Changes in vascular function during breast cancer treatment

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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 languageEnglish
JournalBritish Journal of Clinical Pharmacology
Volume87
Issue11
Pages (from-to)4230-4240
Number of pages11
ISSN0264-3774
DOIs
Publication statusPublished - Nov 2021

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