Vascular endothelial dysfunction is a common pathway by which most risk factors lead to atherosclerosis.1 Lifestyle interventions, including weight loss and physical activity (PA), can improve endothelial function.2 The motivation to improve lifestyle might be enhanced by tracking changes in vascular health in response to lifestyle changes.
Currently, measuring flow-mediated dilation (FMD) of the brachial artery or assessing microcirculatory endothelial function at the fingertip are the most common noninvasive methods of evaluating endothelial function. However, each of these methods has limitations. The FMD method requires a trained operator and has substantial reported variability of measurement.3 Microcirculatory measurements obtained via peripheral arterial tonometry, for example, are complementary but not equivalent to macrocirculatory endothelial function of conduit arteries such as the brachial artery.4 The current devices on the market are also limited by fingernail length, digit deformity, and digit temperature, and some require single use probes.
Currently, there is no widely available, noninvasive, operator-independent, direct measurement of vascular reactivity. The SmartCuff (Cordex Systems, LLC) is a noninvasive, operator-independent, investigational device that measures post-occlusion, hyperemia-induced, time-varying arterial compliance of the brachial artery, through a standard blood pressure cuff attached to the device (Figure). Acute changes in vascular compliance resulting from a hyperemic shear stress stimulus are known to be endothelial-dependent.5 We previously demonstrated that the Cordex SmartCuff output measure, the Flow-mediated Compliance Response (FCR) score, was inversely associated with established cardiovascular disease (CVD) risk indices including Framingham risk score, metabolic syndrome, and increased number of carotid plaques.6
In this study, we investigated how FCR correlated with self-reported PA, measures of obesity, and exercise capacity. We hypothesized that obese and sedentary individuals with lower exercise capacity would have a lower FCR than more fit, more active, and less obese individuals.
METHODS
This cross-sectional clinical study was conducted in an urban academic center. Participants were enrolled from February 2017 to August 2019.
The study was approved by Johns Hopkins Medicine Institutional Review Board and all participants gave written informed consent. Those eligible were invited for two visits separated by 1-7 days. At visit 1, anthropometric data including height, weight, and waist circumference (WC) were obtained. The WC was measured using a laminated tape and was taken at the narrowest part of the torso at the end of a normal expiration. The FCR measurements (Figure) were performed as described in the Supplemental Digital Content, available at: http://links.lww.com/JCRP/A489, along with additional details of the methodology. At visit 2, the participants completed the Rapid Assessment of Physical Activity (RAPA)7 questionnaire which assesses habitual PA, and a 6-min walk test (6MWT) as a measure of exercise capacity.
RESULTS
Among 181 subjects, age was 50.4 +/- 16.3 yr; 58% were female, 9% were smokers, 6% had known coronary artery disease, and 10% had type 2 diabetes. The population consisted of 53% White and 47% African American. The mean +/- SD 6MWT was 494.8 +/- 107.9 m; body mass index: 29.9 +/- 6.6 kg/m2; and WC: 38.1 +/- 6.3 in. The FCR score was higher in females than in males, 89.8 +/- 29.0 versus 73.2 +/- 28.8, P < .001. Based on the RAPA questionnaire, FCR did not differ by being sedentary (83.1 +/- 27.3) or active (82.44 +/- 32.8), P = .88.
Using bivariate analysis, a lower FCR was associated with higher body mass index, r =-0.24, higher WC, r =-0.34, lower 6MWT, r = 0.33, and older age, r =-0.21, all P < .004. In a multivariate model, 6MWT (b = 0.06, P < .01), WC (b =-0.98, P < .01), and biological sex (female, b = 6.9, P < .01) were each independently associated with FCR. There were no interactions for sex with 6MWT and WC.
DISCUSSION
Obesity, cardiorespiratory fitness, and low levels of PA are modifiable risk factors that are important targets for the health care team to address with patients for primary and secondary prevention of CVD. Previous studies have shown that lifestyle changes such as increased cardiorespiratory fitness and weight loss have led to improvement in endothelial function as measured by FMD.8,9 The motivation to improve lifestyle might be enhanced by first identifying vascular dysfunction and then tracking changes in vascular health in response to lifestyle changes.
Current noninvasive measures of arterial compliance including FMD, pulse wave analysis, pulse contour analysis, and peripheral arterial tonometry are limited by cost, reproducibility, and operator dependence. The technique presented herein offers a noninvasive, operator-independent modality of assessing direct, instantaneous changes in brachial artery compliance during postischemic hyperemia obtained through a standard blood pressure cuff. It incorporates the established property that the arterial response to hyperemia is related to the time integral of the endothelial shear stress stimulus, not just one time point of shear.10
There were limitations to our study. The cross-sectional design limits assessment of causality. The study size (N = 181) is moderate but the number of subjects with risk factors of diabetes and smoking is small. The 6MWT, while it has been validated in small trials as a tool for assessing exercise capacity, has known limitations. Self-reported measures of exercise capacity using questionnaires such as RAPA also have known limitations. Furthermore, we have not yet assessed the impact of patient use of vasoactive medications, tobacco, recreational drugs, or exercise on the FCR output and reproducibility. This will be important to help provide clinical guidelines for best use and interpretation of the FCR.
The observed relationship between FCR score and the modifiable lifestyle risk factors for CVD suggests that this device may prove useful for providing feedback on vascular function in individuals wishing to modify their risk factors. A logical next step is to determine whether the FCR responds to weight loss and increased exercise. A prospective longitudinal study would be an important step should the device be considered for use as a prediction tool by observing which patients go on to develop CVD. Also, the relative contributions of endothelial and nonendothelial factors that contribute to FCR have not been fully elucidated. Future studies are needed to establish whether FCR is predominantly endothelial-dependent.
In conclusion, FCR is a measure of vascular reactivity obtained by an operator-independent, noninvasive device, using a standard blood pressure cuff. The FCR was associated with measures of exercise capacity and obesity and may be a useful tool for routine evaluation of vascular health and for motivating patients toward healthier lifestyle practices.
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