An unfavorable dietary pattern is associated with symptomatic peripheral artery disease.

BACKGROUND AND AIMS: Diet has an essential role in primary and secondary cardiovascular prevention by modulating various cardiovascular risk factors. The need to have easily useable tools seems essential to facilitate the daily practice of clinicians in order to propose the most optimal management of their patients' diet. The aim of this study was to compare the diet assessed with a simple food frequency questionnaire (FFQ) between patients with symptomatic peripheral artery disease (PAD) and healthy subjects. MATERIALS AND RESULTS: In this ancillary study (ELECTRO-PAD study), we included symptomatic PAD patients and healthy participants. All participants filled a FFQ previously validated called Cardiovascular-Dietary-Questionnaire 2 (CDQ-2). CDQ-2 allows the calculation of different scores: global food score, saturated fatty acids score (SFA), unsaturated fatty acids score (UFA), fruit and vegetable score. The higher the score, the better the diet. We compared the different scores between PAD patients and healthy participants. We included 37 PAD patients and 40 healthy subjects. Mean global score was significantly lower in PAD patients compared to the healthy participants (5.35 ± 7.65 vs 10.60 ± 5.81; p = 0.0011). Similarly, the sub-scores concerning unsaturated fatty acids and fruits-vegetables were significantly lower in PAD patients (p < 0.010). Only the sub-score concerning saturated fatty acids was not significantly different (p = 0.8803) between PAD patients and healthy participants. CONCLUSION: CDQ-2 highlights that PAD patients have an unfavorable diet compared with healthy participants. CDQ-2 is a tool of interest to help the clinicians for dietary advice of PAD patients.

[Conservative Treatment and Secondary Prevention of PAD (Peripheral Artery Disease)]. / Konservative Therapie und Sekundärprävention der pAVK.

The immediate and long-term success of endovascular and surgical revascularization crucially depends on the conservative treatment of the PAD. The "gentle, preserving" treatment should be understood as he absolutely basic therapy for every PAD patient, because conservative treatment adresses the "big five" of atherosclerotic risk factors. This article presents both the full spectrum of pharmacological and non-pharmacological strategies.

Association Between Genetic Variation in Blood Pressure and Increased Lifetime Risk of Peripheral Artery Disease.

[Figure: see text].

Cohort Study Examining the Prevalence and Relationship with Outcome of Standard Modifiable Risk Factors in Patients with Peripheral Artery Occlusive and Aneurysmal Disease.

OBJECTIVE: The aim was to examine the presentation and outcome of patients with peripheral artery occlusive and aneurysmal disease (POAD) in relation to standard modifiable cardiovascular risk factors (SMuRFs; i.e., hypertension, diabetes, hypercholesterolaemia, and smoking). METHODS: A total of 2 129 participants with POAD were recruited from three vascular clinics in Queensland, Australia. SMuRFs were defined using established criteria. Participants were followed via outpatient appointments and linked data to record the primary outcome event of major adverse cardiovascular events (MACE). The association between SMuRFs and MACE was assessed using Cox proportional hazard analysis. Subanalyses examined the association of individual SMuRFs with MACE and assessed findings separately in participants with occlusive and aneurysmal disease. RESULTS: At recruitment 71 (3.3%), 551 (25.9%), 977 (45.9%), 471 (22.1%), and 59 (2.8%) participants had zero, one, two, three, and four SMuRFs. During a median follow up of 2.6 (interquartile range 0.4, 6.2) years, the risk of MACE was progressively higher with the increasing numbers of SMuRFs (adjusted hazard ratio [HR] 95% confidence interval [CI] 4.09, 1.29 - 12.91; 4.28, 1.37 - 13.41; 5.82, 1.84 - 18.39; and 9.42, 2.77 - 32.08; for one, two, three, or four SMuRFs, respectively) by comparison with those who were SMuRF-less at recruitment. Participants with occlusive disease were significantly more likely to have a greater number of SMuRFs than those with aneurysmal disease. In a subanalysis, there was a significantly higher risk of MACE with three or four SMuRFs in participants presenting with either occlusive or aneurysmal disease compared with those who were SMuRF-less. Hypertension, diabetes, and smoking but not hypercholesterolaemia were independently associated with increased risk of MACE. CONCLUSION: Very few patients presenting with POAD had no SMuRFs. There was a progressive increase in the risk of MACE in relation to the number of SMuRFs identified at entry.

Circulating Amino Acids and Risk of Peripheral Artery Disease in the PREDIMED Trial.

Effective prevention and risk prediction are important for peripheral artery disease (PAD) due to its poor prognosis and the huge disease burden it produces. Circulating amino acids (AA) and their metabolites may serve as biomarkers of PAD risk, but they have been scarcely investigated. The objective was to prospectively analyze the associations of baseline levels of plasma AA (and their pathways) with subsequent risk of PAD and the potential effect modification by a nutritional intervention with the Mediterranean diet (MedDiet). A matched case-control study was nested in the PREDIMED trial, in which participants were randomized to three arms: MedDiet with tree nut supplementation group, MedDiet with extra-virgin olive oil (EVOO) supplementation group or control group (low-fat diet). One hundred and sixty-seven PAD cases were matched with 250 controls. Plasma AA was measured with liquid chromatography/mass spectrometry at the Broad Institute. Baseline tryptophan, serine and threonine were inversely associated with PAD (ORfor 1 SD increase = 0.78 (0.61-0.99); 0.67 (0.51-0.86) and 0.75 (0.59-0.95), respectively) in a multivariable-adjusted conditional logistic regression model. The kynurenine/tryptophan ratio was directly associated with PAD (ORfor 1 SD increase = 1.50 (1.14-1.98)). The nutritional intervention with the MedDiet+nuts modified the association between threonine and PAD (p-value interaction = 0.018) compared with the control group. However, subjects allocated to the MedDiet+EVOO group were protected against PAD independently of baseline threonine. Plasma tryptophan, kynurenine/tryptophan ratio, serine and threonine might serve as early biomarkers of future PAD in subjects at a high risk of cardiovascular disease. The MedDiet supplemented with EVOO exerted a protective effect, regardless of baseline levels of threonine.

Peripheral Artery Disease and Venous Thromboembolic Events After Acute Coronary Syndrome: Role of Lipoprotein(a) and Modification by Alirocumab: Prespecified Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial.

BACKGROUND: Patients with acute coronary syndrome are at risk for peripheral artery disease (PAD) events and venous thromboembolism (VTE). PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors reduce lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C) levels. Our objective was to ascertain whether PCSK9 inhibition reduces the risk of PAD events or VTE after acute coronary syndrome, and if such effects are related to levels of lipoprotein(a) or LDL-C. METHODS: This was a prespecified analysis of the ODYSSEY OUTCOMES randomized clinical trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome), which was conducted in 18 924 patients with recent acute coronary syndrome on intensive or maximum-tolerated statin treatment who were randomized to the PCSK9 inhibitor alirocumab or placebo. In a prespecified analysis, PAD events (critical limb ischemia, limb revascularization, or amputation for ischemia) and VTE (deep vein thrombosis or pulmonary embolism) were assessed. LDL-C was corrected (LDL-Ccorrected) for cholesterol content in lipoprotein(a). RESULTS: At baseline, median lipoprotein(a) and LDL-Ccorrected were 21 and 75 mg/dL, respectively; with alirocumab, median relative reductions were 23.5% and 70.6%, respectively. PAD events and VTE occurred in 246 and 92 patients, respectively. In the placebo group, risk of PAD events was related to baseline quartile of lipoprotein(a) (Ptrend=0.0021), and tended to associate with baseline quartile of LDL-Ccorrected (Ptrend=0.06); VTE tended to associate with baseline quartile of lipoprotein(a) (Ptrend=0.06), but not LDL-Ccorrected (Ptrend=0.85). Alirocumab reduced risk of PAD events (hazard ratio [HR], 0.69 [95% CI, 0.54-0.89]; P=0.004), with nonsignificantly fewer VTE events (HR, 0.67 [95% CI, 0.44-1.01]; P=0.06). Reduction in PAD events with alirocumab was associated with baseline quartile of lipoprotein(a) (Ptrend=0.03), but not LDL-Ccorrected (Ptrend=0.50). With alirocumab, the change from baseline to Month 4 in lipoprotein(a), but not LDL-Ccorrected, was associated with the risk of VTE and the composite of VTE and PAD events. CONCLUSIONS: In statin-treated patients with recent acute coronary syndrome, risk of PAD events is related to lipoprotein(a) level and is reduced by alirocumab, particularly among those with high lipoprotein(a). Further study is required to confirm whether risk of VTE is related to lipoprotein(a) level and its reduction with alirocumab. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01663402.

Protection against peripheral artery disease injury by Ruan Jian Qing Mai formula via metabolic programming.

Ruan Jian Qing Mai formula (RJQM), a multicomponent herbal formula, has been widely used to treat peripheral arterial disease (PAD) in China. However, its active compounds and mechanisms of action are still unknown. First, RNA sequencing analysis of 15 healthy and 16 PAD samples showed that 524 PAD differential genes were significantly enriched in Go Ontology (ribonucleotide metabolic process, oxidoreductase complex, and electron transfer activity), Kyoto Encyclopedia of Genes and Genomes (KEGG) and GSEA pathways (OXPHOS and TCA cycle), miRNA (MIR183), and kinase (PAK6). Fifty-three active ingredients in RJQM had similar structures to the seven drug molecules in CLUE. Then, network topology analysis of the 53 components-target-pathway-disease network yielded 10 active ingredients. Finally, computational toxicity estimations showed that the median lethal dose (LD50) of the 10 active ingredients was above 1000 mg/kg, and eight of them did not cause hepatotoxicity, mutagenicity, carcinogenicity, cytotoxicity, and immunotoxicity nor activate 12 toxic pathways. In conclusion, RJQM has a protection effect on PAD by regulating a complex molecular network. Part of the mechanism is associated with the regulation of OXPHOS by 10 active components, which may alleviate mitochondrial dysfunction and pathological metabolic programming.

[Medication-based secondary prevention in patients with peripheral arterial occlusive disease : An analysis based on secondary data]. / Medikamentöse Sekundärprävention bei Patienten mit peripherer arterieller Verschlusskrankheit : Eine sekundärdatenbasierte Analyse.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) is an atherosclerotic vascular disease with high morbidity and mortality. A consistent medication-based secondary prevention is part of the essential and evidence-based treatment of PAOD. The aim of this study was to ascertain the status quo of medicinal secondary prevention based on submitted prescriptions. METHODS: In the time period from 2014 to 2017 patients with a confirmed PAOD coding (I70.2-/I73.9-) were identified based on secondary data of the Association of Statutory Health Insurance Physicians Westphalia-Lippe (KVWL). The prescriptions submitted with respect to platelet inhibitors, oral anticoagulants, lipid lowering therapy (LLT) and angiotensin-converting enzyme (ACE) inhibitors in the fourth quarter year after diagnosis coding were collated. RESULTS: In the diagnosis period 2014/2015 a total of 238,397 patients had PAOD in the catchment area of the KVWL. The proportion of submitted prescriptions in the fourth quarter year after diagnosis was 25.9% for LLT, 13.6% for acetylsalicylic acid, 4.5% for clopidogrel, 5.5% for vitamin K antagonists (VKA), 3.5% for non-vitamin K­dependent oral anticoagulants (NOAC) and 26.8% for ACE inhibitors. Over the course of the 3 years (n = 241,375 patients with PAOD 2016/2017) the proportion of submitted prescriptions for all substances except VKA increased (p < 0.001), whereby the largest relative increase was noted for NOAC (relative increase of 81.7%). CONCLUSION: The guideline-conform medicinal secondary prevention in patients with PAOD in Germany is still in need of improvement. A consistent implementation of evidence-based medicinal secondary prevention harbors a great potential for improvement of the overall prognosis in patients with PAOD.

[Vascular passport : a tool for secondary prevention among patients with peripheral artery disease]. / Passeport vasculaire : un outil pour la prévention secondaire des patients avec maladie artérielle périphérique.

Peripheral arterial disease (PAD) is a major health problem in Switzerland, as myocardial infarction or stroke, all three sharing common cardiovascular (CV) risk factors and similar pathophysiological mechanisms (atherosclerosis). Unfortunately, PAD is still often overlooked, despite being fraught with significant morbidity/mortality and increasing the patient's overall CV risk. It is therefore essential to improve secondary prevention in order to decrease this burden and the overall CV risk of the patient. We will review the treatment targets for CV risk factors as secondary prevention in patients with PAD and see how the use of a vascular passport may improve management.

La maladie artérielle périphérique (MAP) est une problématique de santé majeure en Suisse, au même titre que l'infarctus du myocarde ou l'AVC, tous les trois partageant des facteurs de risque cardiovasculaire (FRCV) communs et des mécanismes physiopathologiques similaires (athérosclérose). Malheureusement, l'importance de la MAP est encore souvent sous-estimée, alors qu'elle est grevée d'une morbidité et d'une mortalité importantes et augmente le risque cardiovasculaire (CV) global du patient. Il est capital d'améliorer la prévention secondaire afin de diminuer ce fardeau et le risque CV global du patient. Nous allons passer en revue les cibles de traitement des FRCV en prévention secondaire chez les patients avec MAP et voir comment l'utilisation d'un passeport vasculaire permet d'améliorer la prise en charge.

Risk of acute arterial events associated with treatment of inflammatory bowel diseases: nationwide French cohort study.

OBJECTIVE: Patients with IBD are at increased risk of acute arterial events. Antitumour necrosis factor (TNF) agents and thiopurines may, via their anti-inflammatory properties, lower the risk of acute arterial events. The aim of this study was to assess the impact of thiopurines and anti-TNFs on the risk of acute arterial events in patients with IBD. DESIGN: Patients aged 18 years or older and affiliated to the French national health insurance with a diagnosis of IBD were followed up from 1 April 2010 until 31 December 2014. The risks of acute arterial events (including ischaemic heart disease, cerebrovascular disease and peripheral artery disease) were compared between thiopurines and anti-TNFs exposed and unexposed patients with marginal structural Cox proportional hazard models adjusting for baseline and time-varying demographics, medications, traditional cardiovascular risk factors, comorbidities and IBD disease activity. RESULTS: Among 177 827 patients with IBD (96 111 (54%) women, mean age at cohort entry 46.2 years (SD 16.3), 90 205 (50.7%) with Crohn's disease (CD)), 4145 incident acute arterial events occurred (incidence rates: 5.4 per 1000 person-years). Compared with unexposed patients, exposure to anti-TNFs (HR 0.79, 95% CI 0.66 to 0.95), but not to thiopurines (HR 0.93, 95% CI 0.82 to 1.05), was associated with a decreased risk of acute arterial events. The magnitude in risk reduction was highest in men with CD exposed to anti-TNFs (HR 0.54, 95% CI 0.40 to 0.72). CONCLUSION: Exposure to anti-TNFs is associated with a decreased risk of acute arterial events in patients with IBD, particularly in men with CD.

Xarelto plus Acetylsalicylic acid: Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA): Rationale and design of a prospective registry study to assess rivaroxaban 2.5 mg twice daily plus aspirin for prevention of atherothrombotic events in coronary artery disease, peripheral artery disease, or both.

Patients with coronary artery disease (CAD), peripheral artery disease (PAD), or both remain at risk of cardiovascular events (including peripheral ischemic events), even when they receive the current guideline-recommended treatment. The phase III COMPASS trial demonstrated that treatment with rivaroxaban vascular dose 2.5 mg twice daily plus aspirin (dual pathway inhibition [DPI] regimen) significantly reduced the risk of major adverse cardiovascular events (including peripheral ischemic events) and increased the risk of major bleeding, but not fatal bleeding or intracranial hemorrhage, versus aspirin alone in patients with CAD, PAD, or both. The results of the COMPASS trial supported the regulatory approval of the DPI regimen in several geographic regions. However, it is unclear whether the patients selected for treatment with the DPI regimen in clinical practice will have a similar risk profile and event rates compared with the COMPASS trial population. The prospective post-approval XATOA registry study aims to assess treatment patterns, as well as ischemic and bleeding outcomes in patients with CAD, PAD, or both, who receive DPI therapy in routine clinical practice. Up to 10,000 patients from at least 400 centers in 22 countries will be enrolled and followed up for a minimum of 12 months, and all treatment will be at the discretion of the prescribing physician. The primary objective of the XATOA study will be to describe early treatment patterns, while ischemic and bleeding outcomes will be described as a secondary objective. TRIAL REGISTRATION NUMBER: NCT03746275.

Exercise and Peripheral Arteriosclerosis.

Adaptation of a healthy lifestyle including adequate daily physical activity is shown to reduce 80% of cardiovascular mortality and 40% of cancer-related deaths. A large body of evidence exists proving that this relationship is dose dependent, and even half of the recommended normal physical activity yields significant risk reduction. There has been no medical therapy that would provide such high percentages of reduction in mortality to date. The World Health Organization, therefore, has started an initiative to implement exercise into daily life as a primary prevention measure. Herein, we will focus on the effects of exercise on the vasculature, mainly the peripheral vasculature, in the context of atherosclerotic disease. Exercise has a fundamental role in the pathogenesis, diagnosis, and treatment of atherosclerotic vascular disease. It exerts a protective effect against the development of atherosclerosis irrespective of other cardiovascular risk factors. Additionally, exercise induces changes in vascular hemodynamics helping us to elucidate the presence of obscure vascular involvement. Once again, exercise is the main treatment modality in peripheral arterial disease with accumulating evidence to reduce symptoms and improve both exercise capacity and cardiovascular symptoms.

A Randomized Controlled Trial Comparing Flat Times Versus Standard Care in Pediatric Patients Post Cardiac Catheterization.

BACKGROUND: Pediatric patients undergoing cardiac catheterization procedures are required to lie flat for 4 hours for femoral venous access and 6 hours for femoral arterial access. Authors of research in adults suggest the flat time for the same access can be safely reduced to 1.5 to 2 hours post procedure. No literature was found that flat times could be safely reduced for pediatric patients. OBJECTIVE: The purpose of this study was to determine whether decreased flat time for the post-cardiac catheterization pediatric patient would impact the incidence of site bleeding, additional sedation, and the need for a critical care admission. METHODS: A randomized controlled trial was designed and participants were randomly assigned to experimental or control group. The experimental group reduced flat times to 2 hours for venous and 4 hours for arterial. The control group was standard care of 4 hours for venous and 6 hours for arterial. RESULTS: A total of 119 participants were enrolled, 60 in the experimental group and 59 in the control group. Results suggest no difference in the incidence of site bleeding (P = .999), additional sedation (P = .653), or need for a critical care admission. CONCLUSIONS: For pediatric patients undergoing arterial or venous cardiac catheterizations, flat times can safely be reduced without increasing site bleeding, additional sedation, or critical care admissions.

Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) increases the risk of cardiovascular events and deaths, which anticoagulation therapy could prevent. Dabigatran prevents perioperative venous thromboembolism, but whether this drug can prevent a broader range of vascular complications in patients with MINS is unknown. The MANAGE trial assessed the potential of dabigatran to prevent major vascular complications among such patients. METHODS: In this international, randomised, placebo-controlled trial, we recruited patients from 84 hospitals in 19 countries. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS. Patients were randomly assigned (1:1) to receive dabigatran 110 mg orally twice daily or matched placebo for a maximum of 2 years or until termination of the trial and, using a partial 2-by-2 factorial design, patients not taking a proton-pump inhibitor were also randomly assigned (1:1) to omeprazole 20 mg once daily, for which results will be reported elsewhere, or matched placebo to measure its effect on major upper gastrointestinal complications. Research personnel randomised patients through a central 24 h computerised randomisation system using block randomisation, stratified by centre. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary efficacy outcome was the occurrence of a major vascular complication, a composite of vascular mortality and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism. The primary safety outcome was a composite of life-threatening, major, and critical organ bleeding. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01661101. FINDINGS: Between Jan 10, 2013, and July 17, 2017, we randomly assigned 1754 patients to receive dabigatran (n=877) or placebo (n=877); 556 patients were also randomised in the omeprazole partial factorial component. Study drug was permanently discontinued in 401 (46%) of 877 patients allocated to dabigatran and 380 (43%) of 877 patients allocated to placebo. The composite primary efficacy outcome occurred in fewer patients randomised to dabigatran than placebo (97 [11%] of 877 patients assigned to dabigatran vs 133 [15%] of 877 patients assigned to placebo; hazard ratio [HR] 0·72, 95% CI 0·55-0·93; p=0·0115). The primary safety composite outcome occurred in 29 patients (3%) randomised to dabigatran and 31 patients (4%) randomised to placebo (HR 0·92, 95% CI 0·55-1·53; p=0·76). INTERPRETATION: Among patients who had MINS, dabigatran 110 mg twice daily lowered the risk of major vascular complications, with no significant increase in major bleeding. Patients with MINS have a poor prognosis; dabigatran 110 mg twice daily has the potential to help many of the 8 million adults globally who have MINS to reduce their risk of a major vascular complication [corrected]. FUNDING: Boehringer Ingelheim and Canadian Institutes of Health Research.

Effectiveness and safety of rivaroxaban and warfarin for prevention of major adverse cardiovascular or limb events in patients with non-valvular atrial fibrillation and type 2 diabetes.

AIMS: To assess the effectiveness and safety of rivaroxaban versus warfarin for the prevention of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with type 2 diabetes (T2D) and non-valvular atrial fibrillation (NVAF). MATERIALS AND METHODS: Using MarketScan data from January 2012 to December 2017, we identified oral anticoagulant-naïve patients with NVAF and comorbid T2D and ≥12 months of insurance coverage prior to rivaroxaban or warfarin initiation. Differences in baseline covariates between cohorts were adjusted for using inverse probability of treatment weights based on propensity scores (absolute standardized differences <0.1 achieved for all covariates after adjustment). Patients were followed until a MACE, MALE or major bleeding event, oral anticoagulant discontinuation/switch, insurance disenrolment or end of data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the cohorts were calculated using Cox regression. RESULTS: We identified 10 700 rivaroxaban users (24.1% received a reduced dose) and 13 946 warfarin users. The median (25%, 75% range) age was 70 (62, 79) years, CHA2DS2-VASc score was 4 (3, 5) and duration of available follow-up was 1.4 (0.6, 2.7) years. Eleven percent of patients had peripheral artery disease, 5.1% had coronary artery disease, and 5.1% had a prior MALE, at baseline. Rivaroxaban was associated with a 25% (95% CI 4-41) reduced risk of MACE and a 63% (95% CI 35-79) reduced risk of MALE compared to warfarin. Major bleeding risk did not significantly differ between cohorts (HR 0.95). CONCLUSIONS: Among patients with NVAF and T2D treated in routine practice, rivaroxaban was associated with lower risks of both MACE and MALE versus warfarin, with no significant difference in major bleeding.

Intake of α-linolenic acid is not consistently associated with a lower risk of peripheral artery disease: results from a Danish cohort study.

Intake of the plant-derived n-3 fatty acid α-linolenic acid (ALA) has been associated with anti-atherosclerotic properties. However, information on the association between ALA intake and development of peripheral artery disease (PAD) is lacking. In this follow-up study, we investigated the association between dietary intake of ALA and the rate of PAD among middle-aged Danish men and women enrolled into the Danish Diet, Cancer and Health cohort between 1993 and 1997. Incident PAD cases were identified through the Danish National Patient Register. Intake of ALA was assessed using a validated FFQ. Statistical analyses were performed using Cox proportional hazard regression allowing for separate baseline hazards among sexes and adjusted for established risk factors for PAD. During a median of 13·6 years of follow-up, we identified 950 valid cases of PAD with complete information on covariates. The median energy-adjusted ALA intake within the cohort was 1·76 g/d (95 % central range: 0·94-3·28). In multivariable analyses, we found no statistically significant association between intake of ALA and the rate of PAD (P = 0·339). Also, no statistically significant associations were observed in analyses including additional adjustment for co-morbidities and in sex-specific analyses. In supplemental analyses with additional adjustment for potential dietary risk factors, we found a weak inverse association of PAD with ALA intake above the median, but the association was not statistically significant (P = 0·314). In conclusion, dietary intake of ALA was not consistently associated with decreased risk of PAD.

Healthy diet and fiber intake are associated with decreased risk of incident symptomatic peripheral artery disease - A prospective cohort study.

Peripheral artery disease (PAD) is caused by atherosclerosis and associated with an increased risk of leg amputation, cardiovascular disease, and death. A healthy diet has been shown to reduce the risk of cardiovascular events, but relationships between diet, fiber intake, and incidence of PAD are virtually unknown. The aim was to investigate the long-term impact of diet on the development of PAD among 26,010 middle-aged individuals in the prospective Malmö Diet and Cancer study (MDCS). Data on dietary intake were collected through a 7-day food diary combined with a food questionnaire and a 1-hour interview. Adherence to a recommended intake of six dietary components - saturated fat, polyunsaturated fat, fish and shellfish, fiber, fruit and vegetables, and sucrose - was scored (sum 0-6 points) to assess a diet quality index, adjusting for potential confounders. Cox regression analysis was used to estimate associations between diet variables and PAD incidence expressed in hazard ratios (HR) with 95% CI. During a median follow-up of 21.7 years, 1122 participants developed PAD. Diet score was associated with a reduced risk of PAD in multivariable analysis (p = 0.03). When mutually adjusting for all dietary variables, only adherence to recommended levels of fiber intake was associated with a reduced risk of incident PAD (HR 0.84; 95% CI 0.72-0.99). In this prospective, population-based study including 26,010 participants with over 20 years of follow-up, a healthy diet, especially a high intake of fiber, was associated with a reduced risk of PAD. Primary prevention programs directed against PAD should therefore include a fiber recommendation.

The Protective Role of Heme Oxygenase-1 in Atherosclerotic Diseases.

Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme to generate ferrous iron, carbon monoxide (CO), and biliverdin, which is subsequently converted to bilirubin. These products have anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-thrombotic properties. Although HO-1 is expressed at low levels in most tissues under basal conditions, it is highly inducible in response to various pathophysiological stresses/stimuli. HO-1 induction is thus thought to be an adaptive defense system that functions to protect cells and tissues against injury in many disease settings. In atherosclerosis, HO-1 may play a protective role against the progression of atherosclerosis, mainly due to the degradation of pro-oxidant heme, the generation of anti-oxidants biliverdin and bilirubin and the production of vasodilator CO. In animal models, a lack of HO-1 was shown to accelerate atherosclerosis, whereas HO-1 induction reduced atherosclerosis. It was also reported that HO-1 induction improved the cardiac function and postinfarction survival in animal models of heart failure or myocardial infarction. Recently, we and others examined blood HO-1 levels in patients with atherosclerotic diseases, e.g., coronary artery disease (CAD) and peripheral artery disease (PAD). Taken together, these findings to date support the notion that HO-1 plays a protective role against the progression of atherosclerotic diseases. This review summarizes the roles of HO-1 in atherosclerosis and focuses on the clinical studies that examined the relationships between HO-1 levels and atherosclerotic diseases.

Referral from vascular surgery to cardiovascular rehabilitation and related outcomes in patients with peripheral arterial disease: the THINKPAD-RELOADED survey.

The utilization of cardiovascular rehabilitation (CR) programmes in patients with Lower Extremity Peripheral Artery Disease (LEPAD) is generally poor, with limited evidence of current policies for referral. The aim of the study was to evaluate, within a cohesive network of CR and vascular surgery facilities with facilitated referral process, the clinical characteristic of LEPAD patients referred to CR and related outcomes, as compared to patients not referred. The present is an observational prospective study of consecutive patients recruited at vascular surgery facilities. Out of 329 patients observed, the average referral rate to CR was 34% (28% and 39% in patients with and without recent peripheral revascularization, p<0.05). LEPAD patients entering the CR programme were similar to those who did not according to sex, age, the vascular surgery setting of evaluation, and localization of arterial lesions. Patients with moderate intermittent claudication and patients with acute limb ischemia as index event were more represented among those who attended CR (41% vs 21% and 9% vs 2% respectively, p<0.05). Patients referred to CR had five times more episodes of acute coronary syndrome and heart failure as complication of the index event. The cardiovascular risk profile (obesity 29.5% vs 11%, p<0.05; hypercholesterolemia 80% vs 61%, p<0.05) was much worse in LEPAD patients referred to CR, but conversely, they better achieved secondary prevention targets, particularly for blood pressure control (97% vs 57%, p<0.05). All-cause 2-year mortality in the whole patients' population was 6%. Patients entering the CR programme displayed less events (13.5% vs 37.7%, p<0.05), mainly death (3.1% vs 11.3%, p<0.05) and limb-related events (4.2% vs 15.2%, p<0.05). The results of our study suggest that when a cohesive network of vascular surgery and CR facilities becomes available, the referral rate to rehabilitation may increase up to one third of eligible patients. Patients with higher comorbidity and cardiovascular risk seem to have priority in the referral process, nevertheless those with peripheral revascularization are still underestimated. Entering CR may ensure better cardiovascular risk profile and cardiovascular prognosis in LEPAD patients, and consequently the systematic adoption of this care model needs to be strongly recommended and facilitated.