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Title: Investigating the roles of peripheral and central blood pressure and blood pressure variability on the size and growth rate of AAAs in the AARDVARK trial and the CAVE sub-study
Author: Kiru, Gayithri
ISNI:       0000 0004 6422 9357
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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Abstract:
The AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK) trial was designed to investigate whether ACE-inhibition reduces the growth rate of small abdominal aortic aneurysms (AAA), independent of blood pressure (BP) lowering. A cohort of patients from the AARDVARK trial contributed data to the CAVE sub-study which investigated the roles of peripheral and central BP and 3 measures (standard deviation, coefficient of variation and variation independent of the mean) of visit-to-visit BP variability (BPV) of peripheral and central BPs on the size and growth rate of the diameters of small AAAs. Subjects aged ≥55 years with AAA diameter 3.0–5.4 cm were randomised 1:1:1 to receive perindopril 10 mg, or amlodipine 5 mg, or placebo. Three standardised BP measurements and an AAA ultrasound scan were performed at every trial visit (every 3-6 months over 2 years). Five of 14 trial sites were provided with a BP+ machine which measures both peripheral and central BP. Nine sites collected peripheral BP only with an Omron machine. BPV was based on readings taken after 3 months to avoid confounding from the impact of trial treatments. The primary outcome of the AARDVARK trial was AAA diameter growth (based on external antero-posterior ultrasound measurements in the longitudinal plane), determined by multi-level modelling. 224 patients were randomised between 2011 and 2013 to receive either placebo (n = 79), perindopril (n = 73), or amlodipine (n = 72). Mean baseline age, peripheral BP and AAA size among the 224 patients who contributed peripheral BP data were 71.3 years, 131.5/77.7 mmHg and 4.0cm (external diameter) respectively and were not significantly different from the 139 patients who also contributed central BP data. No significant differences in the modelled annual growth rates were apparent among the 3 randomised groups [placebo 1.68 mm (SE 0.2), perinodopril 1.77 mm (0.2), and amlodipine 1.81 mm (0.2), respectively]. The estimated difference in annual growth between the perindopril and placebo group was 0.08 mm (CI 20.50, 0.65). No evidence of an association was found between peripheral or central BP and AAA size at baseline or AAA growth in-trial. However, significant associations were found between central (but not peripheral) BPV and AAA growth using linear regression after adjustment for possible confounders. This association was stronger for central diastolic than systolic BPV. Evidence of a dose-response effect (albeit underpowered due to this comparison being restricted to quartiles) was apparent, with patients having the most variable central BP exhibiting the highest AAA growth rates. In the AARDVARK trial, small AAA growth rates were lower than anticipated thereby reducing the power of the trial, but there was no apparent impact of perindopril compared with placebo or placebo and amlodipine combined on AAA growth rates, despite more effective BP lowering among those allocated to perindopril. However by contrast, in the CAVE sub-study we showed a significant association between all 3 measures of central BPV and AAA growth despite the small sample size and limited numbers of visits. A larger study is required to confirm these results.
Supervisor: Poulter, Neil ; Bicknell, Colin Sponsor: National Institute for Health Research ; Foundation for Circulatory Health
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.726970  DOI: Not available
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