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Predictive value of reactive hyperemia for cardiovascular events in patients

with peripheral arterial disease undergoing vascular surgery

Alex L Huang 1, Annemarie E Silver, Elena Shvenke, David W Schopfer, Eiman Jahangir, Megan A Titas, Alex Shpilman, James O Menzoian, Michael T Watkins, Joseph D Raffetto, Gary Gibbons, Jonathan Woodson, Palma M Shaw, Mandeep Dhadly, Robert T Eberhardt, John F Keaney Jr, Noyan Gokce, Joseph A Vita Affiliations expand

PMID: 17717291
PMCID: PMC2596307
DOI: 10.1161/ATVBAHA.107.147322

Abstract Objective: Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. The predictive value of reactive hyperemia for cardiovascular events in patients with atherosclerosis and the relative importance of reactive hyperemia compared with other measures of vascular function have not been previously studied. Methods and results: We prospectively measured reactive hyperemia and brachial artery flow-mediated dilation by ultrasound in 267 patients with peripheral arterial disease referred for vascular surgery (age 66+/-11 years, 26% female). Median follow-up was 309 days (range 1 to 730 days). Fifty patients (19%) had an event, including cardiac death (15), myocardial infarction (18), unstable angina (8), congestive heart failure (6), and nonhemorrhagic stroke (3). Patients with an event were older and had lower hyperemic flow velocity (75+/-39 versus 95+/-50 cm/s, P=0.009). Patients with an event also had lower flow-mediated dilation (4.5+/-3.0 versus 6.9+/-4.6%, P<0.001), and when these 2 measures of vascular function were included in the same Cox proportional hazards model, lower hyperemic flow (OR 2.7, 95% CI 1.2 to 5.9, P=0.018) and lower flow-mediated dilation (OR 4.2, 95% CI: 1.8 to 9.8, P=0.001) both predicted cardiovascular events while adjusting for other risk factors. Conclusions: Thus, lower reactive hyperemia is associated with increased cardiovascular risk in patients with peripheral arterial disease. Furthermore, flow-mediated dilation and reactive hyperemia incrementally relate to cardiovascular risk, although impaired flow-mediated dilation was the stronger predictor in this population. These findings further support the clinical relevance of vascular function measured in the microvasculature and conduit arteries in the upper extremity.

Figures

Figure 1

Kaplan–Meier plots showing survival according to tertile of hyperemic velocity. Overall, survival differed according to tertile of hyperemic velocity by log-rank test (P=0.03). By pairwise comparison, the survival curves for the lower (8 to 61 cm/sec, n=89) and middle (63 to 105 cm/sec, n=89) tertiles did not differ (P=0.91), but both differed from the highest tertile (105 to 269 cm/sec, n=89) by log-rank test (P=0.01 for both).

Figure 2

Kaplan–Meier plots showing survival according to tertile of flow-mediated dilation. Overall, survival differed according to tertile of flow-mediated dilation by log-rank test (P<0.001). By pairwise comparison, the survival curves for the lower (−2.3 to 4.1%, n=89) and middle (4.2 to 7.9%, n=89) tertiles did not differ (P=0.34), but both differed from the highest tertile (8.0% to 25%, n=89) by log-rank test (P<0.001 and P=0.002, respectively).

Comment in

Reactive hyperemia and cardiovascular risk.Philpott A, Anderson TJ.Arterioscler Thromb Vasc Biol. 2007 Oct;27(10):2065-7. doi: 10.1161/ATVBAHA.107.149740.PMID: 17881738 No abstract available.
Reactive hyperemia revisited.Calderaro D, Monachini MC, Vieira CL, Yu PC, Gualandro DM, Marques AC, Caramelli B.Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):e23-4; author reply e25. doi: 10.1161/ATVBAHA.107.158931.PMID: 18354086 No abstract available.
Commentary. Predictive value of reactive hyperemia for cardiovascular events in patients with peripheral arterial disease undergoing vascular surgery.Bekelis K, Labropoulos N.Perspect Vasc Surg Endovasc Ther. 2008 Jun;20(2):224-6. doi: 10.1177/1531003508319221.PMID: 18644817 No abstract available.