Background High and low birth weight are independently associated with increased cardiovascular disease risk in adulthood. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic cells with preleukemic somatic mutations, predicts incident cardiovascular disease independent of traditional cardiovascular risk factors. Whether birth weight predicts development of CHIP later in life is unknown. Methods and Results A total of 221 047 adults enrolled in the UK Biobank with whole exome sequences and self-reported birth weight were analyzed. Of those, 22 030 (11.5%) had low (<2.5 kg) and 29 292 (14.7%) high birth weight (>4.0 kg). CHIP prevalence was higher among participants with low (6.0%, P=0.049) and high (6.3%, P<0.001) versus normal birth weight (5.7%, ref.). Multivariable-adjusted logistic regression analyses demonstrated that each 1-kg increase in birth weight was associated with a 3% increased risk of CHIP (odds ratio, 1.03 [95% CI, 1.00-1.06]; P=0.04), driven by a stronger association observed between birth weight and DNMT3A CHIP (odds ratio, 1.04 per 1-kg increase [95% CI, 1.01-1.08]; P=0.02). Mendelian randomization analyses supported a causal relationship of longer gestational age at delivery with DNMT3A CHIP. Multivariable Cox regression demonstrated that CHIP was independently and additively associated with incident cardiovascular disease or death across birth weight groups, with highest absolute risks in those with CHIP plus high or low birth weight. Conclusions Higher birth weight is associated with increased risk of developing CHIP in midlife, especially DNMT3A CHIP. These findings identify a novel risk factor for CHIP and provide insights into the relationships among early-life environment, CHIP, cancer, and cardiovascular disease.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Cardiovasculares
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Humans
Idioma:
En
Revista:
J Am Heart Assoc
Ano de publicação:
2023
Tipo de documento:
Article