Flow-mediated vasodilation in end-stage renal disease.

BACKGROUND AND OBJECTIVES: An intact endothelium is essential for adaptations between arterial vasomotor tone and shear stress (SS), i.e., flow-mediated vasodilation (FMD). Endothelial dysfunction occurs in hypertension, cardiac insufficiency, diabetes, atherosclerosis, and in end-stage renal disease (ESRD) patients, whose renal failure is associated with many of those cardiovascular diseases (CVD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using a progressive hand-warming protocol and repeated measures ANOVA, we analyzed SS-mediated increase of brachial artery diameter (ΔBA) in 22 healthy controls, 18 CVD-negative ESRD patients (ESRD-CVD(-)), and 17 CVD-positive ESRD patients (ESRD-CVD(+)) to analyze the role of uremia versus CVD on FMD. RESULTS: Hand-warming increased SS (P < 0.001) and ΔBA (P < 0.001). Negative interactions were observed between ΔBA and ESRD (P < 0.001), and between ΔBA and CVD(+) (P < 0.02), but there was no interaction between ESRD and CVD(+) (P = 0.69). For low and mild SS increases, ESRD-CVD(-) patients were characterized by similar ΔBA as controls, but it was lower than controls at higher SS (P < 0.01). In ESRD-CVD(+) patients, brachial artery diameter did not respond to mild and moderate SS increases, and showed "paradoxical" vasoconstriction at higher SS (P < 0.05). In ESRD, a positive and independent interaction was observed between ΔBA and 25(OH) vitamin D(3) insufficiency (≤15 µg/L; P < 0.02). CONCLUSIONS: These observations indicate that, independently of each other, ESRD and CVD(+) history are associated with endothelial dysfunction. They also suggest the importance of considering the relationships between SS and endothelial function in different clinical conditions.

Comparison of the prognostic value of dipyridamole and dobutamine myocardial perfusion scintigraphy in hemodialysis patients.

Screening for coronary artery disease (CAD) in hemodialysis patients is hampered by contraindications and/or limitations of the available techniques in this population. Myocardial perfusion scintigraphy (MPS) using dipyridamole has been considered inaccurate due to abnormally high basal levels of adenosine in uremia that could blunt the vasodilatory response. Since dobutamine may be more reliable, we directly compared the two in patients on hemodialysis. We performed MPS at rest and after separate dipyridamole or dobutamine stress in 121 chronic hemodialysis patients. More numerous, larger, and more intense reversible lesions were induced with dobutamine than with dipyridamole, mainly in the anteroseptal segments. Reversibility with dipyridamole but not dobutamine MPS was independently and strongly related with mortality associated with CAD and with fatal and non-fatal CAD. We hypothesize that the chronotropic action of dobutamine induced alterations of wall motion, leading to spurious perfusion defects, not unlike artifacts seen with left bundle branch block. Our study shows that even though dobutamine induced more pronounced myocardial ischemia than dipyridamole in chronic hemodialysis patients, dipyridamole MPS more accurately identifies patients at high risk for subsequent cardiac death or non-fatal CAD than dobutamine.

Mineral metabolism and arterial functions in end-stage renal disease: potential role of 25-hydroxyvitamin D deficiency.

In ESRD, arterial function is abnormal, characterized by decreased capacitive function (arterial stiffening) and reduced conduit function, shown by diminished flow-mediated dilation (FMD). The pathophysiology of these abnormalities is not clear, and this cross-sectional study analyzed possible relationships among arterial alterations and cardiovascular risk factors, including mineral metabolism parameters, such as serum parathormone, and vitamin D "nutritional" and "hormonal" status by measuring serum 25-hydroxyvitamin D [25(OH)D(3)] and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] levels. Aortic stiffness (pulse wave velocity), brachial artery (BA) distensibility (echotracking; n = 42), BA FMD (hand-warming; n = 37), and arterial calcification scores (echography and plain x-rays) were measured in 52 stable and uncomplicated patients who were on hemodialysis. 25(OH)D(3) and 1,25(OH)(2)D(3) serum levels were low and weakly correlated (r = 0.365, P < 0.05). After adjustment for BP and age, multivariate analyses indicated that 25(OH)D(3) and 1,25(OH)(2)D(3) were negatively correlated with aortic pulse wave velocity (P < 0.001) and positively correlated with BA distensibility (P < 0.01) and FMD (P < 0.001). Arterial calcification scores were not independently associated with 25(OH)D(3) and 1,25(OH)(2)D(3) serum concentrations. These results suggest that nutritional vitamin D deficiency and low 1,25(OH)(2)D(3) could be associated with arteriosclerosis and endothelial dysfunction in patients who have ESRD and are on hemodialysis.

Local shear stress and brachial artery functions in end-stage renal disease.

Physiologic laminar shear stress (SS) is crucial for normal vascular structure and function. As a result of anemia-related lower whole-blood viscosity (WBV), SS could be reduced in patients with ESRD and might be associated with arterial functional alterations. In 44 patients with ESRD and 25 control subjects, brachial artery (BA) compliance and BA diameter changes (flow-mediated dilation [FMD[) were evaluated in response to local shear rate and SS changes during hand warming-induced hyperemia. Patients with ESRD and control subjects had similar BA blood flow, but SS was lower in patients with ESRD (P < 0.001), with lower shear rate (P < 0.01) and lower WBV (P < 0.0001). In control subjects, SS was positively (and physiologically) correlated with arterial diameter (P < 0.001). In contrast, in patients with ESRD, larger arterial diameter was associated with low SS (P < 0.05) and increased arterial wall elastic modulus (P < 0.001). Anemia-associated low WBV aggravates low shear rate, further contributing to SS reduction. These abnormalities were associated with decreased vasodilating response to endothelial mechanical stimulation. Compared with control subjects, BA compliance and FMD increases in response to hand warming-induced increased SS were lower in ESRD patients (P < 0.01), whereas their BA diameter response to glyceryl trinitrate did not differ. The long-term WBV and SS increases after anemia correction improved FMD (P < 0.01) and BA compliance (P < 0.05) and heightened arterial wall sensitivity to mechanical stimulation. Maintenance low SS as a result of anemia could play an indirect role in arterial dysfunction in patients with ESRD.

Forearm reactive hyperemia and mortality in end-stage renal disease.

BACKGROUND: Reports on the general population indicated that decreased endothelial-mediated vasodilation has a prognostic impact on cardiovascular (CV) morbidity and mortality. Flow-dependent vasodilation of conduit arteries and ischemia-induced forearm reactive hyperemia are impaired in end-stage renal disease (ESRD). Whether deterioration of vasodilator function in ESRD patients has a prognostic impact has not been documented. The aim of this study was to determine whether the impaired forearm postischemic vasodilation is an independent predictor of mortality in ESRD patients, independently from CV end-organ damages, which are usually associated with decreased vasodilatory response. METHODS: Common carotid artery intima-media thickness (CCA-IMT), aortic stiffness (pulse wave velocity-PWV), and LV mass (LVM) were determined for 78 stable ESRD patients on hemodialysis. Forearm postischemic vasodilation [flow debt repayment (FDR)] was measured by venous plethysmography. All-cause mortality served as the outcome variable over a median follow-up of 60 +/- 27 months. RESULTS: Twenty-four deaths occurred (16 of CV origin). According to Cox regression adjusted for age, CCA-IMT, LVM, and PWV, all-cause mortality was independently associated with decreased FDR (RR 0.69 for every 10% increase; 95% CI 0.56-0.85; P= 0.0006) and increased aortic PWV (RR 1.16 for 1 m/s increase; 95% CI 1.04-1.29; P= 0.0091). CONCLUSION: Our data indicate that lower postischemic forearm reactive hyperemia is associated with all-cause mortality of ESRD patients, independently of the presence of end-organ damage such as LVH or arteriosclerosis.