Can an active lifestyle offset the relationship that poor lifestyle behaviours have on frailty?

OBJECTIVE: To examine the association of lifestyle behaviours (LSB) with physical activity (PA) and frailty; also, to examine if associations differ by sex and age. METHODS: 24,828 individuals [49.6 ± 17.6 years (range: 20-85), 51.6 % female] from the National Health and Nutrition Examination Survey (cycles 2009-2018) were included. Individuals were divided into Active (≥150 min/week of moderate-to-vigorous physical activity (MVPA)) and Inactive (<150 min/week MVPA) based on self-reported PA. Frailty was measured by a 46-item Frailty Index (FI). LSB consisted of stationary time, sleep, diet quality, and alcohol and smoking habits. LSB was summed into a score [0-5]. Linear regression models were used with each LSB in isolation and the summed LSB with frailty. RESULTS: There were 7,495 (30.1 %) Active and 17,333 (69.8 %) Inactive individuals. The FI was lower in the Active participants (Active: 0.10 ± 0.08; Inactive: 0.15 ± 0.12; p < 0.01). A worse LSB score was associated with an increased FI in all behaviours but females who binge drink and smoke (p-all>0.14). For inactive individuals, all LSBs were associated with an increased FI except those who binge drink and male smokers (p = 0.08). There was a significant association between increased summed LSB and an increased FI (ß range: Active, 0.024-0.037; Inactive, 0.028, 0.046. p-all<0.01); the Active group had a lower FI at every age group than the Inactive group (p < 0.001). CONCLUSION: PA was associated with a lower FI even among those with a poor LSB score. This association is dependent on age, with older individuals reporting a stronger association.

Knee-high compression socks minimize head-up tilt-induced cerebral and cardiovascular responses following dynamic exercise.

In healthy individuals during a non-exercised state, knee-high compression socks (CS) may reduce the magnitude of lower limb venous pooling during orthostasis but are not effective at minimizing the incidence of pre-syncopal symptoms. However, exaggerated reductions in cerebral blood flow velocity (CBV) and cardiac stroke volume (SV) occur during passive head-up tilt (HUT) testing following dynamic exercise. It is unknown if CS can minimize post-exercise HUT-induced decrements in CBV and SV in this population. To test the hypothesis that CS will attenuate the reductions in SV and CBV during 60° HUT following 60 minutes of moderate-intensity (60% VO2 peak) cycling exercise. Ten healthy volunteers (22.6 ± 2.1 years, 24.1 ± 2.5 kg/m2 ) completed pre- and post-exercise 15-minute HUT tests during randomized CS and Control (no CS) conditions. Changes in blood pressure (finger plethysmography), SV (Modelflow® method), and CBV (Transcranial Doppler) were measured during HUT and preceding supine rest periods. Pre-exercise HUT-induced similar (all, P > .47) reductions in SV (Control; -23.1 ± 11.5%, CS; -20.5 ± 10.9%) and CBV (Control; -18.1 ± 6.3%, CS; -15.3 ± 9.0%). However, larger post-exercise decreases in SV and CBV during HUT were observed in the Control versus CS condition. Specifically, CS attenuated the drop in SV (Control: -32.9 ± 5.6%, CS: -24.3 ± 11.6%; P = .01) and CBV (Control: -25.1 ± 5.8%, CS: -17.6 ± 7.8%; P = .02) during the post-exercise HUT test. These results indicate that CS attenuated HUT-induced reductions in SV and CBV following moderate-intensity cycling exercise and suggest that CS may be an effective countermeasure to reduce the incidence of post-exercise syncope in vulnerable populations.

Central and peripheral response to incremental cycling exercise in older untrained active men: a comparison of those in-between.

The aim of this study was to compare the central and peripheral components of cardiorespiratory fitness during incremental to maximal exercise between older men who were either recreational athletes (RA) or leisurely active (LA) men, i.e., those who fall between trained and untrained. This was a cross-sectional study in which all subjects completed an exercise test on a cycle ergometer. Maximal oxygen consumption (VO(2max)) and ventilatory threshold (VT) were assessed using gas analysis, and central components of VO(2max) were assessed using a non-invasive thoracic bio-impedance device. VO(2max) (RA: 45.1+/-4.8 ml/kg/min; LA: 32.2+/-4.6 ml/kg/min, p

Cardiac mechanoreceptor function implicated during premature ventricular contraction.

In a premature ventricular contraction (PVC), a systolic blood pressure peak is missing during the affected cardiac cycle, leading to a prolonged reduction in blood pressure which is then followed by a large burst of sympathetic outflow. In a normal ventricular contraction, it is generally believed that peak carotid and aortic distensions associated with systolic pressure is the neural feedback that terminates sympathetic outflow through a baroreflex mechanism. Yet, the characteristically large sympathetic burst following a PVC is terminated without a systolic pressure and evidently without this mechanism. To address this anomaly, we examined the possible role of cardiac receptors in providing an alternative mechanism for the termination of sympathetic outflow in a PVC. For this purpose, recordings of electrocardiogram (ECG), arterial blood pressure (ABP), and muscle sympathetic neural activity (MSNA) were made in a human subject during repeated PVC episodes. The time intervals, or "latencies", from key events within the PVC to the peak of the associated MSNA burst were calculated and compared with the latency in a normal ventricular contraction which is associated with central baroreceptor function. It was found that the only event in a PVC that corresponds with a physiologically plausible latency is that which marks the end of ventricular filling. We conclude with the hypothesis that in the unique circumstances of a PVC, where the systolic pressure peak required to trigger arterial baroreceptors to terminate sympathetic outflow is absent, mechanoreceptors in the heart appear to "step in" to perform this sympathoinhibitory function.

Forebrain regions associated with postexercise differences in autonomic and cardiovascular function during baroreceptor unloading.

The cortical regions representing peripheral autonomic reactions in humans are poorly understood. This study examined whether changes in forebrain activity were associated with the altered physiological responses to lower body negative pressure (LBNP) following a single bout of dynamic exercise (POST-EX). We hypothesized that, compared with the nonexercised condition (NO-EX), POST-EX would elicit greater reductions in stroke volume (SV) and larger increases in heart rate (HR) and muscle sympathetic nerve activity (MSNA) during LBNP (5, 15, and 35 mmHg). Forebrain neural activity (n = 11) was measured using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. HR, SV, arterial blood pressure (ABP), and MSNA were collected separately. Compared with NO-EX, baseline ABP was reduced, whereas HR and total vascular conductance (TVC) were elevated in POST-EX (P < 0.05). In both conditions, 5 mmHg LBNP did not elicit a change (from baseline) in any physiological parameter. Compared with NO-EX, 35 mmHg LBNP-mediated decreases in SV and TVC produced greater increases in HR and MSNA during POST-EX (P < 0.05). The right posterior insula and dorsal anterior cingulate cortex demonstrated a larger decrease in BOLD at 5 mmHg LBNP but greater BOLD increase at 15 and 35 mmHg LBNP POST-EX vs. NO-EX (P < 0.005). Conversely, the thalamus and ventral medial prefrontal cortex displayed the opposite BOLD activity pattern (i.e., larger increase at 5 mmHg LBNP but greater decrease at 15 and 35 mmHg LBNP POST-EX vs. NO-EX). Our findings suggest that discrete forebrain regions may be involved with the generation of baroreflex-mediated sympathetic and cardiovascular responses elicited by moderate LBNP.

Forebrain neural patterns associated with sex differences in autonomic and cardiovascular function during baroreceptor unloading.

Generally, women demonstrate smaller autonomic and cardiovascular reactions to stress, compared with men. The mechanism of this sex-dependent difference is unknown, although reduced baroreflex sensitivity may be involved. Recently, we identified a cortical network associated with autonomic cardiovascular responses to baroreceptor unloading in men. The current investigation examined whether differences in the neural activity patterns within this network were related to sex-related physiological responses to lower body negative pressure (LBNP, 5, 15, and 35 mmHg). Forebrain activity in healthy men and women (n = 8 each) was measured using functional magnetic resonance imaging with blood oxygen level-dependent (BOLD) contrast. Stroke volume (SV), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were collected on a separate day. Men had larger decreases in SV than women (P < 0.01) during 35 mmHg LBNP only. At 35 mmHg LBNP, HR increased more in males then females (9 +/- 1 beats/min vs. 4 +/- 1 beats/min, P < 0.05). Compared with women, increases in total MSNA were similar at 15 mmHg LBNP but greater during 35 mmHg LBNP in men [1,067 +/- 123 vs. 658 +/- 103 arbitrary units (au), P < 0.05]. BOLD signal changes (P < 0.005, uncorrected) were identified within discrete forebrain regions associated with these sex-specific HR and MSNA responses. Men had larger increases in BOLD signal within the right insula and dorsal anterior cingulate cortex than women. Furthermore, men demonstrated greater BOLD signal reductions in the right amygdala, left insula, ventral anterior cingulate, and ventral medial prefrontal cortex vs. women. The greater changes in forebrain activity in men vs. women may have contributed to the elevated HR and sympathetic responses observed in men during 35 mmHg LBNP.

Test-retest repeatability of muscle sympathetic nerve activity: influence of data analysis and head-up tilt.

Total integrated muscle sympathetic nerve activity (MSNA) is composed of bursts that vary in both frequency and amplitude. Various quantifiable indices are currently used to characterize MSNA and its reflex-mediated responses. However, a comprehensive and systematic analysis on the test-retest repeatability of these measures has not been conducted. Therefore, the purpose of this study was to compare the consistency of supine and passive head-up tilt-mediated sympathetic nerve activity using different descriptors of MSNA and a statistical paradigm that included Model II ordinary least products (OLP) regression, Bland-Altman method of differences, and analysis of variance. MSNA (microneurography), stroke volume (SV, Doppler), and arterial blood pressure (ABP, Finapres) were measured during repeated supine and 60 degrees head-up tilt (HUT) conditions separated by a minimum of 3 weeks. MSNA was quantified using; burst frequency (and incidence), burst amplitudes (and total integrated activity) normalized to the largest absolute amplitude within each posture, and calculated percent changes (from supine) in absolute burst amplitude and total integrated activity. Most indices of MSNA showed excellent test-retest repeatability during both postures with neither fixed nor proportional bias. However, MSNA expressed as burst incidence demonstrated both fixed and proportional bias in the supine position, but not during HUT. In addition, HUT-induced percent changes in absolute burst amplitude and total activity displayed a fixed bias with greater increases during the second test (P<0.05). The hemodynamic variables associated with the reflex responses were quite similar between tests (i.e., no bias). It was concluded that, with the exception of burst incidence, the majority of MSNA indices provided reliable markers of sympathetic activity on repeated tests. However, care must be taken when using percent changes in MSNA that incorporate absolute amplitudes.

Differential effect of head-up tilt on cardiovagal and sympathetic baroreflex sensitivity in humans.

The purpose of this study was to determine the effect of baroreceptor unloading on the sensitivity of the cardiovagal and sympathetic arms of the baroreflex during upright posture. Beat-by-beat R-R interval, arterial blood pressure and cardiac output (Doppler ultrasound), as well as muscle sympathetic nerve activity (MSNA) were recorded during periods in supine (Supine) and 60 deg head-up tilt (HUT) positions (n = 8 volunteers). Cardiovagal baroreflex sensitivity (BRS) was measured by the spontaneous sequence analysis method using systolic blood pressure and R-R interval, while sympathetic BRS was determined using the slope of the linear relationship between decreasing segments of diastolic blood pressure (DBP) and corresponding increases in MSNA. On changing to HUT, mean R-R interval and cardiac output decreased, while mean measures of MSNA, DBP and total peripheral resistance increased (P < 0.05). Cardiovagal BRS decreased from Supine to 60 deg HUT (19 +/- 2 ms mmHg(-1) versus 7.6 +/- 1.2 ms mmHg(-1); P < 0.01). In contrast, sympathetic BRS increased from -6.1 +/- 1.4 a.u. mmHg(-1) in Supine to -14 +/- 2 a.u. mmHg(-1) in HUT (P < 0.01). Thus, HUT produced differential effects on cardiac versus sympathetic BRS. The data suggest that dynamic baroreflex-mediated cardiovascular control is dominated by sympathetic control during baroreceptor unloading.

Circulating norepinephrine and cerebrovascular control in conscious humans.

BACKGROUND: Cerebral vasoconstriction without concurrent changes in systemic arterial blood pressure has been observed in both normal individuals and those with idiopathic orthostatic intolerance following several minutes of postural stress when circulating catecholamines are elevated. Therefore, we tested the hypothesis that alpha-adrenergic activation with and without elevated circulating norepinephrine (NE) directly affects cerebrovascular tone in healthy individuals. METHODS: Mean arterial pressure (MAP; tonometry) and cerebral blood flow velocity (MFV) in the middle cerebral artery (transcranial Doppler) were measured in seven healthy individuals during 15 min periods of saline and of 50 (low NE) and 100 (high NE) ng kg(-1) min(-1) infusions of NE. Following this, phentolamine (PHO) was administered to return MAP back to baseline while high NE infusion continued (high NE+PHO). Finally, NE infusion was stopped allowing the persistent effects of PHO to dominate. RESULTS: Circulating NE caused a dose-dependent increase in MAP (P<0.05). During combined high NE+PHO, blood pressure was initially reduced to baseline levels but then increased a second time (P<0.05) during the final approximately 5 min of this phase. MFV remained constant during both low NE and high NE. In contrast, the secondary increase in BP during the late high NE+PHO phase was associated with elevated MFV. Cerebral vascular resistance (CVR) increased during high NE but was reduced to baseline during both early and late portions of the combined high NE+PHO phase (i.e. despite the late-phase increase in blood pressure). CONCLUSIONS: The increase in CVR during NE infusion was explained by an autoregulatory response to the increased blood pressure and not an alpha-mediated constriction. However, PHO appeared to interfere with the normal autoregulatory response to increasing blood pressure.

Hypovolemia and MSNA discharge patterns: assessing and interpreting sympathetic responses.

We previously demonstrated that diuretic-induced hypovolemia resulted in an enhanced baroreflex-mediated increase in integrated muscle sympathetic nerve activity (MSNA) and vasomotor tone during lower body negative pressure (LBNP) (Am J Physiol Heart Circ Physiol 282: H645-H655, 2002). The purpose of this study was to perform a retrospective analysis of these data and examine the ability of relative MSNA burst amplitude distributions to highlight differences in baseline sympathetic nerve discharge patterns. An additional purpose was to determine whether differential responses in MSNA burst frequency and burst amplitude affect conclusions regarding sympathetic reflex control. MSNA, stroke volume (SV, Doppler), and estimated central venous pressure (CVP, dependent arm technique) were measured during LBNP within the placebo (Normo) and diuretic (Hypo; 100 mg/day spironolactone for 3 days) conditions (n = 8). Compared with Normo, MSNA burst frequency at rest was elevated, and there was a rightward shift in the median of the relative burst amplitude distribution (P < 0.05) in Hypo. During LBNP, the larger rise in total MSNA during Hypo versus Normo was due to greater increases in relative burst amplitude with no difference in the burst frequency response. The MSNA burst frequency response to LBNP was shifted to a higher position on the same MSNA-CVP curve during Hypo compared with Normo. In contrast, the Hypo burst amplitude response was shifted to a new curve with a slope that was similar to the Normo relationship. These data support the use of probability distribution analysis to examine intraindividual differences in baseline and reflex-mediated increases in MSNA burst amplitude. Furthermore, the differential effect of hypovolemia on the responses of burst frequency and amplitude during graded LBNP suggests that burst frequency data alone may not adequately represent reflex control of sympathetic outflow.

Gender affects sympathetic and hemodynamic response to postural stress.

We tested the hypothesis that differences in sympathetic reflex responses to head-up tilt (HUT) between males (n = 9) and females (n = 8) were associated with decrements in postural vasomotor responses in women. Muscle sympathetic nerve activity (MSNA; microneurography), heart rate, stroke volume (SV; Doppler), and blood pressure (Finapres) were measured during a progressive HUT protocol (5 min at each of supine, 20 degrees, 40 degrees, and 60 degrees ). MSNA and hemodynamic responses were also measured during the cold pressor test (CPT) to examine nonbaroreflex neurovascular control. SV was normalized to body surface area (SV(i)) to calculate the index of cardiac output (Q(i)), and total peripheral resistance (TPR). During HUT, heart rate increased more in females versus males (P < 0.001) and SV(i) and Q(i) decreased similarly in both groups. Mean arterial pressure (MAP) increased to a lesser extent in females versus males in the HUT (P < 0.01) but increases in TPR during HUT were similar. MSNA burst frequency was lower in females versus males in supine (P < 0.03) but increased similarly during HUT. Average amplitude/burst increased in 60 degrees HUT for males but not females. Both males and females demonstrated an increase in MAP as well as MSNA burst frequency, mean burst amplitude, and total MSNA during the CPT. However, compared with females, males demonstrated a greater neural response (DeltaTotal MSNA) due to a larger increase in mean burst amplitude (P < 0.05). Therefore, these data point to gender-specific autonomic responses to cardiovascular stress. The different MSNA response to postural stress between genders may contribute importantly to decrements in blood pressure control during HUT in females.