Effects of serial phlebotomy on vascular endothelial function: Results of a prospective double‐blind randomized study

Abstract

Summary Introduction: Blood donation has been proposed as a potential therapy to reduce risk of cardiovascular disease, but the effects of phlebotomy on vascular function in human subjects have not been well characterized. Aims: We conducted a prospective randomized double-blind study to determine the effects of serial phlebotomy on vascular endothelial function in the brachial artery. Eighty-four iron-replete, non-anemic subjects were randomly assigned to one of three study treatment groups: (a) four serial phlebotomy procedures each followed by intravenous infusion of placebo normal saline; (b) four serial phlebotomy procedures each followed by intravenous infusion to replete lost iron; and (c) four serial sham phlebotomy procedures each followed by intravenous infusion of placebo normal saline. Assigned phlebotomy procedures were conducted at 56-day intervals. We measured brachial artery reactivity (BAR, %) in response to transient oxidative stress induced by oral methionine with high-resolution duplex ultrasound imaging before and one week after the fourth study phlebotomy. Results: Before phlebotomy, oral methionine decreased BAR by −2.04% (95% CI −2.58%, −1.50%), P < 0.001) with no significant difference between groups (P = 0.42). After phlebotomy, the BAR response to oral methionine did not significantly change between groups (P = 0.53). Brachial artery nitroglycerin-mediated dilation did not change in response to phlebotomy. Conclusions: Four serial phlebotomy procedures over six months with or without intravenous iron supplementation did not alter vascular endothelial function in the brachial artery when compared with sham phlebotomy.

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“…1a). Mean NMD at baseline was 17.45% ± 9.55, numerically lower than that reported in non-gout control populations [34,40]. Only 27% of subjects had a baseline NMD value greater than our laboratory norm for healthy controls.…”

“…The mean allopurinol and febuxostat doses at treatment target were 384 ± 131 mg and 53 ± 23 mg/day, respectively. The median [interquartile range] time from initiating ULT (visit 2) to achieving sU target (visit 3) was 21 [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] weeks for the overall group (for non-tophaceous subjects, 17 [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] weeks; for tophaceous patients, 29 [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] weeks).…”

New insights into the role of iron in inflammation and atherosclerosis

“…Likewise, whereas lowering iron levels by phlebotomy was proposed to be athero-protective by increased flow-mediated vasodilation in the brachial artery and decreased oxidative stress in blood donors [31], another study did not detect altered vascular function when compared with sham phlebotomy [32].…”

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