| COMMENTARIES |
Brachial Flow-Mediated Dilation and Cardiovascular disease: Associations, Diagnostic and Prognostic Accuracies in the Elderly
Joseph Yeboah and John R Crouse III, Wake Forest University School of Medicine
Winston- Salem NC
USA
The vascular endothelium plays a major role in the control of vascular tone, platelet aggregation, and inflammation via an extensive paracrine system. Among the mediators of vascular tone produced by the endothelium are nitric oxide, prostaglandins, endothelin-1, and endothelial-derived releasing factor.
Within the endothelial cell, endothelial nitric oxide synthase catalyzes the conversion of arginine to nitric oxide which subsequently acts as a cofactor in the conversion of GMP to cyclic GMP by guanyl cyclase. The cyclic GMP produced then leads to an efflux of calcium from the sarcoplasmic reticulum; a process that results in the disentanglement of actin and myosin fibrils and subsequent dilation of the vessel. This cascade can be initiated by shear stress on the vascular endothelium. Brachial flow-mediated dilation is a method for measuring endothelial function that harnesses the above described pathway.
Brachial flow-mediated dilation (FMD) is a validated physiologic measure of endothelial function. The detailed procedure is beyond the scope of this paper [1] but bri
Brachial FMD (endothelial function) has been shown to be associated with cardiovascular risk factors [2]. The association between brachial FMD and cardiovascular risk factors has been shown to exist even in the elderly with or without cardiovascular disease [3]. Cardio-protective medications have all been shown to improve brachial FMD [4].
Brachial FMD is less reliable than some other measures of arterial structure and function and this limits its ability to be used as a clinical tool for cardiovascular risk assessment. The variability is due to both technical problems encountered during brachial FMD measurement and biologic factors. The current recommended guidelines [1] improve but not eliminate the technical problems. Also not all the biologic variables that affects brachial FMD have been identified. Brachial artery diameter on the other hand is a more reliable measure with acceptable biologic variability. Brachial artery diameter showed stronger associations with cardiovascular risk factors than brachial FMD in older adults [5], and it may be a more precise measure of endothelial function. More studies are needed especially in younger adults to validate this finding.
Impairment of endothelial function is considered an early stage in atherosclerosis development. Carotid intima-media thickness (IMT) has also been shown to be associated with cardiovascular risk factors and r
The diagnostic ability of brachial FMD for subclinical cardiovascular disease in younger adults is unknown. We assessed the diagnostic accuracy of brachial FMD in community dwelling older adults. Brachial FMD and brachial artery diameter had poor diagnostic accuracies in identifying older adults with subclinical cardiovascular disease [5]. Brachial artery diameter (height adjusted) however had a slightly better diagnostic accuracy compared with brachial FMD. Neither brachial FMD nor brachial artery diameter added significantly to the diagnostic accuracy of traditional cardiovascular risk factors in identifying older adults with subclinical cardiovascular disease. Current on-going studies such as the multi-ethnic study on atherosclerosis (
The prognostic ability of brachial FMD for future cardiovascular events in subjects with known cardiovascular disease has been extensively studied. Brachial FMD has been shown to predict cardiovascular events in some studies [9,10] but others fail to show any such association [11,12]. Using a large sample size, we were able to show that brachial FMD predicts future cardiovascular events in older adults [13]. In our subgroup analysis, brachial FMD showed a trend towards predicting cardiovascular events in older adults with/without prevalent cardiovascular events. Brachial artery diameter was also a predictor of cardiovascular events in the whole cohort and also in the subgroup with/without prevalent cardiovascular events. However, neither brachial FMD nor brachial artery diameter added significantly to the predictive accuracy of traditional cardiovascular risk factors.
Although brachial FMD is associated with cardiovascular risk factors and predicts future cardiovascular events in subjects with known cardiovascular disease, its predictive value for future cardiovascular events in apparently healthy individuals (low CV risk) is currently unclear. Also, even though brachial FMD is a measure of early atherosclerosis, it has less accuracy for identifying older adults with subclinical cardiovascular disease. Although this observation awaits confirmation in other cohorts and younger populations, it downgrades the clinical utility of brachial FMD (endothelial function) in general clinical practice. Thus brachial FMD identifies individuals who are likely to have cardiovascular events but not those who have a higher subclinical atherosclerotic burden. Since cardiovascular events are mainly due to plaque rupture rather than atherosclerotic plaque burden, brachial FMD may be a surrogate of the risk for plaque rupture more than plaque burden.
Brachial artery diameter (height adjusted) may be as good as brachial FMD (if not better) in older adults as a measure of endothelial function. More studies evaluating the diagnostic and predictive accuracies of brachial artery diameter (height adjusted) in low risk and relatively young populations are needed. If this measure (brachial artery diameter) proves as good an index of endothelial function as brachial FMD, then scientists/clinicians will have a more readily available tool to help translate research on endothelial function into clinical practice for cardiovascular risk assessment.
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