Heart Arteries and Sickle Cell Disease / Coeur Artères DREpanocytose

Heart, Arteries and Sikle Cell Disease, a Multicentric Cohort of Cardiovascular Complications in Subsaharan Africa

The CADRE study is a multinational observational cohort of patients with sickle-cell disease (SCD) in five west and central sub-Saharan African countries. The aim of this project is to describe the incidence and assess the predictive factors of SCD-related micro- and macro-vascular complications in sub-Saharan Africa.

Sickle cell disease (SCD), one of the lost common genetic diseases worldwide, is caused by a mutation in the β globin gene. Most patients with this disease are homozygous for the βS allele (SS), whereas others have inherited a βS allele with another mutation in the β globin gene. In addition to repeated acute ischemic insults due to the red blood cells sickling in the microcirculation, a chronic vasculopathy leads to organ injuries, such as kidney disease, stroke, pulmonary hypertension, retinopathy, bone infarcts, and leg ulcers.

CADRE is a multinational prospective observational study undertaken in five countries in sub-Saharan Africa. Patients with SCD will be recruited through outpatients' clinics in public, university and private hospitals and research centers in five countries. The CADRE protocol was approved by the relevant national ethics committee in each of the participating countries.

Primary endpoint is to measure the prevalence and the incidence of the main vascular complications in the main types of SCD: glomerulopathy, nephropathy, cardiopathy, pulmonary hypertension, retinopathy, strokes, osteonecrosis and leg ulcers.

Secondary endpoints are:

• to define the clinical and biological predictors of SCD vasculopathy in Africa
• to search for genetic risk factors for the SCD-related cardiovascular complications, in particular alpha thalassemia, persistence of foetal hemoglobin and other candidate genetic polymorphisms
• to search for functional risk factors (pulse wave velocity, capillary vasodilatation, blood visosity) for the SCD-related cardiovascular complications
• to search for new biological determinant of SCD-related cardiovascular complications, in particular alternative markers of hemolysis (microparticules, free heme) and inflammation (cytokines, leucocytes phenotyping, NET (neutrophile extracellular traps))

Inclusion Criteria:

• age: five-year-old or more
• signature of informed consent Patients : major sickle cell syndrome confirmed by hemoglobin phenotyping: SS, SC, SBeta+ or Sbeta0 Controls : healthy parents or siblings of the patients, hospital staff or their children, matched on age+/- 3 years and country (1 control for 4 patients)

Exclusion Criteria:

unstable clinical status such as:

• vaso-occlusive crisis in the previous 15 days
• fever or infectious disease in the previous 15 days
• transfusion in the previous 2 months