Endothelial function and arterial stiffness in sickle-thalassemia patients



      Homozygous sickle-cell anemia and β-thalassemia are characterized by impaired endothelial function, while data on arterial stiffness have hitherto been conflicting. We sought to investigate aortic elastic properties and endothelial function in sickle-thalassemia, which combines molecular and clinical features of the above conditions.

      Methods and results

      Forty-seven sickle-thalassemia patients, younger than 45 years, with preserved left ventricular (LV) function and no history of smoking, systemic or pulmonary hypertension, diabetes mellitus, dyslipidemia or thyroid disease, along with 40 healthy controls were studied. Aortic strain, distensibility and stiffness index were calculated by echocardiographically-obtained aortic root diameters. Brachial artery endothelial function was assessed by ultrasonographic evaluation of flow-mediated dilatation (FMD) and nitrate-mediated dilatation (NMD). Left ventricle was assessed by echocardiography. Patients had an impaired FMD (4.2 ± 2.9% versus 9.2 ± 3.8% in controls, p < 0.001) with a preserved NMD (16.9 ± 5.6% versus 15.2 ± 4.8% in controls, p > 0.05). Aortic strain and distensibility were lower and aortic stiffness index was higher in patients compared to controls (8.1 ± 4.6 versus 5.8 ± 2.9, p < 0.01). Indexed LV diameters and mass were higher in patients. Systolic LV function was preserved, while 14.9% of patients had an impaired relaxation transmitral inflow pattern. Patients’ LV mass index and diastolic mitral E wave deceleration time were positively correlated with aortic stiffness index (p < 0.001).


      Sickle-thalassemia is characterized by a complex vasculopathy, consisting of endothelial dysfunction and increased arterial stiffness, with a global effect on cardiovascular function.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Wang W.C.
        • Lukens J.N.
        Sickle cell anemia and other sickling syndromes.
        in: 10th ed. Wintrobe's clinical hematology. vol. 1. Lippincott Williams & Wilkins, Baltimore1999: 1381
        • Rodgers G.P.
        • Schechter A.N.
        • Noguchi C.T.
        • Klein H.G.
        • Nienhuis A.W.
        • Bonner R.F.
        Periodic microcirculatory flow in patients with sickle-cell disease.
        N Engl J Med. 1984; 311: 1534-1538
        • Lipowsky H.H.
        • Sheikh N.U.
        • Katz D.M.
        Intravital microscopy of capillary hemodynamics in sickle cell disease.
        J Clin Invest. 1987; 80: 117-127
        • Belhassen L.
        • Pelle G.
        • Sediame S.
        • et al.
        Endothelial dysfunction in patients with sickle cell disease is related to selective impairment of shear stress-mediated vasodilation.
        Blood. 2001; 97: 1584-1589
        • Lemogoum D.
        • Van Bortel L.
        • Najem B.
        • et al.
        Arterial stiffness and wave reflections in patients with sickle cell disease.
        Hypertension. 2004; 44: 924-929
        • Fitch R.M.
        • Vergona R.
        • Sullivan M.E.
        • Wang Y.X.
        Nitric oxide synthase inhibition increases aortic stiffness measured by pulse wave velocity in rats.
        Cardiovasc Res. 2001; 51: 351-358
        • Sahn D.J.
        • DeMaria A.
        • Kisslo J.
        • Weyman A.
        The committee on M-mode standardization of the American Society of Echocardiography: results of a survey of echocardiographic measurements.
        Circulation. 1978; 58: 1072-1083
        • Schiller N.B.
        • Shah P.M.
        • Crawford M.
        • et al.
        Recommendations for quantitation of the left ventricle by two-dimensional echocardiography: American Society of Echocardiography Committee on Standards Subcommittee.
        J Am Soc Echocardiogr. 1989; 2: 358-367
        • Devereux R.B.
        • Alonso D.R.
        • Lutas E.M.
        • et al.
        Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings.
        Am J Cardiol. 1986; 57: 450-458
        • Lubien E.
        • DeMaria A.
        • Krishnaswamy P.
        • et al.
        Utility of B-natriuretic peptide in detecting diastolic dysfunction: comparison with Doppler velocity recordings.
        Circulation. 2002; 105: 595-601
        • Stratos C.
        • Stefanadis C.
        • Kallikazaros I.
        • Boudoulas H.
        • Toutouzas P.
        Ascending aorta distensibility abnormalities in hypertensive patients and response to nifedipine administration.
        Am J Med. 1992; 93: 505-512
        • Woo K.S.
        • Chook P.
        • Lolin Y.I.
        • et al.
        Hyperhomocysteinaemia is a risk factor for arterial endothelial dysfunction in humans.
        Circulation. 1997; 96: 2542-2544
        • Corretti M.C.
        • Anderson T.J.
        • Benjamin E.J.
        • et al.
        International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilatation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force.
        J Am Coll Cardiol. 2002; 39: 257-265
        • Stuart M.J.
        • Setty B.N.
        Sickle cell acute chest syndrome: pathogenesis and rationale for treatment.
        Blood. 1999; 94: 1555-1560
        • Morris C.R.
        • Kato G.J.
        • Poljakovic M.
        • et al.
        Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease.
        JAMA. 2005; 294: 81-90
        • Aessopos A.
        • Farmakis D.
        • Loukopoulos D.
        Elastic tissue abnormalities resembling pseudoxanthoma elasticum in beta thalassemia and the sickling syndromes.
        Blood. 2002; 99: 30-35
        • Aessopos A.
        • Farmakis D.
        • Loukopoulos D.
        Elastic tissue abnormalities in inherited haemolytic syndromes.
        Eur J Clin Invest. 2002; 32: 640-642
        • Aessopos A.
        • Farmakis D.
        Sickle cell disease: introducing a distinct elastic tissue defect associated with inherited hemolytic syndromes.
        in: Plasmar R.L. Focus on sickle cell research. Nova Biomedical Books, New York2004: 157-179
        • Aessopos A.
        • Samarkos M.
        • Voskaridou E.
        • et al.
        Arterial calcifications in beta-thalassemia.
        Angiology. 1998; 49: 137-143
        • Aessopos A.
        • Savvides P.
        • Stamatelos G.
        • et al.
        Pseudoxanthoma elasticum-like skin lesions and angioid streaks in beta-thalassemia.
        Am J Hematol. 1992; 41: 159-164
        • Cheung Y.F.
        • Chan G.C.
        • Ha S.Y.
        Arterial stiffness and endothelial function in patients with beta-thalassemia major.
        Circulation. 2002; 106: 2561-2566
        • Blum A.
        • Yeganeh S.
        • Peleg A.
        • et al.
        Endothelial function in patients with sickle cell anemia during and after sickle cell crises.
        J Thromb Thrombolysis. 2005; 19: 83-86
        • London G.M.
        • Cohn J.N.
        Prognostic application of arterial stiffness: task forces.
        Am J Hypertens. 2002; 15: 754-758
        • Safar M.E.
        • Levy B.I.
        • Struijker-Boudier H.
        Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases.
        Circulation. 2003; 107: 2864-2869
        • Wasi P.
        • Na-Nakorn S.
        • Pootrakul P.
        • Sonakul D.
        • Piankijagum A.
        • Pacharee P.
        A syndrome of hypertension, convulsion, and cerebral haemorrhage in thalassaemic patients after multiple blood-transfusions.
        Lancet. 1978; 2: 602-604
        • Aessopos A.
        • Tsironi M.
        • Vassiliadis I.
        • et al.
        Exercise-induced myocardial perfusion abnormalities in sickle beta-thalassemia: Tc-99m tetrofosmin gated SPECT imaging study.
        Am J Med. 2001; 111: 355-360
        • Gladwin M.T.
        • Sachdev V.
        • Jison M.L.
        • et al.
        Pulmonary hypertension as a risk factor for death in patients with sickle cell disease.
        N Engl J Med. 2004; 350: 886-895
        • Adams R.J.
        • McKie V.C.
        • Hsu L.
        • et al.
        Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography.
        N Engl J Med. 1998; 339: 5-11
        • Adams R.J.
        • Brambilla D.
        Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) Trial Investigators. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease.
        N Engl J Med. 2005; 353: 2769-2778
        • Machado R.F.
        • Martyr S.
        • Kato G.J.
        • et al.
        Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension.
        Br J Haematol. 2005; 130: 445-453
        • Derchi G.
        • Forni G.L.
        • Formisano F.
        • et al.
        Efficacy and safety of sildenafil in the treatment of severe pulmonary hypertension in patients with hemoglobinopathies.
        Haematologica. 2005; 90: 452-458