Hyperemic Shear Stress Research Articles

Interrelationships Among Flow-Mediated Vasodilation, Nitroglycerine-Induced Vasodilation, Baseline Brachial Artery Diameter, Hyperemic Shear Stress, and Cardiovascular Risk Factors.

BackgroundFlow‐mediated vasodilation (FMD) of the brachial artery has been used for the assessment of endothelial function. Considering the mechanism underlying the vasodilatory response of the brachial artery to reactive hyperemia, hyperemic shear stress (HSS), a stimulus for FMD; nitroglycerine‐induced vasodilation (NID), an index of endothelium‐independent vasodilation; and baseline brachial artery diameter (BAD) are also involved in vasodilatory response. The purpose of this study was to investigate the interrelationships among FMD, HSS, NID, baseline BAD, and cardiovascular risk factors.Methods and ResultsWe measured FMD, HSS, NID, and baseline BAD simultaneously in 1033 participants (633 men and 400 women; mean age: 58.6±17.0 years). Framingham risk score was negatively correlated with FMD, HSS, and NID and was positively correlated with baseline BAD. HSS and NID were positively correlated with FMD, and baseline BAD was negatively correlated with FMD. In participants with normal NID, FMD was correlated with HSS, NID, and baseline BAD, all of which were independent variables of FMD in multivariate analysis. In participants with impaired NID, FMD was correlated with NID and baseline BAD, both of which were independent variables of FMD in multivariate analysis, but there was no association between FMD and HSS.Conclusions NID and baseline BAD were independent variables of FMD regardless of the status of endothelium‐independent vasodilation, whereas there was a significant association between FMD and HSS in participants with normal NID but not in those with impaired NID. The influence of HSS on FMD seems to be dependent on the status of endothelium‐independent vasodilation.

The relationship between anthropometric indexes of adiposity and vascular function in the FATE cohort

Numerous indexes of adiposity have been proposed and are currently in use in clinical practice and research. However, the correlation of these indexes with measures of vascular health remain poorly defined. This study investigated which measure of adiposity is most strongly associated with endothelial function. Data from the Firefighters And Their Endothelium (FATE) study was used. The relationships between three measures of vascular function: flow-mediated dilation (FMD), hyperemic velocity time integral (VTI), and hyperemic shear stress (HSS), and five measures of adiposity: BMI, waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body adiposity index (BAI) were tested. Univariate comparisons were made, and subsequently models adjusted for traditional risk factors were constructed. A total of 1,462 male firefighters (mean age 49 ± 9) without cardiovascular disease comprised the study population. No measure of adiposity correlated with FMD; all five measures of adiposity were negatively correlated with VTI and HSS (P values <0.0001), with WHtR most strongly correlated with VTI, and WC most strongly correlated with HSS (both P < 0.05). In models including all five measures of obesity simultaneously, BMI, WC, and WHtR were all predictive of HSS (all P values <0.05), and BMI and WHR were both predictive of VTI (P values <0.05). Anthropometric measures of adiposity may help refine estimations of atherosclerotic burden. BMI was most consistently associated with endothelial dysfunction, but measures of adiposity that reflect distribution of mass were additive.

Impact of endovascular treatment of atherosclerotic renal artery stenosis on endothelial function and arterial blood pressure.

Renovascular disease may cause arterial hypertension and decreases renal function, which both impair endothelial function. Endothelial function, a surrogate marker for cardiovascular risk, can be assessed non-invasively by ultrasound. The aim of this study was to investigate the impact of percutaneous transluminal renal artery angioplasty (PTRA) with stenting on endothelial function and arterial blood pressure in patients with renal artery stenosis (RAS). Flow mediated dilatation of the brachial artery, flow velocities and shear stress were measured with high resolution ultrasound in 24 hypertensive patients with renal artery stenosis prior and one day after revascularization by PTRA with stenting. Endothelial-independent brachial dilatation was measured after application of nitroglycerin. Endothelial-dependent dilatation improved from 2.4±0.9% to 6.1±1.4% (P=0.03), whereas endothelial-independent dilatation did not change after PTRA. Endothelial-dependent reactive hyperemic blood flow increased from 195±40 mL/min to 536±94 mL/min (P=0.0008), whereas endothelial-independent hyperemia did not increase after revascularization. After PTRA, shear stress at rest decreased from 37±11 to 23±3 dyne/cm² (P<0.0001), and reactive hyperemic shear stress increased from 89±29 to 107±12 dyne/cm² (P=0.014). The impact of PTRA on arterial blood pressure resulted in a mean decrease of 21±5 mmHg in systolic pressure (P<0.0001), of 9±2 mmHg in diastolic pressure (P=0.03), and of 14±5 mmHg in peripheral pulse pressure (P=0.0003), respectively. Endovascular treatment of renovascular disease improves endothelial function and decreases in resting shear stress.

Relationship between brachial artery flow-mediated dilatation, hyperemic shear stress, and the metabolic syndrome

Metabolic syndrome (MetSyn) may predispose to cardiovascular disease (CVD) by causing vascular dysfunction. This study aimed to determine the association of MetSyn with vascular function, as assessed by brachial artery flow-mediated dilatation (FMD) and hyperemic shear stress (HSS). A total of 1,417 male firefighters without established diabetes and CVD were classified for MetSyn, according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP) definition. MetSyn was present in 267 individuals (19%). Although FMD was lower in those with versus without MetSyn (8.1 +/- 4.1 vs 8.7 +/- 4.0%; p = 0.02), this was not significant after adjusting for baseline differences (age, smoking, and brachial artery diameter) (p = 0.2). However, HSS was significantly lower in those with versus without MetSyn (72.0 +/- 27.8 vs 80.9 +/- 24.8 dyne/cm(2); p < 0.001), and there was a significant inverse graded relationship with the number of NCEP criteria present (mean HSS for those with 0, 1, 2, 3, 4, and 5 criteria: 83.2 +/- 22.5, 82.2 +/- 24.7, 76.5 +/- 27.2, 74.3 +/- 27.4, 66.5 +/- 28.4, 67.1 +/- 27.6 dyne/cm(2); p < 0.001 for trend). The individual NCEP criteria of abdominal obesity, systolic hypertension, and impaired fasting glucose were independent predictors for HSS. In conclusion, MetSyn was not associated with impaired FMD. Alternatively, HSS, a measure of microvascular function, was significantly lower in those with MetSyn. Thus, MetSyn may contribute to CVD by causing microvascular dysfunction.

Normalization of flow-mediated dilation to shear stress area under the curve eliminates the impact of variable hyperemic stimulus

BackgroundNormalization of brachial artery flow-mediated dilation (FMD) to individual shear stress area under the curve (peak FMD:SSAUC ratio) has recently been proposed as an approach to control for the large inter-subject variability in reactive hyperemia-induced shear stress; however, the adoption of this approach among researchers has been slow. The present study was designed to further examine the efficacy of FMD normalization to shear stress in reducing measurement variability.MethodsFive different magnitudes of reactive hyperemia-induced shear stress were applied to 20 healthy, physically active young adults (25.3 ± 0. 6 yrs; 10 men, 10 women) by manipulating forearm cuff occlusion duration: 1, 2, 3, 4, and 5 min, in a randomized order. A venous blood draw was performed for determination of baseline whole blood viscosity and hematocrit. The magnitude of occlusion-induced forearm ischemia was quantified by dual-wavelength near-infrared spectrometry (NIRS). Brachial artery diameters and velocities were obtained via high-resolution ultrasound. The SSAUC was individually calculated for the duration of time-to-peak dilation.ResultsOne-way repeated measures ANOVA demonstrated distinct magnitudes of occlusion-induced ischemia (volume and peak), hyperemic shear stress, and peak FMD responses (all p < 0.0001) across forearm occlusion durations. Differences in peak FMD were abolished when normalizing FMD to SSAUC (p = 0.785).ConclusionOur data confirm that normalization of FMD to SSAUC eliminates the influences of variable shear stress and solidifies the utility of FMD:SSAUC ratio as an index of endothelial function.

Interrelationships among noninvasive measures of postischemic macro- and microvascular reactivity

The clinical importance of vascular reactivity as an early marker of atherosclerosis has been well established, and a number of established and emerging techniques have been employed to provide measurements of peripheral vascular reactivity. However, relations between these methodologies are unclear as each technique evaluates different physiological aspects related to micro- and macrovascular reactive hyperemia. To address this question, a total of 40 apparently healthy normotensive adults, 19-68 yr old, underwent 5 min of forearm suprasystolic cuff-induced ischemia followed by postischemic measurements. Measurements of vascular reactivity included 1) flow-mediated dilatation (FMD), 2) changes in pulse wave velocity between the brachial and radial artery (DeltaPWV), 3) hyperemic shear stress, 4) reactive hyperemic flow, 5) reactive hyperemia index (RHI) assessed by fingertip arterial tonometry, 6) fingertip temperature rebound (TR), and 7) skin reactive hyperemia. FMD was significantly and positively associated with RHI (r=0.47) and TR (r=0.45) (both P<0.01) but not with reactive hyperemic flow or hyperemic shear stress. There was no correlation between two measures of macrovascular reactivity (FMD and DeltaPWV). Skin reactive hyperemia was significantly associated with RHI (r=0.55) and reactive hyperemic flow (r=0.35) (both P<0.05). There was a significant association between reactive hyperemia and RHI (r=0.30; P<0.05). In more than 75% of cases, vascular reactivity measures were not significantly associated. We concluded that associations among different measures of peripheral micro- and macrovascular reactivity were modest at best. These results suggest that different physiological mechanisms may be involved in changing different measures of vascular reactivity.

Shear Stress Mediated Vascular Function across the Menstrual Cycle: The role of Estrogen

The endogenous production of estrogen has been linked with improvements in vascular endothelial function measured via flow-mediated dilation (FMD) with a likely mechanism being the antioxidant properties of estrogen increasing nitric oxide (NO) bioavailability. However, estrogen therapy has been shown to not only provide cardio-protective effects, but also greater blood flow responses. Therefore, as prior FMD measurements across the menstrual cycle did not account for the post occlusion hyperemic shear stress, the stimulus for the FMD response, the role of estrogen is uncertain. PURPOSE: This study aimed to evaluate the FMD normalized for shear across the menstrual cycle. METHODS: Six young adult females (aged 20±1 yrs) reported to the laboratory in a fasted state on days 5±1, 13±1, and 21±1 of their menstrual cycle to reflect the menses, ovulatory, and luteal phases, respectively. All subjects produced a saliva sample via the passive drool technique to confirm the concentration of sex-steroid hormones, estrogen and progesterone. Following a 20 minute supine acclimation phase to achieve hemodynamic steady state, FMD was measured in the brachial artery. Shear was calculated as (mean velocity * 4/diameter) and expressed as area under the curve (AUC) to the point of peak dilation. RESULTS: All data are presented as mean±SE. The cycle length was 30±1 days. The FMD and FMD/shear were 10.9±2.2, 12.7±1.8, 12.3±1.5 % and 0.53±0.1, 0.58±.08, 0.53±0.08 for the menses, ovulatory, and luteal phases, respectively. The shear (AUC) for the menses, ovulatory, and luteal phases was 21392±2488, 23539±3278, and 25200±2605 s−1, respectively. CONCLUSION: Our findings are consistent with the concept that elevated concentrations of endogenous estrogen, and perhaps synergistically with progesterone, improve FMD across the menstrual cycle; however, there appears to be a concomitant increase in blood velocity induced shear stress across the menstrual cycle which attenuates the sex-hormone mediated effects on FMD. Thus, a major component of the estrogen-induced improvement in vascular function assessed by FMD across the menstrual cycle may simply be a consequence of an increased reactive hyperemia. Funding: TRDRP 15RT-0100; Parker B. Francis Foundation.