Changes in vascular function during breast cancer treatment

Stine Overvad Fredslund; Niels Henrik Buus; Cecilie Skjold; Esben Laugesen; Anders Bonde Jensen; Britt Elmedal Laursen

doi:10.1111/bcp.14837

Changes in vascular function during breast cancer treatment

Stine Overvad Fredslund^*, Niels Henrik Buus, Cecilie Skjold, Esben Laugesen, Anders Bonde Jensen, Britt Elmedal Laursen

^*Corresponding author for this work

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Abstract

BACKGROUND: Breast cancer (BC) survivors are at increased risk of cardiovascular disease. We evaluated whether chemotherapy induces early or late vascular dysfunction in vivo.

METHODS: Early-stage BC patients (n=33) underwent measurements of forearm blood flow (FBF), 24-hour blood pressure, aortic pulse wave velocity (PWV) and inflammatory markers before (T0), 14 days after (T1) and 12 months after (T2) chemotherapy. FBF was assessed during intra-arterial infusion of acetylcholine (ACh), ACh during simultaneous nitric oxide synthase inhibition with L-NG -monomethyl arginine (L-NMMA), and during infusion of sodium nitroprusside (SNP). Controls matched by age and menopausal status were examined for baseline comparison.

RESULTS: At T0, absolute FBF in the BC patients did not differ from controls. At T1, ACh-induced absolute FBF was higher compared to T0. ACh-induced FBF decreased significantly at T2, evaluated as area under the dose-response curve (AUC), and when corrected for FBF in the contra-lateral arm, (FBF ratio at T0:4.05[2.54;5.74], and T2:2.77[2.41;3.50]), without difference evident during L-NMMA-infusion. FBF during SNP-infusion remained unchanged. PWV and BP remained unchanged. Asymmetric dimethylarginine (T0:0.68 μmol/L±0.17,T1:0.75 μmol/L±0.16) and the inflammation-related biomarkers Cd163 (T0:1.86 mg/L[1.68;2.05],T1:2.04 mg/L[1.76;2.4]) and Cd206 (T0:0.22 mg/L[0.19;0.26],T1: 0.27 mg/L[0.23;0.30]) all increased significantly at T1, but returned to baseline values at T2. L-arginine was significantly increased at both T1 (78.5 μmol/L[68.9;86.6]) and T2 (76.8 (μmol/L)[66.9;90.6]), compared to T0 (59.6 μmol/L[53.7;68.0]).

CONCLUSION: Chemotherapy for BC seems associated with early amplification of endothelium-dependent vasodilation and inflammation. One year after chemotherapy, microvascular dysfunction persists in terms of reduced NO-dependent vasodilation without alterations in BP or arterial stiffness.

Original language	English
Journal	British Journal of Clinical Pharmacology
Volume	87
Issue	11
Pages (from-to)	4230-4240
Number of pages	11
ISSN	0264-3774
DOIs	https://doi.org/10.1111/bcp.14837
Publication status	Published - Nov 2021

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10.1111/bcp.14837

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@article{e4b9ac744fa24f31933ac270cbbce89a,

title = "Changes in vascular function during breast cancer treatment",

abstract = "BACKGROUND: Breast cancer (BC) survivors are at increased risk of cardiovascular disease. We evaluated whether chemotherapy induces early or late vascular dysfunction in vivo.METHODS: Early-stage BC patients (n=33) underwent measurements of forearm blood flow (FBF), 24-hour blood pressure, aortic pulse wave velocity (PWV) and inflammatory markers before (T0), 14 days after (T1) and 12 months after (T2) chemotherapy. FBF was assessed during intra-arterial infusion of acetylcholine (ACh), ACh during simultaneous nitric oxide synthase inhibition with L-NG -monomethyl arginine (L-NMMA), and during infusion of sodium nitroprusside (SNP). Controls matched by age and menopausal status were examined for baseline comparison.RESULTS: At T0, absolute FBF in the BC patients did not differ from controls. At T1, ACh-induced absolute FBF was higher compared to T0. ACh-induced FBF decreased significantly at T2, evaluated as area under the dose-response curve (AUC), and when corrected for FBF in the contra-lateral arm, (FBF ratio at T0:4.05[2.54;5.74], and T2:2.77[2.41;3.50]), without difference evident during L-NMMA-infusion. FBF during SNP-infusion remained unchanged. PWV and BP remained unchanged. Asymmetric dimethylarginine (T0:0.68 μmol/L±0.17,T1:0.75 μmol/L±0.16) and the inflammation-related biomarkers Cd163 (T0:1.86 mg/L[1.68;2.05],T1:2.04 mg/L[1.76;2.4]) and Cd206 (T0:0.22 mg/L[0.19;0.26],T1: 0.27 mg/L[0.23;0.30]) all increased significantly at T1, but returned to baseline values at T2. L-arginine was significantly increased at both T1 (78.5 μmol/L[68.9;86.6]) and T2 (76.8 (μmol/L)[66.9;90.6]), compared to T0 (59.6 μmol/L[53.7;68.0]).CONCLUSION: Chemotherapy for BC seems associated with early amplification of endothelium-dependent vasodilation and inflammation. One year after chemotherapy, microvascular dysfunction persists in terms of reduced NO-dependent vasodilation without alterations in BP or arterial stiffness.",

author = "Fredslund, {Stine Overvad} and Buus, {Niels Henrik} and Cecilie Skjold and Esben Laugesen and Jensen, {Anders Bonde} and Laursen, {Britt Elmedal}",

year = "2021",

month = nov,

doi = "10.1111/bcp.14837",

language = "English",

volume = "87",

pages = "4230--4240",

journal = "British Journal of Clinical Pharmacology",

issn = "0264-3774",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "11",

}

TY - JOUR

T1 - Changes in vascular function during breast cancer treatment

AU - Fredslund, Stine Overvad

AU - Buus, Niels Henrik

AU - Skjold, Cecilie

AU - Laugesen, Esben

AU - Jensen, Anders Bonde

AU - Laursen, Britt Elmedal

PY - 2021/11

Y1 - 2021/11

N2 - BACKGROUND: Breast cancer (BC) survivors are at increased risk of cardiovascular disease. We evaluated whether chemotherapy induces early or late vascular dysfunction in vivo.METHODS: Early-stage BC patients (n=33) underwent measurements of forearm blood flow (FBF), 24-hour blood pressure, aortic pulse wave velocity (PWV) and inflammatory markers before (T0), 14 days after (T1) and 12 months after (T2) chemotherapy. FBF was assessed during intra-arterial infusion of acetylcholine (ACh), ACh during simultaneous nitric oxide synthase inhibition with L-NG -monomethyl arginine (L-NMMA), and during infusion of sodium nitroprusside (SNP). Controls matched by age and menopausal status were examined for baseline comparison.RESULTS: At T0, absolute FBF in the BC patients did not differ from controls. At T1, ACh-induced absolute FBF was higher compared to T0. ACh-induced FBF decreased significantly at T2, evaluated as area under the dose-response curve (AUC), and when corrected for FBF in the contra-lateral arm, (FBF ratio at T0:4.05[2.54;5.74], and T2:2.77[2.41;3.50]), without difference evident during L-NMMA-infusion. FBF during SNP-infusion remained unchanged. PWV and BP remained unchanged. Asymmetric dimethylarginine (T0:0.68 μmol/L±0.17,T1:0.75 μmol/L±0.16) and the inflammation-related biomarkers Cd163 (T0:1.86 mg/L[1.68;2.05],T1:2.04 mg/L[1.76;2.4]) and Cd206 (T0:0.22 mg/L[0.19;0.26],T1: 0.27 mg/L[0.23;0.30]) all increased significantly at T1, but returned to baseline values at T2. L-arginine was significantly increased at both T1 (78.5 μmol/L[68.9;86.6]) and T2 (76.8 (μmol/L)[66.9;90.6]), compared to T0 (59.6 μmol/L[53.7;68.0]).CONCLUSION: Chemotherapy for BC seems associated with early amplification of endothelium-dependent vasodilation and inflammation. One year after chemotherapy, microvascular dysfunction persists in terms of reduced NO-dependent vasodilation without alterations in BP or arterial stiffness.

AB - BACKGROUND: Breast cancer (BC) survivors are at increased risk of cardiovascular disease. We evaluated whether chemotherapy induces early or late vascular dysfunction in vivo.METHODS: Early-stage BC patients (n=33) underwent measurements of forearm blood flow (FBF), 24-hour blood pressure, aortic pulse wave velocity (PWV) and inflammatory markers before (T0), 14 days after (T1) and 12 months after (T2) chemotherapy. FBF was assessed during intra-arterial infusion of acetylcholine (ACh), ACh during simultaneous nitric oxide synthase inhibition with L-NG -monomethyl arginine (L-NMMA), and during infusion of sodium nitroprusside (SNP). Controls matched by age and menopausal status were examined for baseline comparison.RESULTS: At T0, absolute FBF in the BC patients did not differ from controls. At T1, ACh-induced absolute FBF was higher compared to T0. ACh-induced FBF decreased significantly at T2, evaluated as area under the dose-response curve (AUC), and when corrected for FBF in the contra-lateral arm, (FBF ratio at T0:4.05[2.54;5.74], and T2:2.77[2.41;3.50]), without difference evident during L-NMMA-infusion. FBF during SNP-infusion remained unchanged. PWV and BP remained unchanged. Asymmetric dimethylarginine (T0:0.68 μmol/L±0.17,T1:0.75 μmol/L±0.16) and the inflammation-related biomarkers Cd163 (T0:1.86 mg/L[1.68;2.05],T1:2.04 mg/L[1.76;2.4]) and Cd206 (T0:0.22 mg/L[0.19;0.26],T1: 0.27 mg/L[0.23;0.30]) all increased significantly at T1, but returned to baseline values at T2. L-arginine was significantly increased at both T1 (78.5 μmol/L[68.9;86.6]) and T2 (76.8 (μmol/L)[66.9;90.6]), compared to T0 (59.6 μmol/L[53.7;68.0]).CONCLUSION: Chemotherapy for BC seems associated with early amplification of endothelium-dependent vasodilation and inflammation. One year after chemotherapy, microvascular dysfunction persists in terms of reduced NO-dependent vasodilation without alterations in BP or arterial stiffness.

U2 - 10.1111/bcp.14837

DO - 10.1111/bcp.14837

M3 - Journal article

C2 - 33769580

SN - 0264-3774

VL - 87

SP - 4230

EP - 4240

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

IS - 11

ER -

Changes in vascular function during breast cancer treatment

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