Arterial Stiffness Impairment in Sickle Cell Disease Associated With Chronic Vascular Complications: The Multinational African CADRE Study

Brigitte Ranque; Aymeric Menet; Pierre Boutouyrie; Ibrahima Bara Diop; Samuel Kingue; Mamadou Diarra; Roland N'Guetta; Dapa Diallo; Saliou Diop; Ibrahima Diagne; Ibrahima Sanogo; Aissata Tolo; David Chelo; Guillaume Wamba; Jean Paul Gonzalez; Cochise Abough'elie; Cheick Oumar Diakite; Youssouf Traore; Gaëlle Legueun; Indou Deme-Ly; Blaise Felix Faye; Moussa Seck; Boidy Kouakou; Ismael Kamara; Sylvain Le Jeune; Xavier Jouven

doi:10.1161/CIRCULATIONAHA.115.021015

Arterial Stiffness Impairment in Sickle Cell Disease Associated With Chronic Vascular Complications: The Multinational African CADRE Study

Circulation. 2016 Sep 27;134(13):923-33. doi: 10.1161/CIRCULATIONAHA.115.021015. Epub 2016 Aug 31.

Authors

Brigitte Ranque¹, Aymeric Menet², Pierre Boutouyrie², Ibrahima Bara Diop², Samuel Kingue², Mamadou Diarra², Roland N'Guetta², Dapa Diallo², Saliou Diop², Ibrahima Diagne², Ibrahima Sanogo², Aissata Tolo², David Chelo², Guillaume Wamba², Jean Paul Gonzalez², Cochise Abough'elie², Cheick Oumar Diakite², Youssouf Traore², Gaëlle Legueun², Indou Deme-Ly², Blaise Felix Faye², Moussa Seck², Boidy Kouakou², Ismael Kamara², Sylvain Le Jeune², Xavier Jouven²

Affiliations

¹ From Internal Medicine Unit, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris, France (B.R.); UMR_S970, Inserm, Paris, France (B.R., P.B., S.L.J., X.J.); Faculté de médecine, Université Paris Descartes, France (B.R., P.B., X.J.); Cardiology Unit, groupement des hôpitaux de l'université catholique de Lille, université catholique de Lille, France (A.M.); Physiology Unit, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris, France (P.B.); Cardiology Unit, CHU de Fann, Dakar, Senegal (I.B.D., G.L.); Cardiology Unit, Hôpital Général, Yaoundé, Cameroon (S.K.); Cardiology Unit, Centre Gynéco-obstétrique, Bamako, Mali (M.D., C.O.D.); Institut de cardiologie, Abidjan, Ivory Coast (R.N'G.); Centre de recherche et Lutte contre la Drépanocytose, Bamako, Mali (D.D., Y.T.); Centre National de Transfusion Sanguine, Dakar, Senegal (S.D., B.F.F., M.S.); Pediatrics Unit, Centre Hopital Albert Royer, CHU de Fann, Dakar, Senegal (I.D., I.D.-L.); Hematology Unit, CHU de Yopougon, Abidjan, Ivory Coast (I.S., A.T., B.K., I.K.); Fondation Mère Enfant Chantal Biya, Yaoundé, Cameroon (D.C.); Pediatrics Unit, Centre Hospitalier d'Essos, Yaoundé, Cameroon (G.W.); CIRMF, Libreville, Gabon (J.P.G., C.A.); Internal Medicine Department, Hôpital Avicenne, Assistance Publique des Hôpitaux de Paris, France (S.L.J.); and Cardiology Department, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris France (X.J.). brigitte.ranque@egp.aphp.fr.
² From Internal Medicine Unit, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris, France (B.R.); UMR_S970, Inserm, Paris, France (B.R., P.B., S.L.J., X.J.); Faculté de médecine, Université Paris Descartes, France (B.R., P.B., X.J.); Cardiology Unit, groupement des hôpitaux de l'université catholique de Lille, université catholique de Lille, France (A.M.); Physiology Unit, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris, France (P.B.); Cardiology Unit, CHU de Fann, Dakar, Senegal (I.B.D., G.L.); Cardiology Unit, Hôpital Général, Yaoundé, Cameroon (S.K.); Cardiology Unit, Centre Gynéco-obstétrique, Bamako, Mali (M.D., C.O.D.); Institut de cardiologie, Abidjan, Ivory Coast (R.N'G.); Centre de recherche et Lutte contre la Drépanocytose, Bamako, Mali (D.D., Y.T.); Centre National de Transfusion Sanguine, Dakar, Senegal (S.D., B.F.F., M.S.); Pediatrics Unit, Centre Hopital Albert Royer, CHU de Fann, Dakar, Senegal (I.D., I.D.-L.); Hematology Unit, CHU de Yopougon, Abidjan, Ivory Coast (I.S., A.T., B.K., I.K.); Fondation Mère Enfant Chantal Biya, Yaoundé, Cameroon (D.C.); Pediatrics Unit, Centre Hospitalier d'Essos, Yaoundé, Cameroon (G.W.); CIRMF, Libreville, Gabon (J.P.G., C.A.); Internal Medicine Department, Hôpital Avicenne, Assistance Publique des Hôpitaux de Paris, France (S.L.J.); and Cardiology Department, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris France (X.J.).

PMID: 27582423
DOI: 10.1161/CIRCULATIONAHA.115.021015

Abstract

Background: Although a blood genetic disease, sickle cell disease (SCD) leads to a chronic vasculopathy with multiple organ involvement. We assessed arterial stiffness in SCD patients and looked for associations between arterial stiffness and SCD-related vascular complications.

Methods: The CADRE (Coeur Artères et Drepanocytose, ie, Heart Arteries and Sickle Cell Disease) study prospectively recruited pediatric and adult SCD patients and healthy controls in Cameroon, Ivory Coast, Gabon, Mali, and Senegal. Patients underwent clinical examination, routine laboratory tests (complete blood count, serum creatinine level), urine albumin/creatinine ratio measure, and a measure of carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AI) at a steady state. The clinical and biological correlates of cf-PWV and AI were investigated by using a multivariable multilevel linear regression analysis with individuals nested in families further nested in countries.

Results: Included were 3627 patients with SCD and 943 controls. Mean cf-PWV was lower in SCD patients (7.5±2.0 m/s) than in controls (9.1±2.4 m/s, P<0.0001), and lower in SS-Sβ(0) than in SC-Sβ(+) phenotypes. AI, corrected for heart rate, increased more rapidly with age in SCD patients and was higher in SCD than in control adults. cf-PWV and AI were independently associated with age, sex, height, heart rate, mean blood pressure, hemoglobin level, country, and hemoglobin phenotype. After adjustment for these correlates, cf-PWV and AI were associated with the glomerular filtration rate and osteonecrosis. AI was also associated with stroke, pulmonary hypertension, and priapism, and cf-PWV was associated with microalbuminuria.

Conclusions: PWV and AI are deeply modified in SCD patients in comparison with healthy controls. These changes are independently associated with a lower blood pressure and a higher heart rate but also with the hemoglobin phenotype. Moreover, PWV and AI are associated with several SCD clinical complications. Their prognostic value will be assessed at follow-up of the patients.

Keywords: anemia; anemia, sickle cell; blood pressure; pulse wave analysis; vasculopathy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anemia, Sickle Cell / complications
Anemia, Sickle Cell / physiopathology*
Blood Flow Velocity / physiology
Blood Pressure / physiology*
Drug Discovery
Female
Heart Rate / physiology*
Humans
Male
Middle Aged
Pulsatile Flow / physiology
Pulse Wave Analysis / methods
Risk Factors
Vascular Diseases / etiology*
Vascular Diseases / physiopathology
Vascular Stiffness / physiology*