Harry A. Silber

Exaggerated Exercise Blood Pressure Is Related to Impaired Endothelial Vasodilator Function

BACKGROUND Persons with high normal blood pressure (BP) or mild hypertension who also have an exaggerated BP response to exercise are at risk for worsening hypertension. The mechanisms that explain this relationship are unknown. We examined the relationships of endothelial vasodilator function and of aortic stiffness with exercise BP. METHODS Subjects were 38 men and 44 women, aged 55 to 75 years, with untreated high normal BP or mild hypertension but otherwise healthy. Exercise was performed on a treadmill. Endothelial vasodilator function was assessed as brachial artery flow-mediated vasodilation (FMD) during reactive hyperemia. Aortic stiffness was measured as pulse wave velocity (PWV). RESULTS Among men, resting systolic BP explained 34% of the variance (P < .01) in maximal exercise systolic BP and FMD explained an additional 11% (P < .01); resting systolic BP explained 23% of the variance in maximal pulse pressure (PP) (P < .01), and FMD explained an additional 10% (P < .01). Among women, resting systolic BP was the only independent correlate of maximal systolic BP (R2 = 0.12, P < .03) and FMD correlated negatively with maximal PP (R2 = 0.12, P < .03). Among men, FMD was the only independent correlate of the difference between resting and maximal systolic BP (R2 = 0.20, P < .02). The FMD was the only independent correlate of the difference between resting and maximal PP among men (R2 = 0.17, P < .03) and among women (R2 = 0.12, P < .03). The PWV did not correlate with exercise BP responses. CONCLUSIONS These results suggest that impaired endothelial vasodilator function may be a mechanism contributing to exercise hypertension and may also be one link between exaggerated exercise BP and worsening hypertension.

The relationship between vascular wall shear stress and flow-mediated dilation: endothelial function assessed by phase-contrast magnetic resonance angiography.

OBJECTIVES We sought: 1) to investigate the relationship between vascular wall shear stress and flow-mediated dilation (FMD) in humans, and 2) to investigate whether this relationship could explain why FMD is greater in small arteries. BACKGROUND Arterial wall shear stress (WSS) is considered to be the primary stimulus for the endothelial-dependent FMD response. However, the relationship between WSS and FMD has not been investigated in humans. Furthermore, FMD is greater in small arteries, though the reasons for this phenomenon are unclear. METHODS Using phase-contrast magnetic resonance angiography (PMRCA), we measured hyperemic WSS and FMD in 18 healthy volunteers. Peak systolic WSS was calculated assuming a blunted parabolic velocity profile. Diameter by PCMRA and by ultrasound was compared in nine subjects. RESULTS Flow-mediated dilation was linearly proportional to hyperemic peak systolic WSS (r = 0.79, p = 0.0001). Flow-mediated dilation was inversely related to baseline diameter (r = 0.62, p = 0.006), but the hyperemic peak WSS stimulus was also inversely related to baseline diameter (r = 0.47, p = 0.049). Phase-contrast magnetic resonance angiography and ultrasound diameters were compared in nine subjects and correlated well (r = 0.84, p < 0.0001), but diameter by PCMRA was greater (4.1 +/- 0.7 mm vs. 3.7 +/- 0.5 mm, p = 0.009). CONCLUSION Arterial FMD is linearly proportional to peak hyperemic WSS in normal subjects. Thus, the endothelial response is linearly proportional to the stimulus. Furthermore, the greater FMD response in small arteries is accounted for, at least partially, by a greater hyperemic WSS stimulus in small arteries. By allowing the calculation of vascular WSS, which is the stimulus for FMD, and by imaging a fixed arterial cross-section, thus reducing operator dependence, PCMRA enhances the assessment of vascular endothelial function.

A comparison of prospective and retrospective respiratory navigator gating in 3D MR coronary angiography

A comparison between the prospective and retrospective respiratory navigator gating in MR coronary angiography was performed with eight normal subjects. A three-dimensional (3D) ECG-gated fast gradient echo pulse sequence was used for image data acquisition. The results show that the MR coronary angiography obtained using retrospective gating retains a considerable amount of motion artifacts. In this study, the images acquired using prospective navigator gating demonstrated significantly reduced motion artifacts (p = 0.009), improved vessel visibility (p = 0.021) with reduced imaging time (p = 0.013) compared to the images obtained using retrospective navigator gating.

Finger photoplethysmography during the Valsalva maneuver reflects left ventricular filling pressure

It is often challenging to assess cardiac filling pressure clinically. An improved system for detecting or ruling out elevated cardiac filling pressure may help reduce hospitalizations for heart failure. The blood pressure response to the Valsalva maneuver reflects left heart filling pressure, but its underuse clinically may be due in part to lack of continuous blood pressure recording along with lack of standardization of expiratory effort. In this study, we tested whether Valsalva-induced changes in the pulse amplitude of finger photoplethysmography (PPG), a technology already widely available in medical settings, correlate with invasively measured left ventricular end-diastolic pressure (LVEDP). We tested 33 subjects before clinically scheduled cardiac catheterizations. A finger photoplethysmography waveform was recorded during a Valsalva effort of 20 mmHg expiratory pressure sustained for 10 s, an effort most patients can achieve. Pulse amplitude ratio (PAR) was calculated as the PPG waveform amplitude just before release of expiratory effort divided by the waveform amplitude at baseline. PAR was well correlated with LVEDP (r = 0.68; P < 0.0001). For identifying LVEDP > 15 mmHG, PAR > 0.4 was 85% sensitive [95% confidence interval (95CI): 54-97%] and 80% specific (95CI: 56-93%). In conclusion, finger PPG, a technology already ubiquitous in medical centers, may be useful for assessing clinically meaningful categories of left heart filling pressure, using simple analysis of the waveform after a Valsalva maneuver effort that most patients can achieve.

Effect of exercise on abdominal fat loss in men and women with and without type 2 diabetes

Objective To examine the effect of exercise on abdominal adipose tissue in adults with and without type 2 diabetes mellitus (T2DM). Design Post hoc analysis of two randomised controlled trials. Setting Outpatient secondary prevention programme in Baltimore, Maryland, USA. Participants 97 men and women with prehypertension, stage 1 or medically controlled hypertension. 49% of the sample was also diagnosed with T2DM. Intervention All participants completed a 26-week (6.5 months) supervised aerobic and resistance exercise programme following American College of Sports Medicine guidelines. Primary and secondary outcome measures The main outcomes in this post hoc analysis were total abdominal adipose tissue (TAT), subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) measured by MRI. Secondary outcomes were to determine whether the magnitude of abdominal fat change differed by diabetes status in men and women and to identify the predictors of change in abdominal fat distribution with exercise. Results Overall, participants (mean age 61±6 years; 45% women) significantly improved peak oxygen uptake by 15% (p<0.01) and reduced weight by 2% (p<0.01). No change in SAT was observed after training. The reduction in VAT following exercise was attenuated in participants with T2DM (–3%) compared with participants who were non-T2DM (–18%, p<0.001 for the difference in change). The magnitude of VAT loss was associated with a decrease in body weight (r=0.50, p<0.001). After adjustment for weight change using regression analysis, diabetes status remained an independent predictor of the change in VAT. Conclusions Although participants with and without T2DM attained an exercise training effect as evidenced by increased fitness, VAT was unchanged in T2DM compared to those without T2DM, suggesting that these individuals may be resistant to this important benefit of exercise. The strategies for reducing cardiovascular disease risk in T2DM may be most effective when they include a weight loss component. Clinical Trials Registration Clinicaltrials.gov Registry NCT00212303.

Autonomic dysfunction as a mechanism of intradialytic blood pressure instability

The autonomic nervous system (ANS) is the principal endogenous defense mechanism that maintains blood pressure in the setting of hypotension. Disruption of the ANS impairs this ability and can contribute to blood pressure instability, including hypotension and hypertension. In this narrative review, we provide an overview of the ANS and the consequences of its dysfunction in patients with end‐stage kidney disease treated with dialysis. We also discuss possible mechanisms of this autonomic dysfunction that may need future investigation.

The effect of intermittent pneumatic compression of legs on the levels of nitric oxide related species in blood and on arterial function in the arm.

BACKGROUND Intermittent pneumatic compression (IPC) of legs exerts beneficial local vascular effects, possibly through local release of nitric oxide (NO). However, studies demonstrating systemic transport of nitrogen oxide species and release of NO prompt the question of whether IPC could also exert nonlocal effects. We tested whether IPC (1) affects systemic levels of nitrite, S-nitrosothiols and red blood cell (RBC) NO, and (2) exerts vasoactive effects in the brachial artery (BA), although this hypothesis-generating pilot study did not investigate cause and effect relationship between (1) and (2). METHODS In 10 healthy subjects, ages 24-39 years, we measured plasma nitrite, plasma S-nitrosothiols and RBC-NO from venous blood samples drawn before and after IPC treatment. We also measured BA responses to 5 min of upper arm occlusion at rest and during 1 h of leg IPC. RESULTS There was a significant decrease in plasma nitrite (112±26 nM to 90±15 nM, p=0.0008) and RBC-NO (129±72 nM to 102±41 nM, p=0.02). Plasma S-nitrosothiols were unchanged (5.79±4.81 nM to 6.27±5.79 nM, p=0.3). BA occlusion-mediated constriction (OMC) was significantly attenuated with IPC treatment (-43±13% to -33±12%, p=0.003). High-flow mediated BA dilation was unchanged (13.3±9.4% to 11.5±7.2%, p=0.2). CONCLUSION Plasma nitrite, RBC-NO, and BA OMC decreased with leg IPC. We hypothesize that this decrease in circulatory pool of plasma nitrite and RBC-NO may result from the transfer of their NO-bioactivity from blood to the hypoxic arm tissue, to be stored and released under hypoxic stress and oppose OMC. Future studies should investigate whether IPC-induced decreases in brachial OMC are caused by the changes in systemic NO activity, and whether leg IPC could benefit distant arterial function in systemic cardiovascular disease.

Usefulness of Pulse Amplitude Changes During the Valsalva Maneuver Measured Using Finger Photoplethysmography to Identify Elevated Pulmonary Capillary Wedge Pressure in Patients With Heart Failure

The pulse amplitude ratio, the ratio of pulse pressure at the end of a Valsalva maneuver to before the onset of Valsalva, correlates with filling pressure. This study aimed to noninvasively estimate cardiac filling pressure in patients with heart failure. We developed a noninvasive handheld device to measure pulse amplitude ratio using finger photoplethysmography. In 69 patients who underwent right heart catheterization, photoplethysmography waveforms were recorded during a standardized Valsalva maneuver, and in 60 of these patients, pulse amplitude ratio was able to be calculated. Pulse amplitude ratio correlated with pulmonary capillary wedge pressure (PCWP) (r = 0.58, p <0.0001), particularly among those subjects with reduced ejection fraction (r = 0.60, p = 0.002, n = 25). A multivariable linear regression model for PCWP including pulse amplitude ratio, age, body mass index, systolic blood pressure, diastolic blood pressure, and heart rate yielded an R2 of 0.54. Difference in mean pulse amplitude ratio for subjects with a PCWP ≤15 mm Hg versus >15 mm Hg was statistically significant (p <0.0001, area under receiver operating characteristics curve 0.79 [0.66, 0.92]). Pulse amplitude ratio ≥0.55 predicted PCWP >15 mm Hg with 73% sensitivity and 77% specificity. Pulse amplitude ratio also increased by an average of 0.03 with a leg raise maneuver (p = 0.05, n = 36). In conclusion, we demonstrate that noninvasively measured response to the Valsalva maneuver in patients with HF can estimate PCWP and also detect changes within a single patient.

A NONINVASIVE HAND-HELD DEVICE IDENTIFIES ELEVATED LEFT VENTRICULAR FILLING PRESSURE USING FINGER PHOTOPLETHYSMOGRAPHY DURING THE VALSALVA MANEUVER

The high rate of re-hospitalization for heart failure might be reduced by improving noninvasive techniques for identifying elevated left ventricular (LV) filling pressure. We showed that changes in a finger photoplethysmography (PPG) waveform during the Valsalva maneuver (VM) reflect LV end-

ASSESSING LEFT VENTRICULAR FILLING PRESSURE USING FINGER PHOTOPLETHYSMOGRAPHY DURING THE VALSALVA MANEUVER PREDICTS 30-DAY HEART FAILURE OUTCOMES

One reason for the high re-hospitalization rate for heart failure (HF) is the difficulty detecting elevated cardiac filling pressure after symptoms have improved. We showed that the amplitude of a finger photoplethysmography waveform during a Valsalva maneuver relative to baseline (Pulse Amplitude