Advancing beyond the “heart-healthy diet” for peripheral arterial disease

ObjectivePeripheral arterial disease (PAD) is a burdensome cardiovascular condition that results from chronic inflammatory insults to the arterial vasculature. Key risk factors include age, gender, type 2 diabetes mellitus, hypertension, hypercholesterolemia, hyperhomocysteinemia, smoking, lack of physical fitness, and poor diet, the latter three being modifiable in the development and progression of PAD. A growing body of evidence indicates that imbalanced nutrient intake may contribute to the development and progression of PAD. The purpose of this review is to summarize current knowledge about nutritional patterns among patients with PAD and to ascertain whether certain health-promoting foods and nutrients could benefit patients with this condition.MethodsWe conducted a comprehensive literature review to examine primary source evidence for or against the nutrients that are commonly associated with PAD and their potential utility as therapies.ResultsWe summarized nine categories of nutrients, as well as four diets endorsed by the American Heart Association that may be prescribed to patients with or at risk for PAD. The nutrients reviewed included omega-3 polyunsaturated fatty acids (n-3 PUFAs), folate and B-series vitamins, and antioxidants. The diet plans described include the Dietary Approaches to Stop Hypertension (DASH) diet, Mediterranean diet, low-fat diet, low carbohydrate diet, Dr Dean Ornish's Spectrum Diet and Dr Andrew Weil's Anti-Inflammatory Diet.ConclusionsPAD is a chronic inflammatory condition that is associated with longstanding poor nutrition habits. We advocate for an intensified use of diet in PAD therapy, and we specifically recommend following eating patterns that are rich in nutrients with anti-inflammatory and antioxidant properties

Validation of a Russian Language Oswestry Disability Index Questionnaire.

Study Design Retrospective reliability and validity study. Objective To validate a recently translated Russian language version of the Oswestry Disability Index (R-ODI) using standardized methods detailed from previous validations in other languages. Methods We included all subjects who were seen in our spine surgery clinic, over the age of 18, and fluent in the Russian language. R-ODI was translated by six bilingual people and combined into a consensus version. R-ODI and visual analog scale (VAS) questionnaires for leg and back pain were distributed to subjects during both their initial and follow-up visits. Test validity, stability, and internal consistency were measured using standardized psychometric methods. Results Ninety-seven subjects participated in the study. No change in the meaning of the questions on R-ODI was noted with translation from English to Russian. There was a significant positive correlation between R-ODI and VAS scores for both the leg and back during both the initial and follow-up visits (p < 0.01 for all). The instrument was shown to have high internal consistency (Cronbach α = 0.82) and moderate test-retest stability (interclass correlation coefficient = 0.70). Conclusions The R-ODI is both valid and reliable for use among the Russian-speaking population in the United States

Structural and Synthetic Aspects of Small Ring Oxa- and Aza-Heterocyclic Ring Systems as Antiviral Activities

Antiviral properties of different oxa- and aza-heterocycles are identified and properly correlated with their structural features and discussed in this review article. The primary objective is to explore the activity of such ring systems as antiviral agents, as well as their synthetic routes and biological significance. Eventually, the structure–activity relationship (SAR) of the heterocyclic compounds, along with their salient characteristics are exhibited to build a suitable platform for medicinal chemists and biotechnologists. The synergistic conclusions are extremely important for the introduction of a newer tool for the future drug discovery program

Walking disability in patients with peripheral artery disease is associated with arterial endothelial function

ObjectivePatients with peripheral artery disease (PAD) have varying degrees of walking disability that do not completely correlate with ankle-brachial index (ABI) or angiographic anatomy. We hypothesized that endothelial function (EF) is an independent predictor of symptom severity in PAD patients.MethodsThis was a cross-sectional study of 100 PAD patients presenting to a vascular surgery clinic. All patients received ABI testing and brachial artery flow-mediated, endothelium-dependent vasodilation (FMD) to assess arterial EF. Symptom severity and walking disability reported by Rutherford category was based on the patient's self-report during the clinic visit and recorded by the investigator-vascular surgeons. Demographic, biochemical, and physiologic parameters were entered into regression equations to determine association with symptom severity.ResultsPatients were a mean age of 66 ± 8 years, and 43% had diabetes. Mean FMD was 7.4%, indicating impaired EF. EF progressively declined as Rutherford category increased (P = .01). Brachial artery FMD, ABI, systolic blood pressure, C-reactive protein, low-density lipoprotein, high-density lipoprotein, β-blocker use, and a history of diabetes or coronary artery disease were all associated with Rutherford category (all P < .05). Multivariable regression showed EF (P < .02) and ABI (P < .0001) were independently associated with walking disability. When the cohort was restricted to claudicant patients (n = 73), EF remained associated with walking disability after adjustment for other covariates (P = .0001).ConclusionsSymptom severity in PAD is multifactorial, reflecting impaired hemodynamics and vascular dysfunction. This is the first report demonstrating that walking disability in PAD is associated with arterial EF. The mechanistic link underlying these observations remains to be defined

Association between n-3 polyunsaturated fatty acid content of red blood cells and inflammatory biomarkers in patients with peripheral artery disease

ObjectiveThe n-3 polyunsaturated fatty acids are dietary components derived from fish oil with beneficial cardiovascular effects that may relate in part to anti-inflammatory properties. Peripheral artery disease (PAD) is characterized by a marked proinflammatory state. We hypothesized that the n-3 polyunsaturated fatty acids content of red blood cells (omega-3 index) would be correlated with biomarkers of inflammation and vascular function in a PAD cohort.MethodsThis was a cross-sectional study of subjects who presented to an outpatient vascular surgery clinic for evaluation of PAD. We used linear regression to evaluate the independent association between the omega-3 index, inflammatory biomarkers (C-reactive protein [CRP], intercellular adhesion molecule-1, interleukin-6, and tumor-necrosis-factor-α) and endothelial function (brachial artery flow mediated dilation).Results64 subjects (61 claudicants and three with critical limb ischemia) were recruited for the study. The mean CRP level was 5.0 ± 5.0 mg/L, and the mean omega-3 index was 5.0% ± 1.8%. In an unadjusted model, the omega-3 index was negatively associated with CRP (38% increase in CRP for one standard deviation decrease in the omega-3 index; P = .007), which remained significant after adjustment for age, body mass index, smoking, ankle-brachial index, and high-density lipoprotein (33%; P = .04). There was also evidence for independent associations between the omega-3 index and IL-6 (P = .001). There were no significant associations between the omega-3 index and vascular function tests.ConclusionsIn a cohort of patients with PAD, the omega-3 index was inversely associated with biomarkers of inflammation even after adjustment for covariates including the ankle-brachial index. Because patients with PAD have a high inflammatory burden, further studies should be conducted to determine if manipulation of omega-3 index via dietary changes or fish oil supplementation could improve inflammation and symptoms in these patients

Clinical correlates of red blood cell omega-3 fatty acid content in male veterans with peripheral arterial disease

ObjectiveDespite available medical therapies, patients with peripheral arterial disease (PAD) remain at high risk for cardiovascular events. The n-3 polyunsaturated fatty acids (PUFA), derived from marine sources, have been shown to improve cardiovascular mortality. The Omega-3 Index (O3I), a proportion of the n-3 PUFA eicosapentaenoic acid and docosahexaenoic acid in the red blood cell membrane, correlates with cardiovascular risk. Previous investigations have found that n-3 PUFA supplementation, fish consumption, older age, and smoking history affect the O3I in different patient populations, although similar correlations have never been explored in PAD. We hypothesized that in our PAD cohort, blood content of omega-3 fatty acids would directly and positively correlate with a history of fish oil supplementation and older age and inversely correlate with a smoking history and obesity.MethodsThis cross-sectional study included 111 patients who had an ankle-brachial index of <0.9 associated with claudication symptoms. We used linear regression to determine the association between clinical factors and the O3I.ResultsThe mean age of the cohort was 69 ± 8 years; 37% had diabetes mellitus (hemoglobin A1c, 7% ± 1%), and 94% reported current smoking or a history of smoking. The mean O3I was 5% ± 2%. In multivariate linear regression analysis, the O3I was associated with older age, increasing body mass index, and a history of smoking and fish oil intake.ConclusionsThis is the first report of the relation between blood content of omega-3 fatty acids and clinical factors in a PAD population. In patients with PAD, older age, elevated body mass index, and prior fish oil supplementation predicted a higher O3I. A history of smoking correlated with a lower O3I. These results demonstrate that the O3I is a reliable measure of dietary n-3 PUFA intake and that clinical factors related to the O3I in PAD are similar to those observed in other populations

Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Omega-3 Fatty Acid–Derived Mediators in Patients With Peripheral Artery Disease (the OMEGA-PAD I Trial)

Background: Patients with peripheral artery disease (PAD) experience significant morbidity and mortality. The OMEGA-PAD I Trial, a randomized, double-blinded, placebo-controlled trial, addressed the hypothesis that short-duration, high-dose n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation improves endothelial function and inflammation in PAD. Methods and Results: Eighty patients with stable claudication received 4.4 g of fish oil or placebo for 1 month. The primary end point was endothelial function as measured by brachial artery flow-mediated vasodilation. Secondary end points included biomarkers of inflammation, n-3 polyunsaturated fatty acids metabolome changes, lipid profile, and walking impairment questionnaires. Although there was a significant increase in FMD in the fish oil group following treatment (0.7±1.8% increase from baseline, P=0.04), this response was not different then the placebo group (0.6±2.5% increase from baseline, P=0.18; between-group P=0.86) leading to a negative finding for the primary endpoint. There was, however, a significant reduction in triglycerides (fish oil: −34±46 mg/dL, P<0.001; placebo −10±43 mg/dL, P=0.20; between-group differential P-value: 0.02), and an increase in the omega-3 index of 4±1% (P<0.001) in the fish oil group (placebo 0.1±0.9%, P=0.49; between-group P<0.0001). We observed a significant increase in the production of pathway markers of specialized pro-resolving mediators generated from n-3 polyunsaturated fatty acids in the fish oil group. Conclusions: High-dose, short-duration fish oil supplementation did not lead to a different response in the primary end point of endothelial function between the treatment and placebo group, but improved serum triglycerides and increased the production of downstream n-3 polyunsaturated fatty acids–derived products and mediators in patients with PAD. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01310270