Assessing the effect of regular swimming exercise on the micro- and macrovascular physiology of older adults (ACELA II study).

Introduction: Cardiovascular disease (CVD) remains the main cause of death in the Western world. Our recent findings demonstrate potential CVD risk reduction in older adults who undertake regular swimming exercise. Nevertheless, it remains unknown whether an exercise intervention based on swimming is feasible and effective prior to a wider implementation of a CVD risk prevention strategy. Methods: This was a pragmatic, two-group, randomised controlled trial. A total of 40 older adults were randomly split into two groups (n = 20 per group). The swimming exercise group consisted of participants who engaged in swimming exercise (2-3 days/week, for 8 weeks). The control group did not perform any exercise. Flow-mediated dilation (%FMD) was the primary outcome. Secondary outcomes included raw cutaneous vascular conductance. Feasibility outcomes (e.g., recruitment, adherence, and attrition rates) were also assessed. Results: Statistically significant macrovascular (%FMD; swimming group: 9.8% ± 4.2%, p <0.001; control group: 4.6% ± 2.5%) and microvascular function (raw cutaneous vascular conductance; swimming group: 4.1 ± 0.9, p <0.01; control group: 3.2 ± 1.1) improvements were observed in the swimming group compared to the control group. Compliance to twice and thrice weekly in an 8-week swimming exercise was 92.6% and 88.4%, respectively, with no dropouts. Conclusion: Our 8-week, community-based, pragmatic swimming exercise intervention is a feasible and effective exercise programme that could be implemented in older adults for the prevention of age-related CVD. These findings suggest that swimming exercise could significantly reduce CVD risk in older adults, and a large research clinical trial is warranted to establish these findings.

The effects of upper and lower limb exercise on the microvascular reactivity in limited cutaneous systemic sclerosis patients.

BACKGROUND: Aerobic exercise in general and high-intensity interval training (HIIT) specifically is known to improve vascular function in a range of clinical conditions. HIIT in particular has demonstrated improvements in clinical outcomes, in conditions that have a strong macroangiopathic component. Nevertheless, the effect of HIIT on microcirculation in systemic sclerosis (SSc) patients is yet to be investigated. Therefore, the purpose of the study was to compare the effects of two HIIT protocols (cycle and arm cranking) on the microcirculation of the digital area in SSc patients. METHODS: Thirty-four limited cutaneous SSc patients (65.3 ± 11.6 years old) were randomly allocated in three groups (cycling, arm cranking and control group). The exercise groups underwent a 12- week exercise program twice per week. All patients performed the baseline and post-exercise intervention measurements where physical fitness, functional ability, transcutaneous oxygen tension (ΔTcpO2), body composition and quality of life were assessed. Endothelial-dependent as well as -independent vasodilation were assessed in the middle and index fingers using LDF and incremental doses of acetylcholine (ACh) and sodium nitroprusside (SNP). Cutaneous flux data were expressed as cutaneous vascular conductance (CVC). RESULTS: Peak oxygen uptake increased in both exercise groups (p < 0.01, d = 1.36). ΔTcpO2 demonstrated an increase in the arm-cranking group only, with a large effect, but not found statistically significant,(p = 0.59, d = 0.93). Endothelial-dependent vasodilation improvement was greater in the arm-cranking (p < 0.05, d = 1.07) in comparison to other groups. Both exercise groups improved life satisfaction (p < 0.001) as well as reduced discomfort and pain due to Raynaud's phenomenon (p < 0.05). Arm cranking seems to be the preferred mode of exercise for study participants as compared to cycling (p < 0.05). No changes were observed in the body composition or the functional ability in both exercise groups. CONCLUSIONS: Our results suggest that arm cranking has the potential to improve the microvascular endothelial function in SSc patients. Also notably, our recommended training dose (e.g., a 12-week HIIT program, twice per week), appeared to be sufficient and tolerable for this population. Future research should focus on exploring the feasibility of a combined exercise such as aerobic and resistance training by assessing individual's experience and the quality of life in SSc patients. TRIAL REGISTRATION: ClinicalTrials.gov (NCT number): NCT03058887 , February 23, 2017.

Supervised exercise training as an adjunct therapy for venous leg ulcers: a randomized controlled feasibility trial.

BACKGROUND: Venous leg ulcers (VLUs) are typically painful and heal slowly. Compression therapy offers high healing rates; however, improvements are not usually sustained. Exercise is a low-cost, low-risk and effective strategy for improving physical and mental health. Little is known about the feasibility and efficacy of supervised exercise training used in combination with compression therapy patients with VLUs. OBJECTIVES: To assess the feasibility of a 12-week supervised exercise programme as an adjunct therapy to compression in patients with VLUs. METHODS: This was a two-centre, two-arm, parallel-group, randomized feasibility trial. Thirty-nine patients with venous ulcers were recruited and randomized 1 : 1 either to exercise (three sessions weekly) plus compression therapy or compression only. Progress/success criteria included exercise attendance rate, loss to follow-up and patient preference. Baseline assessments were repeated at 12 weeks, 6 months and 1 year, with healing rate and time, ulcer recurrence and infection incidents documented. Intervention and healthcare utilization costs were calculated. Qualitative data were collected to assess participants' experiences. RESULTS: Seventy-two per cent of the exercise group participants attended all scheduled exercise sessions. No serious adverse events and only two exercise-related adverse events (both increased ulcer discharge) were reported. Loss to follow-up was 5%. At 12 months, median ulcer healing time was lower in the exercise group (13 vs. 34·7 weeks). Mean National Health Service costs were £813·27 for the exercise and £2298·57 for the control group. CONCLUSIONS: The feasibility and acceptability of both the supervised exercise programme in conjunction with compression therapy and the study procedures is supported.

Dietary nitrate does not modify blood pressure and cardiac output at rest and during exercise in older adults: a randomised cross-over study.

Dietary nitrate (NO3-) supplementation has been associated with improved vascular and metabolic health. We conducted a double-blind, cross-over, placebo-controlled RCT to investigate the effects of 7-d consumption of beetroot juice compared with placebo on (1) blood pressure (BP) measured in resting conditions and during exercise, (2) cardiac and peripheral vascular function and (3) biomarkers of inflammation, oxidative stress and endothelial integrity. Twenty non-smoking healthy participants aged 60-75 years and BMI 20.0-29.9 kg/m2 were recruited. Measurement was conducted before and after each 7-d intervention period. Consumption of NO3- had no effect on resting systolic and diastolic BP. NO3- consumption did not improve indexes of central and peripheral cardiac function responses during cardiopulmonary exercise testing. Dietary NO3- supplementation did not modify biomarkers of inflammation, oxidative stress and endothelial integrity. This study does not support the short-term benefits of dietary NO3- supplementation on physiological and biochemical markers of vascular health in older healthy adults.

Brief Report: Implementing a Mediterranean Diet Intervention into a RCT: Lessons Learned from a Non-Mediterranean Based Country.

OBJECTIVE: To examine the participant experiences regarding perceived barriers and facilitators which impact on consuming the Mediterranean diet in the East of England. DESIGN: Qualitative methodology with focus groups. SETTING: A healthy, middle-aged population situated in the East of England. INTERVENTION: An 8-week Mediterranean dietary intervention trial. PARTICIPANTS: Eleven participants (including three co-habiting partners) in three focus groups, ranging between 50-65 yrs with a mean age of 54.3 yrs (±4.0) RESULTS: Thematic analysis from the focus groups revealed that participants considered that the MD intervention had introduced a better quality of food, widening the food-horizon and allowed them to re-define cultural eating habits. They also reported several physical benefits from adapting to this diet and found the experience as positive. Whilst claiming that the MD was an enjoyable and pleasurable, the participants did express difficulty adapting to the eating pattern, finding difficulty in purchasing food items, an increase in food costs and found work, stress and time pressures undermining adherence. CONCLUSION: The participants' experiences suggested that the MD was an encouraging dietary change with a middle aged non-Mediterranean based population group. Future MD interventions should tailor interventions and support participants closely, particularly with the necessary planning, organisation and purchasing involved with implementing this diet in non-Mediterranean countries. Secondly, researchers should also challenge any erroneous assumptions regarding the consumption of Mediterranean food, which may hinder implementation.

Effect of diabetes on the cutaneous microcirculation of the feet in patients with intermittent claudication.

AIMS: To evaluate endothelial-dependent and - independent cutaneous vasodilator responses in the feet of patients with peripheral arterial disease (PAD) with or without Type 2 diabetes. METHODS: Cutaneous microvascular responses in the dorsum of both lower limbs were measured in the supine position using Laser Doppler Fluximetry combined with iontophoretic administration of endothelial-dependent (acetylcholine, Ach) and -independent (sodium nitroprusside, SNP) vasodilators in diabetic (n = 19) and non diabetic (n = 17) patients with PAD (presenting as unilateral calf intermittent claudication (IC). RESULTS: In patients with diabetes and IC, endothelial-dependent vasodilation was significantly impaired in the symptomatic limb [74 (57,105) vs 68 (24,81) PU, Z =-2.79, p = 0.005] compared to the asymptomatic limb. Patients without diabetes showed no impairment of vasodilation. Resting ankle-brachial pressure index did not identify the presence of abnormalities in microvascular function. CONCLUSIONS: The combination of diabetes and PAD is associated with a reduction in endothelial-dependent cutaneous vasodilation in the feet without an associated reduction in endothelial independent vasodilation.

Association between pretreatment haemoglobin levels and morphometric characteristics of the tumour, response to neoadjuvant treatment and long-term outcomes in patients with locally advanced rectal cancers.

AIM: The study was carried out to investigate whether pretreatment haemoglobin (Hb) levels act as a biomarker in the management of patients with locally advanced rectal cancer. METHOD: We prospectively collected data on all patients within our cancer network with localized low rectal cancer treated with preoperative radiotherapy/chemoradiotherapy at Mount Vernon Centre for Cancer Treatment between March 1994 and July 2008. Pretreatment Hb level was assessed as an independent variable for the whole study sample and dichotomised at a value of 12 g/dl. A multivariate analysis of covariance (MANCOVA) was conducted on parameters that had significant association on univariate analysis of covariance (ANCOVA) and correlational (Kendall tau/Pearson) analyses. Kaplan-Meier survival analysis and Cox proportional hazard models were used to determine significant prognostic markers. Statistical significance was set at 0.05. RESULTS: 463 patients (male/female 2:1; median age = 66 years, interquartile range = 56.5-73.0) were included in the analysis. There was significant tumour response of T stage (P < 0.001) and N stage (P < 0.001), with 17.6% of patients achieving a pathological complete response. Pretreatment Hb value was inversely related to the craniocaudal vertical tumour length (P = 0.02) and pretreatment T stage of the tumour (P = 0.01). Patients with Hb levels of < 12 g/dl and moderately differentiated adenocarcinoma were less responsive. Local recurrence was more common in patients with a pretreatment Hb of < 12 g/dl (hazard ratio = 1.78) over a median follow up of 24 months, but this was not statistically significant (P = 0.08). CONCLUSION: The pretreatment Hb level might be used as a biomarker of rectal tumour morphology, response to neoadjuvant chemoradiation and risk of local recurrence.

Assessment of lower limb microcirculation: exploring the reproducibility and clinical application of laser Doppler techniques.

PURPOSE OF STUDY: Non-invasive laser Doppler fluximetry (LDF) and laser Doppler imaging (LDI), combined with iontophoresis, have been used to study the microcirculation in a range of clinical conditions including lower limb venous disease. A prerequisite for an accurate measurement tool is that it is reproducible. However, there is currently no literature with respect to the reproducibility of LDF and LDI combined with iontophoresis in the lower limb (in general) and in the upright position (in specific). Furthermore, the two techniques have been used interchangeably by researchers and the association between these two different measurement methods has not been explored, nor have the factors that affect them been well described. Thus the aim of this study was to determine the reproducibility of LDF and LDI with iontophoresis in the lower limb and investigate factors that influence their clinical application. PROCEDURES: Cutaneous microvascular responses in the lower limb were measured in the supine and standing positions using LDF and LDI combined with iontophoretic administration of endothelial-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside) vasodilators in 25 patients with uncomplicated isolated superficial venous incompetence (ISVI) and 26 healthy controls. RESULTS: Maximum perfusion had the best reproducibility assessed by LDF (CV 20.5-24.3%) and LDI (15.8-17.6%). Both techniques were positively influenced by iontophoretic dose (e.g. p = 0.0001 for LDF) and the use of vasodilator agents (e.g. p = 0.0001 for LDF), but negatively influenced in the standing position and/or in the presence of ISVI (p = 0.0016 and 0.045, respectively, for LDF). There was a statistically significant positive relationship between the two techniques, for example ACh maximum perfusion versus LDF ACh maximum perfusion (r = 0.404, p = 0.016). CONCLUSIONS: Both techniques are reproducible, in line with similar studies undertaken in other areas of the human body, and provide useful information for the study of the lower-limb microcirculation. Direct comparison between techniques based on absolute numbers should be avoided and the technique choice should be based on individual study needs.

Suppression of the postoperative neutrophil leucocytosis following neoadjuvant chemoradiotherapy for rectal cancer and implications for surgical morbidity.

OBJECTIVE: The extent to which neoadjuvant chemoradiotherapy for rectal cancer influences postoperative morbidity is controversial. This study investigated whether this treatment suppresses the normal perioperative inflammatory response and explored the clinical implications. METHOD: Prospective databases were queried to identify 37 consecutive study patients undergoing definitive surgery following 5-FU/capecitabine-based chemoradiotherapy and 34 consecutive untreated control patients operated upon for rectal or rectosigmoid cancer. Preoperative (< 10 days) and postoperative (< 24 h) neutrophil counts, along with morbidity data, were confirmed retrospectively. Univariate and multivariate analyses assessed the apparent effect of chemoradiotherapy on change in neutrophil count. The latter's association with postoperative morbidity was then examined. RESULTS: Sufficient data were available for 34 study and 27 control patients. Repeated-measures ANCOVA revealed significant differences between their perioperative neutrophil counts (P = 0.02). Of the other characteristics which differed between the groups, only age and tumour location were prognostically significant regarding perioperative change in neutrophil count. Accounting for relevant covariates, chemoradiotherapy was significantly associated with a suppressed perioperative neutrophil leucocytosis. Local postoperative complications affected 25 of 61 patients, who had lower perioperative neutrophil increases than their counterparts (P = 0.016). CONCLUSION: Chemoradiotherapy appears to suppress the perioperative inflammatory response, thereby increasing susceptibility to local postoperative complications.

Exercise training improves cutaneous microvascular endothelial function in post-surgical varicose vein patients.

This study investigated the effects of exercise training on cutaneous microvascular function in post-surgical varicose vein patients. Sixteen post-surgical (4-5 weeks) varicose vein patients were randomised to a treadmill-walking exercise group or a non-exercise control group. The exercise group trained twice weekly for 8 weeks. Changes in cutaneous microvascular function of the gaiter area were assessed using laser Doppler flowmetry combined with incremental-dose iontophoretic administration of acetylcholine chloride (ACh) and sodium nitroprusside (SNP) in both supine and standing positions. At 8 weeks, peak flux responses to ACh in the supine position were increased in the exercise group (44+/-30 to 62+/-33 PU; P=0.03) with a similar trend in the standing position (37+/-27 to 74+/-31 PU; P=0.08). There were no such changes in the control group (P>0.05). Additionally, peak flux responses to SNP were unchanged in both groups and body positions (P>0.05). The results suggest that moderate-intensity lower-limb exercise training improves microvascular endothelial vasodilator function in post-surgical varicose vein patients.

Contrasting effects of varicose vein surgery on endothelial-dependent and -independent cutaneous vasodilation in the perimalleolar region.

OBJECTIVES: To evaluate the effects of varicose vein surgery on cutaneous microvascular perfusion and vasodilator responses to acetylcholine (Ach) and sodium nitroprusside (SNP) in the gaiter area of patients with great saphenous vein insufficiency. METHODS: Twenty-nine patients with isolated great saphenous vein incompetence attended three study mornings (before surgery, and 6-8 weeks and 6 months after sapheno-femoral ligation+partial stripping) during which cutaneous microvascular responses were measured in the supine and standing positions using laser Doppler fluximetry (LDF) combined with incremental-dose iontophoretic administration of endothelial-dependent (Ach) and -independent (SNP) vasodilators. RESULTS: Varicose vein surgery had no significant effect on baseline cutaneous perfusion or the microvascular response to Ach: e.g. peak vasodilator responses to the 1000 microC stimulus were mean 58 SEM 7, 64 SEM 6 and 65 SEM 7PU on the pre-operative, 6-8 weeks and 6 months assessments. In contrast, the corresponding responses to SNP were significantly increased following surgery: e.g. at 2000 microC, mean 63 SEM 9, 142 SEM 4 and 157 SEM 9PU (p<0.0001) in the upright position. CONCLUSIONS: Sapheno-femoral ligation and partial stripping in patients with great saphenous vein insufficiency improves endothelial-independent cutaneous vasodilator function at the gaiter area, which may at least partly explain the benefits of surgery in reducing the risk of venous ulceration.

Effects of posture and venous insufficiency on endothelial-dependent and -independent cutaneous vasodilation in the perimalleolar region.

OBJECTIVES: To assess the effects of posture, endothelial function and venous insufficiency on cutaneous microvascular vasodilator function in the gaiter area, in particular defining factors which may affect microangiopathy and ulcer formation. METHODS: Endothelial-dependent and -independent vasodilator responses to incremental-doses of acetylcholine (Ach) and sodium nitroprusside (SNP) were evaluated in the perimalleolar region in the supine and standing positions in middle-aged patients with isolated superficial venous insufficiency (ISVI) (n = 25) and healthy controls (n = 28) using laser Doppler fluximetry (LDF) and iontophoresis of vasodilators. RESULTS: The venoarteriolar reflex (vasoconstriction on standing) was equally present in both groups, and reduced the vasodilator responses to SNP in the upright position (e.g., for patients with ISVI, peak SNP response was 82 +/- 11 PU [standing] vs 123 +/- 15 PU [supine]). The presence of ISVI had no effect on endothelial vasodilator function in the supine position, but on standing cutaneous reactivity to Ach was significantly reduced (e.g., peak Ach response 69 +/- 8 PU [ISVI] vs 109 +/- 11 PU [controls], p < 0.003). CONCLUSIONS: Upright posture impairs cutaneous endothelial-dependent vasodilation in the gaiter area of patients with ISVI. This may be of clinical and prognostic utility in identifying which patients with uncomplicated ISVI are at highest risk of tissue breakdown and ulcer formation in the gaiter area.