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Biomedical subjects

Ann E Donald

Publications and source records attributed to Ann E Donald.

10 recordsLinked to original sources
PubMed2006

Non-invasive assessment of endothelial function: which technique?

OBJECTIVES: The purpose of this study was to compare 3 non-invasive techniques for assessment of endothelial function in adults and children and evaluate their utility in acute inflammation. BACKGROUND: Endothelial dysfunction is a key early event in pre-clinical atherosclerosis. Flow-mediated dilation (FMD), although the established technique, is expensive and technically demanding. Measurements of vascular responses to inhaled salbutamol by pulse wave analysis (PWA) or pulse contour analysis (PCA) are potential alternatives. METHODS: Sixteen adults (mean age 28 years, range 18 to 39) and 16 children (mean age 13 years, range 7 to 17) underwent concurrent vascular function testing on 2 occasions with ultrasound, PWA, and PCA. Eighteen men were also studied before and after typhoid vaccination. RESULTS: Reproducibility of FMD was high in adults and children (coefficient of variation [CV] = 7.1 and 6.3, respectively). Salbutamol responses were more variable with PWA (adults CV = 11.5, children CV = 17.1) and PCA particularly in children (adults CV = 18.2, children CV = 36.3). Flow-mediated dilation (p < 0.001) and PWA with salbutamol (p = 0.03) responses fell after typhoid vaccination, and PCA (p = 0.7) was unchanged. CONCLUSIONS: Vascular dysfunction during acute inflammation can be measured by FMD and by PWA with salbutamol. Flow-mediated dilation is less variable than PWA. Variability of PCA makes this technique currently unsuited to serial measures of endothelial function in children. Flow-mediated dilation remains the most reproducible method.

Adolescent↗
PubMed2006

Delayed blood pressure recovery after psychological stress is associated with carotid intima-media thickness: Whitehall psychobiology study.

OBJECTIVE: Delayed blood pressure (BP) recovery after psychological stress is associated with low socioeconomic status (SES) and prospectively with increases in clinic BP. We tested whether poststress BP recovery was related to carotid atherosclerosis. METHODS AND RESULTS: Psychophysiological stress testing was performed with a healthy subgroup of the Whitehall II epidemiological cohort, and recovery systolic BP was monitored 40 to 45 minutes after stressful behavioral tasks. Carotid ultrasound scanning was conducted on 136 men and women (aged 55.3+/-2.7 years) 3 years after stress testing. Participants were divided into those whose systolic BP had returned to baseline in the recovery period (adequate recovery, n=37), and those whose BP remained elevated (delayed recovery, n=99). Systolic BP stress responses did not differ in the 2 groups. Carotid intima-media thickness (IMT) was associated with delayed recovery in lower SES (means 0.78 versus 0.65 mm) but not higher SES participants (means 0.75 versus 0.74 mm) after adjustment for age, gender, baseline systolic BP, and resting BP, smoking, body mass and fasting cholesterol at the time of ultrasound scanning (P=0.010). CONCLUSIONS: Variations in poststress recovery reflect dysfunction of biological regulatory processes, and may partly mediate psychosocial influences on cardiovascular disease.

Blood Pressure↗
PubMed2006

Circadian variation in endothelial function is attenuated in postmenopausal women.

OBJECTIVE: The present study was undertaken to investigate the possible existence of an endogenously generated circadian rhythm in endothelial function in women and whether this rhythm is altered after the menopause. METHODS: Healthy non smoking women (11 pre-menopausal and 13 postmenopausal women) were studied during a 22 h period under constant routine conditions; endothelium-dependent (flow-mediated dilation (%FMD)) and -independent (glyceryl-trintrate (GTN)-mediated) function was assessed every 2 and 4 h, respectively, by high-resolution ultrasound of the brachial artery. RESULTS: %FMD and %GTN was significantly higher in pre-menopausal women (9.9+/-1.0%FMD (mean+/-S.E.M.); 18.2+/-1.8%GTN; P<0.01) compared with postmenopausal women (6.5+/-0.5%FMD; 11.5+/-1.6%GTN). A significant day-night variation in %FMD was observed pre-menopausal women (day 9.2+/-0.8%; night 10.4+/-1%; P<0.05) with an attenuated rhythm in postmenopausal women (day 6.8+/-0.6%; night 6.0+/-0.4%). CONCLUSIONS: The findings show a circadian rhythm in %FMD in pre-menopausal women, which disappears after the menopause. The reduction in %FMD and an absence of a day-night variation in %FMD in postmenopausal women may have important implications for the incidence of coronary heart disease in women after the menopause.

Adult↗
PubMed2005

Vasculopathy in Turner syndrome: arterial dilatation and intimal thickening without endothelial dysfunction.

CONTEXT: Women with Turner syndrome (TS) have an increased cardiovascular mortality rate from both structural and ischemic heart disease, especially aortic dissection. OBJECTIVE: We hypothesized that TS women have a fundamental arterial wall defect that may be due to genetic factors or estrogen deficiency. DESIGN, SETTING, AND PATIENTS: TS women (n = 93) were compared with normal controls (n = 25) and women with 46,XX primary amenorrhea (PA) (n = 11) with a similar history of estrogen deficiency. Clinical parameters, aortic root diameter, extraaortic arterial structure [common carotid (CD), brachial artery diameter, and carotid intima-media thickness (IMT)], arterial stiffness (pulse-wave velocity, augmentation index), and endothelial function (flow-mediated dilatation) were assessed. MAIN OUTCOME MEASURES: These included arterial diameters and vascular physiology parameters. RESULTS: Differences in arterial structure were observed among TS, normal controls, and 46,XX PA women: IMT (0.61 +/- 0.07 vs. 0.55 +/- 0.06 vs. 0.60 +/- 0.05 mm, respectively; P < 0.001), CD (5.71 +/- 0.64 vs. 5.27 +/- 0.34 vs. 5.22 +/- 0.38 mm; P < 0.001), and brachial artery diameter (3.29 +/- 0.44 vs. 3.06 +/- 0.36 vs. 2.97 +/- 0.30 mm; P = 0.006). Aortic root diameter was greater in TS than normal control women. TS status, height, weight, and IMT were independently associated with increased CD after multivariate adjustment (P < 0.05). TS status, age, diastolic blood pressure, and CD remained independently associated with increased IMT after multivariate adjustment (P < 0.05). Pulse-wave velocity and flow-mediated dilatation were similar among the three groups. CONCLUSION: Women with TS have greater IMT and conduit artery diameters than normal controls. Similarly, increased IMT in TS and 46,XX PA women suggests that estrogen deficiency contributes to intimal thickening. Interventional studies are required to determine the extent to which blood pressure and estrogen deficiency may be appropriate therapeutic targets to reduce cardiovascular risk in TS.

Adult↗
PubMed2005

Early structural and functional changes of the vasculature in HIV-infected children: impact of disease and antiretroviral therapy.

BACKGROUND: Premature cardiovascular disease is increasingly recognized in HIV-infected patients, but the mechanisms involved are unclear. The purpose of this study was to determine the impact of HIV infection and antiretroviral therapy (ART) on markers of early vascular disease in children. METHODS AND RESULTS: We studied 83 HIV-infected children (56 had taken ART, of whom 31 received a regimen containing protease inhibitors [PIs]; 27 were never treated) and a control group of 59 healthy children. Carotid intima-media thickness (IMT) and brachial artery flow-mediated dilatation (FMD) were measured. IMT was significantly greater in HIV-infected children compared with the control subjects (P<0.001). Among the HIV-infected children, age and treatment were significantly associated with increased IMT. Children exposed to PIs had greater IMT compared with both non-PI-treated children and untreated children (P=0.02). FMD was also significantly reduced in the HIV-infected children compared with control subjects (P=0.02). Pairwise comparisons of different treatment exposure groups revealed that FMD was impaired by a mean of 3.6% (95% CI, 1.8 to 5.3; P<0.001) for children exposed to PIs compared with untreated children and by a mean of 1.8% (95% CI, 0.01 to 3.5; P=0.05) compared with non-PI-treated children. HIV-infected children had lipid abnormalities, but they did not account for the observed differences in either FMD or IMT. CONCLUSIONS: HIV infection in childhood is associated with adverse structural and functional vascular changes that are most pronounced in children exposed to PI therapy. Longitudinal studies are required to differentiate the relative impact of HIV disease and ART and to assess the potential for prevention.

Adolescent↗
PubMed2005

Endothelial dysfunction in childhood infection.

BACKGROUND: Atherosclerosis begins in early life, and endothelial dysfunction is recognized as a key initiating event in the development of atherosclerosis. Although infection has been implicated in endothelial dysfunction and atherogenesis, the impact of acute common childhood infections on the vascular endothelium is unknown. METHODS AND RESULTS: We studied 600 children aged 10 years drawn from the Avon Longitudinal Study of Parents and Children. The children were divided into 3 groups: those with current acute infection (AI; n=135; 73 boys and 62 girls); a convalescent group with infection in the past 2 weeks (n=166; 78 boys and 88 girls), and a healthy control group (n=299; 131 boys and 168 girls). Endothelial function was determined in all subjects by high-resolution ultrasound to measure brachial artery flow-mediated dilation (FMD) and was expressed as the percentage change in diameter from baseline after reactive hyperemia. FMD was repeated in 40 children in the AI group and 50 in the control group after a mean interval of 1 year. FMD was lower in both the AI group (6.3+/-2.7%, mean+/-SD) and the convalescent group (8.1+/-3.1%) than in the control group (9.7+/-2.5%; P<0.001 for both). The observed differences in FMD remained after adjustment for potential confounding variables. At the repeat visit, FMD was unchanged in controls (P=0.85) but improved in the AI group (P<0.001). CONCLUSIONS: Acute infection in childhood is associated with impaired endothelium-dependent vasodilation. These findings support a potential role for previously unsuspected extrinsic inflammatory stimuli in the pathogenesis of early atherosclerosis.

Arteriosclerosis↗
PubMed2003

Vitamin C improves resistance but not conduit artery endothelial function in patients with chronic renal failure.

BACKGROUND: Chronic renal failure is associated with impaired endothelium-dependent vasodilation and accelerated atherogenesis. To examine whether endogenous reactive oxygen species (ROS) modify endothelial function in renal failure, we evaluated the effect of the antioxidant vitamin C on endothelium-dependent responses in both the conduit and resistance vasculature of subjects with severe renal impairment. METHODS: Endothelial function of the forearm resistance vasculature was assessed using plethysmography to measure the dilator response to intra-arterial acetylcholine (Ach) (25 to 100 nmol/min). Endothelial function of radial and brachial arteries was assessed using vascular ultrasound to measure the dilator response to flow during reactive hyperemia [flow-mediated dilatation (FMD)]. Studies were performed before and after administration of vitamin C by intra-arterial infusion (25 mg/min) in 33 predialysis patients or by intravenous infusion (3 g) in 17 hemodialysis patients. RESULTS: Parenteral administration of vitamin C resulted in a 100-fold increase (intra-arterial studies) and a 4.5-fold increase (intravenous studies) in serum antioxidant activity. Vitamin C administration increased the dilator response to ACh in resistance vessels (P = 0.01), but did not alter the dilator response to flow in conduit vessels of either dialysis (P = 0.3) or predialysis subjects (P = 0.8). In the presence of the nitric oxide (NO) synthase inhibitor NGmonomethyl-L-arginine (L-NMMA), there was no effect of vitamin C on resistance vessel endothelial function. In all cases the dilator response to the endothelium-independent dilators was unaffected by vitamin C. CONCLUSION: Acute administration of vitamin C reduces oxidant stress in renal failure and improves NO-mediated resistance vessel dilatation.

Adult↗
PubMed2002

Flow-mediated dilatation of the brachial artery in pregnancy at high altitude.

OBJECTIVE: Pregnancy at high altitude has been associated with increased prevalence of pre-eclampsia and reduced maternal oestrogen levels, factors that have been associated with endothelial dysfunction. The aim of this study was to examine the effect of high altitude (4370 m above sea level) on endothelial function during pregnancy as assessed by a non-invasive method. DESIGN: Cross-sectional study. SETTING: Two maternity units providing routine antenatal care: one at high altitude (District General Hospital--IPSS in Cerro de Pasco, Peru) and one at sea level (Instituto Materno-Perinatal in Lima, Peru). POPULATION: Sixty pregnant women at 6-42 weeks of gestation resident at high altitude (Cerro de Pasco, Peru, 4370 m above sea level) and 54 at sea level (Lima, Peru). Comparisons were performed also in 11 and 14 non-pregnant women at each altitude, respectively. METHODS: Endothelial function was assessed by flow-mediated dilatation of the brachial artery using high-resolution ultrasound. MAIN OUTCOME MEASURES: Differences in flow mediated dilatation of the brachial artery in two groups of pregnant women, one at high altitude and one at sea level. RESULTS: Both at high altitude and sea level flow-mediated dilatation of the brachial artery increased in the first two trimesters to levels 32% higher than non-pregnant controls. However, in the third trimester, flow-mediated dilatation of the brachial artery was lower than non-pregnant levels. Resting vessel size increased during pregnancy by 15% compared with non-pregnant controls at term, with no difference between the two populations at high and low altitude. Pregnancy at high altitude, compared with sea level, was associated with 59% lower baseline blood flow and 76% higher reactive hyperaemia. Similarly, non-pregnant controls at high altitude compared with sea level demonstrated similar flow-mediated dilatation of the brachial artery and 40% lower resting blood flow of the brachial artery. However, the difference in reactive hyperaemia did not reach statistical significance. CONCLUSION: These data suggest that, during pregnancy at high altitude, endothelial function, as assessed by flow-mediated dilatation of the brachial artery, is not impaired.

Adult↗
PubMed2002

Oral L-arginine does not improve endothelial dysfunction in children with chronic renal failure.

BACKGROUND: Cardiovascular disease is a major cause of mortality amongst patients with chronic renal failure (CRF). L-arginine has been used to improve endothelial function by increasing nitric oxide (NO) bioavailability and in animal models this in turn has attenuated the progression of atherosclerosis. We examined whether dietary L-arginine supplementation improved endothelial function in children with CRF. METHODS: A randomized, double-blind, placebo-controlled, crossover trial of L-arginine was conducted in 21 normotensive children aged 11.5 +/- 3 (7 to 17) years with CRF (GFR 27.4 +/- 13.2 mL/min/1.73 m(2)) in whom endothelial dysfunction had previously been demonstrated. We examined the effect of L-arginineon the endothelial response to shear stress (NO-dependent) using a non-invasive technique of high-resolution ultrasound. Each subject was studied before and after 4 weeks of L-arginine (2.5 g/m(2) or 5 g/m(2) x 3/day) or placebo, separated by a rest period of 4 weeks. Brachial artery diameter was measured at rest, during increased flow (endothelial-dependent dilation) and after 25 microg of glyceryl trinitrate (endothelial-independent dilation) at each visit. RESULTS: After oral L-arginine, plasma L-arginine levels rose from 82 +/- 20 to 179 +/- 110 micromol/L (P < 0.001). No significant change in endothelial-dependent dilation during L-arginine (7.96 +/- 2.35 to 7.71 +/- 3.22%; P> 0.05) or placebo (8.2 +/- 2.89 to 8.3 +/- 3.14%; P> 0.05) was noted. There was no change in endothelial-independent dilation. CONCLUSION: Endothelial function was not improved with L-arginine, suggesting that dietary supplementation is not a useful clinical approach in children with CRF.

Administration, Oral↗