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.

Pharmacological management of obstructive peripheral arterial disease: two case reports.

Peripheral artery disease (PAD), also abbreviated as LEAD or lower extremity artery disease, is an important predictor of cardiovascular morbidity and mortality. Rivaroxaban, a selective direct factor Xa inhibitor, is proposed as an additional pharmacologic option for managing this disease. Two patients presented with PAD and high-risk comorbidities. The first case showed how the evaluation of the cardiovascular risk guided the therapeutic management of the patient. The second case was about a patient diagnosed with LEAD who experienced worsening from exertional ischemia toward critical ischemia requiring amputation despite distal revascularization, and parenteral vasodilator therapy to relieve pain. This case suggested a comprehensive care management approach, adapted to PAD progression stages. The PAD management consists nowadays of optimizing the management of cardiovascular risk factors and disease progression. Diagnosis, treatment, monitoring, and patient education should be handled by a vascular specialist in a specialized care unit.

Intake of marine n-3 polyunsaturated fatty acids and the risk of incident peripheral artery disease.

BACKGROUND: A high intake of marine n-3 polyunsaturated fatty acids (PUFAs) may lower the risk of coronary heart disease and ischemic stroke. The association between intake of marine n-3 PUFAs and development of peripheral artery disease (PAD), however, remains unexplored. We hypothesised that intake of marine n-3 PUFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the sum of EPA + DHA was associated with a lower risk of incident PAD. METHODS: We used data from the Danish Diet, Cancer and Health cohort and investigated the associations between intake of EPA, DHA and EPA + DHA and development of PAD. Information on intake of n-3 PUFAs was obtained through a validated food frequency questionnaire. Potential PAD cases were identified through linkage to the Danish National Patient Register and subsequently, all cases were validated. RESULTS: Data were available from 55,248 participants and during a median of 13.6 years of follow-up, 950 cases of PAD were identified. Multivariate Cox regression analyses with adjustments for established risk factors showed no statistically significant associations between intake of EPA (p = 0.255), DHA (p = 0.071) or EPA + DHA (p = 0.168) and the rate of incident PAD. CONCLUSIONS: We did not confirm our hypothesis that intake of EPA, DHA or EPA + DHA was associated with a lower risk of incident PAD.

[Antithrombotic therapy after peripheral revascularization]. / Antithrombotische Therapie nach peripherer Revaskularisation.

Patients with lower extremity arterial disease are at increased risk for cardiovascular events. Antithrombotic therapy improves prognosis in these patients especially after peripheral revascularization. After endovascular revascularization duale anti-platelet therapy with Aspirin and Clopidogrel is used for up to 3 months in most cases, although there is only little evidence for this practice. Following peripheral bypass grafting most guidelines recommend single anti-platelet therapy. In some patients, anticoagulation with Vitamin K antagonists or dual anti-platelet therapy is indicated. But this practice is also based on small studies. The Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease (VOYAGER PAD) study is the largest randomized trial concerning antithrombotic therapy after peripheral revascularization. In total 6564 patients were included after successful surgical or endovascular lower-extremity revascularization. Rivaroxaban 2.5 mg twice daily plus Aspirin 100 mg reduced cardiac and peripheral events compared with Aspirin 100 mg alone with increased risk for relevant but not for critical bleeding complications. In addition to antithrombotic medication risk factor management and regular follow-up examinations are important improve long-term prognosis after peripheral revascularization.

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.

Treatment With a Marine Oil Supplement Alters Lipid Mediators and Leukocyte Phenotype in Healthy Patients and Those With Peripheral Artery Disease.

Background Peripheral artery disease (PAD) is an advanced form of atherosclerosis characterized by chronic inflammation. Resolution of inflammation is a highly coordinated process driven by specialized pro-resolving lipid mediators endogenously derived from omega-3 fatty acids. We investigated the impact of a short-course, oral, enriched marine oil supplement on leukocyte phenotype and biochemical mediators in patients with symptomatic PAD and healthy volunteers. Methods and Results This was a prospective, open-label study of 5-day oral administration of an enriched marine oil supplement, assessing 3 escalating doses in 10 healthy volunteers and 10 patients with PAD. Over the course of the study, there was a significant increase in the plasma level of several lipid mediator families, total specialized pro-resolving lipid mediators, and specialized pro-resolving lipid mediator:prostaglandin ratio. Supplementation was associated with an increase in phagocytic activity of peripheral blood monocytes and neutrophils. Circulating monocyte phenotyping demonstrated reduced expression of multiple proinflammatory markers (cluster of differentiation 18, 163, 54, and 36, and chemokine receptor 2). Similarly, transcriptional profiling of monocyte-derived macrophages displayed polarization toward a reparative phenotype postsupplementation. The most notable cellular and biochemical changes over the study occurred in patients with PAD. There were strong correlations between integrated biochemical measures of lipid mediators (specialized pro-resolving lipid mediators:prostaglandin ratio) and phenotypic changes in circulating leukocytes in both healthy individuals and patients with PAD. Conclusions These data suggest that short-term enriched marine oil supplementation dramatically remodels downstream lipid mediator pathways and induces a less inflammatory and more pro-resolution phenotype in circulating leukocytes and monocyte-derived macrophages. Further studies are required to determine the potential clinical relevance of these findings in patients with PAD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02719665.

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.

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.

Anticoagulation in Atherosclerotic Disease.

The prevention of atherothrombotic events is an essential therapeutic goal in the treatment of patients with arteriosclerotic diseases. After plaque rupture, a rapidly growing thrombus can lead to acute vascular occlusion and thus heart attack, stroke or limb ischaemia. The acute therapy combines anticoagulation and platelet inhibition. However, the only available therapy so far in the primary and secondary prevention of stable patients is the platelet inhibitors aspirin and clopidogrel. Despite the use of antiplatelet therapies, including aspirin and P2Y12-receptor antagonists, some patients with artery disease continue to experience recurrent cardiovascular ischaemic events due to excessive thrombin generation beyond the acute period. As a result, studies have tested non-vitamin K antagonist oral anticoagulants (NOACs), specifically the factor Xa inhibitors, either alone or in combination with antiplatelet therapy, in the management of arterial disease. For the first time, the COMPASS study investigated low-dose anticoagulation in stable coronary heart disease or peripheral arterial disease. The addition of 2 × 2.5 mg rivaroxaban to long-term aspirin therapy not only prevented cardiovascular death, myocardial infarction and stroke, but even reduced all-cause mortality by a relative 18% after a mean follow-up of 23 months. This benefit came at the expense of more gastrointestinal bleeding, which might be reduced by the addition of a proton pump inhibitor (investigations are ongoing). Interestingly, however, there was no increase in fatal or intracranial haemorrhages. Therefore, a new standard therapy for high-risk patients with atherosclerotic disease may become available in the near future.

Dietary intake and peripheral arterial disease incidence in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study.

Background: Peripheral arterial disease (PAD) is a costly source of morbidity and mortality among older persons in the United States. Dietary intake plays a role in the development of atherosclerotic cardiovascular disease; however, few studies have examined the relation of food intake or dietary patterns with PAD.Objective: We examined the relation between habitual dietary intake at midlife and incident PAD over ∼20 y of follow-up.Design: Among 14,082 participants enrolled in the ARIC (Atherosclerosis Risk in Communities) Study initially free of PAD, dietary intake was assessed at baseline in 1987-1989 by using a modified Harvard food-frequency questionnaire. Food groups were created, and principal components analysis was used to develop "healthy" and "Western" dietary patterns; both were categorized into quintiles or quartiles. Incident PAD was determined by an ankle-brachial index <0.9 assessed at 2 subsequent examinations and hospital discharge codes through 2012. Multivariate-adjusted Cox proportional hazards regression was used.Results: During a mean follow-up of 19.9 y, 1569 participants developed incident PAD. In models adjusted for demographic characteristics, behaviors, and food groups, the HRs (95% CIs) for incident PAD increased across quintiles of meat consumption [quintile 1: reference, quintile 2: 1.38 (1.16, 1.65), quintile 3: 1.38 (1.16, 1.65), quintile 4: 1.45 (1.20, 1.74), quintile 5: 1.66 (1.36, 2.03); P-trend <0.001]. Compared with those who drank no alcohol, those who had 1-6 drinks/wk had a lower risk of incident PAD [0.78 (0.68, 0.89)]. For coffee, ≥4 cups/d compared with none was inversely associated with incident PAD [quintile 5 compared with quintile 1: 0.84 (0.75, 1.00); P-trend = 0.014]. There was no association between other food groups or patterns and incident PAD.Conclusions: In this prospective cohort study, greater meat consumption was associated with a higher risk, and moderate alcohol consumption was associated with a lower risk of incident PAD. Whether these associations are causal remains to be seen. This trial was registered at clinicaltrials.gov as NCT00005131.

High-dose atorvastatin is superior to moderate-dose simvastatin in preventing peripheral arterial disease.

OBJECTIVES: To study whether high-dose versus usual-dose statin treatment reduces the incidence of peripheral artery disease (PAD) and what is the effect of high-dose statin treatment on cardiovascular disease (CVD) outcome in patients with PAD. METHODS AND RESULTS: In the Incremental Decrease in End Points Through Aggressive Lipid Lowering trial, 8888 post-myocardial infarction patients were randomised to high-dose or usual-dose statin therapy (atorvastatin 80 mg/day vs simvastatin 20-40 mg/day). We investigated the effect of high-dose versus usual-dose statins on the pre-specified outcome PAD incidence, and additionally performed a posthoc analysis of the efficacy of high-dose statins in reducing CVD risk among patients with PAD. During a median follow-up of 4.8 years, 94 patients (2.2%) receiving atorvastatin and 135 patients (3.2%) receiving simvastatin developed PAD (HR=0.70, 95% CI 0.53 to 0.91; p=0.007). The risk of major coronary events was almost twofold higher in patients with PAD at baseline, but was no longer significant after adjusting for the adverse cardiovascular risk profile. In PAD patients, major coronary events occurred in fewer patients in the atorvastatin group (14.4%) than in the simvastatin group (20.1%), but the difference did not reach statistical significance. (HR=0.68, 95% CI 0.41 to 1.11; p=0.13). Atorvastatin treatment significantly reduced overall cardiovascular (p=0.046) and coronary events (p=0.004), and coronary revascularisation (p=0.007) in these patients. CONCLUSIONS: High-dose statin therapy with atorvastatin significantly reduced the incidence of PAD compared with usual-dose statin therapy with simvastatin. Patients with a history of PAD at baseline were at higher risk of future coronary events and this risk was reduced by high-dose atorvastatin treatment. TRIAL REGISTRATION NUMBER: NCT00159835 (URL: http://clinicaltrials.gov/show/NCT00159835).

Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease.

OBJECTIVE: Few studies have examined the roles of homocysteine and related nutrients in the development of peripheral artery disease (PAD). We examined the associations between plasma homocysteine, dietary B vitamins, betaine, choline, and supplemental folic acid use and incidence of PAD. METHODS: We used two cohort studies of 72,348 women in the Nurses' Health Study (NHS, 1990-2010) and 44,504 men in the Health Professionals Follow-up Study (HPFS, 1986-2010). We measured plasma homocysteine in nested matched case-control studies of clinically recognized PAD within both cohorts, including 143 PAD cases and 424 controls within the NHS (1990-2010) and 143 PAD cases and 428 controls within the HPFS (1994-2008). We examined the association between diet and risk of incident PAD in the cohorts using a food frequency questionnaire and 790 cases of PAD over 3.1 million person-years of follow-up. RESULTS: Higher homocysteine levels were positively associated with risk of PAD in men (adjusted IRR 2.17; 95% CI, 1.08-4.38 for tertile 3 vs. 1). There was no evidence of an association in women (adjusted IRR 1.14; 95% CI, 0.61-2.12). Similarly, higher folate intake, including supplements, was inversely associated with risk of PAD in men (adjusted HR 0.90; 95% CI, 0.82-0.98 for each 250 µg increase) but not women (HR 1.01, 95% CI, 0.88-1.15). Intakes of the other B vitamins, betaine, and choline were not consistently associated with risk of PAD in men or women. CONCLUSION: Homocysteine levels were positively associated and dietary folate intake was inversely associated with risk of PAD in men but not in women.

Increased tea consumption is associated with decreased arterial stiffness in a Chinese population.

BACKGROUND: Tea has attracted considerable attention for its potential cardioprotective effects. The primary chemical components of tea are thought to have a beneficial effect by reducing arterial stiffness. The objective of this study was to assess the association between tea consumption and brachial-ankle pulse wave velocity (baPWV) in a relatively healthy Chinese population. METHODS: We enrolled 3,135 apparently healthy subjects from October 2006 to August 2009. Subjects taking medication for diabetes, hypertension, or hyperlipidemia, or with a history of cardiovascular disease, were excluded from the study. The subjects were categorized into three groups according to their tea-drinking habits: (1) none to low (n = 1615), defined as non-habitual tea drinkers, or drinking for <1 year, or drinking ≤150 mL per day for ≥1 year ; (2) moderate tea consumption, defined as drinking for ≥1 year and consumption between 151 and 450 mL per day; and (3) heavy tea consumption, defined as a drinking for ≥1 year and consumption >450 mL per day. Multiple logistic regression was used to determine whether different levels of consumption were independently associated with the highest quartile of baPWV values, defined as ≥1428.5 cm/s. RESULTS: Of the 3,135 subjects, 48.5% had drunk >150 mL of tea per day for at least 1 year. In multivariate regression analysis with adjustment for co-variables, including, age, sex, current smoking, alcohol use, habitual exercise, total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio >5, obesity, newly diagnosed hypertension and diabetes, subjects with high tea consumption had a decreased risk of highest quartile of baPWV by 22% (odds ratio = 0.78, 95% confidence interval = 0.62-0.98, p = 0.032), while subjects with moderate tea consumption did not (p = 0.742), as compared subjects with none to low tea consumption. CONCLUSIONS: High, but not moderate, habitual tea consumption may decrease arterial stiffness.

Hypovitaminosis D and peripheral arterial disease: emerging link beyond cardiovascular risk factors.

Vitamin D has received increasing interest for its beneficial effect on health. Beyond its conventional role in bone metabolism, emerging evidence suggests a possible link between low vitamin D levels and cardiovascular disease (CVD), including peripheral arterial disease (PAD), and cardiovascular risk factors. Vitamin D interacts either directly with the vascular tree or indirectly through its association with cardiovascular risk factors, but the exact mechanism remains controversial. This review outlines the association between hypovitaminosis D and PAD. Both entities are quite prevalent in the general population and, therefore, their potential association might have important clinical implications. Whether vitamin D deficiency represents a novel risk factor for PAD/CVD, and whether vitamin D supplementation would reduce the burden of CVD still remains to be answered. Until then, vitamin D intake is not recommended for PAD/CVD prevention. Outdoor physical activity, coupled with adequate but safe sun exposure, is a healthy lifestyle practice suggested for the prevention of both PAD and hypovitaminosis D.

Dietary fatty acids and peripheral artery disease in adults.

BACKGROUND: Peripheral artery disease (PAD) is a debilitating condition involving atherosclerosis. Although saturated, monounsaturated and polyunsaturated fatty acids have strong associations with atherosclerosis, it is unclear if diets high in these fatty acids affect PAD. METHODS: We studied 6352 adults aged 40 years and older who participated in the U.S. National Health and Nutrition Examination Survey between 1999 and 2004. Ankle brachial index (ABI) was assessed by standardized blood pressure measurements, and we defined PAD as an ABI<0.9. Fatty acid intake was assessed by validated 24-h dietary recall. We used multivariable linear and logistic regression to estimate associations between intakes of dietary saturated fatty acids (SFAs), monounsaturated fatty acids (MFAs), marine omega-3 fatty acids (N-3), linolenic acid (LNA), and omega-6 fatty acids (N-6) and ABI/PAD. RESULTS: The prevalence and 95% confidence interval (CI) of PAD was 5.2% (95% CI 4.6-5.8). There were no associations between ABI and intakes of marine N-3 (p=0.83) or N-6 (p=0.19) in adjusted models. In contrast, LNA was associated with higher ABI (p=0.04) and SFA tended to be associated with lower ABI (p=0.06) in adjusted models. In addition, higher SFA was associated with a higher prevalence of PAD: adjusted odds ratio 1.30 (95% CI 1.01-1.67; p=0.04) and a trend toward slower gait speed (p=0.08). CONCLUSION: In this nationally representative sample, higher dietary intakes of LNA and SFAs were associated with higher and lower ABI, respectively. Prospective studies are needed to confirm the potential protective effects of dietary LNA and detrimental effects of dietary SFAs on PAD.

Polyunsaturated fatty acids and peripheral artery disease.

There is substantial evidence that polyunsaturated fatty acids (PUFAs) such as n-3 and n-6 fatty acids (FAs) play an important role in prevention of atherosclerosis. In vitro and in vivo studies focusing on the interactions between monocytes and endothelial cells have explored the molecular effects of FAs on these interactions. Epidemiological surveys, followed by large, randomized, control trials have demonstrated a reduction in major cardiovascular events with supplementation of n-3 FAs in secondary prevention settings. The evidence of beneficial effects specific to patients with peripheral artery disease (PAD) remains elusive, and is the focus of this review.