Flow Mediated Dilatation and Progression of Abdominal Aortic Aneurysms

Abstract

Objective/background: Biomarker(s) for prediction of the future progression rate of abdominal aortic aneurysms (AAA) may be useful to stratify the management of individual patients. AAAs are associated with features of systemic inflammation and endothelial dysfunction. Flow mediated dilatation (FMD) of the brachial artery is a recognised non-invasive measurement for endothelial function. We hypothesised that FMD is a potential biomarker of AAA progression and reflects the temporal changes of endothelial function during AAA progression.

Methods: In a prospectively recruited cohort of patients with AAAs (Oxford Abdominal Aortic Aneurysm Study), AAA size was recorded by antero-posterior diameter (APD) (outer to outer) on ultrasound. Annual AAA progression was calculated by (ΔAPD/APD at baseline)/(number of days lapsed/365 days). FMD was assessed at the same time as AAA size measurement. Analyses of data were performed in the overall cohort, and further in subgroups of AAA by size (small: 30-39 mm; moderate: 40-55 mm; large: > 55 mm).

Results: FMD is inversely correlated with the diameter of AAAs in all patients (n=162, Spearman's r=-.28, p<.001). FMD is inversely correlated with AAA diameter progression in the future 12 months (Spearman's r=-.35, p=.001), particularly in the moderate size group. Furthermore, FMD deteriorates during the course of AAA surveillance (from a median of 2.0% at baseline to 1.2% at follow-up; p=.004), while surgical repair of AAAs (n=50 [open repair n=22, endovascular repair n=28)] leads to an improvement in FMD (from 1.1% pre-operatively to 3.8% post-operatively; p<.001), irrespective of the type of surgery.

Conclusion: FMD is inversely correlated with future AAA progression in humans. FMD deteriorates during the natural history of AAA, and is improved by surgery. The utility of FMD as a potential biomarker in the context of AAA warrants further investigation.

Keywords: AAA Progression; Abdominal aortic aneurysm; Biomarkers; Flow mediated dilatation.

Figure 1

Correlation between flow mediated dilatation (FMD) and size of abdominal aortic aneurysm (AAA). There is a significant inverse correlation between the size of AAAs and FMD of forearm brachial artery at the initial assessment. (A) The percentage change in brachial artery diameter after stimuli is presented as FMD(%) (Spearman’s r = −.28, p < .001). (B) There is also a significant reduction of FMD across the different size groups of AAAs (Kruskale–Wallis test p < .001). (C) This significant negative correlation between AAA size and FMD is still present when the large AAAs (> 55 mm) were excluded from the analyses (Spearman’s r = −.27, p = .005). (D) However, such correlation is not observed within the group of moderate sized AAAs (40–55 mm) (Spearman’s r = −.1, p = .4).

Figure 2

Correlations between baseline abdominal aortic aneurysm (AAA) diameter, flow mediated dilatation (FMD), and future 12 month AAA growth. Participants with small and moderate sized AAAs (30–55 mm) under surveillance were reassessed at 12 months. The median duration of follow-up for this group was 365 days (interquartile range [IQR] 343–381 days). Annual AAA growth was calculated by [(ΔAP diameter/antero-posterior diameter at baseline)/(number of days lapsed/365days)]. The median progression rate over this period for this group of patients was 2.8% per year (IQR 0–5.7%/year). (A) There is a significant correlation between the baseline diameter of AAAs and the growth rate in the future 12 months (Spearman’s r = .30, p < .005). (B) The correlation between baseline AAA diameter and future growth rate was no longer observed in the moderate sized AAA group (40–55 mm) (Spearman’s r = .12, p = .39). (C) Within the subgroup of small sized AAAs (30–39 mm), there was no correlation between baseline diameter and future growth rate either (Spearman’s r = −.02, p = .9). (D) During the same follow-up period, FMD at baseline correlated significantly with the future growth rate. This significant correlation was observed in both small and moderate sized AAAs (30–55 mm) (Spearman’s r = −.35, p < .005). (E) There was also a significant correlation between FMD and future 12 month growth in the moderate sized AAAs (40–55 mm) (Spearman’s r = −.40, p < .005). (F) In contrast, there was no correlation between FMD and future 12 month growth in the small AAAs (30–39 mm) (Spearman’s r = −.17, p = .34). This evidence suggests FMD to be a predictive marker for future AAA growth, particularly in the moderate sized AAAs.

Figure 3

Flow mediated dilatation (FMD) deteriorates during abdominal aortic aneurysm (AAA) progression, and is improved by AAA surgery. FMD reduced significantly between assessments during AAA surveillance (from a median of 2.0% at baseline to 1.2% at follow-up, Wilcoxon matched pairs signed rank test [WMPST] p = .004). FMD was measured in 50 patients prior to AAA surgery, and repeated 8–12 weeks afterwards. FMD improved significantly after surgical repair (from 1.1% pre-operatively to 3.8% post-operatively, WMPST p < .001), irrespective of the type of surgery performed (endovascular repair [EVAR] n = 28; open surgical repair [OSR] n = 22).

Figure 4

Nitroglycerin mediated dilatation (NMD) and abdominal aortic aneurysm (AAA) progression. (A) There was no correlation between AAA size and NMD. (B) NMD did not deteriorate under AAA surveillance. Ethically, the NMD protocol could not be carried out in most patients with large AAAs scheduled for surgery, as the side effect of hypotension in this setting could potentially have complicated clinical management. As such, no comparison could be made for the pre- and post-operative NMD measurements.

Figure 5

Low flow mediated constriction and the progression of abdominal aortic aneurysm (AAA). The low flow mediated constriction (FMC) response of brachial artery at the same time points was investigated, as an extension to the FMD protocol. We hypothesised that the significant changes in FMD observed were driven by the derangement in vasoconstrictive tone in these patients, thereby masking the otherwise normal FMD response. However, there was no correlation between (A) FMC and AAA size or (B) future growth rate of AAA. (C) FMC did not change during the natural history of AAA progression (Wilcoxon matched pairs signed rank test [WMPST] p = .8), and (D) is unaffected by AAA surgery (WMPST p = .8).