Clonal Hematopoiesis and Atherosclerosis

Jaiswal, Siddhartha; Natarajan, Pradeep; Ebert, Benjamin L.

doi:10.1056/nejmc1710381

Cited by 30 publications

(8 citation statements)

References 14 publications

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“…Not surprisingly, follow up studies showed that patients with clonal hematopoiesis (CH) are at an increased risk of developing hematological malignancies. However, the same study showed that patients with CH are also at an increased risk of atherosclerotic cardiovascular disease compared to individuals without CH (Jaiswal et al, 2014 , 2017a , b ). Atherosclerotic cardiovascular disease has long been thought of as an inflammatory disease; however, only recently, data from the CANTOS study was published reporting that selectively targeting inflammation by using a therapeutic monoclonal anti-IL-1β antibody can reduce cardiovascular risk (Ridker et al, 2017a ).…”

Section: Causes Of An Inflammatory Microenvironmentmentioning

confidence: 95%

Underlying Causes and Therapeutic Targeting of the Inflammatory Tumor Microenvironment

Comen

Bowman

Kleppe

2018

Front. Cell Dev. Biol.

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Historically, the link between chronic inflammation and cancer has long been speculated. Only more recently, pre-clinical and epidemiologic data as well as clinical evidence all point to the role of the tumor microenvironment as inextricably connected to the neoplastic process. The tumor microenvironment (TME), a complex mix of vasculature, inflammatory cells, and stromal cells is the essential “soil” helping to modulate tumor potential. Increasingly, evidence suggests that chronic inflammation modifies the tumor microenvironment, via a host of mechanisms, including the production of cytokines, pro-inflammatory mediators, angiogenesis, and tissue remodeling. Inflammation can be triggered by a variety of different pressures, such as carcinogen exposure, immune dysfunction, dietary habits, and obesity, as well as genetic alterations leading to oncogene activation or loss of tumor suppressors. In this review, we examine the concept of the tumor microenvironment as related to both extrinsic and intrinsic stimuli that promote chronic inflammation and in turn tumorigenesis. Understanding the common pathways inherent in an inflammatory response and the tumor microenvironment may shed light on new therapies for both primary and metastatic disease. The concept of personalized medicine has pushed the field of oncology to drill down on the genetic changes of a cancer, in the hopes of identifying individually targeted agents. Given the complexities of the tumor microenvironment, it is clear that effective oncologic therapies will necessitate targeting not only the cancer cells, but their dynamic relationship to the tumor microenvironment as well.

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Section: Causes Of An Inflammatory Microenvironmentmentioning

confidence: 95%

Underlying Causes and Therapeutic Targeting of the Inflammatory Tumor Microenvironment

Comen

Bowman

Kleppe

2018

Front. Cell Dev. Biol.

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“…67 Patients with CHIP have an increased mortality rate that is primarily due to cardiovascular events rather than from hematological malignancy. 68 A recent prospective Dutch population-based cohort study showed no difference in the prevalence of DNMT3A, TET2 and ASXL1 mutations between controls with and without anemia. This result showed that single mutations of DNMT3A, TET2 and ASXL1 are not correlated with the presence of UAE.…”

Section: Clonal Hematopoiesismentioning

confidence: 95%

Anemia in older adults as a geriatric syndrome: A review

Katsumi

Abe

Tamura

et al. 2021

Geriatrics Gerontology Int

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Anemia, a frequently occurring condition in older patients, has no standard definition; however, in most studies, it is defined as hemoglobin level <12 and <13 g/dL in women and men, respectively. Approximately 10% of older adults living in the community have anemia. The prevalence of anemia is significantly correlated with advanced age and male sex. Anemia is associated with falls, frailty and other negative outcomes, including early mortality. However, there remains little consensus regarding whether anemia treatment favorably affects these adverse outcomes. Therefore, this article reviews the prevalence of anemia, and provides updates on its common causes and treatments in older adults. While excluding wellestablished hematopoietic diseases, the etiology of anemia in older adults has been grouped into four categories: (i) nutritional deficiency; (ii) inflammation; (iii) clonal hematopoiesis; and (iv) "unexplained anemia," when there is no clear mechanism to account for the anemia. Recently, clonal leukocytes were detected in a considerable number of older individuals. The number of somatic mutations in blood leukocytes increases with age; however, single mutations of DNMT3A, TET2 and ASXL1 are not correlated with the presence of unexplained anemia in older adults. With an increased understanding of anemia etiology and the availability of innovative anti-anemic drugs, future studies that evaluate the causes and benefits of treatment are required.

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“…Having a normal body mass index compared to being obese is associated with lower frequency of CHIP in postmenopausal women [ 19 ]. Jaiswal et al reported a 1.3-fold increased odds of CHIP in diabetes patients [ 22 ]. Obesity, diabetes, and CHIP may be related to one another through increased activation of pro-inflammatory pathways [ 21 ].…”

Section: Cardiovascular Risk Factors and Chipmentioning

confidence: 99%

“…In a seminal paper on “Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease,” Jaiswal et al showed that presence of CHIP in peripheral blood cells was associated with accelerated atherosclerosis and coronary heart disease [ 15 , 22 ]. Subsequent studies have expanded our understanding on CHIP carrier status and CVD (Table 2 ).…”

Section: Chip and Age-related Cardiovascular Riskmentioning

confidence: 99%

Somatic Mutations and Clonal Hematopoiesis as Drivers of Age-Related Cardiovascular Risk

2022

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Purpose of Review Clonal hematopoiesis of indeterminate potential (CHIP) has been identified as a novel cardiovascular risk factor. Here we review the relationship of lifestyle and environmental risk factors predisposing to somatic mutations and CHIP and provide an overview on age-related cardiovascular outcomes. Recent Findings CHIP has been associated with accelerated atherosclerosis and cardiovascular disease in both epidemiological and experimental studies. The most commonly mutated candidate driver genes are DNMT3A, TET2, JAK2, and ASXL1. The underlying mechanisms appear predominantly related to inflammatory pathways. Although age is the dominant risk factor for developing CHIP, emerging evidence suggests that other factors such as smoking, obesity/type 2 diabetes, or an unhealthy diet play a role in the occurrence of somatic mutations. Summary Evidence suggests a strong link between vascular risk factors, somatic hematopoietic mutations, and age-related cardiovascular disease. Further studies on CHIP biology are required to identify targeted interventions for risk reduction in patients with CHIP and inform the utility of screening strategies.

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Clonal Hematopoiesis and Atherosclerosis

Cited by 30 publications

References 14 publications

Underlying Causes and Therapeutic Targeting of the Inflammatory Tumor Microenvironment

Underlying Causes and Therapeutic Targeting of the Inflammatory Tumor Microenvironment

Anemia in older adults as a geriatric syndrome: A review

Somatic Mutations and Clonal Hematopoiesis as Drivers of Age-Related Cardiovascular Risk

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