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Assessment of endothelial dysfunction by flow-mediated dilatation in men on long-term androgen deprivation therapy for prostate cancer

Gilbert, Stephen E., Tew, Garry ORCID: https://orcid.org/0000-0002-8610-0613, Bourke, Liam, Winter, Edward M. and Rosario, Derek J. (2013) Assessment of endothelial dysfunction by flow-mediated dilatation in men on long-term androgen deprivation therapy for prostate cancer. Experimental Physiology, 98 (9). pp. 1401-1410.

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Androgen deprivation therapy (ADT) in men with prostate cancer has been linked to an increased incidence of cardiovascular events and mortality, but the underpinning mechanisms are unclear. Endothelial dysfunction is considered a precursor for cardiovascular disease. Previous studies have reported variably on the association between ADT and endothelial function. This blinded case–control study examined endothelial function, using high-resolution ultrasound to measure flow-mediated dilatation (FMD) and glyceryl trinitrate (GTN)-mediated-dilatation in the brachial artery, in 20 men with prostate cancer (69 ± 7 years old) treated by ADT (median duration 22 months, range 6–133 months) and 20 men without prostate cancer (69 ± 5 years old) matched for age, physical activity, coexistent cardiovascular disease and body mass index. The magnitude of dilatation was calculated traditionally and allometrically scaled, adjusting for baseline diameter. There were no differences between groups for resting vascular measures (means ± SD). Flow-mediated dilatation was lower in men on ADT than in control subjects (3.9 ± 2.1 versus 5.9 ± 3.8% for traditional, P= 0.047; 3.7 ± 2.7 versus 6.0 ± 2.7% for allometrically scaled, P= 0.023). Response to GTN was similar in both groups (12.2 ± 4.2 versus 14.8 ± 5.7% for traditional, P= 0.113; 12.3 ± 4.6 versus 14.4 ± 4.6% for allometrically scaled, P= 0.163). The magnitude of difference in mean FMD between groups was marginally altered to 2.4% (95% confidence interval 0.3–4.5) after adjustment for the difference in body fat mass and concomitant cardiovascular medication, with the difference in FMD remaining significant (P= 0.029). There is evidence of endothelial dysfunction in men with prostate cancer on long-term ADT. Although a causal relationship is unproven, the findings are consistent with observational reports of adverse cardiovascular outcomes associated with long-term ADT for prostate cancer.

Item Type: Article
Status: Published
DOI: https://doi.org/10.1113/expphysiol.2013.073353
School/Department: School of Science, Technology and Health
URI: https://ray.yorksj.ac.uk/id/eprint/6764

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