Email: xavier.jouven@inserm.fr

Team: Cardiovascular Epidemiology and Sudden Death

Website: http://parcc.inserm.fr

The Professor Xavier Jouven is a cardiologist, professor of Public Health who has focused his research on cardiovascular epidemiology. His team is part of the UMR 970 located at the PARCC (adjacent to the Georges Pompidou European Hospital (HEGP), Paris 15ème) and encompasses more than 25 persons belonging to INSERM and/or AP-HP: epidemiologists, statisticians, clinical research workers or physicians of different specialties, who constantly collaborate.

The team works on the identification of new markers of cardiovascular diseases in general population and in high-risk populations, using national and international cohorts.

Main axes of research:

• Sudden death in adults: risk factors and prognosis of survivals
  • Biomarkers and cardiovascular diseases: added value in cardiovascular risk prediction
  • Kidney graft and cardiovascular prognosis

Furthermore, the Prof. Jouven has extended his clinical work in a humanitarian way by establishing an association of cardiologists to teach counterparts in Africa and Asia how to implant pacemakers and then see them go on to teach the techniques to their immediate colleagues. Following this successful experience, XJ has set up a working group of cardiologists in developing countries. This, in turn, has aroused a secondary research interest in “newly neglected diseases” – the cardiac conditions that are no longer prevalent in the industrialised world but are still common, and often untreated, in developing countries. Cardiac rheumatism was the first disease to be studied in this new area of research. CADRE study has emerged next, to investigate the vascular complications of sickle cell disease in Africa. Dr. Brigitte Ranque who is MCU-PH in internal medicine, and has a PhD in genetic epidemiology coordinates the study. Besides her methodological implication in the CADRE study, she works as a clinician in the Internal Medicine department of HEGP, which is one of the reference centers for sickle cell disease. 

Background

Sickle cell disease (SCD) occurs mainly in people or their descendants from tropical and sub tropical regions particularly in Africa. Nevertheless, the natural history of the disease in Africa remains largely unknown. Average life expectancy is around 50 years in Europe and United States of America, but is much shorter in Africa (probably less than 10). Most of the clinical studies concerning SCD chronic complications involve patients from developed countries (mostly the USA and Europe) and are based on few hundreds cases. These complications encompass many macro- or micro-vascular events, such as stroke, heart failure, pulmonary hypertension, kidney disease, retinopathy, bone infarcts and leg ulcers whereas SCD patients have fewer classic cardiovascular risk factors than controls. It has been demonstrated that SCD patients have endothelial dysfunction, probably due to impaired NO bioavailability and formation of reactive oxygen and nitrite species by plasma haemoglobin released by chronic hemolysis. However, most physiopathological hypotheses rely on in vitro or animal studies.

Patients and methods

The aim of the CADRE study is to build a large register of SCD patients that will encompass more than 2500 adults and 1500 children in five African countries: Senegal, Ivory Coast, Mali, Gabon and Cameroon, based on our expertise in population-based epidemiological studies and on current medical collaborations and scientific studies ongoing in Africa. Our INSERM research unit has created this register with the help of the medical teams within each country. SCD patients listed in the haematology unit of the university hospitals in Dakar, Abidjan, Bamako (West Africa), Libreville and Yaoundé (Central Africa) are included into the study and prospectively followed.

The following data are collected and computerized: administrative data, medical history, clinical examination, biological examination including sickle cell genotype, hematological parameters (blood cells count, hemolysis markers) and renal function (serum creatinin, urine creatinin and urine proteins), as well as two additional examinations: cardiac echocardiography and pulse wave velocity (PWV).

The first aim is to assess the correlation between the severity of the SCD, assessed by the frequency of VOC and hospitalizations, the chronic microvascular complications (osteonecrosis, stroke, leg ulcers, retinopathy, renal insufficiency…) and the endothelial dysfunction assessed by arterial stiffness and wave reflexion. Correlations between hematological parameters (hemoglobin level, hemolysis markers…), renal function (serum creatinin level, urine albumin/creatinin level) and sickle cell genotypes will also be studied. This large cohort will be also used to test other potential biological prognostic markers and physiopathological hypotheses emerging from the work of other GrEx teams, at the epidemiological level.

Finally, this register will allow comparison of SCD natural history in Africa and in Europe, using existing cohorts of SCD patients of the french SCD reference center in Paris area. Further epidemiological studies comparing these two groups of patients will help unraveling the respective roles of genetic and environment factors in the course of SCD. This African register will remain open for several years enabling one to build additive educated studies.

Expertise

Main publications