Micro- and macrovascular function in children with sickle cell anaemia and sickle cell haemoglobin C disease

Abstract

It is unclear whether vascular function is affected similarly in children with sickle cell anaemia (SS) and children with sickle haemoglobin C (SC) disease. Therefore, we compared micro and macrovascular functions in healthy (AA) children, children with SS and SC disease, and assessed their association with physical activity. Participants (24 SS, 22 SC and 16 AA), were compared in terms of 1) thermal hyperaemic response (finger pad warming to 42°C) measured by Laser Doppler techniques, 2) arterial stiffness determined by pulse wave velocity, 3) daily energy expenditure related to moderate and intense physical activities estimated by questionnaire and 4) fitness level, evaluated by the six-minute walk test. Response to heating differed between SS, SC and controls. Peripheral microvascular reactivity was lower and pulse wave velocity higher in SS compared to AA. SC had blunted microvascular reactivity in response to heating compared to AA but pulse wave velocity was not different within the two groups. Physical activity and fitness levels were markedly lower in sickle cell patients compared to healthy controls but no association was observed with vascular function. Microvasodilatory reserve is decreased in both SS and SC patients but only SS patients were also characterised by impaired macrovascular function.

Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia

“…CR-PWV was measured in a cohort of 24 SCA patients, and compared to a group of AA (n = 16) of the same ethnic origin. As previously reported ( 21 ), PWV was higher in SCA than in AA ( Figure 3C , p < 0.01), indicating increased arterial stiffness in the former group. Circulating RBC-MPs were also measured in 24 patients of this cohort to test the association with the carotid-radial PWV.…”

“…Arterial stiffness is considered to be a relevant indicator of macrovascular function ( 20 ), and is increased in patients with SCA ( 21 ). We evaluated arterial stiffness by measuring carotid-radial pulse wave velocity (CR-PWV) with a non-invasive automated device (SphygmoCor System, Actor, Sydney, Australia).…”

“…Measurements were repeated two times at each measurement site, and the mean values were calculated and used for analyses. This technique has been demonstrated to be highly reproducible in both healthy and diseased populations ( 22 , 23 ), and has been previously been used in individuals with SCA ( 21 , 24 ).…”

The Red Blood Cell—Inflammation Vicious Circle in Sickle Cell Disease

“…This oxidative milieu results in exacerbated NO scavenging via an oxygen free radicaldependent mechanism, and further affects the vascular system. Mockesch et al (20) recently showed that the impairment of microvascular regulation in children with SCD was significantly associated with both nitrotyrosine and markers of systemic oxidative stress, confirming the important roles of oxidative stress and NO scavenging in the development of vascular dysfunction in SCD.…”

“…Belhassen et al (19) reported increased diameter in the brachial artery at baseline in SCD patients, compared to a control group, but the vessel was not able to further dilate in response to a flow-mediated dilation procedure. At the microcirculatory level, Moeckesch et al (20) reported decreased hyperemic response to skin heating localized stress in children with SCD, compared to healthy children, suggesting impaired microcirculatory NO-driven vasodilation in the former population.…”