Cerebrovascular function and its association with systemic artery function and stiffness in older adults with and without mild cognitive impairment.

PURPOSE: Our aim was to compare cerebrovascular and systemic vascular function between older adults with and without mild cognitive impairment (MCI), and to determine which measures of vascular function best predict the presence of MCI. METHODS: In 41 adults with MCI and 33 adults without MCI (control) we compared middle cerebral artery velocity (MCAv) and cerebrovascular pulsatility index (PI) at rest, cerebrovascular reactivity to CO2, and responsiveness to changes in blood pressure (%∆MCAv/%∆MAP). Systemic vascular function was assessed by flow-mediated dilation (FMD) and stiffness by pulse wave velocity (PWV). RESULTS: Cerebrovascular PI was higher in MCI compared with control (mean ± SD: 1.17 ± 0.27 vs. 1.04 ± 0.21), and MCI exhibited a lower %∆MCAv/%∆MAP (1.26 ± 0.44 vs. 1.50 ± 0.55%). Absolute (p = 0.76) and relative cerebrovascular reactivity to CO2 (p = 0.34) was similar between MCI and control. When age was included as a covariate the significant difference in cerebral PI between groups was lost. PWV was higher (13.2 ± 2.2 vs. 11.3 ± 2.5 m s-1) and FMD% (4.41 ± 1.70 vs. 5.43 ± 2.15%) was lower in MCI compared with control. FMD% was positively associated with PI across the cohort. Logistic regression analysis indicated that FMD and PWV significantly discriminated between MCI and controls, independent of age, whereas the inclusion of cerebrovascular measures did not improve the predictive accuracy of the model. CONCLUSION: These findings raise the possibility that early changes in systemic vascular stiffness and endothelial function may contribute to altered cerebrovascular haemodynamics and impaired cognitive function, and present potential targets for prevention and treatment strategies in people with MCI.

Leg blood flow and skeletal muscle microvascular perfusion responses to submaximal exercise in peripheral arterial disease.

Peripheral arterial disease (PAD) is characterized by stenosis and occlusion of the lower limb arteries. Although leg blood flow is limited in PAD, it remains unclear whether skeletal muscle microvascular perfusion is affected. We compared whole leg blood flow and calf muscle microvascular perfusion after cuff occlusion and submaximal leg exercise between patients with PAD ( n = 12, 69 ± 9 yr) and healthy age-matched control participants ( n = 12, 68 ± 7 yr). Microvascular blood flow (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after the following: 1) 5 min of thigh-cuff occlusion, and 2) a 5-min bout of intermittent isometric plantar-flexion exercise (400 N) using real-time contrast-enhanced ultrasound. Whole leg blood flow was measured after thigh-cuff occlusion and during submaximal plantar-flexion exercise using strain-gauge plethysmography. Postocclusion whole leg blood flow and calf muscle microvascular perfusion were lower in patients with PAD than control participants, and these parameters were strongly correlated ( r = 0.84, P < 0.01). During submaximal exercise, total whole leg blood flow and vascular conductance were not different between groups. There were also no group differences in postexercise calf muscle microvascular perfusion, although microvascular blood volume was higher in patients with PAD than control participants (12.41 ± 6.98 vs. 6.34 ± 4.98 arbitrary units, P = 0.03). This study demonstrates that the impaired muscle perfusion of patients with PAD during postocclusion hyperemia is strongly correlated with disease severity and is likely mainly determined by the limited conduit artery flow. In response to submaximal leg exercise, microvascular flow volume was elevated in patients with PAD, which may reflect a compensatory mechanism to maintain muscle perfusion and oxygen delivery during recovery from exercise. NEW & NOTEWORTHY This study suggests that peripheral arterial disease (PAD) has different effects on the microvascular perfusion responses to cuff occlusion and submaximal leg exercise. Patients with PAD have impaired microvascular perfusion after cuff occlusion, similar to that previously reported after maximal exercise. In response to submaximal exercise, however, the microvascular flow volume response was elevated in patients with PAD compared with control. This finding may reflect a compensatory mechanism to maintain perfusion and oxygen delivery during recovery from exercise.

Acute Effects of Breaking up Sitting Time With Isometric Wall Squat Exercise on Vascular Function and Blood Pressure in Sedentary Adults: Randomized Crossover Trial.

PURPOSE: The World Health Organization has recommended breaking up sitting time to improve cardiovascular health. However, whether isometric exercise can be effectively used as a strategy to break up sitting time remains unclear. Thus, the aim of this study was to analyze the acute effects of breaking up prolonged sitting with isometric wall squat exercise (IWSE) on vascular function and blood pressure (BP) in sedentary adults. METHODS: This randomized crossover trial included 17 adults (53% male, 26 ± 6 yr, 22.4 ± 3.6 kg/m2) with high sedentary behavior (≥ 6 hr/d). The participants completed 2 experimental sessions in a randomized order, both sharing a common sitting period of 180 min: Breaks (2-min breaks were incorporated into the IWSE, with participants maintaining their knees at the angle determined by the incremental test, which occurred every 30 min) and Control (sitting for 180 min continuously). Popliteal artery flow-mediated dilation (FMD) and brachial BP were measured before and at 10 and 30 min after the experimental sessions. RESULTS: The results did not indicate significant session vs time interaction effects on popliteal FMD and brachial BP (P > .05). A subanalysis including only participants with popliteal FMD reduction after the Control session (n = 11) revealed that Breaks enhanced popliteal FMD after 10 min (1.38 ± 6.45% vs -4.87 ± 2.95%, P= .002) and 30 min (-0.43 ± 2.48% vs -2.11 ± 5.22%, P= .047). CONCLUSION: Breaking up prolonged sitting with IWSE mitigates impaired vascular function resulting from prolonged sitting but has no effect on BP in sedentary adults.

Effects of resistance training on endothelial function: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The effects of resistance training on flow-mediated dilation (FMD), which has been the gold standard non-invasive assessment of endothelial function and is associated with the risk of cardiovascular events, are not well known. We conducted a systematic review to analyze the effects of resistance training on FMD. METHODS: We searched Pubmed, Embase, CINAHL, SPORTDiscuss, Scopus, Web of Science and PEDro databases for studies that met the following criteria: (a) randomized controlled trials of resistance exercise with a comparative non-exercise group or contralateral untrained limb in adults and/or elderly; (b) studies that measured post-occlusion brachial artery FMD by ultrasonography, before and after intervention. Mean differences (MDs) with 95 % confidence interval (95 % CI) were calculated using an inverse variance method with a random effects model. RESULTS: Twenty-three studies were included in the meta-analysis (n = 785 participants; 53 % females). Resistance training on FMD responses showed a favorable result for the resistance training group (n = 366) compared to the control group (n = 358) (MD 2.39, 95%CI 1.65, 3.14; p<0.00001). Subgroup analysis indicated favorable results for the dynamic resistance training (n = 545; MD 2.12, 95 % CI 1.26, 2.98; p<0.00001) and isometric handgrip training (n = 179; MD 3.32, 95 % CI 1.68, 4.96; p<0.0001) compared to the control group. The effect of resistance training on FMD responses was also favorable regardless of the condition of the participants (Healthy [n = 261]: MD 2.11, 95 % CI 1.04, 3.18; p<0.0001; Cardiovascular disease [n = 310]: MD 2.89, 95 % CI 0.88, 4.90; p = 0.005; metabolic disease [n = 153]: MD 2.40, 95 % CI 1.59, 3.21; p<0.00001). CONCLUSIONS: Resistance training improves FMD in healthy individuals and patients with cardiovascular and metabolic diseases.

Skeletal muscle microvascular perfusion responses to cuff occlusion and submaximal exercise assessed by contrast-enhanced ultrasound: The effect of age.

Impairments in skeletal muscle microvascular function are frequently reported in patients with various cardiometabolic conditions for which older age is a risk factor. Whether aging per se predisposes the skeletal muscle to microvascular dysfunction is unclear. We used contrast-enhanced ultrasound (CEU) to compare skeletal muscle microvascular perfusion responses to cuff occlusion and leg exercise between healthy young (n = 12, 26 ± 3 years) and older (n = 12, 68 ± 7 years) adults. Test-retest reliability of CEU perfusion parameters was also assessed. Microvascular perfusion (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after: (a) 5-min of thigh-cuff occlusion, and (b) 5-min of submaximal intermittent isometric plantar-flexion exercise (400 N) using CEU. Whole-leg blood flow was measured using strain-gauge plethysmography. Repeated measures were obtained with a 15-min interval, and averaged responses were used for comparisons between age groups. There were no differences in post-occlusion whole-leg blood flow and muscle microvascular perfusion between young and older participants (p > .05). Similarly, total whole-leg blood flow during exercise and post-exercise peak muscle microvascular perfusion did not differ between groups (p > .05). The overall level of agreement between the test-retest measures of calf muscle perfusion was excellent for measurements taken at rest (intraclass correlation coefficient [ICC] 0.85), and in response to cuff occlusion (ICC 0.89) and exercise (ICC 0.95). Our findings suggest that healthy aging does not affect muscle perfusion responses to cuff-occlusion and submaximal leg exercise. CEU muscle perfusion parameters measured in response to these provocation tests are highly reproducible in both young and older adults.

An Experimental Series Investigating the Effects of Hyperinsulinemic Euglycemia on Myocardial Blood Flow Reserve in Healthy Individuals and on Myocardial Perfusion Defect Size following ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Incomplete restoration of myocardial blood flow (MBF) is reported in up to 30% of ST-segment elevation myocardial infarction (STEMI) despite prompt mechanical revascularization. Experimental hyperinsulinemic euglycemia (HE) increases MBF reserve (MBFR). If fully exploited, this effect may also improve MBF to ischemic myocardium. Using insulin-dextrose infusions to induce HE, we conducted four experiments to determine (1) how insulin infusion duration, dose, and presence of insulin resistance affect MBFR response; and (2) the effect of an insulin-dextrose infusion given immediately following revascularization of STEMI on myocardial perfusion. METHODS: The MBFR was determined using myocardial contrast echocardiography. Experiment 1 (insulin duration): 12 participants received an insulin-dextrose or saline infusion for 120 minutes. MBFR was measured at four time intervals during infusion. Experiment 2 (insulin dose): 22 participants received one of three insulin doses (0.5, 1.5, 3.0 mU/kg/minute) for 60 minutes. Baseline and 60-minute MBFRs were determined. Experiment 3 (insulin resistance): five metabolic syndrome and six type 2 diabetes (T2DM) participants received 1.5 mU/kg/minute of insulin-dextrose for 60 minutes. Baseline and 60-minute MBFRs were determined. Experiment 4 (STEMI): following revascularization for STEMI, 20 patients were randomized to receive either 1.5 mU/kg/minute insulin-dextrose infusion for 120 minutes or standard care. Myocardial contrast echocardiography was performed at four time intervals to quantify percentage contrast defect length. RESULTS: Experiment 1: MBFR increased with time through to 120 minutes in the insulin-dextrose group and did not change in controls. Experiment 2: compared with baseline, MBFR increased in the 1.5 (2.42 ± 0.39 to 3.25 ± 0.77, P = .002), did not change in the 0.5, and decreased in the 3.0 (2.64 ± 0.25 to 2.16 ± 0.33, P = .02) mU/kg/minute groups. Experiment 3: compared with baseline, MBFR increase was only borderline significant in metabolic syndrome and T2DM participants (1.98 ± 0.33 to 2.59 ± 0.45, P = .04, and 1.67 ± 0.35 to 2.14 ± 0.21, P = .05). Experiment 4: baseline percentage contrast defect length was similar in both groups but with insulin decreased with time and was significantly lower than in controls at 60 minutes (2.8 ± 5.7 vs 13.7 ± 10.6, P = .02). CONCLUSIONS: Presence of T2DM, insulin infusion duration, and dose are important determinants of the MBFR response to HE. When given immediately following revascularization for STEMI, insulin-dextrose reduces perfusion defect size at one hour. Hyperinsulinemic euglycemia may improve MBF following ischemia, but further studies are needed to clarify this.

The Effect of Different Exercise Modes on Domain-Specific Cognitive Function in Patients Suffering from Parkinson's Disease: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Supervised exercise training alleviates motor symptoms in people with Parkinson's disease (PD). However, the efficacy of exercise to improve nonmotor symptoms such as cognitive function is less well known. OBJECTIVE: To systematically review evidence on the efficacy of different exercise modes (coordination exercise, resistance exercise, aerobic exercise) on domain-specific cognitive function in patients with PD. METHODS: Parallel-group randomized controlled trials published before March 2018 were included. Primary outcome measures included global cognitive function and its subdomains, and the Unified Parkinson's Disease Rating Scale was included as a secondary outcome. Methodological quality was assessed using the Physiotherapy Evidence Database scale. RESULTS: The literature search yielded 2,000 articles, of which 11 met inclusion criteria. 508 patients (mean age 68±4 years) were included with a disease severity from 1 to 4 on the Hoehn & Yahr stage scale. Overall study quality was modest (mean 6±2, range 3-8/10). In 5 trials a significant between-group effect size (ES) was identified for tests of specific cognitive domains, including a positive effect of aerobic exercise on memory (ES = 2.42) and executive function (ES = 1.54), and of combined resistance and coordination exercise on global cognitive function (ES = 1.54). Two trials found a significant ES for coordination exercise (ES = 0.84-1.88), which led to improved executive function compared with that of non-exercising control subjects. CONCLUSION: All modes of exercise are associated with improved cognitive function in individuals with PD. Aerobic exercise tended to best improve memory; however, a clear effect of exercise mode was not identified.

Association of time spent in physical activities and sedentary behaviors with carotid-femoral pulse wave velocity: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Increased arterial stiffness is linked to increased risk of cardiovascular disease and mortality. Studies have reported conflicting results regarding the relationship between arterial stiffness and time spent in sedentary behavior (SB) and physical activity (PA). The objective of this systematic review and meta-analysis was to assess the relationship between objectively measured light PA (LPA), moderate to vigorous PA (MVPA), and SB with the gold standard measurement of arterial stiffness, carotid-femoral pulse wave velocity (cfPWV). METHODS: PubMed, Scopus, and Web of Science were searched for relevant studies published until November 2016. Studies reporting the correlation of objectively measured PA and SB with cfPWV in human adults >18 years old were included in this analysis. Correlation coefficients (CCs) were converted to Z scores via Fisher's z values for the analysis of summary effects, using a random-effects model. RESULTS: Twelve studies were included in the systematic review. The meta-analysis showed a negative correlation between cfPWV and LPA (CC -0.16; 95% CI: -0.29 to -0.03; p=0.02) and MVPA (CC -0.16; 95% CI: -0.26 to -0.06; p<0.01), and a positive relationship between cfPWV and SB (CC 0.23; 95% CI: 0.12 to 0.35; p<0.01). CONCLUSIONS: Time spent in light and moderate physical activities is associated with lower arterial stiffness, while time spent in SB is related to higher arterial stiffness. It suggests that PA at any intensity is favorable for arterial stiffness, whereas SB leads to increased arterial stiffness. Considering that cfPWV has an independent prognostic value, these associations may have important clinical implications.

Combined Lower Limb Revascularisation and Supervised Exercise Training for Patients with Peripheral Arterial Disease: A Systematic Review of Randomised Controlled Trials.

BACKGROUND: Both revascularisation and supervised exercise training improve functional outcomes and quality of life in patients with peripheral arterial disease (PAD). However, the value of combined therapy, where exercise therapy is delivered as an adjunct to revascularisation, is less clear. OBJECTIVE: To systematically review evidence on the efficacy of lower limb revascularisation combined with supervised exercise training in patients with PAD. METHODS: Parallel-group randomised controlled trials indexed in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Scopus, CINAHL, SPORTDiscus and Web of Science were searched (up to Jan 2016). Outcome measures were pain-free and maximum walking distances, ankle-brachial index (ABI), leg blood flow and quality of life. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. RESULT: Eight trials were included that enrolled a total of 726 patients (mean age 66 ± 3 years, ABI 0.66 ± 0.05). Combined therapy led to greater improvements in pain-free (mean difference [MD] range 38-408 m) and maximal walking distances (MD range 82-321 m) compared with revascularisation or supervised training alone. Combined therapy had no added effect on resting ABI over revascularisation (MD range -0.05 to 0.13), and had a significantly greater effect than supervised exercise training alone (MD range 0.13-0.31). Limited evidence (one to three trials) also suggested that combined therapy led to greater improvements in leg blood flow and physical domains of quality of life than supervised exercise training alone, and that improvements in leg blood flow, as well as the physical and mental domains of quality of life were not different to that achieved with revascularisation alone. CONCLUSION: Current evidence suggests that PAD patients treated with combined therapy achieve greater functional benefits than those treated with revascularisation or supervised exercise training alone. Limited evidence also suggests that the effect of combined therapy on leg haemodynamics and quality of life may be superior to supervised exercise training alone, and similar to revascularisation alone.

Clinical predictors of ventilatory threshold achievement in patients with claudication.

PURPOSE: Ventilatory threshold (VT) is considered a clinically important marker of cardiovascular function in several populations, including patients with claudication, because it is related to walking capacity and hemodynamics. The purpose of this study was to identify clinical predictors for VT achievement in patients with intermittent claudication. METHODS: One hundred and seventy-seven (n = 177) patients with intermittent claudication performed a progressive graded cardiopulmonary treadmill test until maximal claudication pain. Oxygen uptake (V˙O2) was continuously measured during the test, and afterwards, VT was visually detected. Clinical characteristics, demographic data, comorbid conditions, and cardiovascular risk factors were obtained. Patients who achieved and did not achieve VT were compared, as well as the workload that VT occurred in the former group. RESULTS: VT was achieved in 134 patients (76%), and the mean V˙O2 at VT for these patients was 10.8 ± 2.4 mL·kg(-1)·min(-1). Patients who did not achieve VT presented lower ankle brachial index (ABI), claudication onset time, peak walking time, and V˙O2peak, and the proportion of women was higher compared with patients who achieved VT (P < 0.05). Multiple linear regression analysis identified that sex (b = 0.25, P = 0.002), body mass index (b = -0.18, P = 0.025), peak walking time (b = 0.17, P = 0.044), and ABI (b = 0.23, P = 0.006) were predictors of V˙O2 at VT. CONCLUSIONS: Forty-three patients (24%) with intermittent claudication did not achieve VT, and these patients were mostly women and those with greater severity of disease. Moreover, in those who reached VT, the predictors of poor VT were female sex, high body mass index, low peak walking time, and low ABI.