Effect of Dietary Supplements Which Upregulate Nitric Oxide on Walking and Quality of Life in Patients with Peripheral Artery Disease: A Meta-Analysis.

This systematic review pooled evidence from randomised controlled trials (RCTs) on the effectiveness of dietary upregulators of nitric oxide (NO) in improving the walking and quality of life of patients with peripheral artery disease (PAD). RCTs examining the effect of dietary upregulators of NO in patients with PAD were included. The primary outcome was the maximum walking distance. Secondary outcomes were the initial claudication distance, the six-minute walking distance, quality of life, the ankle-brachial pressure index (ABI), adverse events and risk of mortality, revascularisation or amputation. Meta-analyses were performed using random effects models. The risk of bias was assessed using Cochrane's ROB-2 tool. Leave-one-out and subgroup analyses were conducted to assess the effect of individual studies, the risk of bias and intervention type on pooled estimates. Thirty-four RCTs involving 3472 participants were included. Seven trials tested NO donors, nineteen tested antioxidants, three tested NO synthase inducers and five tested enhancers of NO availability. Overall, the dietary supplements significantly improved the initial claudication (SMD 0.34; 95%CI 0.04, 0.64; p = 0.03) but not maximum walking (SMD 0.13; 95%CI -0.17, 0.43; p = 0.39) distances. Antioxidant supplements significantly increased both the maximum walking (SMD 0.36; 95%CI 0.14, 0.59; p = 0.001) and initial claudication (SMD 0.58; 95%CI 0.26, 0.90; p < 0.001) distances. The dietary interventions did not improve the physical function domain of the Short Form-36 (SMD -0.16; 95%CI -0.32, 0.00; p = 0.38), ABI or risk of adverse events, mortality, revascularisation or amputation. Dietary NO upregulators, especially antioxidants, appear to improve the initial claudication distance in patients with PAD. Larger high-quality RCTs are needed to fully examine the benefits and risks of these treatments. PROSPERO Registration: CRD42022256653.

Dietary fatty acids and mortality risk from heart disease in US adults: an analysis based on NHANES.

We investigated the association of dietary intake of major types of fatty acids with heart disease mortality in a general adult cohort with or without a prior diagnosis of myocardial infarction (MI). This cohort study included US adults who attended the National Health and Nutrition Examination Surveys from 1988 to 2014. Heart disease mortality was ascertained by linkage to the National Death Index records through 31 December 2015. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of fatty acid intake for heart disease mortality. This cohort included 45,820 adults among which 1,541 had a prior diagnosis of MI. Participants were followed up for 532,722 person-years (mean follow-up, 11.6 years), with 2,313 deaths recorded from heart disease being recorded. Intake of saturated (SFAs) and monounsaturated fatty acids (MUFAs) was associated with heart disease mortality after adjustment for all the tested confounders. In contrast, a 5% higher calorie intake from polyunsaturated fatty acids (PUFAs) was associated with a 9% (HR, 0.91; 95% CI 0.83-1.00; P = 0.048) lower multivariate-adjusted risk of heart disease mortality. Sub-analyses showed that this inverse association was present in those without a prior diagnosis of MI (HR,0.89; 95% CI 0.80-0.99) but not in those with the condition (HR, 0.94; 95% CI 0.75-1.16). The lack of association in the MI group could be due to a small sample size or severity and procedural complications (e.g., stenting and medication adherence) of the disease. Higher PUFA intake was associated with a favourable lipid profile. However, further adjustment for plasma lipids did not materially change the inverse association between PUFAs and heart disease mortality. Higher intake of PUFAs, but not SFAs and MUFAs, was associated with a lower adjusted risk of heart disease mortality in a large population of US adults supporting the need to increase dietary PUFA intake in the general public.

Potential Benefits of Phytochemicals for Abdominal Aortic Aneurysm.

BACKGROUND: Abdominal aortic aneurysms (AAAs) are a leading cause of death in older adults due to aortic rupture. There are currently no effective medical therapies for AAA, with surgery being the only acceptable treatment. There is frequently an extended period between AAA diagnosis and treatment by corrective surgery, during which an effective drug therapy could prevent or delay the need for AAA repair. OBJECTIVE: This review aimed to critically summarize prior research investigating the potential benefits of phytochemicals in preventing or treating AAA. METHODS: In vitro, in vivo, and human studies examining the effect of phytochemicals in AAA models and patients were critically summarised. RESULTS: Some preliminary data support the further investigation of curcumin, radix astragali, grape seed polyphenols, resveratrol, Ginkgo biloba extract (EGb 761), Ginsenoide Rb1, Dan Hong, Epigallocatechin-3-gallate, Baicalein, Fucoidan, Quercetin, and Salvianolic acid as potential treatments for AAA. CONCLUSION: Experimental in vivo and in vitro studies suggest the potential benefits of a number of medicinal herbs and phytochemicals in preventing or reducing the progression of AAA. In order to assess whether these findings can be translated into proven treatments, adequately designed double-blind randomized clinical trials will be required.

Evidence-Based Recommendations for Medical Management of Peripheral Artery Disease.

Patients with lower limb artery stenosis or occlusion (peripheral artery disease; PAD) have been determined to be at very high risk of both major adverse cardiovascular events, such as myocardial infarction and stroke, and major adverse limb events, such as amputation and requirement for artery surgery.Effective medical management has been identified as key in reducing this risk; however, this is often poorly implemented in clinical practice. Thus, the aim of this narrative review was to summarize the current evidence on the medical management of PAD in order to inform clinicians and highlight recommendations for clinical practice. International guidelines, randomized controlled trials, and relevant systematic reviews and meta-analyses have been included in this study. The focus was the management of the key modifiable risk factors to mitigate possible adverse events through prescription of anti-platelet and anticoagulation drugs and medications to control low-density lipoprotein cholesterol, blood pressure, and diabetes and aid smoking cessation. The available evidence from randomized clinical trials provide a strong rationale for the need for holistic medical management programs that are effective in achieving uptake of these medical therapies in patients with PAD. In conclusion, people with PAD have some of the highest adverse event rates among those with cardiovascular diseases. Secondary preventive measures have been proven effective in reducing these adverse events; however, they remain to be adequately implemented. Thus, the need for an effective implementation program has emerged to reduce adverse events in this patient group.

Vitamin D deficiency promotes large rupture-prone abdominal aortic aneurysms and cholecalciferol supplementation limits progression of aneurysms in a mouse model.

Vitamin D deficiency has been associated with human abdominal aortic aneurysm (AAA); however, its role in AAA pathogenesis is unclear. The aim of the present study was to investigate the effect of vitamin D deficiency on AAA development and examine if administering cholecalciferol (CCF) could limit growth of established AAA within the angiotensin-II (AngII) infused apolipoprotein E-deficient mouse model. Mice were rendered vitamin D deficiency through dietary restriction and during AngII infusion developed larger AAAs as assessed by ultrasound and ex vivo morphometry that ruptured more commonly (48% vs. 19%; P=0.028) than controls. Vitamin D deficiency was associated with increased aortic expression of osteopontin and matrix metalloproteinase-2 and -9 than controls. CCF administration to mice with established aortic aneurysms limited AAA growth as assessed by ultrasound (P<0.001) and ex vivo morphometry (P=0.036) and reduced rupture rate (8% vs. 46%; P=0.031). This effect was associated with up-regulation of circulating and aortic sclerostin. Incubation of human aortic smooth muscle cells with 1,25-dihyroxyvitamin D3 (the active metabolite of vitamin D) for 48 h induced up-regulation of sclerostin (P<0.001) and changed the expression of a range of other genes important in extracellular matrix remodeling. The present study suggests that vitamin D deficiency promotes development of large rupture-prone aortic aneurysms in an experimental model. CCF administration limited both growth and rupture of established aneurysms. These effects of vitamin D appeared to be mediated via changes in genes involved in extracellular matrix remodeling, particularly sclerostin.

The Potential Role of Sensors, Wearables and Telehealth in the Remote Management of Diabetes-Related Foot Disease.

Diabetes-related foot disease (DFD), which includes foot ulcers, infection and gangrene, is a leading cause of the global disability burden. About half of people who develop DFD experience a recurrence within one year. Long-term medical management to reduce the risk of recurrence is therefore important to reduce the global DFD burden. This review describes research assessing the value of sensors, wearables and telehealth in preventing DFD. Sensors and wearables have been developed to monitor foot temperature, plantar pressures, glucose, blood pressure and lipids. The monitoring of these risk factors along with telehealth consultations has promise as a method for remotely managing people who are at risk of DFD. This approach can potentially avoid or reduce the need for face-to-face consultations. Home foot temperature monitoring, continuous glucose monitoring and telehealth consultations are the approaches for which the most highly developed and user-friendly technology has been developed. A number of clinical studies in people at risk of DFD have demonstrated benefits when using one of these remote monitoring methods. Further development and evidence are needed for some of the other approaches, such as home plantar pressure and footwear adherence monitoring. As yet, no composite remote management program incorporating remote monitoring and the management of all the key risk factors for DFD has been developed and implemented. Further research assessing the feasibility and value of combining these remote monitoring approaches as a holistic way of preventing DFD is needed.

Opinions of vascular surgeons and podiatrists in Australia and New Zealand on the use of hyperbaric oxygen therapy for lower limb ulcers.

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) has been suggested to improve healing of lower limb ulcers, though the quality of available evidence is weak to moderate. This study assessed the opinions and use of HBOT by specialists treating lower limb ulcers. RESEARCH DESIGN AND METHODS: Accredited vascular surgeons and podiatrists in Australia and New Zealand were sent an online survey via their professional organizations. The survey asked about their use and opinions of HBOT in treating lower limb ischemic, neuropathic and venous ulcers. Data were summarized with descriptive statistics. Non-parametric tests were used to compare survey results obtained from vascular surgeons and podiatrists. RESULTS: 61 vascular surgeons and 40 podiatrists completed the survey. Thirty-seven specialists used HBOT for treating lower limb ulcers, with the remainder indicating they did not feel there was a role for HBOT (n=25) or did not have access to HBOT (n=39). Less than 8% of specialists indicated that HBOT frequently or always had a role in treating ischemic, neuropathic or venous ulcers. Compared with podiatrists, vascular surgeons were significantly less likely to indicate HBOT had a treatment role for any ulcer type (p<0.001, p=0.004, and p<0.001, respectively), though significantly more likely to indicate they currently used HBOT for treating lower limb ulcers (p<0.001). Most specialists (n=76) believed that a large clinical trial is needed to determine the efficacy of HBOT in treating lower limb ulcers. CONCLUSIONS: Vascular surgeons and podiatrists do not feel HBOT has a frequent role in treating lower limb ulcers, but do feel there needs to be a large clinical trial to test its value.

Omega-3 fatty acids decrease oxidative stress and inflammation in macrophages from patients with small abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is associated with inflammation and oxidative stress, the latter of which contributes to activation of macrophages, a prominent cell type in AAA. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to limit oxidative stress in animal models of AAA. The aim of this study was to evaluate the effect of the n-3 PUFA docosahexaenoic acid (DHA) on antioxidant defence in macrophages from patients with AAA. Cells were obtained from men with small AAA (diameter 3.0-4.5 cm, 75 ± 6 yr, n = 19) and age- matched male controls (72 ± 5 yr, n = 41) and incubated with DHA for 1 h before exposure to 0.1 µg/mL lipopolysaccharide (LPS) for 24 h. DHA supplementation decreased the concentration of tumour necrosis factor-α (TNF-α; control, 42.1 ± 13.6 to 5.1 ± 2.1 pg/ml, p < 0.01; AAA, 25.2 ± 9.8 to 1.9 ± 0.9 pg/ml, p < 0.01) and interleukin-6 (IL-6; control, 44.9 ± 7.7 to 5.9 ± 2.0 pg/ml, p < 0.001; AAA, 24.3 ± 5.2 to 0.5 ± 0.3 pg/ml, p < 0.001) in macrophage supernatants. DHA increased glutathione peroxidase activity (control, 3.2 ± 0.3 to 4.1 ± 0.2 nmol/min/ml/µg protein, p = 0.004; AAA, 2.3 ± 0.5 to 3.4 ± 0.5 nmol/min/ml/µg protein, p = 0.008) and heme oxygenase-1 mRNA expression (control, 1.5-fold increase, p < 0.001). The improvements in macrophage oxidative stress status serve as a stimulus for further investigation of DHA in patients with AAA.

n-3 PUFAs improve erythrocyte fatty acid profile in patients with small AAA: a randomized controlled trial.

Abdominal aortic aneurysm (AAA) is an important cause of death in older adults, which has no current drug therapy. Inflammation and abnormal redox status are believed to be key pathogenic mechanisms for AAA. In light of evidence correlating inflammation with aberrant fatty acid profiles, this study compared erythrocyte fatty acid content in 43 AAA patients (diameter 3.0-4.5 cm) and 52 healthy controls. In addition, the effect of omega-3 PUFA (n-3 PUFA) supplementation on erythrocyte fatty acid content was examined in a cohort of 30 AAA patients as part of a 12 week randomized placebo-controlled clinical trial. Blood analyses identified associations between AAA and decreased linoleic acid (LA), and AAA and increased Δ6-desaturase activity and biosynthesis of arachidonic acid (AA) from LA. Omega-3 PUFA supplementation (1.5 g DHA + 0.3 g EPA/day) decreased red blood cell distribution width (14.8 ± 0.4% to 13.8 ± 0.2%; P = 0.003) and levels of pro-inflammatory n-6 PUFAs (AA, 12.46 ± 0.23% to 10.14 ± 0.3%, P < 0.001; adrenic acid, 2.12 ± 0.13% to 1.23 ± 0.09%; P < 0.001). In addition, Δ-4 desaturase activity increased (DHA/docosapentaenoic acid ratio, 1.85 ± 0.14 to 3.93 ± 0.17; P < 0.001) and elongase 2/5 activity decreased (adrenic acid/AA ratio, 0.17 ± 0.01 to 0.12 ± 0.01; P < 0.01) following supplementation. The findings suggest that n-3 PUFAs improve fatty acid profiles and ameliorate factors associated with inflammation in AAA patients.

A diet enriched with tree nuts reduces severity of atherosclerosis but not abdominal aneurysm in angiotensin II-infused apolipoprotein E deficient mice.

BACKGROUND AND AIMS: Diets enriched with tree nuts have been demonstrated to reduce the risk of atherosclerosis-related cardiovascular events. Abdominal aortic aneurysm (AAA) shares common risk factors with atherosclerosis and AAA patients commonly have atherosclerosis related cardiovascular events. AAA has some distinct pathological and clinical characteristics to those of atherosclerosis. No previous study has examined the effect of a diet enriched with tree nuts on experimental or clinical AAA. This study investigated the effect of a diet enriched with tree nuts on the development and severity of AAA within an experimental rodent model. METHODS: Male apolipoprotein E deficient mice were allocated to a diet enriched with tree nuts or control diet for 56 days (n = 17 per group). After 28 days, all mice were infused with angiotensin II whilst being maintained on their respective diets. The primary outcome was AAA severity assessed by the supra-renal aortic diameter, measured by ultrasound and ex vivo morphometric analysis. The severity of atherosclerosis was assessed by computer-aided analysis of Sudan IV stained aortic arches and sections of brachiocephalic arteries prepared with Van Gieson's stain. RESULTS: The diet enriched with tree nuts did not influence aortic diameter or aortic rupture incidence. Mice receiving the diet enriched with tree nuts had significantly less atherosclerosis within the brachiocephalic artery (p = 0.033) but not in the aortic arch. CONCLUSIONS: This experimental study suggests that a diet enriched with tree nuts does not reduce the severity of AAA, but does reduce the severity of atherosclerosis within the brachiocephalic artery. The study was not powered to identify a moderate effect of the diet on the primary outcome and therefore this cannot be excluded.