High Frequency of Microvascular Dysfunction in US Outpatient Clinics: A Sign of High Residual Risk? Data from 7,105 Patients

Previous studies have linked peripheral microvascular dysfunction measured by arterial tonometry to high residual risk in on-statin patients. Digital thermal monitoring (DTM) of microvascular function is a new and simplified technique based on fingertip temperature measurements that has been correlated with the burden of atherosclerosis and its risk factors. Here, we report analyses of DTM data from two large US registries: Registry-I (6,084 cases) and Registry-II (1,021 cases) across 49 US outpatient clinics. DTM tests were performed using a VENDYS device during a 5-minute arm-cuff reactive hyperemia. Fingertip temperature falls during cuff inflation and rebounds after deflation. Adjusted maximum temperature rebound was reported as vascular reactivity index (VRI). VRI distributions were similar in both registries, with mean ± SD of 1.58 ± 0.53 in Registry-I and 1.52 ± 0.43 in Registry-II. In the combined dataset, only 18% had optimal VRI (≥2.0) and 82% were either poor (<1.0) or intermediate (1.0-2.0). Women had slightly higher VRI than men ( 1.62 ± 0.56 vs. 1.54 ± 0.47 , p < 0.001 ). VRI was inversely but mildly correlated with age ( r = − 0.19 , p < 0.001 ). Suboptimal VRI was found in 72% of patients <50 years, 82% of 50-70 years, and 86% of ≥70 years. Blood pressure was not correlated with VRI. In this largest registry of peripheral microvascular function measurements, suboptimal scores were highly frequent among on-treatment patients, possibly suggesting a significant residual risk. Prospective studies are warranted to validate microvascular dysfunction as an indicator of residual risk.

An Alignment-Free Sensing Module for Noninvasive Radial Artery Blood Pressure Measurement

Sensor–artery alignment has always been a significant problem in arterial tonometry devices and prevents their application to wearable continuous blood pressure (BP) monitoring. Traditional solutions are to use a complex servo system to search for the best measurement position or to use an inefficient pressure sensor array. In this study, a novel solid–liquid mixture pressure sensing module is proposed. A flexible film with unique liquid-filled structures greatly reduces the pulse measurement error caused by sensor misplacement. The ideal measuring location was defined as −2.5 to 2.5 mm from the center of the module and the pressure variation was within 5.4%, which is available in the real application. Even at a distance of ±4 mm from the module center, the pressure decays by 23.7%, and its dynamic waveform is maintained. In addition, the sensing module is also endowed with the capability of measuring the pulse wave transmit time as a complementary method for BP measuring. The capability of the developed alignment-free sensing module in BP measurement was been validated. Twenty subjects were selected for the BP measurement experiment, which followed IEEE standards. The experimental results showed that the mean error of SBP is −4.26 mmHg with a standard deviation of 7.0 mmHg, and the mean error of DBP is 2.98 mmHg with a standard deviation of 5.07 mmHg. The device is expected to provide a new solution for wearable continuous BP monitoring.

Impact of Peripheral Microvascular Endothelial Dysfunction on White Matter Hyperintensity

Background White matter hyperintensity (WMH), characterized by hyperintensities on T2‐weighted fluid‐attenuated inversion recovery brain magnetic resonance imaging, has been linked to an increased risk of ischemic stroke (IS). Endothelial dysfunction is an indicator of vascular dysfunction, predicting the risk of IS. This study aimed to investigate the association between endothelial dysfunction and regional WMH, and its impact on future risk of IS. Methods and Results We enrolled 219 patients (mean age, 53.1±14.1 years; 34.7% men) who underwent peripheral endothelial function assessment using reactive hyperemia peripheral arterial tonometry and brain magnetic resonance imaging without any history of IS. Volumetric WMH segmentation was automatically extrapolated using a validated automated digital tool. Total and juxtacortical WMH volume/intracranial volume (%) increased with aging and became more prominent in patients aged >50 years (n=131) than those aged ≤50 years (n=88) (total WMH: ≤50 years, Pearson r =0.24, P =0.03; >50 years, Pearson r =0.62, P <0.0001; juxtacortical WMH: ≤50 years, Pearson r =0.09, P =0.40; >50 years, Pearson r =0.55, P <0.0001). Reactive hyperemia peripheral arterial tonometry index was negatively associated with total and juxtacortical WMH volume/intracranial volume (%) in patients aged >50 years after adjustment for other covariates (reactive hyperemia peripheral arterial tonometry index, standardized β coefficient −0.17, P =0.04). Juxtacortical WMH volume/intracranial volume (%) was associated with an increased risk of IS during median follow‐up of 6.5 years (hazard ratio, 1.47; 95% CI, 1.05–1.92; P =0.03). Conclusions Peripheral endothelial dysfunction is associated with an increased volume of juxtacortical WMH in patients aged >50 years, which is a potential marker to predict future risk of IS.

Effect of exercise training on vascular function and endothelial repair in heart failure with preserved ejection fraction: results from the OptimEx trial

Background Exercise training improves peak oxygen uptake (VO2) in heart failure with preserved ejection fraction (HFpEF), but the underlying mechanisms are unknown. In other cardiovascular diseases, exercise training improves vascular function and increases levels of circulating endothelium-repairing cells. We aimed to investigate the effects of moderate continuous training (MCT) and high intensity interval training (HIIT) on vascular function and cellular endothelial repair in HFpEF. Methods This was a prespecified subanalysis of the Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure randomized trial. HFpEF patients (n=180) were randomized to HIIT, MCT or attention control. At baseline and after 12 weeks, we measured peak VO2, fingertip arterial tonometry (n=109), brachial artery flow-mediated dilation (n=59), aortic pulse wave velocity (n=94), and flow cytometry (n=136) for endothelial progenitor cells (CD45dimCD34+VEGFR2+) and angiogenic T cells (CD3+CD31+CD184+). Changes in these parameters were compared between groups using linear mixed models. Parameters were correlated using Spearman's rho. Results At 3 months, we did not observe significant differences between HIIT, MCT and control group regarding changes in vascular function throughout the vascular tree (fingertip arterial tonometry, brachial artery flow-mediated dilation and central arterial stiffness, Table 1) or levels of circulating endothelium-repairing cells (endothelial progenitor cells and angiogenic T cells, Table 1). Results were similar at 12 months and when restricting analysis to patients with at least 70% adherence to training sessions. Patients with higher peak VO2 at baseline had lower numbers of circulating endothelial progenitor cells (rho=−0.22, p=0.011). Conclusions In patients with HFpEF, exercise training did not change vascular function or levels of endothelium-repairing cells. Thus, improved vascular function likely does not contribute to the change in peak VO2 after training. These findings are in contrast with the benefits of exercise on vascular function in heart failure with reduced ejection fraction and coronary artery disease. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU Framework Programme 7 Table 1

Does overnight duty affect vascular endothelial function?

Background The reactive hyperemia index (RHI), which is obtained from the measurement of peripheral arterial tonometry (PAT), is highly associated with the percentage change in the end-diastolic arterial diameter (%flow-mediated dilatation) at reactive hyperemia. Low RHI is reported to be a mortality risk in patients with a high risk of cardiovascular (CV) disease. CV events are thought to be induced by physical and mental stress, including long-term fatigue and lack of sleep. However, the relationship between fatigue, lack of sleep, and endothelial function has not yet been established. Methods Healthy hospital workers (n = 13, 6 men and 7 women) with an average age of 31.6 years were assigned to this study after they provided written informed consent. During the study period, we conducted 72 measurements of reactive hyperemia-peripheral arterial tonometry (RH-PAT) in the morning before or after their duty. At each measurement of the RH-PAT, we recorded the participants’ hours of sleep and evaluated their degree of fatigue using a visual analog scale (VAS). Results Although the VAS was significantly less (36 ± 16% and 64 ± 12%, p < 0.001) and the hours of sleep were longer (6.0 ± 1.1 h and 2.3 ± 1.0 h, p < 0.001) before duty compared to those after duty, the RHI was comparable between them (2.12 ± 0.53 vs. 1.97 ± 0.50, p = 0.21). The VAS score was significantly higher in participants with low RHI (< 1.67) than in those with normal RHI (≥ 2.07) (59 ± 13% and 46 ± 21%, respectively, p < 0.05). However, binary logistic regression showed no significant association between low RHI and the VAS when adjusted for systemic blood pressure (SBP) and heart rate variability (HRV). In a simple regression analysis, the RHI was significantly correlated with the VAS score but not with sleep duration. A multiple linear regression analysis also showed no significant association between the RHI and VAS scores after adjustment for SBP and HRV. Conclusions Vascular endothelial function was not associated with overnight duty, hours of sleep, or degree of fatigue in healthy young adults. Since the RHI may be decreased in severe fatigue conditions through autonomic nerve activity, one should consider the physical and mental conditions of the examinee when evaluating the RH-PAT results.

Abstract P113: IMPACT OF ARTERIAL SITE AND PRESSURE WAVE ACQUISITION METHOD ON ARTERIAL FORM FACTOR AND MEAN AND CENTRAL ARTERIAL PRESSURE

Accurate mean arterial pressure (MAP) measurement requires an integrated arterial pressure waveform but MAP is often estimated from systolic (S) and diastolic (D) BP using a fixed form factor (FF, usually 0.33): MAP = DBP + FF*pulse pressure (PP), also solvable for FF if MAP is known. MAP is constant in the arterial tree but central (c) PP is lower than peripheral (p) PP, so cFF should be higher than pFF, and MAP and FF values should be similar among devices. We tested these principles for 2 transfer function-dependent devices: SphygmoCor (SPG), which generates high fidelity radial arterial tonometry waveforms and integrates MAP, and Mobil-O-Graph (MOB), a 24-hour ambulatory oscillometric brachial pulse wave analysis system that reports a proprietary MAP. SPG data were obtained after 5-10 minutes of rest and MOB values were obtained at 20 min intervals. For SPG (n =371) [mean(SD)]: pBP 140(28)/80(15) and cBP 126(28)/81(15) mmHg, age 48(20) yr, BMI 28(6.6), 54% women, 17% black. SPG-pFF was lower than cFF [0.34(.056) vs 0.44(.049), p<0.000]; SPG-pFF and cFF were correlated (r 2 = 0.23, p<0.000); and on stepwise multiple regression, pFF was related to MAP > gender > age (multiple-r 2 = 0.37, p<0.000; BMI and race excluded). For MOB (n = 157): pBP 135(18)/81(12) and cBP 123(16)/83(12) mmHg, age 59(16) yr, BMI 30(6), 52% women, 24% black. MOB-pFF was a fixed value [0.46(0.00098)] that was lower than cFF [0.57(0.048), p<0.000] and MOB-cFF was not correlated with MAP or any other characteristic. To compare SPG and MOB directly, 101 pairs were matched precisely (SPSS software) for pSBP and pDBP (130.9/78.7 mmHg for each device group); SPG-MAP was lower than MOB-MAP [96.3 vs 102.6 mmHg (p<0.000)] and SPG-cSBP was lower than MOB-cSBP [117.5 (18.0) vs 119.7(14.6), p=.015], with respective FF’s similar to the full groups. We conclude that: 1) FF varies within-subjects by arterial location and (at constant MAP) cFF > pFF; 2) SPG-pFF (but not MOB-pFF) varies between-subjects and is affected by MAP, gender, and age; 3) the proprietary MOB-pFF is fixed and much higher than traditional FF or SPG-pFF; and 4) compared to SPG, MOB overestimates MAP by about 5% and underestimates cSBP by about 2%. These findings have implications for FF methods and proprietary devices such as Mobil-O-Graph.

Improvement of Vascular Endothelial Function Reflects Nonrecurrence After Catheter Ablation for Atrial Fibrillation

Background The clinical implication of vascular endothelial dysfunction in patients with atrial fibrillation (AF) remains unclear. This study aimed to elucidate the correlation between changes in vascular endothelial function assessed by reactive hyperemia‐peripheral arterial tonometry and the effect of sinus rhythm restoration after catheter ablation (CA) for AF. Methods and Results Consecutive 214 patients who underwent CA for AF were included in this single center, retrospective study. The natural logarithmic transformed reactive hyperemia‐peripheral arterial tonometry index (LnRHI) of all patients was measured before CA as well as 3 and 6 months after CA. LnRHI in sinus rhythm was significantly higher than that in AF before CA. Multivariate logistic regression analysis revealed that the presence of AF was an independent risk factor for lowering of LnRHI (odds ratio, 4.092; P =0.002) before CA. The LnRHI was significantly improved 3 and 6 months after CA in patients without AF recurrence. Multivariate Cox hazard analysis revealed that changes in LnRHI from before to 3 months after CA independently correlated with recurrence of AF (hazard ratio, 0.106; P =0.001). Receiver operating characteristic analysis showed the decrease in LnRHI levels from before to 3 months after CA as a significant marker that suspects AF recurrence (area under the curve, 0.792; log‐rank test, P <0.001). Conclusions The presence of AF was independently correlated with the impaired vascular endothelial function assessed by the reactive hyperemia‐peripheral arterial tonometry. Long‐term sinus rhythm restoration after CA for AF might contribute to the improvement of vascular endothelial function, which may reflect the nonrecurrence of AF.