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.     

Dietary intake of participants with peripheral artery disease and claudication

We compared the dietary intake of participants with peripheral artery disease (PAD) and claudication with diet recommendations of the National Cholesterol Education Program (NCEP) and dietary reference intake values recommended by the Institute of Medicine (IOM) of the National Academy of Sciences. Forty-six participants consumed a mean macronutrient composition of 17% protein, 51% carbohydrate, and 30% fat. Compared to the NCEP and IOM recommendations, few participants met the recommended daily intake for sodium (0%), vitamin E (0%), folate (13%), saturated fat (20%), fiber (26%), and cholesterol (39%). Participants with PAD and claudication have poor nutrition, with diets particularly high in saturated fat, sodium, and cholesterol, and low in fiber, vitamin E, and folate intakes. Participants should be encouraged to reduce consumption of dietary fat, saturated fat, cholesterol, and sodium and to increase fiber and vitamin intakes to meet recommendations of the NCEP and IOM.     

Dietary fatty acids and insulin resistance

High-fat diets have been associated with insulin resistance, a risk factor for both Type II diabetes and heart disease. The effect of dietary fat on insulin varies depending on the type of fatty acid consumed. Saturated fatty acids have been consistently associated with insulin resistance. On the other hand, medium and long-chain fatty acid intakes are associated with insulin sensitivity, as are high intakes of ϕ3 fatty acids. Trans fatty acids appear to potentiate insulin secretion, at least in the short-term, to a greater degree than cis fatty acids. This may reflect chronic alterations in insulin sensitivity, although this remains to be tested. In summary, although it must be emphasized that all diets high in fat cause insulin resistance relative to high-carbohydrate diets, it appears that dietary saturated, short-chain and ϕ6 fatty acids have the most deleterious effects on insulin action.     

Dietary fatty acids and the haemostatic system

Studies of the effects of dietary fatty acids on the haemostatic system, and their potential relevance for the thrombotic component of coronary heart disease (CHD), have a pedigree as long as those linking dietary fat, plasma lipoprotein metabolism and atheroma. Achievements have not been as impressive, however, partly owing to the relatively slow evolution of our understanding of the complicated physiology, biochemistry and pathology of haemostasis and fibrinolysis, which remains incomplete. Progress was also retarded up to 1980 by a general reluctance to acknowledge the pathogenic importance of thrombosis for myocardial infarction. Interest in dietary fat and the haemostatic mechanism re-emerged with reports of associations of haemostatic variables with plasma triacylglycerol levels and risk of CHD. This review summarises the history, focuses on evidence for dietary C18-unsaturated fatty acids as important determinants of factor VII (FVII) activation and plasminogen activator inhibitor type 1 (PAI-1) levels, and discusses possible underlying mechanisms involving ATP binding cassette (ABC) transporters and peroxisome proliferator-activated receptors. The potential relevance of these effects for CHD is discussed. In the presence of unstable atheromatous plaques, increased levels of activated FVII and PAI-1 induced by diets rich in mixtures of saturated and unsaturated fats may raise the risk of occlusive thrombosis in the event of plaque rupture.     

Dietary monounsaturated fatty acids and liver cholesterol

Evidence is accumulating that diets rich in monounsaturated fatty acids might be of value in the treatment of hypercholesterolemia and prevention of coronary heart disease. This communication shows that such diets cause increased concentrations of liver cholesterol in rats and rabbits. It is not known whether this effect is harmful. Caution is warranted in extrapolating the animal data to man, but the possibility that monounsaturated fatty acids increase liver cholesterol in man should be considered.     

Dietary fatty acids and kidney transplantation in the rat

In five groups of 15 rats allogeneic kidney transplantations were performed. Four groups received pre- and postoperatively a semisynthetic diet, isocalorically but differing in quantity and quality of fatty acids: group I received a diet high in saturated fat; group II, a diet high in linoleic acid; group III, a diet containing fish oil; group IV, a diet high in monoenoic acid. Finally, the fifth group of rats was fed a standard commercial chow and served as a control for the procedure of technique and immunological regimen. All groups received the same immunosuppressive regimen of immunological enhancement induced by pretreatment with complete donor blood. Survival and several parameters of graft function were studied. The results showed that the technical mortality, i.e. animals dying in the first week after transplantation, was substantially higher in rats on the semisynthetic diets in comparison with the group of rats on the commercial diet. A statistically significant better graft function could be observed in the group of rats on the diet high in linoleic acid in the first period after kidney transplantation, compared to the other groups on semisynthetic diets. This difference disappeared in the course of the study when a number of animals was lost due to graft rejection. Furthermore, in the same diet group mortality due to rejection was significantly decreased as well.     

Relation of omega-3 fatty acid and C-reactive protein to peripheral artery disease in patients with coronary artery disease

Eicosapentaenoic acid (EPA), a member of the omega-3 polyunsaturated fatty acid family, prevents cardiovascular disease. C-reactive protein (CRP) is a marker of inflammation, which promotes atherosclerosis. The aim of this study was to investigate the relationship among EPA, CRP, and the prevalence of peripheral artery disease (PAD), which is a manifestation of systemic atherosclerosis. A cross-sectional study was performed on 238 patients with coronary artery disease (CAD). Blood EPA and CRP levels and ankle-brachial pressure indices were measured. Cut-off values for plasma EPA levels and serum CRP levels were determined using receiver operating characteristic (ROC) analysis. Patients with ABIs ≤0.9 were defined as having PAD. EPA levels were significantly lower and CRP levels were significantly higher in patients with PAD than in those without [48 (26–77) vs. 58 (41–83) μg/ml, p = 0.026 and 3.3 (0.64–14.0) vs. 0.70 (0.32, 2.4) mg/l, p = 0.004]. Multivariate analysis for PAD revealed that high CRP levels and low EPA levels were significant and independent predictors of PAD [odds ratio 3.1 (95 % CI 1.4–6.9), p = 0.006 and odds ratio 4.9 (95 % CI 1.5–9.7), p = 0.004]. Furthermore, to predict PAD, adding high CRP levels and low EPA levels to the established risk factors significantly improved the area under the ROC curves, from 0.66 to 0.78, of the PAD prediction model (p = 0.004). A significant relationship among EPA, CRP, and PAD was confirmed in patients with CAD.     

Dietary N-3 polyunsaturated fatty acids decrease biliary cholesterol saturation in gallstone disease.

Because fatty acid composition of biliary phospholipids influences cholesterol secretion into bile, we investigated whether replacement of n-1 monounsaturated or n-6 polyunsaturated fatty acids with n-3 polyunsaturated fatty acids in biliary phosphatidylcholines reduces supersaturation with cholesterol and prevents precipitation of cholesterol crystals in bile of gallstone patients. Seven patients with radiolucent gallstones in functioning gallbladders were studied before (control) and after 5 wk of dietary supplementation with marine fish oil (11.3 gm/day = 3.75 gm n-3 polyunsaturated fatty acids/day). Duodenal bile was collected for analysis during intravenous infusion of cholecystokinin. Gallbladder emptying in response to cholecystokinin was comparable before and during intake of n-3 polyunsaturated fatty acids. Intake of n-3 polyunsaturated fatty acids increased (p less than 0.001) the fractions of eicosapentaenoic and docosahexaenoic acids and decreased the fractions of linoleic (p less than 0.001) and arachidonic acids (p less than 0.02) in biliary phospholipids. Concomitantly, the molar ratio of cholesterol to phospholipids decreased (-19%; p less than 0.05). As a consequence, the cholesterol saturation index was reduced by -25% (p = 0.01), from 1.60 +/- 0.44 to 1.24 +/- 0.38. However, in vitro nucleation time of duodenal bile was not prolonged. The decrease in cholesterol saturation was not sufficient to prevent nucleation of cholesterol crystals in bile of gallstone patients. In conclusion, our data suggest that cholesterol saturation can be influenced by the fatty acid composition of the phosphatidylcholines secreted in bile.     

Omega-6 fatty acids and coronary artery disease: The pros and cons

Polyunsaturated fatty acids have long been recommended as a beneficial substitute for atherogenic saturated fat. The connection between dietary lipids and blood cholesterol is still under debate, as is the connection between dietary fat and coronary artery disease. Thus, the lipid hypothesis is still a hypothesis. The major dietary polyunsaturated fatty acid, linoleic acid of the omega-6 family, has several properties that render it hyperinsulinemic and atherogenic. The potential benefits of linoleic acid intake regarding coronary artery disease, and its possible harms, are discussed.     

Dietary n-3 fatty acid intake and risk of sudden death and coronary artery disease

Opinion statement Based upon the data from observational epidemiologic studies and randomized clinical trials that are summarized in this article, as well as plausible mechanisms for benefit, the American Heart Association and several international health agencies recommend that all adults eat fish, particularly fatty fish, at least two times per week to lower risk of coronary heart disease (CHD). Patients with established CHD are advised to consume 1 g/d of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) combined. However, many individuals may find it difficult to consume 1 g/d of EPA and DHA, which translates into several meals of fish per week. Thus, fish oil in the form of supplements may be a preferable way to achieve compliance with these recommendations. Because only one large-scale secondary-prevention randomized trial of n-3 fatty acid supplements has been published to date, fish oil supplements have not been routinely recommended after myocardial infarction (MI). However, based upon the present evidence, this treatment option could be considered as one possible avenue to decrease risk of sudden cardiac death (SCD) in the early post-MI period when implantable cardioverter-defibrillator (ICD) therapy appears to be less efficacious. n-3 Fatty acid supplements are currently not indicated for prevention of recurrent ventricular arrhythmias in patients with ICDs due to the conflicting and primarily null randomized trial results in this patient population. Finally, based upon the current state of evidence, it is unclear whether dietary intake of α-linolenic acid (ALA), a plant-based intermediate-chain n-3 fatty acid, influences risk of CHD or SCD. Therefore, increasing intake of ALA specifically for the prevention of CHD cannot be recommended at this time.     

Altered erythrocyte n-3 fatty acids in Mediterranean patients with coronary artery disease

A low frequency of ischaemic heart diseases in Eskimos has been related to polyunsaturated fatty acids. We therefore studied fatty acid patterns associated with coronary artery disease (CAD) for a possible relationship between fatty acid profile and CAD diagnosis in Mediterranean patients. The gas chromatography method was used to analyze the membranes of patients' erythrocytes. The patients without coronary stenosis were used as controls. Patients with CAD showed increased percentages of saturated fatty acids (35.8 vs. 34.2%, P<0.001) and monounsaturated fatty acids (14.6 vs. 13.6%, P<0.01), as well as reduced percentages of polyunsaturated fatty acids (38.5 vs. 41.3%, P<0.001). The decrease in polyunsaturated fatty acids percentages was due to the series of n-3 fatty acids (9.2 vs. 11.4%, P<0.001), mainly at the expense of docosahexaenoic acid [C22:6 (n-3)] (4.9+/-0.25% vs. 6.4+/-0.23%, P<0.001) and docosapentaenoic acid [C22:5 (n-3)] (3.0+/-0.19% vs. 3.9+/-0.12%, P<0.001). The study shows altered n-3 fatty acids in Mediterranean patients with CAD. Our data suggest that the percentage of docosahexaenoic and docosapentaenoic acids in erythrocytes could be used as indicators of an independent risk factor for coronary artery disease.     

Medium-term outcomes for peripheral pulmonary artery stenting in adults with congenital heart disease

Objective: We describe our medium‐term outcomes for peripheral pulmonary artery stenting in adults with congenital heart disease. Background: Improved outcomes in congenital heart disease have lead to the evolution of transcatheter therapies in adults aimed at maintaining normal hemodynamics. Stenting for pulmonary artery narrowing is effective in children, however little is known about outcomes in adults. Methods: Retrospective data analysis and follow‐up review of our complete experience with peripheral pulmonary artery stenting in adults. Results: Over a 9‐year period we carried out 15 procedures, implanting 23 stents (11—left pulmonary artery) in the pulmonary arteries of 12 adult patients (7 female). Eleven patients had previous cardiac surgery. Median age at implantation was 32.5 years (range, 18.7–56.7 years) with median weight of 71.3 kg (range, 44.5–95 kg). Six patients underwent bilateral pulmonary artery stenting. Median procedure time was 140 minutes (range, 76–263 minutes) and 4 patients had other interventions performed during the same procedure. Median systolic pressure gradient across the narrowing's of 24 mmHg (range, 11–61 mmHg) was reduced to 3 mmHg (range, 0–17 mmHg) postprocedure (P < 0.001). Three patients had acute stent embolization, one of whom required surgical removal. No aneurysm formation or significant stent fractures have been noted on median follow‐up of 27.4 months (range, 1–97 months). Two patients required reintervention with further stent implantation. Conclusions: Pulmonary artery stenting provides effective relief of narrowing in adults with congenital heart disease. Bilateral and/or multiple stenting are often required. Stent embolization may occur particularly in patients with associated significant pulmonary regurgitation. (J Interven Cardiol 2011;24:373–377)     

Dietary omega-3 fatty acids prevent carbohydrate-induced hypertriglyceridemia

Dietary fish oils rich in omega-3 fatty acids are remarkably hypotriglyceridemic in both normal and hypertriglyceridemic subjects. This present study was designed to examine the hypothesis that dietary fish oils could prevent the usual sharp increase in plasma triglyceride and very low-density lipoprotein (VLDL) levels that occur physiologically after the induction by a high-carbohydrate diet. Seven healthy volunteers consumed three experimental liquid formula diets: the baseline diet (45% fat, 10% protein, 45% carbohydrate) and two high-carbohydrate diets (15% fat, 10% protein, 75% carbohydrate), one as a control diet and the other containing fish oil. The baseline and control dietary fats were a mixture of peanut oil and cocoa butter, whereas the fish oil diet contained high levels of omega-3 fatty acids. The plasma triglyceride levels rose from 105 mg/dL during baseline diet to 194 mg/dL during the high-CHO control diet (P less than 0.005). VLDL triglyceride levels increased from 69 to 156 mg/dL (P less than 0.005) and VLDL cholesterol from 18 to 34 mg/dL (P less than 0.005). When fish oil was substituted for the control fats, plasma triglyceride levels fell from 194 to 75 mg/dL (P less than 0.005), VLDL triglyceride and cholesterol levels were reduced from 156 to 34 mg/dL (P less than 0.005) and from 34 to 12 mg/dL (P less than 0.005), respectively. These effects were noted by two to three days after beginning the fish oil diet. Thus, dietary omega-3 fatty acids from fish oil rapidly and markedly reduced VLDL triglyceride levels even in the face of a high-carbohydrate diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary fibre and fatty acids in chronic obstructive pulmonary disease risk and progression: a systematic review

Dietary intake attracts increasing interest in the risk for and progression of chronic obstructive pulmonary disease (COPD). In particular, dietary fibre and fatty acids have drawn specific attention for their immunomodulating potential. The study aimed to review the current evidence on the potential roles of dietary fibre or fatty acid intake in the risk and progression of COPD. Pubmed, EMBASE, Cochrane Collaboration Database and conference databases for original studies in adults addressing the association between fibre or fatty acid intake and COPD in terms of risk, lung function and respiratory symptoms were searched. Nine articles were included of which four reported on dietary fibre and five on fatty acids. Data of studies could not be pooled because of methodological diversity. Greater intake of dietary fibre has been consistently associated with reduced COPD risk, better lung function and reduced respiratory symptoms. Results on the associations between fatty acids and COPD are inconsistent. Dietary quality deserves further attention in developing COPD prevention and management programs.