title: Assessment of endothelial dysfunction by flow-mediated dilatation in men on long-term androgen deprivation therapy for prostate cancer.
abstract: What is the central question of this study? Androgen deprivation therapy (ADT) for prostate cancer has been linked with increased cardiovascular risk, but the mechanisms are unclear. Is there evidence that endothelial dysfunction, as evidenced by reduced flow-mediated dilatation (FMD), is associated with ADT? What is the main finding and its importance? Reduction in FMD with preservation of glyceryl trinitrate-mediated dilatation indicates endothelial dysfunction in men with prostate cancer on long-term ADT compared with well-matched control subjects. Vascular endothelial dysfunction associated with long-term ADT for prostate cancer might explain the observed epidemiological increases in adverse cardiovascular events. Assessment of FMD may be useful in the monitoring of cardiovascular risk in men with prostate cancer on ADT. 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.
authors.affiliation: Centre for Sport and Exercise Science, Sheffield Hallam University, Sheffield, UK.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Gilbert
authors.forename: Garry A
authors.initials: GA
authors.lastname: Tew
authors.forename: Liam
authors.initials: L
authors.lastname: Bourke
authors.forename: Edward M
authors.initials: EM
authors.lastname: Winter
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Rosario
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000502:physiology; D002318:Cardiovascular Diseases / Q000209:etiology; D016022:Case-Control Studies; D004106:Dilatation / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D012307:Risk Factors; D014664:Vasodilation / Q000502:physiology*
chemical_list: D000726:Androgen Antagonists; D005996:Nitroglycerin