Common risk factors for CVD such as hyperlipidaemia, hypertriglyceridemia, low HDL-C, obesity, insulin resistance, impaired glucose tolerance, inflammation and hypertension may increase the risk of atherosclerosis through altering vascular function. Modification of dietary intake and weight loss can ameliorate these risk factors and may impede the development of atherosclerosis. CVD risk can be assessed by measurement of both traditional e.g. lipid levels, glucose and blood pressure and novel risk markers of CVD e.g. FMD, levels of adhesion molecules, inflammatory markers and adipokines. Changes in these measurements are used to determine effects, if any, of dietary interventions. The studies in this thesis focus on the relationship between nutrition and vascular function and the effects of modifying dietary composition either with, or without weight loss. The primary hypotheses addressed were that a high saturated fat diet would have adverse effects on markers of CVD risk., that short and long term weight loss would have beneficial effects on these markers, that a conventional low fat, high glycaemic load diet would also have adverse effects on these markers and that weight loss would attenuate the BP response to salt. Six studies were conducted to address these hypotheses. The effects of saturated fat were investigated in chapters 3 and 6. In chapter 3, a high saturated fat diet impaired FMD and increased the level of the adhesion molecule Pselectin compared with a high MUFA, a high PUFA, or a low fat, high glycaemic load diet in weight stability. The high fat, high glycaemic load caused increases of 23-39% in TG and decreases of 10-15% in HDL-C but despite these adverse effects there was no change in FMD. In chapter 6, subjects on a very low carbohydrate/high saturated fat diet lost approximately 1 kg more weight over 8 weeks than those on a conventional low fat diet. While other CVD risk factors, glucose, insulin, E and P-selectin, ICAM-1 and PAI-1 levels all improved FMD did not change in either diet. Reductions in LDL-C and CRP were greater on the conventional diet. The effects of weight loss on CVD risk factors were also investigated in the studies in chapters 4, 5, 7 & 8. In chapter 4, moderate weight loss using 2 different low fat diets resulted in improvements in PAI-1 and sICAM-1 but there was no change in FMD. Similarly in chapter 5 weight loss on a low carbohydrate/low saturated fat diet did not change FMD but there were other benefits including reductions in glucose and insulin, LDL-C, adhesion molecules, VCAM1 and ICAM1. Adiponectin did not change after short term weight loss in either of the studies in chapters 5 or 6. In chapter 7 salt loading increased ambulatory day time BP and this response was not altered by short term moderate weight loss. The long term effects of weight loss were investigated in chapters 5, 7 and 8. In chapter 5, after 52 weeks, there was sustained weight loss of 5% but no change in FMD while adiponectin levels increased and LDL-C and insulin were substantially reduced. In chapter 7 the BP response to salt loading remained unchanged despite weight loss maintenance. Finally in chapter 8 weight loss was predicted by protein intake and there were reductions in CVD risk demonstrated by decreases in insulin, TG and CRP and increases in HDL-C. The studies in this thesis demonstrate that moderate weight loss has beneficial effects on traditional and novel cardiovascular disease risk markers but does not have a beneficial effect on FMD regardless of dietary composition. A high saturated fat diet has detrimental effects on novel CVD risk markers in weight stability but weight loss attenuates this effect. A high saturated fat diet may have detrimental effects on adhesion molecules in weight stability and may attenuate the beneficial effects of weight loss on LDL-C and CRP. Moderate long term weight loss maintenance has beneficial effects on most but not all CVD risk markers. / http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1293779 / Thesis (Ph.D.) -- School of Medicine, 2007

Ischaemia reperfusion injury (IR-injury) occurs when blood supply to a certain area of the body is blocked, and is subsequently followed by reperfusion. During the period of ischaemia, tissue is damaged as a result of lack of oxygen. Rapid reperfusion is mandatory, but unfortunately causes damage in addition to the damage induced by ischaemia alone. While a prolonged period of ischaemia is harmful to the bodily tissue, short periods of ischaemia interspersed with short bouts of reperfusion have protective effects. This mechanism is called ischaemic preconditioning (IPC). In this thesis, the impact of co-morbidity and age on IR-injury and IPC are explored. Moreover, the possible role of IPC to enhance exercise performance is investigated. Finally an attempt is made to understand the interchangeable effects of IPC and exercise performance in the prevention of IR-injury. Using the brachial artery endothelial function as a surrogate marker, first the consequences of IR-injury in both young and older individuals on endothelial function were studied. It was also assessed whether IPC could prevent endothelial IR-injury. It was found that endothelial function in both groups declined, when IR-injury was not preceded with IPC. However, when IPC was applied prior to IR-injury, a protective effect was detected in young subjects, but not in older participants. In chapter 5, this study was repeated in patients with heart failure, as they are at an increased risk for IR-injury. While in both groups a significant decline in endothelial function was observed, a much larger decline was established in the heart failure group. Moreover, IPC failed to protect against endothelial dysfunction in heart failure patients after IR-injury. The third study presented in this thesis, focused on the question whether exercise performance enhancement during a 5-km time trial was comparable when IPC on the upper legs was applied immediately before the time trial versus 24 hours (24-IPC) prior to exercise. Interestingly, a significant and strong correlation was found in finish time between acute IPC and 24-IPC, suggesting comparable effects of IPC and 24-IPC on exercise performance. In a follow-up study, it was determined whether local IPC applied on the upper arm, or remote IPC applied on the legs, would lead to an improved maximum incremental arm crank exercise test in individuals with a complete spinal cord lesion. The main finding was that upper arm IPC led to an increased performance enhancement, whilst remote IPC (stimulus below the lesion) did not lead to any significant differences. These studies help to inform the best or most practical application of IPC in daily life situations. Some previous work has suggested that exercise may resemble some of the effects of IPC. More specifically, acute exercise might possess the same protective effects against ischaemia-reperfusion injury as IPC. Therefore, in young healthy individuals it was studied, whether an acute bout of endurance or interval exercise is able to protect against brachial endothelial IR-injury. It was established that interval exercise prevented endothelial dysfunction after an IR stimulus, while no protective effect of endurance exercise was found. It was concluded that interval exercise, but not endurance exercise, prevented endothelial dysfunction after an ischaemic period. In conclusion, this thesis provides further evidence for the protective effects of (remote) IPC, both on the prevention of endothelial IR-injury as well as improvement in exercise performance. However, effects may depend on the protocol and population studied.

Rheumatoid arthritis (RA) is a chronic disabling disease that is associated with a shortened life span. Cardiovascular disease (CVD) contributes to this increased mortality, and also to a great extent to the co-morbidity observed in patients with RA. This thesis aimed to investigate these issues further. The incidence of, and prognosis after an acute myocardial infarction (AMI) /or stroke in a cohort of RA patients was compared with that in the general population within the northern Sweden MONICA register. The standard incidence ratio (SIR) for AMI was 2.9 and for stroke 2.7 in RA patients compared with the general population (p<0.05 for both). During the first 10 years following an event, RA patients had a higher overall case fatality (CF) compared with controls (HR for AMI=1.67, 95%CI [1.02, 2.71], HR for stroke=1.65, 95%CI [1.03, 2.66]). An elevated level of homocysteine is regarded to be a risk marker for CVD. The effects of treatment with B vitamins on the homocysteine level in patients with RA were studied in a consecutive cohort of patients with RA. Sixty-two patients with RA having a homocysteine level of 12 mol were randomized to receive either a placebo or a combination of the vitamins B6, B12 and folic acid. The patients were treated and evaluated in a double-blind manner over 12 months. The homocysteine level was found to be significantly decreased in the B-vitamin treated patients compared with the placebo group (p<0.0001). To evaluate the progression of sub-clinical atherosclerosis in patients with very early RA compared with controls, all patients from the three most northern counties of Sweden newly diagnosed with RA and aged ≤60 years were consecutively recruited. Age and sex matched controls from the general population were also included. Intima media thickness (IMT) of the common carotid artery and endothelium dependent flow mediated dilation (ED-FMD) of the brachial artery were measured using ultrasonography. After 18 months the same measurements were undertaken in a sub-group of the patients with early RA and the relevant controls. There were no differences between patients with early RA and controls in terms of IMT or ED-FMD at inclusion into the study. However, after 18 months there was a significant increase in the IMT among the patients with early RA (p<0.05); no such increase occurred in the control group. Biomarkers of endothelial activation that may reflect the early atherosclerosis that occurs in RA were also evaluated. At inclusion, both IMT and ED-FMD among the patients with early RA related significantly to several of the biomarkers of endothelial activation. Furthermore, markers of inflammation (e.g., DAS28) were significantly related to biomarkers of endothelial activation. In conclusion, RA patients had a higher incidence of CVD and a higher CF after a CV event. The increased homocysteine level among patients with RA was as easy to decrease as in the general population. At the time of diagnosis of RA there were no differences in atherosclerosis between patients and controls, however the patients with RA had a more rapid progression of atherosclerosis than the control subjects. Moreover, there were implications of endothelial activation already in patients with very early RA. Taken together, these results emphasize the necessity of optimizing the preventive, diagnostic and caring strategies for CVD in patients with RA.

Preeclampsia is one of the leading causes of maternal and fetal mortality and morbidity. Furthermore, women who have had preeclampsia have an increased risk of cardiovascular events over the next 10-15 years. Indeed, preeclampsia is associated with a four-fold increase in the risk of hypertension and double the risk of fatal and non fatal ischaemic heart disease and stroke. In addition, offspring born to preeclampsia are more likely to have higher blood pressure from childhood and stroke in later life. The risk to mother and offspring is greatest when preeclampsia is diagnosed at an earlier gestation, suggesting a more severe form of preeclampsia. As the long term cardiovascular risk to both mother and child is known from delivery, the main interest of my research was to identify key phenotypic variations in mothers and children during the years between the episode of preeclampsia and emergence of established cardiovascular disease, which might explain the link between the two conditions. This information could then be used to devise ways to identify subjects at greatest risk of later cardiovascular disease and to establish intermediate endpoints for future preventative interventions. Therefore, in a case control study, women diagnosed with preeclampsia between 1998 and 2003 and their offspring were recruited and underwent comprehensive cardiovascular and metabolic phenotyping. Furthermore, young adults born preterm to hypertensive pregnancy were also investigated in their twenties. The research demonstrates that early-onset preeclampsia, diagnosed before 34 weeks gestation, is associated with blood pressure patterns in mothers 6-13 years after pregnancy that are distinct from those seen following later-onset disease. Furthermore, there is evidence of distinct differences in cardiac, vascular and metabolic profiles in these individuals with women having evidence of increased arterial stiffness, changes in cardiac function and reduced capillary density. Preterm offspring of hypertensive pregnancies similarly have higher blood pressure than seen in those born following late-onset disease and, in young adult life, have reduced endothelial function and changes in cardiac size proportional to this dysfunction. This research demonstrates adverse cardiac and vascular remodelling after preeclampsia in mothers and offspring that are evident before the development of clinical cardiovascular disease. The identified differences in cardiac and vascular function may be useful as surrogate endpoints in future preventive trials.

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No. of bitstreams: 2 Tese - Glaucimeire Marquez Franco - 2015.pdf: 1831506 bytes, checksum: fc557ab2fef5a0036ed0efa86a2a0880 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2015-03-07 / Introduction: Preeclampsia and eclampsia are important causes of maternal and perinatal morbidity and mortality worldwide Objectives: To evaluate the maternal brain centralization in pregnant women with specific gestational hypertension. Produce a systematic review article on the ophthalmic artery Doppler and uterine artery and the flow-mediated dilation. Develop an original article in order to assess the possible occurrence of maternal brain centralization in pregnant women with specific gestational hypertension. Establish normal values of the ratio of uterine artery to the ophthalmic artery (mean and standard deviation). Compare the ratio of uterine with the ophthalmic artery in normal and pathological group. Set the cut-off point, using the ROC curve for specific diagnosis of patients with hypertensive disease of pregnancy. Methods: A systematic literature review involved 260 indexed articles from Medline via PubMed and Virtual Health Library (VHL), published between 1989 and 2014. For the original article, we performed a case-control study of 178 pregnant women divided into two groups: a control group of normal patients (PN), a total of 83 normotensive pregnant women; and one case group of 95 patients with specific gestational hypertension. The analyzed parameters which formed part of the variables studied were: systolic velocity (VS), diastolic velocity (RV), the resistance index, systole-diastole relationship. In addition to these variables were also studied epidemiological variables of pregnancy, parity, abortion, weight, height, BMI, maternal age, gestational age. Results: Through the search strategy, were located 260 articles, of which 33 articles were eligible, with fifteen articles on the ophthalmic artery, eight articles on the brachial artery and eight articles on uterine artery. A total of 178 patients took part in study. The average age of normal pregnant women group of patients was 29.8 ± 4.7 and patients with specific gestational hypertension, of 26.14 ± 6.17. The mean gestational age of normal pregnant patients was 34.3 ± 3.5 weeks and the patients with specific gestational hypertension, of 32.40 ± 3.37. The mean body mass index (BMI) of healthy patients was 26.8 ± 5.6 and patients with specific gestational hypertension, of 30.55 ± 5.12. A normality curve systole-diastole compared with the respective cutoff was performed. A ROC curve was developed, with the cutoff point, considering the systolic velocity, diastolic velocity, systolic-diastolic ratio and the resistance index of the ophthalmic artery, respectively. Conclusion: The Doppler uterine artery and ophthalmic artery flow-mediated dilatation can be useful to identify patients at risk for allowing the monitoring of disease progression and perform effective interventions. It is observed that the possibility of maternal centralization in high-risk pregnancy as the PE is real, whereas in the average normal values and the standard deviation of the Doppler AU / AO-systole-diastole ratio were 0.43 ± 0 16. The cutoff point more sensitive, verified by the ROC curve, which defines maternal brain centralization in patients with hypertensive disorders of pregnancy, is 0.57 for the S / D for UD / AO, with 78% sensitivity and 13 % false positive and 77% specificity. / Introdução: A pré-eclâmpsia é um importante problema em obstetrícia, com altos índices de morbidade perinatal e mortalidade em todo o mundo, principalmente nos países em desenvolvimento. Objetivos: Avaliar a ocorrência de centralização cerebral materna em gestantes portadoras de doença hipertensiva específica da gestação. Produzir um artigo de revisão sistemática sobre Doppler da artéria oftálmica e da artéria uterina e sobre a dilatação fluxo-mediada da artéria braquial. Elaborar um artigo original para avaliar a ocorrência da centralização cerebral materna em gestantes portadoras de doença hipertensiva específica da gestação. Estabelecer a curva de normalidade da relação do Doppler da artéria uterina com o Doppler da artéria oftálmica. Comparar a relação do Doppler da uterina com o Doppler da artéria oftálmica no grupo normal e patológico. Definir o ponto de corte, através da curva ROC, para diagnóstico de pacientes com doença hipertensiva específica da gestação. Métodos: A revisão sistemática da literatura envolveu 260 artigos indexados das bases de dados Medline via PubMed e Biblioteca Virtual em Saúde (BVS), publicados entre 1989 e 2014. Para o artigo original, foi realizado um estudo caso controle com 178 gestantes distribuídas em dois grupos: um grupo-controle de pacientes normais (PN), num total de 83 gestantes normotensas; e um grupo casos de 95 pacientes com doença hipertensiva específica da gestação. As variáveis estudadas foram: a velocidade sistólica (VS), a velocidade diastólica (VD), o índice de resistência, a relação sístole-diástole. Além dessas variáveis foram estudadas paridade, aborto, peso, altura, IMC, idade materna, idade gestacional. Resultados: Por meio da estratégia de busca, localizaram-se 260 artigos, dos quais foram elegíveis 32 artigos, sendo dezesseis artigos sobre a artéria oftálmica, oito artigos sobre a artéria braquial e oito artigos sobre a artéria uterina. Um total de 178 pacientes fez parte do estudo. A média de idade das pacientes do grupo de gestantes normais foi de 29,8±4,7 e das pacientes com doença hipertensiva específica da gestação, de 26,14±6,17. A média da idade gestacional das pacientes gestantes normais foi de 34,3±3,5 semanas e das pacientes com doença hipertensiva específica da gestação, de 32,40±3,37. A média do índice de massa corporal (IMC) das gestantes normais foi de 26,8±5,6 e das pacientes com doença hipertensiva específica da gestação, de 30,55±5,12. Foi realizada uma curva de normalidade da relação sístole-diástole com o respectivo ponto de corte. Desenvolveu-se uma curva ROC com o ponto de corte, considerando a velocidade sistólica, a velocidade diastólica, a relação sístole-diástole e o índice de resistência da artéria oftálmica, respectivamente. Conclusão: O Doppler da artéria oftálmica e da artéria uterina e a dilatação fluxo mediada podem ser úteis para identificar pacientes em risco. Observou-se que a ocorrência de centralização materna em gravidez de alto risco como a pré-eclâmpsia (PE) é real, visto que na curva de normalidade a média e o desvio padrão do Doppler da AU/AO da relação sístole-diástole foram de 0,43 ± 0,16. O ponto de corte mais sensível, verificado por meio da curva ROC, que define centralização cerebral materna nas pacientes com doença hipertensiva específica da gestação, é de 0,57 para a S/D da UD/AO, com 78% de sensibilidade e 13% de falso positivo e 77% de especificidade.

Epidemiological studies have shown strong and consistent associations between exposure to air pollution and increases in morbidity and mortality. Key air pollutants that have been identified include fine particulate matter (PM) and ozone (O3), both major contributors to smog. However, there is a lack of understanding of the mechanisms involved and the relative contributions of individual pollutants. A controlled human exposure facility was used to carry out inhalation studies of concentrated ambient fine particles (CAP), O3, CAP+O3 and filtered air following a randomized design. Exposures were 2 hrs in duration at rest. Subjects included mild asthmatics and non-asthmatics. This thesis focuses on acute cardiovascular responses including blood pressure (BP), brachial artery reactivity (flow-mediated dilatation [FMD]) and markers of systemic inflammation (blood neutrophils and interleukin [IL]-6). Results showed that for CAP-containing exposures (CAP, CAP+O3) there were small but significant transient increases in diastolic BP (DBP) during exposures. Furthermore, neutrophils and IL-6 increased 1 - 3 hrs after and FMD decreased 20 hrs after CAP-containing exposures. Responses to O3 were smaller, comparable to filtered air. The data suggests that adverse responses were mainly driven by PM. The DBP increase was rapid-developing and quick to dissipate, which points to an autonomic irritant response. The magnitude of the DBP increase was strongly negatively associated with the high frequency component of heart rate variability, suggesting parasympathetic withdrawal as a mechanism. In comparison, IL-6, neutrophil and FMD responses were slower to develop, indicative of an inflammatory mechanism. An intriguing finding was that IL-6 increased 3 hrs after CAP, but not after CAP+O3. Further investigation revealed that exposure to CAP+O3 in some individuals may trigger a reflex inhibition of inspiration, decreasing their tidal volume and inhaled pollutant dose, leading to a reduction in systemic IL-6, a potential protective mechanism. Together the findings support the epidemiological evidence of adverse fine PM health effects. Many questions remain to be answered about the health effects of air pollution including a better understanding of how inhaled pollutants result in cardiovascular effects. It is hoped that the insights gained from this thesis will advance the understanding of air pollution health effects.

Epidemiological studies have shown strong and consistent associations between exposure to air pollution and increases in morbidity and mortality. Key air pollutants that have been identified include fine particulate matter (PM) and ozone (O3), both major contributors to smog. However, there is a lack of understanding of the mechanisms involved and the relative contributions of individual pollutants. A controlled human exposure facility was used to carry out inhalation studies of concentrated ambient fine particles (CAP), O3, CAP+O3 and filtered air following a randomized design. Exposures were 2 hrs in duration at rest. Subjects included mild asthmatics and non-asthmatics. This thesis focuses on acute cardiovascular responses including blood pressure (BP), brachial artery reactivity (flow-mediated dilatation [FMD]) and markers of systemic inflammation (blood neutrophils and interleukin [IL]-6). Results showed that for CAP-containing exposures (CAP, CAP+O3) there were small but significant transient increases in diastolic BP (DBP) during exposures. Furthermore, neutrophils and IL-6 increased 1 - 3 hrs after and FMD decreased 20 hrs after CAP-containing exposures. Responses to O3 were smaller, comparable to filtered air. The data suggests that adverse responses were mainly driven by PM. The DBP increase was rapid-developing and quick to dissipate, which points to an autonomic irritant response. The magnitude of the DBP increase was strongly negatively associated with the high frequency component of heart rate variability, suggesting parasympathetic withdrawal as a mechanism. In comparison, IL-6, neutrophil and FMD responses were slower to develop, indicative of an inflammatory mechanism. An intriguing finding was that IL-6 increased 3 hrs after CAP, but not after CAP+O3. Further investigation revealed that exposure to CAP+O3 in some individuals may trigger a reflex inhibition of inspiration, decreasing their tidal volume and inhaled pollutant dose, leading to a reduction in systemic IL-6, a potential protective mechanism. Together the findings support the epidemiological evidence of adverse fine PM health effects. Many questions remain to be answered about the health effects of air pollution including a better understanding of how inhaled pollutants result in cardiovascular effects. It is hoped that the insights gained from this thesis will advance the understanding of air pollution health effects.

Contexte L’américanisation des habitudes de vie, notamment de l’alimentation, semble être en grande partie responsable de l’augmentation incessante de l’incidence élevée des maladies cardiovasculaires. La période postprandiale, où l’homéostasie vasculaire et métabolique est mise à l’épreuve, est d’une importance considérable dans le développement ou la prévention de l’athérosclérose et représente maintenant la majeure partie du temps d’éveil. La compréhension de l’influence de la composition d’un repas sur son impact postprandial est donc essentielle dans notre lutte dans la prévention de ces maladies. Objectifs L’objectif principal de ce projet de recherche était d’étudier les réponses endothéliale et métabolique à un repas de type méditerranéen mixte (MMM), puisqu’elles sont inconnues. Ce projet avait aussi pour objectifs d’évaluer l’impact microvasculaire d’un tel repas et de caractériser la composition postprandiale des acides gras plasmatiques. À titre comparatif, ces éléments ont aussi été étudiés suite à un repas riche en gras saturés (HSFAM). Méthodes Vingt-huit (28) hommes sains, exempts de facteurs de risque de maladies cardiovasculaires ont reçu de façon randomisée les deux repas à l’étude. Le MMM, composé de saumon frais et de légumes cuits dans l'huile d'olive, contenait 7.87g de SFA et 2.29g d’acides gras polyinsaturés oméga-3, tandis que le HSFAM, composé d'un sandwich déjeuner avec œuf, saucisse et fromage, contenait 14.78g de SFA. Les mesures de la fonction endothéliale mesurée par échographie brachiale (FMD), de la fonction microvasculaire mesurée par spectroscopie proche de l’infrarouge (NIRS) et de la composition des acides gras plasmatique ont été effectuées à jeun et en période postprandiale. Résultats Deux sous-groupes de répondeurs aux repas à l’étude se sont dégagés de ces travaux. Un premier sous-groupe de sujets ayant une triglycéridémie à jeun élevée, mais normale (hnTG) a démontré des altérations endothéliales seulement suivant le repas HSFAM. Un second sous-groupe de sujets ayant une triglycéridémie plus faible et normale (lnTG) n’a quant à lui pas subi d’altérations endothéliales suivant les deux repas à l’étude. Les sujets hnTG ont aussi démontré une charge triglycéridémique postprandiale (iAUC) plus importante et qui était de surcroît enrichie en acide stéarique suivant la HSFAM et en acide gras polyinsaturés oméga-3 suivant le MMM. L’évaluation par NIRS de la fonction microvasculaire nous révèle un ralentissement de la réoxygénation post-ischémique qui suggère une altération postprandiale du recrutement capillaire chez les sujets hnTG seulement. De telles altérations, qui semblent être plus importantes suivant le HSFAM, pourraient être en partie responsables de l’impact endothélial de ce repas. Conclusions Cet essai clinique démontre donc de façon novatrice qu’un repas MMM n’a pas d’effet endothélial délétère et que cette neutralité est indépendante de la triglycéridémie à jeun. De plus, une triglycéridémie à jeun élevée mais normale semble indiquer des dysfonctions endothéliales et métaboliques à des épreuves nutritionnelles tel un repas HSFAM. La consommation de repas méditerranéens par des individus sains à la triglycéridémie marginale serait bénéfique, peut-être même davantage que pour des individus de triglycéridémie plus faible, dans la prévention de l’athérogénèse et des maladies cardiovasculaires. / Background The Westernization of lifestyles, notably dietary habits, seems to be largely responsible for the ongoing increase of incidence of cardiovascular diseases. The postprandial period, where vascular and metabolic homeostatic regulating processes are under pressure, is of considerable importance in the development or prevention of atherosclerosis and now represents the majority of waking hours. The understanding of the postprandial effects of meals of varying composition is therefore essential in our effort to prevent such diseases. Objectives The main objective of this research project was to study the endothelial and metabolic responses to a mixed Mediterranean meal (MMM), since they are unknown. This project also aimed to evaluate the microvascular impact of such a meal and to characterize the composition of postprandial plasma fatty acids. These elements were also evaluated following a saturated fatty meal (HSFAM) for comparison. Methods Twenty-eight (28) healthy men free of cardiovascular diseases and risk factors were randomly assigned one of two test meals. The MMM, consisting of fresh salmon and vegetables cooked in olive oil, contained 7.87g of SFA and 2.29g of omega- 3 fatty acids, while the HSFAM, consisting of a breakfast sandwich with egg, sausage and cheese contained 14.78g of SFA. Evaluations of endothelial function by brachial ultrasound (FMD), of microvascular function by near-infrared spectroscopy (NIRS) and of plasma fatty acids composition were done in the fasted and postprandial states. Results Two subgroups of responders to the test meals emerged from this work. A first subgroup of subjects with high-normal fasting triglyceridemia (hnTG) experienced impairments of endothelial function following the HSFAM while a second subgroup of subjects with low-normal triglyceridemia (lnTG) did not experience any endothelial alterations following this meal. Interestingly, the MMM had no deleterious endothelial impact in any of those subgroups. Moreover, the hnTG subjects demonstrated greater postprandial triglyceridemic load (iAUC) that was in addition enriched with stearic acid after HSFAM and omega-3 PUFA following the MMM. Assessment of microvascular function revealed postprandial prolongation of post-ischemic reoxygenation only in hnTG subjects suggestive of alterations of capillary recruitment. These changes, which seemed to be more important after the HSFAM, could be partly responsible for its negative impact on FMD. Conclusions This clinical trial demonstrates in innovative ways that a MMM has no deleterious effects on endothelial function irrespective of triglyceridemia in normal ranges. In addition, high but normal fasting triglyceride levels suggest metabolic and endothelial dysfunctions following nutritional challenges such as a HSFAM. Consumption of Mediterranean meals by healthy individuals with marginal triglyceride levels would be beneficial, perhaps even more so than for individuals with lower triglyceride levels, in preventing atherogenesis and cardiovascular diseases.

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