Lower cutaneous microvascular reactivity in adult cancer patients receiving chemotherapy

Abstract

Cancer patients with a history of anticancer chemotherapy are at an increased cardiovascular disease risk compared with cancer-free populations. Therefore, we tested the hypothesis that cancer patients receiving adjuvant chemotherapy would have a lower cutaneous microvascular reactivity and lower endothelium-dependent flow-mediated dilation (FMD) of the brachial artery compared with matched cancer-free control subjects. To test this hypothesis, we performed a case control study with seven cancer patients receiving adjuvant chemotherapy and seven matched healthy reference control subjects. Red blood cell flux was measured as an index of cutaneous blood flow via laser Doppler flowmetry. Acetylcholine (ACh)-mediated vasodilation was determined by iontophoresis. Data were expressed as percent increase in cutaneous vascular conductance. Endothelium-dependent FMD of the brachial artery via ultrasonography was determined as an index of macrovessel endothelial function. Cutaneous microvascular reactivity was attenuated in cancer patients compared with control subjects [cancer: 959.9 ± 187.3%, control: 1,556.8 ± 222.2%; P = 0.03, effect size (ES) = 1.1]. Additionally, cancer patients demonstrated a significantly lower area under the curve response to ACh iontophoresis compared with healthy control subjects. Brachial artery FMD was also significantly lower in cancer patients compared with control subjects (cancer: 2.2 ± 0.6%, control: 6.6 ± 1.4%; P = 0.006, ES = 1.6), which was significantly associated with measurements of microvascular reactivity. These findings suggest that decreases in vascular reactivity can occur during cancer chemotherapy, which may have implications for the long-term risk of cardiovascular disease morbidity and mortality. NEW & NOTEWORTHY Cancer survivors treated with chemotherapy experience an increased risk of cardiovascular events, linked to both cardiac and vascular toxicity. The major finding of this study is that microvascular reactivity and macrovascular endothelium-dependent flow-mediated dilation are lower in cancer patients currently receiving adjuvant chemotherapy compared with healthy counterparts.

Lower endothelium-dependent microvascular function in adult breast cancer patients receiving radiation therapy

“…The ACh protocol consisted of a baseline measurement followed by seven current pulses (100-μA anodal current) of 20 s, separated by 60 s current-free intervals. This delivery protocol is consistent with our previous work and has been shown to elicit no detectable current-induced axon-mediated vasodilation [ 14 , 18 ]. To determine endothelium-independent dilation ( part 2 ), 200 μL of a 1% SNP solution was administered.…”

“…There are several experimental considerations regarding this study. First, some of the patients in the present study also received chemotherapy, which by itself has previously been shown to decrease cutaneous microvascular function [ 14 ]. Since the effects of chemotherapy are systemic and patients served as their own control, this allowed these patients to be included in the study.…”

“…effect size (ES)) to obtain sufficient power to detect differences in the peak ACh response. Based on our previous work, an effect size of 0.8 [ 14 ], with a 5% level of significance, the total required sample size for reaching the minimum power of 0.8 was 7–8 patients. The peak ACh and SNP responses were determined by paired t-tests.…”

Microvascular blood flow during vascular occlusion tests assessed by diffuse correlation spectroscopy

“…Microvascular cutaneous blood flow using laser-Doppler flowmetry (LDF cut ) has often been utilized to non-invasively measure the flux of red blood cells in the skin to assess endothelial function in healthy and clinical populations (Farkas, Kolossvary, Jarai, Nemcsik, & Farsang, 2004;Sutterfield et al, 2018;Verma, Buchanan, & Anderson, 2003).…”

“…Microvascular cutaneous blood flow using laser‐Doppler flowmetry (LDF cut ) has often been utilized to non‐invasively measure the flux of red blood cells in the skin to assess endothelial function in healthy and clinical populations (Farkas, Kolossvary, Jarai, Nemcsik, & Farsang, ; Sutterfield et al., ; Verma, Buchanan, & Anderson, ). It has been suggested that LDF cut could be utilized as a model to determine dysfunction in the global microvasculature (Holowatz, Thompson‐Torgerson, & Kenney, ).…”