Peter Picton

Short-Term Blood Pressure, Noradrenergic, and Vascular Effects of Nocturnal Home Hemodialysis

Abstract—Long-term nocturnal hemodialysis, which uses longer and more frequent sessions than conventional hemodialysis, lowers clinic blood pressure and left ventricular mass. We tested the hypotheses that short-term nocturnal hemodialysis would (1) reduce ambulatory blood pressure; (2) cause peripheral vasodilation; (3) lower plasma norepinephrine concentration; and (4) improve the arterial response to reactive hyperemia (a marker of endothelium-dependent vasodilation). We studied 18 consecutive patients (age, 41±2; [mean±SEM]) before and 1 and 2 months after conversion from conventional (three 4-hour sessions per week) to nocturnal (six 8-hour sessions per week) hemodialysis. As the dialysis dose per session (Kt/V) increased from 1.24±0.06 to 2.04±0.08 after 2 months (P =0.02), symptomatic hypotension developed and most antihypertensive medications were withdrawn. Nocturnal hemodialysis nonetheless lowered 24-hour mean arterial pressure (from 102±3 to 90±2 mm Hg after 2 months; P =0.01), total peripheral resistance (from 1967±235 to 1499±191 dyne · s · cm−5; P <0.01) and plasma norepinephrine (from 2.66±0.4 to 1.96±0.2 nmol; P =0.04). Endothelium-dependent vasodilation could not be elicited during conventional hemodialysis (−2.7±1.8%) but was restored (+8.0±1.0%; P =0.001) after 2 months of nocturnal hemodialysis. The brachial artery response to nitroglycerin also improved (from 6.9±2.8 to 15.7±1.6%; P <0.05). Nocturnal hemodialysis had no effect on weight or on stroke volume. Rapid reversal of these markers of adverse cardiovascular events with more intense hemodialysis may translate into improved outcome in this high-risk group of patients.

Hemodynamic after-effects of acute dynamic exercise in sedentary normotensive postmenopausal women.

Objectives To determine, in sedentary normotensive postmenopausal women, the after-effects of exercise on systemic and regional hemodynamics, and whether changes in total peripheral conductance after exercise relate to changes in brachial artery flow-mediated vasodilation (FMD). Methods In 13 sedentary postmenopausal women, the blood pressure (BP), cardiac output, total peripheral resistance and total peripheral conductance, calf vascular resistance and FMD were measured during baseline rest, and again commencing 45 min after treadmill exercise. Fourteen premenopausal women completed the identical protocol to obtain reference values for the after-effects of exercise in healthy females. Results In postmenopausal women, exercise was followed by falls in systolic BP (P < 0.01) and diastolic BP (P < 0.001). BP did not fall after exercise in premenopausal women. In both groups the cardiac output (P < 0.01) increased and the calf vascular resistance (P < 0.01) and total peripheral resistance (P < 0.05) decreased after exercise, but resistance fell more (P < 0.05) in postmenopausal women. Baseline FMD was greater in premenopausal women (12.1 ± 1.5 versus 5.3 ± 1.3%, P < 0.01), and similar before and after exercise, whereas prior exercise nearly doubled the FMD of postmenopausal women (to 9.9 ± 1.4%, P < 0.01). These increases in FMD correlated with baseline values (r = −0.75, P < 0.01) and with relative changes in total peripheral conductance (r = 0.72, P < 0.02). The latter relationship was absent in premenopausal women (r = −0.29). Conclusions In postmenopausal women, acute dynamic exercise elicits sustained increases in FMD that could facilitate post-exercise hypotension in this population. These observations reinforce the concept of exercise as an important non-pharmacological intervention to modify cardiovascular risk in postmenopausal women.

Behavioral Neurocardiac Training in Hypertension A Randomized, Controlled Trial

It is not established whether behavioral interventions add benefit to pharmacological therapy for hypertension. We hypothesized that behavioral neurocardiac training (BNT) with heart rate variability biofeedback would reduce blood pressure further by modifying vagal heart rate modulation during reactivity and recovery from standardized cognitive tasks (“mental stress”). This randomized, controlled trial enrolled 65 patients with uncomplicated hypertension to BNT or active control (autogenic relaxation), with six 1-hour sessions over 2 months with home practice. Outcomes were analyzed with linear mixed models that adjusted for antihypertensive drugs. BNT reduced daytime and 24-hour systolic blood pressures (−2.4±0.9 mm Hg, P=0.009, and −2.1±0.9 mm Hg, P=0.03, respectively) and pulse pressures (−1.7±0.6 mm Hg, P=0.004, and −1.4±0.6 mm Hg, P=0.02, respectively). No effect was observed for controls (P>0.10 for all indices). BNT also increased RR-high-frequency power (0.15 to 0.40 Hz; P=0.01) and RR interval (P<0.001) during cognitive tasks. Among controls, high-frequency power was unchanged (P=0.29), and RR interval decreased (P=0.03). Neither intervention altered spontaneous baroreflex sensitivity (P>0.10). In contrast to relaxation therapy, BNT with heart rate variability biofeedback modestly lowers ambulatory blood pressure during wakefulness, and it augments tonic vagal heart rate modulation. It is unknown whether efficacy of this treatment can be improved with biofeedback of baroreflex gain. BNT, alone or as an adjunct to drug therapy, may represent a promising new intervention for hypertension.

Dose-related effects of red wine and alcohol on heart rate variability

In healthy subjects a standard drink of either red wine (RW) or ethanol (EtOH) has no effect on muscle sympathetic nerve activity or on heart rate (HR), whereas two drinks increase both. Using time- and frequency-domain indexes of HR variability (HRV), we now tested in 12 subjects (24-47 yr, 6 men) the hypotheses that 1) this HR increase reflects concurrent dose-related augmented sympathetic HR modulation and 2) RW with high-polyphenol content differs from EtOH in its acute HRV effects. RW, EtOH, and water were provided on 3 days, 2 wk apart according to a randomized, single-blind design. Eight-minute segments were analyzed. One alcoholic drink increased blood concentrations to 36 + or - 2 mg/dl (mean + or - SE), and 2 drinks to 72 + or - 4 (RW) and 80 + or - 2 mg/dl (EtOH). RW quadrupled plasma resveratrol (P < 0.001). HR fell after both water drinks. When compared with respective baselines, one alcoholic drink had no effect on HR or HRV, whereas two glasses of both increased HR (RW, +5.4 + or - 1.2; and EtOH, +5.7 + or - 1.2 min(-1); P < 0.001), decreased total HRV by 28-33% (P < 0.05) and high-frequency spectral power by 32-42% (vagal HR modulation), and increased low-frequency power by 28-34% and the ratio of low frequency to high frequency by 98-119% (sympathetic HR modulation) (all, P < or = 0.01). In summary, when compared with water, one standard drink lowered time- and frequency-domain markers of vagal HR modulation. When compared with respective baselines, two alcoholic drinks increased HR by diminished vagal and augmented sympathetic HR modulation. Thus alcohol exerts dose-dependent HRV responses, with RW and EtOH having a similar effect.

Vagal heart rate responses to chronic beta‐blockade in human heart failure relate to cardiac norepinephrine spillover

We have documented a pre‐junctional β‐2 adrenoceptor mediated reduction in cardiac norepinephrine spillover (CNES) in heart failure patients receiving chronic β‐blockade. Our present objective was to ascertain the consequence of this decrease for vagal heart rate (HR) regulation by determining CNES, arterial baroreflex sensitivity for HR (BRS) and arterial baroreflex modulation of muscle sympathetic nerve activity (MSNA) before and upon 4 months of β‐blockade with either carvedilol or metoprolol. In 19 heart failure patients in sinus rhythm (age: 55±2 [mean±S.E.]; ejection fraction: 20±2%), β‐blockade increased BRS from 4.8±0.9 to 7.9±1.3 ms/mm Hg (P<0.005) but had no effect on arterial baroreflex modulation of MSNA. Changes in CNES and BRS were inversely related (r=–0.52; n=16, P<0.05). Chronic β‐blockade in heart failure augments reflex vagal control of HR at an efferent site of interaction involving blockade of cardiac sympathetic pre‐junctional β‐2 adrenoceptors that facilitate NE release.

Discordance between microneurographic and heart rate spectral indices of sympathetic activity in pulmonary arterial hypertension

Objectives: To determine, in patients with pulmonary arterial hypertension (PAH), whether there is a relationship: (1) between sympathetic nerve firing rate and spectral indices of sympathetic neural heart rate modulation; and (2) between heart rate variability (HRV) and right atrial pressure, a stimulus to sinoatrial node stretch. Design: Characterisation of patients and healthy controls. Setting: Teaching hospital-based study. Patients: 9 PAH patients without elevated pulmonary capillary wedge pressure and nine age-matched control subjects. Interventions: Heart rate (HR) and muscle sympathetic nerve activity (MSNA) were recorded during 10 min of supine rest in both PAH patients studied after right heart catheterisation, and healthy volunteers. Coarse-graining spectral analysis determined HR spectral power. Main outcome measures: (1) Low-frequency (PL) spectral component of HRV; (2) MSNA burst frequency; and in PAH patients: (3) right atrial pressure. Results: MSNA burst frequency was higher in PAH patients (48 (24) and 29 (11) bursts/min, respectively; mean (SD); p = 0.05), whereas total power (p = 0.01), its fractal (p<0.01) and harmonic (p = 0.04) components, and PL (p = 0.01) were all reduced. PL related inversely to both MSNA burst frequency (r = −0.86, p = 0.005) and right atrial systolic pressure (r = −0.77, p = 0.04). Conclusions: Thus, in PAH (as in patients with left ventricular systolic dysfunction) loss of PL relates inversely to gain in MSNA burst frequency. Diminished sympathetic neural heart rate modulation and increased right atrial stretch may combine to attenuate HRV, an adverse prognostic marker.

Nocturnal home hemodialysis improves baroreflex effectiveness index of end-stage renal disease patients.

Background In patients with end-stage renal disease receiving conventional hemodialysis, both the frequency with which brief rises or falls in systolic blood pressure initiate concordant changes in pulse interval (arterial baroreflex effectiveness index), and the gain of reflex heart rate responses to these stimuli (arterial baroreflex sensitivity) are diminished. In chronic renal failure, low baroreflex effectiveness index and baroreflex sensitivity are associated with increased rates of all-cause mortality and sudden death, respectively. Conversion to home nocturnal hemodialysis augments baroreflex sensitivity but its effects on baroreflex effectiveness index have not been reported. Methods In 20 consecutive hypertensive conventional hemodialysis patients training to transition to nocturnal hemodialysis (age 41 ± 2 years; mean ± standard error), baroreflex effectiveness index, baroreflex sensitivity (sequence method) and total arterial compliance (stroke volume/pulse pressure) were determined during quiet rest before and 2 months after conversion. Results With nocturnal hemodialysis, dialysis frequency doubled, the dose per session increased by 70% and antihypertensive medications were withdrawn (from 2.5 ± 0.3 to 0.2 ± 0.1 drugs/patient, P < 0.01) because systolic blood pressure fell (from 139 ± 5 to 119 ± 4 mmHg, P < 0.05). Baroreflex effectiveness index increased from (0.33 ± 0.03 to 0.42 ± 0.03, P = 0.01). Baroreflex sensitivity increased from 5.60 ± 0.88 to 8.48 ± 1.60 ms/mmHg (P < 0.05). Changes in total arterial compliance correlated with changes in baroreflex sensitivity (r = 0.63, P = 0.004) but not baroreflex effectiveness index (r = 0.05, P = 0.95), suggesting independent mechanisms for their attenuation and recovery in end-stage renal disease. Conclusion Nocturnal hemodialysis increases baroreflex effectiveness index in addition to baroreflex sensitivity. The hypothesis that such changes might reduce cardiovascular event rates in this high-risk population merits prospective evaluation. More frequent engagement of the arterial baroreflex after conversion to nocturnal hemodialysis may improve short-term cardiovascular regulation.

Uptake of a Consumer-Focused mHealth Application for the Assessment and Prevention of Heart Disease: The <30 Days Study

Background Lifestyle behavior modification can reduce the risk of cardiovascular disease, one of the leading causes of death worldwide, by up to 80%. We hypothesized that a dynamic risk assessment and behavior change tool delivered as a mobile app, hosted by a reputable nonprofit organization, would promote uptake among community members. We also predicted that the uptake would be influenced by incentives offered for downloading the mobile app. Objective The primary objective of our study was to evaluate the engagement levels of participants using the novel risk management app. The secondary aim was to assess the effect of incentives on the overall uptake and usage behaviors. Methods We publicly launched the app through the iTunes App Store and collected usage data over 5 months. Aggregate information included population-level data on download rates, use, risk factors, and user demographics. We used descriptive statistics to identify usage patterns, t tests, and analysis of variance to compare group means. Correlation and regression analyses determined the relationship between usage and demographic variables. Results We captured detailed mobile usage data from 69,952 users over a 5-month period, of whom 23,727 (33.92%) were registered during a 1-month AIR MILES promotion. Of those who completed the risk assessment, 73.92% (42,380/57,330) were female, and 59.38% (34,042/57,330) were <30 years old. While the older demographic had significantly lower uptake than the younger demographic, with only 8.97% of users aged ≥51 years old downloading the app, the older demographic completed more challenges than their younger counterparts (F 8, 52,422 = 55.10, P<.001). In terms of engagement levels, 84.94% (44,537/52,431) of users completed 1–14 challenges over a 30-day period, and 10.03% (5,259/52,431) of users completed >22 challenges. On average, users in the incentives group completed slightly more challenges during the first 30 days of the intervention (mean 7.9, SD 0.13) than those in the nonincentives group (mean 6.1, SD 0.06, t 28870=–12.293, P<.001, d=0.12, 95% CI –2.02 to –1.47). The regression analysis suggested that sex, age group, ethnicity, having 5 of the risk factors (all but alcohol), incentives, and the number of family histories were predictors of the number of challenges completed by a user (F 14, 56,538 = 86.644, P<.001, adjusted R 2 = .021). Conclusion While the younger population downloaded the app the most, the older population demonstrated greater sustained engagement. Behavior change apps have the potential to reach a targeted population previously thought to be uninterested in or unable to use mobile apps. The development of such apps should assume that older adults will in fact engage if the behavior change elements are suitably designed, integrated into daily routines, and tailored. Incentives may be the stepping-stone that is needed to guide the general population toward preventative tools and promote sustained behavior change.

Advancement of the artificial pancreas through the development of interoperability standards.

Despite advancements in the development of the artificial pancreas, barriers in the form of proprietary data and communication protocols of diabetes devices have made the integration of these components challenging. The Artificial Pancreas Standards and Technical Platform Project is an initiative funded by the JDRF Canadian Clinical Trial Network with the goal of developing device communication standards for the interoperability of diabetes devices. Stakeholders from academia, industry, regulatory agencies, and medical and patient communities have been engaged in advancing this effort. In this article, we describe this initiative along with the process involved in working with the standards organizations and stakeholders that are key to ensuring effective standards are developed and adopted. Discussion from a special session of the 12th Annual Diabetes Technology Meeting is also provided. Conclusion This session provided the project team an excellent opportunity to interact with a diverse group of stakeholders and brought a number of new collaborators to the table who will contribute to the initiative. Starting in January 2013, the project team has convened regular meetings with collaborating researchers and industry representatives to discuss the direction of the standards development, focusing on the IEEE-11073 PHD standards for the insulin pump and CGM. Through this ongoing collaboration, the barriers to the interoperability of diabetes devices will eventually be eliminated, fostering greater innovation in the development of the AP and other diabetes management tools.

Atrial natriuretic peptide augments the variability of sympathetic nerve activity in human heart failure.

Objectives Activation of the sympathetic nervous system, decreased heart rate variability (HRV), and loss of modulation of muscle sympathetic nerve activity (MSNA) within the low frequency (LF, 0.05–0.15 Hz) range are three adverse features of advanced congestive heart failure (CHF). In healthy men, atrial natriuretic peptide (ANP) infusion attenuates reflex increases in MSNA and reduces LF components of HRV spectral power. Sympathoinhibitory actions have also been documented in CHF, but effects on the variability of MSNA and HRV have not been described. Design and methods Heart rate and MSNA were recorded in 10 men (aged 39 ± 3 years, mean ± SE) with dilated cardiomyopathy (mean EF 20 ± 4%) treated with angiotensin converting enzyme (ACE) inhibitors. Subjects received i.v. ANP (50 μ g bolus then 50 ng/kg/min) and nitroglycerin (NTG, 8 mg/min) as a hemodynamic control. Signals at baseline, and 13–20 min into each infusion were submitted to spectral analysis. Results ANP had no effect on HRV, but increased MSNA LF (from 7.9 ± 1.5 to 12.1 ± 2.6 U2;P < 0.02) and total spectral power (from 47.9 ± 5.4 to 61.9 ± 6.8 U2;P < 0.05). NTG had no effect on the variability of MSNA or HRV. Conclusions In CHF patients receiving ACE inhibitors, ANP (i) does not suppress HRV and (ii) enhances the modulation of MSNA, particularly within the LF range. This latter action is not observed with NTG. These findings suggest beneficial actions of exogenous ANP on neurogenic circulatory control.