Correlation Between Clonal Hematopoiesis, Cardio-vascular Events, Inflammation and Atherosclerosis

Frequency of Clonal Hematopoiesis in Patients Over 75 With a First Cardio Vascular Event. Consequences on Inflammation and Atherosclerosis

This study aims at evaluating the prevalence of Clonal Hematopoiesis of Indeterminate Potential (CHIP) in patients over 75 presenting with a first cardio-vascular event (CVE). The investigators will also determine if CHIPs are more frequent in this population compared to a control cohort without CVE. An association between CHIP, a systemic inflammation and increased atherosclerosis will also be assessed.

Despite increasing knowledge on the pathophysiology of cardio-vascular diseases (in particular the role of inflammation in the development of atherosclerosis), predicting their occurrence remains largely difficult. Aging remains the most powerful factor for predicting the occurrence of myocardial infarction, independently from other identified risk factors. Few years ago, acquired mutations were described in the hematopoietic system of apparently healthy subjects. This phenomenon, now described as CHIP (Clonal Hematopoiesis of Indeterminate Potential) is more frequently observed in elderly people, and has been recently linked to an increased risk of cardio-vascular events. Experiments in mice demonstrated that these CHIPs are responsible for an inflammation that supports the development of atherosclerosis. However the link between CHIP, inflammation and atherosclerosis has never been demonstrated in humans.

In this study, the investigators will search for an increased frequency of CHIP in patients with a first cardio-vascular event (CVE). Seven months after the CVE, a blood sample will be taken. Mutations in the 9 most frequently mutated genes in CHIP will be evaluated by Next Generation Sequencing. Systemic inflammation will be evaluated by measurement of circulating levels of CRP, IL-1β, IL-6, IL-10 and TNF-α. Atherosclerosis will be evaluated via the volume of atherosclerotic plaques as assessed by 3D ultrasound analysis. The presence of CHIP will be correlated to traditional cardiovascular risk factors, systemic inflammation markers and the level of atherosclerosis. The investigators will also assess the relationship between the presence of CHIP and the risk of CVE reoccurrence.

Inclusion Criteria:

• Patients (male or female) over 75 years old
• Patients with a first CVE (myocardial infarction) of atheromatous origin that occurred between 2 and 7 months before inclusion
• Absence of evidence of hematological malignancy (known or obvious by the results of blood counts)
• Subject registered with a social security scheme
• Written informed consent obtained

Exclusion Criteria:

• Patients who did not presented any CVE in the last 7 months

• Patients with CVE with a non-atheromatous origin (dissection, embolic, …)

• Presence of an unbalanced diabetes (defined as HbA1C > 10%)

• History of previous CVE before 75 year-old : myocardial infarction, stroke of atheromatous origin

• Hematological malignancy (known or obvious on the results of blood counts)

• Chronic inflammatory disease (cancer, vasculitis, rheumatism, hepato-gastro-intestinal diseases).

• Long term anti-inflammatory treatments:

  • Corticoids
  • Nonsteroidal anti-inflammatory drugs
  • Aspirin (> 325 mg per day)
  • Cyclo-oxygenase II inhibitors

• Persons under judicial safeguards, trustee or curators

• Person deprived of judicial or administrative freedom

• Person unable to give her consent

• Non-cooperative person

• Exclusion period after another clinical study or participation to another interventional clinical study testing a drug in the 30 days before inclusion