Urinary albumin-creatinine ratio is a marker of diabetic nephropathy and microvascular damage. Metabolic-related traits are observationally associated with ACR but their causal role is uncertain. Here, we confirmed ACR as a marker of microvascular damage and tested whether metabolic-related traits have causal relationships with ACR. The association between ACR and microvascular function (responses to acetylcholine and sodium nitroprusside) were tested in the SUMMIT study. Two sample Mendelian randomization (MR) was used to infer the causal effects of eleven metabolic risk factors, including glycemic, lipid and adiposity traits on ACR. MR was performed in up to 440,000 UK Biobank and 54,451 CKDGen participants. ACR was robustly associated with microvascular function measures in SUMMIT. Using MR we inferred that higher triglyceride and LDL-cholesterol levels caused elevated ACR. A one standard deviation (SD) higher triglyceride and LDL-C level caused a 0.062 [95%CI: 0.040, 0.083] and a 0.026 [95%CI: 0.008, 0.044] SD higher ACR respectively. There was evidence that higher body fat and visceral body fat distribution caused elevated ACR, whilst a metabolically "favourable adiposity" phenotype lowered ACR. ACR is a valid marker for microvascular function. MR suggested that 7 traits have causal effects on ACR, highlighting the role of adiposity related traits in causing lower microvascular function.
Previous studies have reported a vasoconstrictor response in the radial artery during a cuff‐induced low‐flow condition, but a similar low‐flow condition in the brachial artery results in nonuniform reactivity. This variable reactivity to low‐flow influences the subsequent flow‐mediated dilatation (FMD) response following cuff‐release. However, it is uncertain whether reactivity to low‐flow is important in data interpretation in clinical populations and older adults. This study aimed to determine the influence of reactivity to low‐flow on the magnitude of brachial artery FMD response in middle‐aged and older individuals with diverse cardiovascular risk profiles. Data were analyzed from 165 individuals, divided into increased cardiovascular risk (CVR: n = 115, 85M, 67.0 ± 8.8 years) and healthy control (CTRL: n = 50, 30M, 63.2 ± 7.2 years) groups. Brachial artery diameter and blood velocity data obtained from Doppler ultrasound were used to calculate FMD, reactivity to low‐flow and estimated shear rate (SR) using semiautomated edge‐detection software. There was a significant association between reactivity to low‐flow and FMD in overall (r = 0.261), CTRL (r = 0.410) and CVR (r = 0.189, all P < 0.05) groups. Multivariate regression analysis found that reactivity to low‐flow, peak SR, and baseline diameter independently contributed to FMD along with sex, the presence of diabetes, and smoking (total R 2 = 0.450). There was a significant association between reactivity to low‐flow and the subsequent FMD response in the overall dataset, and reactivity to low‐flow independently contributed to FMD. These findings suggest that reactivity to low‐flow plays a key role in the subsequent brachial artery FMD response and is important in the interpretation of FMD data.
Wall shear rate (WSR) is an important stimulus for the brachial artery flow-mediated dilation (FMD) response. However, WSR estimation near the arterial wall by conventional Doppler is inherently difficult. To overcome this limitation, we utilized multigate Doppler to accurately determine the WSR stimulus near the vessel wall simultaneously with the FMD response using an integrated FMD system [Ultrasound Advanced Open Platform (ULA-OP)]. Using the system, we aimed to perform a detailed analysis of WSR-FMD response and establish novel WSR parameters in a healthy young population. Data from 33 young healthy individuals (27.5 ± 4.9 yr, 19 females) were analyzed. FMD was assessed with reactive hyperemia using ULA-OP. All acquired raw data were postprocessed using custom-designed software to obtain WSR and diameter parameters. The acquired velocity data revealed that nonparabolic flow profiles within the cardiac cycle and under different flow states, with heterogeneity between participants. We also identified seven WSR magnitude and four WSR time-course parameters. Among them, WSR area under the curve until its return to baseline was the strongest predictor of the absolute ( R = 0.25) and percent ( R = 0.31) diameter changes in response to reactive hyperemia. For the first time, we identified mono- and biphasic WSR stimulus patterns within our cohort that produced different magnitudes of FMD response [absolute diameter change: 0.24 ± 0.10 mm (monophasic) vs. 0.17 ± 0.09 mm (biphasic), P < 0.05]. We concluded that accurate and detailed measurement of the WSR stimulus is important to comprehensively understand the FMD response and that this advance in current FMD technology could be important to better understand vascular physiology and pathology. NEW & NOTEWORTHY An estimation of wall shear rate (WSR) near the arterial wall by conventional Doppler ultrasound is inherently difficult. Using a recently developed integrated flow-mediated dilation ultrasound system, we were able to accurately estimate WSR near the wall and identified a number of novel WSR variables that may prove to be useful in the measurement of endothelial function, an important biomarker of vascular physiology and disease.
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