Arterial Stiffness Impairment in Sickle Cell Disease Associated with Chronic Vascular Complications: The Multinational African CADRE Study
Background—Although a blood genetic disease, sickle cell disease (SCD) leads to a chronic vasculopathy with multiple organ involvement. We aimed at assessing arterial stiffness in SCD patients and at looking for associations between arterial stiffness and SCD-related vascular complications.
Methods—The CADRE study prospectively recruited pediatric and adult SCD patients and healthy controls in Cameroon, Ivory Coast, Gabon, Mali and Senegal. The subjects underwent clinical examination, routine laboratory tests (complete blood count, serum creatinine level), urine albumine/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 using a multivariable multilevel linear regression analysis with individuals nested in families further nested in countries.
Results—3627 patients with SCD and 943 controls were included. 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-Sβ0 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 with microalbuminuria.
Conclusions—PWV and AI are deeply modified in SCD patients compared to 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 during the follow up of the patients.
- Received December 23, 2015.
- Revision received April 26, 2016.
- Accepted July 27, 2016.