Sex-specific predictors of improved walking with step-monitored, home-based exercise in peripheral artery disease

The aim of this study was to determine whether baseline clinical characteristics and the duration and intensity of ambulation during our step-monitored home-based exercise program were predictive of changes in ambulatory outcomes at completion of the program in symptomatic patients with peripheral artery disease (PAD). Twenty-two men (ankle–brachial index (ABI) = 0.71 ± 0.19) and 24 women (ABI = 0.66 ± 0.23) completed the home exercise program, consisting of intermittent walking to mild-to-moderate claudication pain for 3 months. Ambulatory outcome measures were peak walking time (PWT) and claudication onset time (COT) during a treadmill test, and the distance recorded during a 6-minute walk distance test (6MWD). Men experienced significant increases (p<0.01) in COT, PWT, and 6MWD following the home exercise program, and women had significant increases in 6MWD (p<0.01) and PWT (p<0.05). In women, average exercise cadence during the home exercise sessions was the only predictor that entered the model for change in COT (p=0.082), and was the first predictor in the model for change in PWT (p=0.029) and 6MWD (p=0.006). In men, the ABI was the only predictor that entered the model for change in 6MWD (p=0.002), and ABI was a predictor along with metabolic syndrome in the model for change in COT (p=0.003). No variables entered the model for change in PWT. Faster ambulatory cadence during the step-monitored home-based exercise program may predict greater improvements in ambulatory function in women, whereas having less severe PAD and comorbid burden at baseline may predict greater improvements in ambulatory function in men. ClinicalTrials.gov Identifier: NCT00618670Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Response to exercise rehabilitation in smoking and nonsmoking patients with intermittent claudication

AbstractBackgroundThe purpose was to compare the changes in claudication pain, ambulatory function, daily physical activity, peripheral circulation, and health-related quality of life following a program of exercise rehabilitation in smoking and nonsmoking patients with peripheral arterial disease (PAD) limited by intermittent claudication.Methods and resultsThirty-nine smokers (63 ± 4 pack-year smoking history; mean ± SE) and 46 nonsmokers (former smokers who had a 51 ± 7 pack-year smoking history who quit 14 ± 2 years prior to investigation) completed the study. The 6-month exercise rehabilitation program consisted of intermittent treadmill walking to near maximal claudication pain 3 days per week, with progressive increases in walking duration and intensity during the program. Measurements were obtained on each patient before and after rehabilitation. Following exercise rehabilitation the smokers and nonsmokers had similar improvements in these measures, as initial claudication distance increased by 119% in the smokers (P < .001) and by 97% in the nonsmokers (P < .001), and absolute claudication distance increased by 82% (P < .001) and 59% (P < .001) in the smokers and nonsmokers, respectively. Furthermore, exercise rehabilitation improved (P < .05) ambulatory function, daily physical activity, peripheral circulation, and health-related quality of life in the smokers and nonsmokers.ConclusionExercise rehabilitation is an effective therapy to improve functional independence in both smoking and nonsmoking patients with PAD limited by intermittent claudication. Therefore, smokers with intermittent claudication are prime candidates for exercise rehabilitation because their relatively low baseline physical function does not impair their ability to regain lost functional independence to levels similar to nonsmoking patients with PAD

Physical activity is related to quality of life in older adults

BACKGROUND: Physical activity is associated with health-related quality of life (HRQL) in clinical populations, but less is known whether this relationship exists in older men and women who are healthy. Thus, this study determined if physical activity was related to HRQL in apparently healthy, older subjects. METHODS: Measures were obtained from 112 male and female volunteers (70 ± 8 years, mean ± SD) recruited from media advertisements and flyers around the Norman, Oklahoma area. Data was collected using a medical history questionnaire, HRQL from the Medical Outcomes Survey short form-36 questionnaire, and physical activity level from the Johnson Space Center physical activity scale. Subjects were separated into either a higher physically active group (n = 62) or a lower physically active group (n = 50) according to the physical activity scale. RESULTS: The HRQL scores in all eight domains were significantly higher (p < 0.05) in the group reporting higher physical activity. Additionally, the more active group had fewer females (44% vs. 72%, p = 0.033), and lower prevalence of hypertension (39% vs. 60%, p = 0.041) than the low active group. After adjusting for gender and hypertension, the more active group had higher values in the following five HRQL domains: physical function (82 ± 20 vs. 68 ± 21, p = 0.029), role-physical (83 ± 34 vs. 61 ± 36, p = 0.022), bodily pain (83 ± 22 vs. 66 ± 23, p = 0.001), vitality (74 ± 15 vs. 59 ± 16, p = 0.001), and social functioning (92 ± 18 vs. 83 ± 19, p = 0.040). General health, role-emotional, and mental health were not significantly different (p > 0.05) between the two groups. CONCLUSION: Healthy older adults who regularly participated in physical activity of at least moderate intensity for more than one hour per week had higher HRQL measures in both physical and mental domains than those who were less physically active. Therefore, incorporating more physical activity into the lifestyles of sedentary or slightly active older individuals may improve their HRQL

The influence of obesity on calf blood flow and vascular reactivity in older adults

OBJECTIVE: To determine whether differences in vascular reactivity existed among normal weight, overweight, and obese older men and women, and to examine the association between abdominal fat distribution and vascular reactivity. METHODS: Eighty-seven individuals who were 60 years of age or older (age = 69 ± 7 yrs; mean ± SD) were grouped into normal weight (BMI < 25; n = 30), overweight (BMI ≥ 25 and < 30; n = 28), or obese (BMI ≥ 30; n = 29) categories. Calf blood flow (BF) was assessed by venous occlusion strain-gauge plethysmography at rest and post-occlusive reactive hyperemia. RESULTS: Post-occlusive reactive hyperemia BF was lower (p = 0.038) in the obese group (5.55 ± 4.67 %/min) than in the normal weight group (8.34 ± 3.89 %/min). Additionally, change in BF from rest to post-occlusion in the obese group (1.93 ± 2.58 %/min) was lower (p = 0.001) than in the normal weight group (5.21 ± 3.59 %/min), as well as the percentage change (75 ± 98 % vs. 202 ± 190 %, p = 0.006, respectively). After adjusting for age, prevalence in hypertension and calf skinfold thickness, change in BF values remained lower (p < 0.05) in obese subjects compared to the normal weight subjects. Lastly, the absolute and percentage change in BF were significantly related to BMI (r = -0.44, p < 0.001, and r = -0.37, p < 0.001, respectively) and to waist circumference (r = -0.36, p = 0.001, and r = -0.32, p = 0.002). CONCLUSION: Obesity and abdominal adiposity impair vascular reactivity in older men and women, and these deleterious effects on vascular reactivity are independent of conventional risk factors

The Relationship Between Arterial Elasticity and Metabolic Syndrome Features

The purpose of this study was to examine the effects of metabolic syndrome (MS) features on arterial elasticity of the large and small arteries in apparently healthy adults, to examine the effect of clustered features of MS, and to determine which features are most predictive of large and small artery elasticity. The subjects for this study consisted of 126 men and women, age 45 years and older. The subjects rested supine while pulse contour analysis was measured from the radial artery by using an HDI/Pulsewave CR-2000 instrument (Hypertension Diagnostic, Inc) to assess arterial elasticity in the large and small arteries. Medical history was obtained along with body mass index, waist circumference, body surface area, and blood pressure. Large artery elasticity was lower (p=0.002) in subjects with hypertension (12.7 ∓4.3 mL/mm Hg × 10) than in those with normotension (15.0 ∓4.2 mL/mm Hg × 10; mean ∓ SD), and small artery elasticity was lower (p=0.001) as well (3.9 ∓2.3 mL/mm Hg × 100 vs 5.3 ∓2.5 mL/mm Hg × 100). Large artery elasticity was lower (p=0.02) in obese subjects (12.2 ∓4.9 mL/mm Hg × 10) than in nonobese subjects (14.2 ∓4.5 mL/mm Hg × 10), and large artery elasticity was lower (p=0.04) in subjects with abdominal obesity (12.2 ∓4.5 mL/mm Hg × 10) than in those without (14.5 ∓4.8 mL/mm Hg × 10). Large artery elasticity decreased as the number of features of MS increased (p<0.01). Multiple regression showed that body mass index and the presence of hypertension were predictors of large artery elasticity (R =0.61, R 2 =0.37, p=0.003, SEE = 3.60 mL/mm Hg × 10), and hypertension was a predictor of small artery elasticity (R =0.53, R 2 =0.28, p=0.001, SEE = 2.12 mL/mm Hg × 100). Hypertension and obesity are the features of MS that are most predictive of impairment in large and small artery elasticity in apparently healthy middle-aged and older adults. Furthermore, impairment in large artery elasticity is more evident in subjects with at least three features of MS.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Influence of diabetes on ambulation and inflammation in men and women with symptomatic peripheral artery disease

AbstractObjectiveTo determine whether diabetes and sex were factors associated with ambulatory function, endothelial cell inflammation, oxidative stress, and apoptosis, and with circulating biomarkers of inflammation and antioxidant capacity in patients with peripheral artery disease (PAD) and claudication.Materials/MethodsAmbulatory function of 180 symptomatic men and women with PAD was assessed during a graded maximal treadmill test, 6-minute walk test, and 4-meter walk test. Patients were further characterized on endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells, and on circulating inflammatory and vascular biomarkers.ResultsMen and women with diabetes had greater prevalence (p = 0.007 and p = 0.015, respectively) of coronary artery disease (CAD) than patients without diabetes. To assure that this difference did not influence planned comparisons, the data set was stratified on CAD. Diabetic men with CAD had a lower peak walking time (PWT) during the treadmill test and a slower 4-meter gait speed compared to non-diabetic men with CAD (p < 0.05). Diabetic women with CAD had a lower PWT compared to their non-diabetic counterparts (p < 0.01). Additionally, diabetic men with CAD had higher pigment epithelium-derived factor (p < 0.05) than their non-diabetic counterparts, and diabetic women with CAD had higher leptin (p < 0.01) and interleukin-8 levels (p < 0.05).ConclusionsIn patients with PAD, diabetic men and women with CAD had more severe claudication than their non-diabetic counterparts, as measured by shorter PWT, and the men had further ambulatory impairment manifested by slower 4-meter gait speed. Furthermore, the diabetic patients with CAD had elevations in interleukin-8, leptin, and PEDF

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Background: High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods: We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK-based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings: Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants' systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p&lt;0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups. Interpretation: Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultra-acute prehospital setting

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Multiple Common Susceptibility Variants near BMP Pathway Loci GREM1, BMP4, and BMP2 Explain Part of the Missing Heritability of Colorectal Cancer

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