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.

Purpose Cancer patients with a history of radiotherapy are at an increased risk of ischemic heart disease. Preclinical animal studies demonstrate markedly impaired acetylcholine (ACh)-mediated endothelium-dependent vasorelaxation within days to weeks post-irradiation, however, whether microvascular function is affected in the intact human circulation during cancer radiation therapy has yet to be determined. Materials and methods Using laser-Doppler flowmetry, microvascular endothelium-dependent and independent responses were evaluated through iontophoresis of acetylcholine (ACh) (part 1, n = 7) and sodium nitroprusside (SNP) (part 2, n = 8), respectively, in women currently receiving unilateral chest adjuvant radiation therapy for breast cancer. Measurements were performed at the site of radiation treatment and at a contralateral control, non-radiated site. Cutaneous vascular conductance (CVC) was calculated by normalizing for mean arterial pressure. Results and Conculsions In part 1, patients received an average radiation dose of 2104 ± 236 cGy. A significantly lower peak ACh-mediated endothelium-dependent vasodilation was observed within the radiated microvasculature when compared to non-radiated (radiated: 532 ± 167%, non-radiated 1029 ± 263%; P = 0.02). In part 2, the average radiation dose received was 2251 ± 196 cGy. Iontophoresis of SNP elicited a similar peak endothelium-independent vasodilator response in radiated and non-radiated tissue (radiated: 179 ± 58%, non-radiated: 310 ± 158; P = 0.2). The time to 50% of the peak response for ACh and SNP was similar between radiated and non-radiated microvasculature (P < 0.05). These data provide evidence of early endothelium-dependent microvascular dysfunction in cancer patients currently receiving chest radiation and provide the scientific premise for future work evaluating coronary endothelial function and vasomotor reactivity using more detailed and invasive procedures.

Chemotherapy is associated with acute and long-term cardiotoxicity. To date, risk assessment has primarily focused on the heart; however, recent findings suggest that vascular and autonomic function may also be compromised. Whether this occurs during chemotherapy treatment remains unknown. Therefore, the present study evaluated carotid artery stiffness, cardiovagal baroreflex sensitivity (cBRS), and heart rate variability (HRV) in cancer patients currently being treated with adjuvant chemotherapy. Eleven current cancer patients receiving adjuvant chemotherapy and 11 matched (1:1) controls were studied. Carotid artery stiffness was assessed via two-dimensional ultrasonography. cBRS was assessed from the spontaneous changes in beat-to-beat time series of R-R interval and systolic blood pressure via the cross-correlation technique. HRV was assessed using the standard deviation of R-R intervals (SDNN) and low (LF) and high (HF) power frequencies. Carotid artery β-stiffness was significantly higher in the cancer patients compared with control participants (8.0 ± 0.8 vs. 6.3 ± 0.6 U, respectively; P = 0.02). cBRS was lower in the cancer patients compared with controls (4.3 ± 0.7 vs. 10.7 ± 1.9 ms/mmHg, respectively; P = 0.01), and all indices of HRV were lower in the cancer patients (SDNN, P = 0.02; LF, P = 0.01; HF, P = 0.02). There was no significant correlation between β-stiffness and cBRS ( P = 0.4). However, LF power was significantly correlated with cBRS (r = 0.66, P < 0.001). Compared with matched healthy controls, cancer patients undergoing chemotherapy demonstrated a significantly higher arterial stiffness and lower cBRS. The previously reported adverse effects of chemotherapy on the heart appear to also influence other aspects of cardiovascular health. NEW & NOTEWORTHY Patients treated with anticancer chemotherapy exhibit an impaired baroreflex control of arterial blood pressure and increased arterial stiffness. These findings hold significant value, in particular as part of a risk-stratification strategy in current cancer patients receiving chemotherapy. This is the first investigation, to our knowledge, to demonstrate an attenuated spontaneous baroreflex control of arterial blood pressure in cancer patients currently undergoing chemotherapy.

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Individuals with hypertension exhibit abnormal pressor responses during rest‐to‐exercise transitions, significantly increasing the likelihood of sudden cardiac events. Dietary nitrate supplementation can lower resting blood pressure in patients with hypertension and improve bulk muscle blood flow in older healthy adults. However, investigations using dietary nitrate as a non‐pharmacological intervention in post‐menopausal women diagnosed with hypertension are lacking. Therefore, the purpose of the current investigation was to determine if acute dietary nitrate supplementation would improve the pressor response to exercise and increase forearm blood flow during steady‐state hand‐grip exercise in post‐menopausal hypertensive women. It was hypothesized that the pressor response to exercise would be attenuated and muscle blood flow would be improved in the nitrate‐rich (NR) versus nitrate‐poor (NP) treatment.METHODSTen hypertensive post‐menopausal women [age 56 ± 3 years (mean±SD); height 165 ± 2 cm; mass 84 ± 13 kg; body mass index 31 ± 5 kg/m2] agreed to participate in the current study. Patients underwent a randomized double‐blind placebo‐controlled trial with a NR or NP beet root juice supplement. Blood samples were taken at the beginning of each testing session (~2 h post ingestion) to determine plasma nitrite levels. Forearm blood flow (FBF) was measured via ultrasonography at the brachial artery of the exercising limb. Beat‐by‐beat blood pressure and heart rate were recorded throughout the trial on the non‐exercising limb. After resting measurements were completed, patients performed hand‐grip exercise at 20% maximal voluntary contraction (MVC) for five minutes to obtain steady‐state blood flow and blood pressure response to exercise.RESULTSPlasma nitrite levels were significantly higher during the NR (809 ± 146 nM) than the NP (79 ± 19 nM) condition. No differences were found between conditions for resting blood flow (NR: 64±2; NP: 62 ± 4 ml min−1; P > 0.05), systolic (NR: 144 ± 2; NP: 145 ± 2 mmHg−1; P > 0.05) or diastolic blood pressure (NR: 78 ± 1; NP: 80 ± 1 mmHg−1; P > 0.05). In addition, there were no significant differences across 10‐second bins (e.g., 0–10, 11–20 seconds) during the first minute pressor response to hand‐grip exercise in either condition (systolic: P > 0.05; diastolic: P > 0.05). As such, the rate pressure product was not significantly different during steady‐state between conditions (NR: 11,562 ± 437; NP: 11,728 ± 437 bpm · mmHg−1; P > 0.05). During steady‐state exercise, FBF (NR: 189 ± 8; NP: 218 ± 8 ml min−1; P = 0.03) and forearm vascular conductance (FVC) (NR: 157 ± 4; NP: 183 ± 4 ml min−1; P = 0.04) were significantly lower during the steady‐state NR condition.CONCLUSIONAcute dietary nitrate supplementation did not improve the pressor response to hand‐grip exercise in hypertensive post‐menopausal women. However, it is important to note that steady‐state FBF (~30 ml min−1) and FVC (~27 ml min mmHg−1) were significantly reduced during the nitrate‐rich condition, which suggests a reduced O2 cost for a given workload because blood flow typically matches metabolic rate.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.