Flow-mediated dilation: can new approaches provide greater mechanistic insight into vascular dysfunction in preeclampsia and other diseases?

Abstract

Endothelial dysfunction is a key feature of preeclampsia and may contribute to increased cardiovascular disease risk years after pregnancy. Flow-mediated dilation (FMD) is a non-invasive endothelial function test that predicts cardiovascular event risk. New protocols allow researchers to measure three components of the FMD response: FMD, low flow-mediated constriction, and shear stimulus. This review encourages researchers to think beyond "low FMD" by examining how these three components may provide additional insights into the mechanisms and location of vascular dysfunction. The review then examines what FMD studies reveal about vascular dysfunction in preeclampsia while highlighting opportunities to gain greater mechanistic insight from new protocols. Studies using traditional protocols show that FMD is low in mid-pregnancy prior to preeclampsia, at diagnosis, and for 3 years post-partum. However, FMD returns to normal by 10 years post-partum. Studies using new protocols are needed to gain more mechanistic insight.

Figures

Figure 1. How FMD Works

The FMD protocol typically includes one minute of baseline measurement, 5 minutes of distal cuff occlusion, and up to five minutes of data collection following cuff release. In newer protocols, diameter and velocity are measured continuously throughout the test and used to calculate shear rate.

Figure 2. Measuring FMD, LFMC and Shear Rate AUC

This figure illustrates the three components of the FMD test – FMD, LFMC and shear rate AUC. Diameter and velocity are measured continuously throughout the test. FMD and LFMC may be calculated as an absolute or a percent change in artery diameter. FMD is calculated as the change in diameter from baseline, to the maximum diameter reached after cuff release. LFMC is the change in diameter from baseline to the end of cuff inflation. Shear rate is calculated as blood flow velocity/diameter. Shear rate AUC is the area under the curve from the time of peak diameter, to the time of cuff release. Only increases in shear rate above baseline values are included.

Figure 3. Using FMD, LFMC and shear rate AUC to gain more insight into the nature and location of vascular dysfunction

Profile 1 shows expected responses in the brachial artery of a healthy subject, when FMD is measured above the occlusion cuff. Profiles 2-5 show multiple pathways that could potentially result in low FMD. The pathways and evidence supporting each are described in detail in the text.