Dietary ellagic acid improves oxidant-induced endothelial dysfunction and atherosclerosis: role of Nrf2 activation.

BACKGROUND: Oxidative stress-induced vascular endothelial cell injury is a major factor in the pathogenesis of atherosclerosis. Several evidences indicate that ellagic acid (EA), a phenolic compound, contributes to cardiovascular health. This study was to investigate the effects of EA on endothelial dysfunction and atherosclerosis via antioxidant-related mechanisms. METHODS: In animal studies, wild-type (WT) C57BL/6 mice and apolipoprotein E-deficient mice (ApoE(-/-)) mice were fed: a high-fat (21%) diet (HFD) or a HFD plus with EA (HFD+EA), for 14weeks. Vascular reactivity was studied in mice aortas. The effect of EA in human umbilical vein endothelial cells (HAECs) exposed to hypochlorous acid (HOCl) was also investigated. RESULTS: Compared with animals on HFD alone, EA attenuated atherosclerosis in WT mice. In aortic rings from two mice models, EA significantly improved endothelium-dependent relaxation and attenuated HOCl-induced endothelial dysfunction. Besides, EA significantly improved nitric oxide synthase activity, antioxidant capacity and markers of endothelial dysfunction in plasma. Western blot analysis showed that EA increased NF-E2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) expression in the aortas (P<0.05). In a separate experiment, EA did not protect against HOCl-induced endothelial dysfunction in arteries obtained from Nrf2 gene knockout mice compared with WT mice. In HAECs, EA prevented HOCl-induced cellular damage and induced HO-1 protein expression, and these effects markedly abolished by the siRNA of Nrf2. CONCLUSIONS: Our results provide further support for the protective effects of dietary EA particularly oxidant-induced endothelial dysfunction and atherosclerosis partly via Nrf2 activation.

Omega-3 fatty acids do not improve endothelial function in virologically suppressed HIV-infected men: a randomized placebo-controlled trial.

Omega-3 fatty acids decrease cardiovascular disease (CVD) mortality possibly due to antiinflammatory effect. Inflammation and endothelial dysfunction likely play a role in the heightened CVD risk in HIV. Our goal was to evaluate the effect of omega-3 fatty acids primarily on endothelial function and inflammation in HIV-infected adults with moderate CVD risk on stable antiretroviral therapy. We conducted a 24-week, randomized, double-blind, placebo-controlled study to evaluate the effect of omega-3-acid ethyl esters 1 g twice a day. Flow-mediated dilation (FMD) of the brachial artery, lipoproteins and markers of inflammation, endothelial activation, coagulation, and insulin resistance were measured at entry and week 24. There were no within- or between-group differences in change in FMD over 24 weeks (mean change in FMD -0.13% vs. 1.5% for treatment vs. placebo; p=0.21). There were no between-group differences in changes in lipoprotein levels or biomarkers tested, except soluble tumor necrosis factor receptor-I, which favored omega-3-acid ethyl esters. Omega-3 fatty acids did not improve endothelial function or activation, coagulation, or insulin resistance in virologically suppressed, HIV-infected men with moderate CVD risk; however, inflammation tended to improve. This suggests that omega-3 fatty acids may not be potent enough to counteract the enhanced inflammation and endothelial dysfunction due to HIV and antiretrovirals.

[Why should vascular patients have a dietary assessment?]. / Pourquoi devons-nous évaluer l'alimentation des sujets à risque vasculaire ?

Vascular diseases are a major health problem in Western countries. Coronary heart disease (CHD), stroke, and peripheral arterial disease (PAD) share many common risk factors such as age, smoking, dyslipidemia, and diabetes. Although the dietary pattern is considered as a risk factor for CHD, the impact of dietary pattern on stroke and PAD is debated. However, new studies showed that dietary pattern could also be considered as a risk factor in stroke and PAD. Dietary pattern should be evaluated in vascular patients and new tools of dietary assessment must be developed for a better prevention of vascular disease.

Evaluación de la ingesta de grasas y minerales en un grupo de ciclistas de equipos juvenil y sub-23 / Evaluation of fat and mineral intake by a group of cyclists belonging to junior and sub-23 teams

Introducción. El propósito fue determinar si un equipo de 34 ciclistas españoles jóvenes sigue las pautas recomendadas en la ingesta de macronutrientes (principalmente grasas) y minerales (sodio, calcio, potasio y magnesio). Una dieta desequilibrada a largo plazo está asociada a enfermedades crónicas tales como obesidad, dislipemias, arteriosclerosis e hipertensión arterial (HTA). Es fundamental la formación nutricional de los jóvenes promoviendo hábitos saludables y también una alimentación que favorezca el rendimiento deportivo a corto plazo. Material y método. Evaluación nutricional basada en la ingesta reportada en un cuestionario de 7 días consecutivos. Resultados. Un porcentaje de los ciclistas estudiados consume cantidades excesivas de colesterol (94% de los ciclistas), grasas saturadas, ácido grasos saturados (74%) y sodio (47%), mientras que no consumen las cantidades recomendadas de calcio (29%), magnesio (10%) y potasio (44%). Esta misma tendencia se ha observado en la población general de jóvenes españoles del estudio en Kid. Conclusiones. Este trabajo ha contribuido a un mejor conocimiento de la dieta que siguen jóvenes que son muy activos físicamente. La dieta que sigue un porcentaje de los ciclistas jóvenes estudiados presenta desequilibrios nutricionales (excesivo consumo de grasas y sodio), que se deben corregir educando no solamente a los ciclistas, sino también a los padres y entrenadores. Se debe fomentar la correcta hidratación con electrolitos y la dieta mediterránea, rica en vegetales, frutas, pescado y aceite de oliva, lo que proporciona la cantidad adecuada de grasas monoinsaturadas (AGM) y poliinsaturadas (AGP) que protegen el sistema cardiovascular (AU)

Introduction. The aim of this study was to determine whether 34 young Spanish males belonging to Junior and Sub-23 cycling teams followed recommendations for optimal macronutrient (mainly fats) and mineral (sodium, calcium, potassium and magnesium) intake. In the long term, an unbalanced diet has been associated with chronic diseases such as obesity, dyslipidemia, atherosclerosis, and hypertension. Promotion of nutritional education is essential to achieve good nutritional practices in the long term, while precompetition diets aiming to improve the sporting performance of young cyclists are important in the short term. Material and method. Nutritional evaluation was based on the intake reported over 7 consecutive days in a questionnaire. Results. A percentage of the cyclists studied consumed excessive quantities of cholesterol (94% of cyclists), saturated fats (74%), and sodium (47%) and did not consume the recommended quantities of calcium (29%), magnesium (10%) and potassium (44%). The same nutritional pattern was found in young Spanish males in the EnKid study. Conclusions. The present study increases knowledge of the diets followed by highly active young Spanish males. A percentage of these cyclists followed unbalanced diets (excessive intake of fats and sodium) that should be modified by educating not only the cyclists, but also their parents and coaches. Adequate hydration (water and electrolytes) and the Mediterranean diet, rich in vegetables, fruits, fish and olive oil, should be promoted to ensure appropriate intake of fats (monounsaturated and polyunsaturated fatty acids) to protect the cardiovascular system (AU)

Óxidos de colesterol en alimentos cocinados con presencia habitual en nuestra dieta / Cholesterol oxidation products in common cooked foods

Los productos de oxidación del colesterol (COPs) poseen demostrados efectostóxicos y están implicados en el desarrollo de aterosclerosis. Pueden estar presentesen organismos animales y por ende, en alimentos de origen animal, siendosusceptibles de ser absorbidos a través de la dieta. Su formación en los alimentosse favorecería, al tratarse de un proceso de oxidación química, por la elevación dela temperatura y la presencia de oxígeno. En este trabajo se presenta una estimaciónde la presencia de COPs en diferentes tipos de alimentos cocinados mediantediferentes tecnologías culinarias y almacenados mediante distintas modalidades deconservación. El análisis se llevó a cabo por cromatografía de gases-espectrometríade masas. Tanto pescados (salmón y langostinos) como carnes (hamburguesas,pechugas de pollo, lomo y salchichas tipo frankfurt) mostraron valores bajos deCOPs en crudo (0.003-0.552 mg/100 g alimento), incrementándose significativamentetras el cocinado (hasta 0.7 mg/100 g alimento). El cocinado con microondassupuso el mayor incremento de COPs en comparación con la fritura, plancha yasado. El almacenamiento a vacío disminuyó drásticamente la formación de COPs respecto al almacenamiento en aerobiosis. La congelación ralentizó más eficazmentela formación de COPs que la refrigeración

Cholesterol oxidation products (COPs) have shown different toxic effects andare involved in the development of atherosclerosis. These compounds can be foundin animal organisms, and inconsequence in animal origin foods, and they aresusceptible to be absorbed from the diet. Their formation in foods would be increasedby high temperatures and the presence of oxygen, as it is a chemicaloxidation process. In this paper, an estimation of the presence of COPs in differenttypes of foods treated by different cooking technologies are shown. Also differentstorage conditions are studied. The analysis was carried out by gas chromatography-mass spectrometry. Both fish (salmon and shrimps) and meat (hamburgers,breast chicken, pork loin and frankfurters) showed low COPs values in raw products(0.003-0.552 mg/100 g food), increasing significantly after the application ofcooking technologies (up to 0.7 mg/100 g food). Microwave treatment leaded to thehighest increase of COPs in comparison to frying, grilling and roasting. Vacuumstorage dramatically decreased COPs formation with regard to aerobic storage.Freezing minimized COPs formation more efficiently than refrigeration

Plasma fibrinogen concentration in pediatric patients treated with an elimination diet based on soy proteins and casein hydrolyzate.

PURPOSE: Fibrinogen is one of the most discussed new risk factors of atherosclerosis. The aim of the study was to assess the relationship between fibrinogen concentration and classic risk markers of atherosclerosis in a group of children aged from 2 to 6 with or without a family history of circulatory system diseases (FHCAD) (American Academy of Pediatrics--AAP criteria). The study also considered the impact of allergies/food intolerance treatment with elimination diets on the concentration of atherosclerosis markers specially fibrinogen. INCLUSION CRITERIA: a) family history of early occurrence of circulatory system diseases (FHCAD+) according to AAP standards; b) the type and duration of elimination diet continued in infancy and early childhood. 134 of 388 children were included in the investigation. RESULTS: The analysis of data relating to the so-called classic biochemical risk factors of atherosclerosis (total cholesterol--TC, HDL, LDL, triglycerides, glucose) did not reveal any differences between the tested groups. It was found that in the FHCAD+ group the concentration of fibrinogen was statistically higher than in the group with a negative family history. It was discovered that the type of elimination diet had no effect on fibrinogen level in the FHCAD+ group. In the group of children with negative family history the concentration of fibrinogen was statistically lower in the group on casein hydrolysate than in children treated with soy formula. CONCLUSIONS: The initial interview in pediatrics should include information on the patient's family history of atherosclerosis. In case of a positive family history, fibrinogen, as one of atherosclerosis risk factors, should be monitored.

Terapia dietética para la hipercolesterolemia en niños y adolescentes / Dietary treatment for hipercolesterolemia in children and adolescents

Objetivo: Determinar la eficacia de la restricción dietética en un grupo de niños y adolescentes con hipercolesterolemia. Diseño. Estudio prospectivo de intervención. Participantes. 265 niños y adolescentes de ambos sexos, con edades comprendidas entre los 2 y los 13 años diagnosticados de hipercolesterolemia. Todos ellos fueron tratados con restricción dietética mediante las dietas fase 1 o fase 2 de la Asociación Americana de Cardiología. El período de seguimiento osciló entre 5 y 15 años. Resultados. Los niveles de colesterol total, colesterol LDL, apolipoproteína B-100, apolipoproteína A y triglicéridos, descendieron significativamente (P<0,0001). El cociente colesterol LDL/colesterol HDL descendió significativamente. Conclusiones. El tratamiento dietético es efectivo en el tratamiento de la hipercolesterolemia en niños y adolescentes. La restricción dietética tiene un efecto beneficioso, no sólo en los niveles de colesterol total y LDL colesterol, sino también en los niveles de apolipoproteínas A-I y B-100 (AU)

Objective. To determine the effectiveness of dietary restriction in a group of children and adolescents with hypercholesterolemia. Research design. Intervention prospective study. Participants. Two hundred sixty-five children and adolescents of both sexes age 2 to 13 years diagnosed as having hypercholesterolemia. All to them were treated with dietary restriction (American Heart Association Step-One and Step Two Diets). The follow-up period ranged from 5 to 15 years. Results. Total cholesterol, low-density lipoprotein cholesterol, triglycerides and apolipoproteins A and B levels decreased significantly (p<0.0001). Low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio decreased significantly (p<0.0001). Conclusions. Diet therapy is effective in the treatment of hypercholesterolemia in children and adolescents. Dietary restriction has a beneficial effect not only on total cholesterol and low-density lipoprotein cholesterol levels but also on apolipoprotein A-I and B -100 levels (AU)

Weight loss associated with reduced intake of carbohydrate reduces the atherogenicity of LDL in premenopausal women.

The effect of a 3-tier intervention including dietary modifications (ie, moderate energy restriction, decreased carbohydrate, increased protein), increased physical activity, and the use of carnitine as a dietary supplement was evaluated on plasma lipids and the atherogenicity of low-density lipoprotein (LDL) particles in a population of overweight and obese premenopausal (aged 20-45 years) women. Carnitine or a placebo (cellulose) was randomly assigned to the participants using a double-blind design. Carnitine supplementation was postulated to enhance fat oxidation resulting in lower concentrations of plasma triglycerides. Seventy women completed the 10-week protocol, which followed a reduction in their energy intake by 15% and a macronutrient energy distribution of 30% protein, 30% fat, and 40% carbohydrate. In addition, subjects increased the number of steps taken per day by 4500. As no differences were observed between the carnitine and placebo groups in all the measured parameters, all subjects were pooled together for statistical analysis. Participants decreased (P<.01) their caloric intake (between 4132.8 and 7770 kJ) and followed prescribed dietary modifications as assessed by dietary records. The average number of steps increased from 8950+/-3432 to 12764+/-4642 (P<.001). Body weight, plasma total cholesterol, LDL cholesterol, and triglyceride were decreased by 4.5%, 8.0%, 12.3%, and 19.2% (P<.0001), respectively, after the intervention. Likewise, apolipoproteins B and E decreased by 4.5% and 15% (P<.05) after 10 weeks. The LDL mean particle size was increased from 26.74 to 26.86 nm (P<.01), and the percent of the smaller LDL subfraction (P<.05) was decreased by 26.5% (P<.05) after 10 weeks. In addition, LDL lag time increased by 9.3% (P<.01), and LDL conjugated diene formation decreased by 23% (P<.01), indicating that the susceptibility of LDL to oxidation was decreased after the intervention. This study suggests that moderate weight loss (<5% of body weight) associated with reduced caloric intake, lower dietary carbohydrate, and increased physical activity impacts the atherogenicity of LDL.

Dietary copper supplements modulate aortic superoxide dismutase, nitric oxide and atherosclerosis.

The objective was to test the hypothesis that dietary copper inhibits atherosclerosis by inducing superoxide dismutase (SOD) and potentiating nitric oxide (NO). New Zealand White rabbits were fed either a cholesterol diet (n = 8) or a cholesterol diet containing 0.02% copper acetate (n = 8) for 13 weeks. We found that the intimal area was significantly smaller in the animals supplemented with copper (P < 0.005), although integrated plasma cholesterol levels were not significantly different. This was associated with a significant increase in aortic copper content (P < 0.05), SOD activity (P < 0.05) and Cu/Zn SOD mRNA (P < 0.05) and a significant decrease in nitrotyrosine content (P < 0.05). Furthermore, there was a positive correlation between aortic copper content and SOD activity (P < 0.005, R(2) = 0.83) and a negative correlation between aortic superoxide dimutase activity and nitrotyrosine content (P < 0.005, R(2) = 0.93). In organ bath experiments, the relaxation of precontracted carotid artery rings to calcium ionophore was greater in animals supplemented with copper. No difference in response to sodium nitroprusside was observed. These data suggest that in the cholesterol-fed rabbit, copper supplements inhibit the progression of atherosclerosis by increasing SOD expression, thereby reducing the interaction of NO with superoxide, and hence potentiating NO-mediated pathways that may protect against atherosclerosis.

The case for dietary calcium restriction in patients with atherosclerosis.

An increasingly vast set of data is linking the process of vascular calcification to the metabolism of calcium and phosphorus. This phenomenon is already relatively well understood in renal failure patients. A similar phenomenon, however, could be taking place in the general population. This may indicate a need for a reassessment of calcium supplementation, including the ingestion of milk, not only in dialysis patients, but also in patients with preserved renal function. Given the fact that no clear prospective randomized evidence exists to show what may be the impact on prognosis of patients with atherosclerosis, caused by the ingestion of milk and milk derivatives, containing calcium and lactose, as is currently recommended to prevent bone disease in the general population, a case could be made to recommend restriction of such dietary products in atherosclerosis patients, until precise data have been obtained, in controlled, prospective studies, and especially so in patients with no evidence of osteoporosis. Such a case would not be a strong one at the present stage, but neither would be the opposite view. The recommendation that could be made at this stage would be that patients with significant atherosclerotic disease should be informed that the ingestion of milk, and calcium supplementation in general, has neither been conclusively proven to be safe, nor the opposite.

Animales de experimentación utilizados como modelos en la investigación de la arteriosclerosis / Experimental animals used as models in arteriosclerosis research

La presente revisión aborda el metabolismo lipoproteico comparado y la inducción de la aterosclerosis con sus controversias en varios modelos animales pertenecientes a un amplio espectro evolutivo que abarca desde los roedores (ratón, conejo, rata, hámster, cobaya), las aves (paloma), los cetartiodáctilos (cerdo) y los carnívoros (perro) hasta los primates (macacos, Rhesus, mono verde africano) (AU)

Current review presents an overview of the compared lipoprotein metabolism and atherosclerosis development and their controversies in several animal models covering a wide phylogenetic spectrum. Orders are rodents (mice, rabbits, rats, hamsters, guinea pigs), birds (pigeons), cetartiodactyla (pigs), carnivores (dogs) and primates (macaques, Rhesus, African green monkey) (AU)

Apolipoprotein E promotes the regression of atherosclerosis independently of lowering plasma cholesterol levels.

OBJECTIVE: The mechanisms by which apolipoprotein E (apoE) can promote the regression of atherosclerosis are not well understood. This study examined whether apoE can promote atherosclerosis regression independently of lowering plasma cholesterol levels. METHODS AND RESULTS: We studied hypomorphic apoE mice (Apoe(h/h)), which express an apoE4-like form of mouse apoE at approximately 2% to 5% of normal levels in plasma and are normolipidemic. After 18 weeks of diet-induced hypercholesterolemia, which resulted in advanced aortic atherosclerotic lesions composed of a lipid-rich layer of foam cells covering a fibrotic core, 2 groups of mice were fed a chow diet for 16 weeks. One group continued to express low levels of apoE; the other was induced to express physiological levels of plasma apoE by Cre-mediated recombination of the hypomorphic Apoe allele. In both groups, plasma cholesterol levels fell rapidly to similar levels, and histological analysis at 16 weeks revealed elimination of the foam-cell layer. However, physiological levels of plasma apoE also enhanced the removal of neutral lipids from the fibrotic cores. CONCLUSIONS: These findings demonstrate for the first time that apolipoprotein E promotes the regression of atherosclerosis independently of lowering plasma cholesterol levels. Using Apoeh/hMx1-Cre mice we have begun to address apolipoprotein E-mediated mechanisms of atherosclerosis regression. We report the existence of a cholesterol-independent role of apolipoprotein E in atherosclerosis regression. This mechanism is critical for lipid removal from the fibrotic component of the plaque but not from the foam cell-rich layer beneath the endothelium.

Effect of low dose atorvastatin versus diet-induced cholesterol lowering on atherosclerotic lesion progression and inflammation in apolipoprotein E*3-Leiden transgenic mice.

OBJECTIVE: To evaluate whether low-dose atorvastatin suppresses atherosclerotic lesion progression and inflammation in apolipoprotein E*3 (apoE*3)-Leiden mice beyond its cholesterol-lowering effect. METHODS AND RESULTS: ApoE*3-Leiden mice were fed a high-cholesterol (HC) diet until mild atherosclerotic lesions had formed. Subsequently, HC diet feeding was continued or mice received HC supplemented with 0.002% (w/w) atorvastatin (HC+A), resulting in 19% plasma cholesterol lowering, or mice received a low-cholesterol (LC) diet to establish a plasma cholesterol level similar to that achieved in the HC+A group. HC+A and LC diet reduced, significantly and to the same extent, lesion progression and complication in the aortic root, as assessed by measuring total atherosclerotic lesion area, lesion severity, and macrophage and smooth muscle cell area. In the aortic arch, HC+A but not LC blocked lesion progression. HC+A and LC reduced vascular inflammation (ie, expression of macrophage migration inhibitory factor , plasminogen activator inhibitor- 1, matrix metalloproteinase-9), but HC+A additionally suppressed vascular cell adhesion molecule-1 expression and, in parallel, monocyte adhesion. In contrast, low-dose atorvastatin showed no antiinflammatory action toward hepatic inflammation markers (serum amyloid A, C-reactive protein [CRP]) in apoE*3-Leiden mice and human CRP transgenic mice. CONCLUSIONS: Low-dose atorvastatin cholesterol-dependently reduces lesion progression in the aortic root but shows antiinflammatory vascular activity and tends to retard atherogenesis in the aortic arch beyond its cholesterol-lowering effect.

Conjugated linoleic acid isomer effects in atherosclerosis: growth and regression of lesions.

Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers of octadecadienoic acid, has been shown to inhibit experimentally induced atherosclerosis in rabbits and also to cause significant regression of pre-established atheromatous lesions in rabbits. The two major CLA isomers (cis9,trans11 and trans10,cis12), now available at 90% purity, have been tested individually for their anti-atherogenic or lesion regression potency. The two major isomers and the mixture were fed for 90 d to rabbits fed 0.2% cholesterol. Atherosclerosis was inhibited significantly by all three preparations. The two CLA isomers and the isomer mix were also fed (1.0%) as part of a cholesterol-free diet for 90 d to rabbits bearing atheromatous lesions produced by feeding an atherogenic diet. A fourth group was maintained on a cholesterol-free diet. On the CLA-free diet atherosclerosis was exacerbated by 35%. Reduction of severity of atheromatous lesions was observed to the same extent in all three CLA-fed groups. The average reduction of severity in the three CLA-fed groups was 26 +/- 2% compared with the first control (atherogenic diet) and 46 +/- 1% compared with the regression diet. Insofar as individual effects on atherosclerosis were concerned, there was no difference between the CLA mix and the cis9,trans11 and trans10,cis12 isomers. They inhibit atherogenesis by 50% when fed as a component of a semipurified diet containing 0.2% cholesterol; and when fed as part of a cholesterol-free diet, they reduce established lesions by 26%. Reduction of atheromata to the observed extent by dietary means alone is noteworthy.

A dietary and exercise intervention slows menopause-associated progression of subclinical atherosclerosis as measured by intima-media thickness of the carotid arteries.

OBJECTIVES: The object of this study was to assess the effects of menopause and a diet/exercise intervention on subclinical atherosclerosis progression. BACKGROUND: Subclinical atherosclerosis has been linked to higher coronary heart disease and stroke rates and is greater among postmenopausal women according to cross-sectional analyses. Whether menopause is associated with an accelerated progression of subclinical disease is unknown, as is the extent to which lifestyle intervention can alter the course of progression. METHODS: Intima-media thickness (IMT) measures of the common carotid artery (CCA), internal carotid artery (ICA), and bulb segments of the carotid arteries were measured twice during the course of 4 years in 353 women from the Women's Healthy Lifestyle Project, a dietary and exercise clinical trial designed to prevent adverse risk factor changes through the menopause. A third measure was obtained 2.5 years later for 113 women. RESULTS: The progression of IMT was observed for the average of all segments (AVG), the CCA, and the bulb (0.007 mm/year, 0.008 mm/year, and 0.012 mm/year; p < 0.01 for all), but not for the ICA. Among controls, menopause was associated with accelerated IMT progression (0.003 mm/year for premenopausal women vs. 0.008 mm/year for perimenopausal/postmenopausal women for AVG IMT; p = 0.049). Additionally, among the 160 perimenopausal/postmenopausal women, the intervention slowed IMT progression (0.008 mm/year for the control group vs. 0.004 mm/year for the intervention group for AVG IMT; p = 0.02). Similar results were found for the CCA and bulb segments. CONCLUSIONS: These data demonstrate that the menopause transition is associated with accelerated subclinical atherosclerosis progression and that a diet/exercise intervention slows menopause-related atherosclerosis progression.

Fisiopatologia e fatores de risco ligados à aterotrombose / Pathophysiology and risk factors linked to atherothrombosis

Grande parte da morbidade e mortalidade nos países ocidentais é devido à doença cardiovascular, sendo que se destaca, pela freqüência e gravidade, a doença arterial coronária. Na maioria dos casos, uma ou mais artérias coronárias sofrem processo aterosclerótico, sobre o qual se assesta um trombo, precipitando o evento agudo - daí a denominação aterotrombose para o quadro.Em geral, o desenvolvimento do processo aterotrombótico tem a seguinte seqüência: disfunção endotelial, aderência e infiltração de monócitos à parede arterial, penetração de partículas de LDL (lipoproteínas de baixa densidade), formação da estria gordurosa, lesão gelatinosa, placa fibrosa, ulceração e trombose. Esta última pode obstruir parcial ou totalmente a luz do vaso, levando ou não ao quadro clínico agudo e, eventualmente, ao crescimento da placa aterosclerótica. Há anos foram reconhecidos os denominados fatores de risco, atributos de cada indivíduo que predispõem ao processo aterotrombótico. Seu reconhecimento e controle permite a prevenção do desenvolvimento ou a progressão da doença aterotrombótica. Importante salientar que é comum a presença, no mesmo indivíduo, de mais de um fator de risco, o que traz muitas vezes potencialização de seu efeito deletério. Daí a necessidade da avaliação global de risco...

Increased alpha-linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis.

OBJECTIVE: To investigate the effects of increased alpha-linolenic acid (ALA)-intake on intima-media thickness (IMT), oxidized low-density lipoprotein (LDL) antibodies, soluble intercellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and interleukins 6 and 10. DESIGN: Randomized double-blind placebo-controlled trial. SUBJECTS: Moderately hypercholesterolaemic men and women (55 +/- 10 y) with two other cardiovascular risk factors (n = 103). INTERVENTION: Participants were assigned to a margarine enriched with ALA (fatty acid composition 46% LA, 15% ALA) or linoleic acid (LA) (58% LA, 0.3% ALA) for 2 y. RESULTS: Dietary ALA intake was 2.3 en% among ALA users, and 0.4 en% among LA users. The 2-y progression rate of the mean carotid IMT (ALA and LA: +0.05 mm) and femoral IMT (ALA:+0.05 mm; LA:+0.04 mm) was similar, when adjusted for confounding variables. After 1 and 2 y, ALA users had a lower CRP level than LA users (net differences -0.53 and -0.56 mg/l, respectively, P < 0.05). No significant effects were observed in oxidized LDL antibodies, and levels of sICAM-1, interleukins 6 and 10. CONCLUSIONS: A six-fold increased ALA intake lowers CRP, when compared to a control diet high in LA. The present study found no effects on markers for atherosclerosis. SPONSORSHIP: The Dutch 'Praeventiefonds'.