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Abstract

Impaired flow-mediated vasodilation in large arteries is an expression of endothelial dysfunction and an established marker of early atherosclerosis. Post-prandial lipemia can induce an impairment of the endothelial function. The aim of our study was to evaluate the effects of post-prandial phase on flow-mediated vasodilation in a group of ten young (23 +/- 2 years) healthy men without cardiovascular risk factors, who underwent an oral fat-loading test. Flow-mediated vasodilation of the brachial artery and serum lipid profile were assessed under fasting conditions and 2, 4, 6 and 8 h after a high-fat meal. Triglycerides increased from 0.6 +/- 0.2 fasting to 1.1 +/- 0.5 and 1.3 +/-0.6 mmol/l at the 2nd and 4th hour (both P < 0.01), and decreased thereafter. Flow-mediated vasodilation fell significantly from 14.5 +/- 6.6% fasting to 3.5 +/- 1.5% and 4.0 +/- 2.2% at the 2nd and 4th hour (both P < 0.01), and returned to the basal values at the 6th and 8th hour. A strong inverse correlation was observed between the area under the incremental curve of post-prandial triglycerides (i.e. after subtraction of baseline triglycerides) and the area under the decremental curve of post-prandial flow-mediated vasodilation (r = -0.70, P = 0.025). No association was found between post-prandial vasodilation changes and fasting triglycerides, other lipid parameters or insulin. We conclude that a transient post-prandial impairment in brachial artery flow-mediated vasodilation is evident in young healthy men after a high-fat meal, and is closely associated with triglyceride levels. These data provide support for a role of post-prandial phase in vascular regulation in young healthy subjects.

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... The progression of atherosclerosis is characterized by chronic oxidative stress, activation of proinflammatory pathways, and recruitment and adhesion of immune cells to the endothelium (4). Previous research suggests that consumption of a single high-fat meal (HFM) may induce transient postprandial atherogenic responses including impairment of vascular endothelial function, hypertriglyceridemia, hyperglycemia, inflammation, and oxidative stress (5)(6)(7)(8)(9)(10) that are exacerbated in individuals with overweight and obesity (8). Indeed, even mildly elevated postprandial glucose and triglyceride concentrations have been linked to the development of atherosclerosis and other CVDs in the general population (5,11). ...
... In a separate study by Raitakari et al. (47), a saturated fatty acid-rich HFM (1030 kcal, 61 g fat) was actually found to increase brachial artery basal diameter, FBF, and post-ischemic hyperemia with no change in FMD. Other studies with healthy adults have shown that transient impairment of FMD at 2, 3, and 4 h following HFM consumption were strongly associated with the magnitude of postprandial triglyceride concentrations, as well as leukocyte superoxide production (9,10). In a dose-response study, Schwander et al. (48) observed significant increases in plasma triglyceride iAUC over a 6-h period in men with obesity following consumption of HFMs containing 1000 kcal (68 g fat) or 1500 kcal (102 g fat), and in serum IL-6 concentrations but only following consumption of the 1500 kcal HFM. ...
... It is possible the timing of endothelial function assessment could have influenced the present findings. Although impairment of endothelial function has been observed at 2-and 4-h post-HFM consumption (9,10), the 4-h time point was chosen for our study due to the fact that postprandial triglycerides and maximal impairment of FMD have been shown to occur 3-4 h following HFM consumption (6). Nonetheless, impaired FMD has been observed 2 h following HFM consumption due to enhanced oxidative stress (9) and we therefore cannot rule out the possibility that RHI may have been impaired at the 2-h time point. ...
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Background: High-fat meal (HFM) consumption may induce transient postprandial atherogenic responses, including impairment of vascular endothelial function, in individuals with overweight/obesity. Red beetroot juice (RBJ) may modulate endothelial function and other measures of cardiometabolic health. Objective: This study investigated the impact of acute and chronic RBJ consumption, including nitrate-dependent and -independent effects, on postprandial endothelial function and other cardiometabolic responses to a HFM. Methods: Fifteen men and postmenopausal women with overweight/obesity were enrolled in this randomized, double-blind, placebo-controlled, 4-period, crossover clinical trial. Following an overnight fast, participants underwent baseline assessment of endothelial function (reactive hyperemia index; RHI) and hemodynamics, and biological sample collection. In random order, participants consumed 70 mL (acute visit) of: 1) RBJ, 2) nitrate-free RBJ (NF-RBJ), 3) placebo + nitrate (PBO + NIT), or 4) placebo (PBO), followed by a HFM. RHI was remeasured 4 h post-HFM, and hemodynamic assessment and biological sample collection were performed 1, 2, and 4 h post-HFM consumption. Participants consumed treatments daily for 4 wk (chronic visit), and assessments were repeated before/after the HFM (without consuming treatments). Results: HFM consumption did not induce significant impairment of postprandial RHI. No significant differences in RHI were detected across treatment groups following acute or chronic exposure, despite increases in circulating nitrate/nitrite (NOx) concentrations in the RBJ and PBO + NIT groups compared with PBO and NF-RBJ (P < 0.0001 for all time points at the acute visit; P < 0.05 for all time points at the chronic visit). Although the HFM led to significant alterations in several secondary outcomes, there were no consistent treatment effects on postprandial cardiometabolic responses. Conclusions: HFM consumption did not impair postprandial endothelial function in this population, and RBJ exposure did not alter postprandial endothelial function or other outcomes despite increasing NOx concentrations. This trial is registered at clinicaltrials.gov as NCT02949115.
... Brachial artery flow-mediated dilation (FMD) is the most widely used non-invasive technique to assess endothelial function in humans [11], and a meta-analysis demonstrated that impairment of the brachial artery FMD is significantly associated with future cardiovascular morbidity and mortality [12]. Impairment of the endothelial function could be due in large part to transient increases in postprandial triglycerides [13][14][15][16][17][18][19] and glucose [20]. ...
... Although several studies have shown that high-fat meals contribute to the transient impairment of endothelial function [13][14][15][16][17][18][19], this finding is not universal [21,22]. In adults, impairment in endothelial function after a high-fat meal has been reported to be significantly correlated with an increase in postprandial plasma triglycerides [13][14][15]17,18]. ...
... Although several studies have shown that high-fat meals contribute to the transient impairment of endothelial function [13][14][15][16][17][18][19], this finding is not universal [21,22]. In adults, impairment in endothelial function after a high-fat meal has been reported to be significantly correlated with an increase in postprandial plasma triglycerides [13][14][15]17,18]. Two studies on adolescents, however, indicated that decrements in FMD after ingestion of a high-fat meal were not significantly correlated with postprandial triglyceridemia [23,24]. ...
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The consumption of fiber-rich foods may negate the deleterious effects of high-fat meals on postprandial triglyceridemia and endothelial function. Despite supportive data in adults, little is known about the effects of high-fat and high-fiber foods on cardiovascular health parameters in pediatric populations. In this crossover trial, male and female adolescents (n = 10; 14.1 + 2.6 years; range 10-17 years) consumed (1) low-fat, low-fiber, (2) low-fat, high-fiber, (3) high-fat, low-fiber, and (4) high-fat, high-fiber breakfast meals in randomized order, each following an overnight fast. Baseline and 4 h post-meal blood was obtained for determination of glucose, insulin and triglyceride concentrations. Endothelial function was assessed via brachial artery flow-mediated dilation (FMD). Postprandial FMD was not significantly changed after any meal. However, regression analyses revealed a significant inverse relationship between the change in 4 h triglyceride concentration and change in 4 h FMD for the high-fat, low-fiber meal (β = −0.087; 95% CI = −0.138 to −0.037; p = 0.001) that was no longer significant in the high-fat, high-fiber meal (β = −0.044; 95% CI = −0.117 to 0.029; p = 0.227). Interpretation of these analyses must be qualified by acknowledging that between-meal comparison revealed that the two regression lines were not statistically different (p = 0.226). Addition of high-fiber cereal to the high-fat meal also reduced 4 h postprandial triglyceride increases by ~50% (p = 0.056). A high-fiber breakfast cereal did not attenuate postprandial glucose and insulin responses after consumption of a low-fat meal. While further work is needed to confirm these results in larger cohorts, our findings indicate the potential importance of cereal fiber in blunting the inverse relationship between postprandial hypertriglyceridemia and FMD after consumption of a high-fat meal in adolescents.
... Although the majority of human vascular reactivity studies have been performed in the fasting state, impairment in vascular reactivity has also been documented in the postprandial state, particularly after a high-fat meal (HFM). [3][4][5] These findings generated great interest because they added to the pathophysiological mechanisms by which fat intake contributes to cardiovascular disease. Not all studies, however, have been consistent with these findings, and some report no change, 6 or even improvement in vascular reactivity after an HFM mostly in African Americans. ...
... Previous studies demonstrated a significant effect of HFM on FMD with a similar number of subjects. 3,4 Results Protocol 1. Repeatability Studies Table 1 shows the patient's characteristics. Except for hypertension, all participants were free of cardiovascular disease. ...
... The effect of an HFM on endothelial function remains controversial. Impaired endothelial function has been reported in most, 3,4,21,22 but not all, 6,23 previous studies. Recently, 2 different studies reported no effect of a high-fat diet on endothelial function in obese African Americans, suggesting a racial disparity. ...
Article
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Background Flow‐mediated dilation (FMD) is used to assess endothelial function through changes in vascular diameter after hyperemia. High‐fat meal (HFM) has been shown to induce endothelial dysfunction; recent studies, however, reported conflicting results in obese African American women (AAW). Differences in the method used to analyze FMD may explain these discrepancies. Methods and Results In protocol 1, we assessed the time course of FMD and compared the repeatability of FMD using the individual maximum peak dilation (FMD peak) and the dilation at 60 seconds (FMD 60). Sixteen AAW (age, 42±10.4 years; body mass index [BMI], 39±5.8 kg/m²) were studied on 2 occasions, 4 weeks apart, under fasting conditions (study 1 and study 2). In protocol 2, we used the most repeatable measurement from protocol 1 to assess changes in endothelial function after an HFM in 17 AAW (agen 42±11.1 years; BMIn 38±5.6 kg/m²). We found that FMD peak was the most repeatable measurement (N=16; study 1, 5.31±3.12% and study 2, 5.80±2.91%; r=0.94). After an HFM, the baseline brachial artery diameter significantly increased at 2 hours (0.10 mm; 95% confidence interval [CI], 0.01–0.18; P=0.03) and at 4 hours (0.17 mm; 95% CI, 0.09–0.25; P<0.001). At 2 hours, the FMD peak decreased compared with pre‐HFM (−1.76; 95% CI, −3.55–0.02; P≤0.05). Conclusions The individual's maximum peak dilation after hyperemia is the most consistent measure to assess the effect of an HFM on endothelial function. Endothelial dysfunction occurred at 2 hours after an HFM in AAW. Clinical Trial Registration URL: https://clinicaltrials.gov/ Unique identifiers: NCT01334554 and NCT02126735.
... This observed endothelial dysfunction (as indicated by a decline in FMD) following the consumption of high-fat meals has been demonstrated repeatedly in adults. While this decline in FMD in asymptomatic adults can range between 17 (29) and 70 % (2) , the majority of studies report changes between 30 and 50 % (3,4,30 -32) . Importantly, * Data were analysed using a mixed-effects general linear model with two fixed factors (trial and time) and one random factor (participant) for both basal and peak diameter: main effect trial, P.0·05; main effect trial, P,0·05; and interaction effect trial £ time, P.0·05. ...
... Therefore, a substantial number of adolescents may be exposed, on a regular basis, to the risks associated with the consumption of meals high in fat. While the observation period in the present study was very short and the endothelial dysfunction following ingestion of a high-fat meal has been shown to be transient, certainly in adults (2,4) , if the responses observed in the present study were to be repeated on a regular basis over many years, then the strain on the vasculature could be substantial and have a lasting deleterious effect. Interventions that might reduce or prevent this strain on the vasculature could have important clinical implications. ...
... In previous research, a relationship between TAG concentrations and FMD has been demonstrated postprandially, but no relationship between these variables was evident in the fasted state (4,42,43) . In previous studies, where a relationship has been found between postprandial TAG concentrations and change in endothelial function, Pearson correlations have ranged from 20·31 (30) to 20·70 (2) . This has led to the hypothesis that prior exercise can prevent the postprandial endothelial dysfunction by reducing postprandial TAG concentrations (1) . ...
Article
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The ingestion of high-fat meals induces a state of endothelial dysfunction in adults. This dysfunction is attenuated by prior exercise. The response of young people to these nutritional and physiological stressors has not been established. Thus, the purpose of the present study was to investigate if a bout of moderate-intensity exercise influenced endothelial function (as indicated by flow-mediated dilation (FMD)) following the ingestion of a high-fat breakfast and lunch in adolescent boys (aged 12·6-14·3 years). Two, 2 d main trials (control and exercise) were completed by thirteen adolescent boys in a counter-balanced, cross-over design. Participants were inactive on day 1 of the control trial, but completed 60 min of walking at 60 % peak oxygen uptake in the exercise trial. On day 2, endothelial function was assessed via FMD prior to, and following, ingestion of a high-fat breakfast and lunch. There was no difference in fasting FMD between the control and exercise trial (P = 0·449). In the control trial, FMD was reduced by 32 % following consumption of the high-fat breakfast and by 24 % following lunch. In the exercise trial, the corresponding reductions were 6 and 10 %, respectively (main effect trial, P = 0·002). These results demonstrate that moderate-intensity exercise can attenuate the decline in FMD seen following the consumption of high-fat meals in adolescent boys.
... The increased circulating levels of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 adversely affect the cardiovascular system causing endothelial dysfunction by increased oxidative stress and vascular hypertrophy (151,152). The impact is particularly pathogenic in central or abdominal obesity marked by increased visceral adipose tissue (dispersed around the omental (OM), intestines and peri-renal areas, (153)) which is more metabolically active by secreting more proinflammatory cytokines (154,155) than peripheral adipose tissue such as subcutaneous tissue (SC) (156,157). Both chronic inflammation and insulin resistance in these circumstances are strongly associated with impaired vasodilatory responses (156,157), endothelial dysfunction and the initiation and progression of atherosclerosis (158). ...
... The impact is particularly pathogenic in central or abdominal obesity marked by increased visceral adipose tissue (dispersed around the omental (OM), intestines and peri-renal areas, (153)) which is more metabolically active by secreting more proinflammatory cytokines (154,155) than peripheral adipose tissue such as subcutaneous tissue (SC) (156,157). Both chronic inflammation and insulin resistance in these circumstances are strongly associated with impaired vasodilatory responses (156,157), endothelial dysfunction and the initiation and progression of atherosclerosis (158). However, the key molecular determinants of the severity of the impact of the adipose tissue microenvironment on the local blood vessels are still not well understood especially for a relatively young obese population such as in Qatar. ...
Conference Paper
Cyclooxygenase (COX), which can be expressed as COX-1 or COX-2 in endothelial cells has the unique ability to regulate microvascular tone through balanced production of dilator/constrictor prostanoids. This study investigated the roles of these isoforms in microvascular endothelial dilator function and how these are affected by supplement-derived ecdysteroids. Acetylcholine or 20-hydroxyecdysone relaxation were recorded in Skeletal muscle (SKM) and mesenteric (ME) arteries from healthy sheep and omental (OM) and subcutaneous (SC) fat arteries from obese humans by wire myography in the absence and presence of inhibitors of nitric oxide synthase, cyclooxygenase (COX) isoforms 1 and 2 and endothelium-derived hyperpolarizing factors. Gene and protein expression analysis were also carried out to fully characterize the roles of COX in these arteries. Non-selective COX inhibition attenuated acetylcholine relaxation in SKM arteries but enhanced it in ME arteries. Selective inhibition of COX-1 in both SKM and ME arteries also attenuated acetylcholine relaxation. In contrast, selective inhibition of COX-2 enhanced acetylcholine relaxation in ME arteries and had no effect in SKM arteries. In OM arteries from obese patients, selective inhibition of COX-1 but not COX-2 significantly improved acetylcholine relaxation. The OM arteries also displayed enhanced responsiveness to thromboxane A2 mimetic (U46619) compared with SC arteries. 20-hydroxyecdysone caused relaxation which was attenuated by NOS inhibition compared with COX inhibition in SKM and ME arteries. COX roles in microvascular endothelial dilator function are isoform-specific and dependent on type and health of the vasculature. In healthy arteries, COX-1 promotes but COX-2 opposes vasodilation. In human obesity, COX-1 opposes while COX plays no part in OM endothelial dilator function. Although 20-hydroxyecdysone alters COX expression, its vasodilatory effect is more eNOS-dependent than COX-dependent.
... CVDs cause~35% of all deaths for Americans 65 years of age or older, making them the leading causes of death in this age group [1]. Furthermore, with advancing age, the prevalence of CVDs among Americans increases progressively, from~5.5% in [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] year olds to~41% in people 65 years of age or older [1]. Thus, CVDs can be considered true diseases of aging. ...
... Lastly, it is known that with advancing age post prandial clearance of elevated glucose and lipids decreases significantly even in healthy adults [39,40]. Furthermore, this post prandial state is associated with acute endothelial dysfunction in young and middle-aged adults [41,42]. Thus, it is a tenable hypothesis that this post prandial state underlies the vascular aging phenotype since endothelial culture studies suggest that physiological elevations in glucose and lipids induce oxidative stress and inflammation and also negatively alter "energy sensitive" pathways [43][44][45]. ...
Article
Cardiovascular disease (CVD) is the leading cause of death in the United States and aging is a major risk factor for CVD development. One of the major age-related arterial phenotypes thought to be responsible for the development of CVD in older adults is endothelial dysfunction. Endothelial function is modulated by traditional CVD risk factors in young adults, but advancing age is independently associated with the development of vascular endothelial dysfunction. This endothelial dysfunction results from a reduction in nitric oxide bioavailability downstream of endothelial oxidative stress and inflammation that can be further modulated by traditional CVD risk factors in older adults. Greater endothelial oxidative stress with aging is a result of augmented production from the intracellular enzymes NADPH oxidase and uncoupled eNOS, as well as from mitochondrial respiration in the absence of appropriate increases in antioxidant defenses as regulated by relevant transcription factors, such as FOXO. Interestingly, it appears that NFkB, a critical inflammatory transcription factor, is sensitive to this age-related endothelial redox change and its activation induces transcription of pro-inflammatory cytokines that can further suppress endothelial function, thus creating a vicious feed-forward cycle. This review will discuss the two macro-mechanistic processes, oxidative stress and inflammation, that contribute to endothelial dysfunction with advancing age as well as the cellular and molecular events that lead to the vicious cycle of inflammation and oxidative stress in the aged endothelium. Other potential mediators of this pro-inflammatory endothelial phenotype are increases in immune or senescent cells in the vasculature. Of note, genomic instability, telomere dysfunction or DNA damage has been shown to trigger cell senescence via the p53/p21 pathway that results in increased inflammatory signaling in arteries from older adults. This review will discuss the current state of knowledge regarding the emerging concepts of senescence and genomic instability as mechanisms underlying oxidative stress and inflammation in the aged endothelium. Lastly, energy sensitive/stress resistance pathways (SIRT-1, AMPK, mTOR) are altered in endothelial cells and/or arteries with aging and these pathways may modulate endothelial function via key oxidative stress and inflammation-related transcription factors. This review will also discuss what is known about the role of “energy sensing” longevity pathways in modulating endothelial function with advancing age. With the growing population of older adults, elucidating the cellular and molecular mechanisms of endothelial dysfunction with age is critical to establishing appropriate and measured strategies to utilize pharmacological and lifestyle interventions aimed at alleviating CVD risk. This article is part of a Special Issue entitled “SI: CV Aging”.
... "Leukocyte activation; "adhesion molecule expression [92][93][94][95] "Oxidative stress 88,96 Foam cell formation 88 "Neutrophil count; "pro-inflammatory cytokines 97 "Complement component 3 98,99 "Endothelial cells activation 92 PP lipemia and endothelial dysfunction #Flow mediated dilation 92,[104][105][106][107] PP lipemia and IMT IMT values correlate with remnant levels in healthy subjects [108][109][110][111] "IMT values in T2D subjects with postprandial hypertriglyceridemia [112][113][114] PP lipemia and CV risk Non-fasting TG levels are associated with increased CV risk [115][116][117] High postprandial TG are associated with higher risk of MI, IHD and death 115 Non-fasting TG levels predicts incident CV events in healthy women 116 Non-fasting TG levels are associated with increased risk of ischemic stroke in the general population 119 PP metabolism in primary dyslipidemias FH subjects exhibit delayed postprandial chylomicron clearance 126,127 FCH subjects exhibit " hepatic VLDL production and # TG clearance At the molecular level, postprandial TRLs from type IV hyperlipidemic patients induce to a larger extent, compared with fasting TRLs, phosphorylation of p38 MAPK, CREB and IKB-a in human endothelial cells and increase the DNA binding activity of CREB, NFAT and NF-kB 92 . This is associated with the upregulation of a large set of pro-inflammatory genes (including VCAM-1, PECAM-1, ELAM-1, ICAM-1, P-selectin, MCP-1, IL-6, TLR-4, CD40, ADAMTS1 and PAI-1) induced by postprandial TRLs from HTG patients but not from normotriglyceridemic subjects 92 . ...
... Form the clinical perspective, the transient increase of TG levels following a high-fat meal induces a transient reduction of flow-mediated dilation (FMD) in healthy subjects without risk factors [104][105][106] , by inducing a temporary increase of oxidative stress 96 and inflammation 103 . Flowdependent vasoactivity decreased significantly for at least 4 h after ingestion of a high-fat meal compared with a lowfat meal 104 , confirming a negative impact of fatty acids or TRLs on endothelial function. ...
Article
Abstract High levels of fasting circulating triglycerides (TG) represent an independent risk factor for cardiovascular disease. In western countries ,however people spend most time in postprandial conditions, with continuous fluctuation of the lipemia due to increased levels of TG-rich lipoproteins (TRLs), including chylomicrons (CM), very low density lipoproteins (VLDL), and their remnants. Several factors contribute to postprandial lipid metabolism, including dietary, physiological, pathological and genetic factors. The presence of coronary heart disease, type 2 diabetes, insulin resistance and obesity is associated with higher postprandial TG levels compared with healthy conditions, also in subjects with normal fasting TG levels. Increasing evidence indicates that impaired metabolism of postprandial lipoproteins contributes to the pathogenesis of coronary artery disease, suggesting that lifestyle modifications as well as pharmacological approaches aimed at reducing postprandial TG levels might help to decrease the cardiovascular risk.
... Arterial stiffness, measured as aortic pulse wave velocity (PWV) is a validated, independent predictor of mortality from CVD [9] and is an unavoidable element of CV aging [10]. Whilst a number of studies have examined the postprandial effect of a fat-rich meal on components of vascular function such as flowmediated dilatation (FMD) and forearm blood flow (FBF) in healthy subjects [11][12][13][14][15][16][17][18][19][20][21][22][23][24], there is conflicting evidence on the effect on arterial stiffness which is dependent on the methodology used [25][26][27]. Moreover, there is a lack of conclusive evidence on the acute effect of a test-meal rich in monounsaturated fat (MUFA) compared with an isoenergetic test-meal rich saturated fat (SFA) on postprandial vascular function but specifically on arterial stiffness [8]. ...
... It has been suggested that this hypertriglyceridaemic state may affect non-serum risk factors for CVD such as vascular function [34]. A number of studies have examined the acute effect of fat quantity on postprandial vascular function in healthy participants [12][13][14][15][16][17][18][19][20][21][22][23][24]35,36] and although there were methodological differences between the studies, results concluded an impairment in vascular function following a meal rich in fat [8]. ...
Article
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Arterial stiffness is a component of vascular function and an established risk factor for cardiovascular disease. There is a lack of conclusive evidence on the effect of a meal rich in monounsaturated fat (MUFA) compared with an isoenergetic meal rich in saturated fat (SFA) on postprandial vascular function and specifically on arterial stiffness. Twenty healthy, non-smoking males (BMI 24 +/- 2 kg/m2; age 37.7 +/- 14.4 y) participated in this single-blind, randomised, cross-over dietary intervention study. Each subject was randomised to receive a high-fat test-meal (3 MJ; 56 +/- 2 g fat) at breakfast on 2 separate occasions, one rich in oleic acid (MUFA-meal) and one rich in palmitic acid (SFA-meal), and the meals were isoenergetic. Blood pressure (BP), arterial stiffness (PWV) and arterial wave reflection (augmentation index, AIx) were measured using applanation tonometry at baseline and every 30 minutes up to 4 hours after the ingestion of the test-meals. All subjects completed both arms of the dietary intervention. There was no significant difference in BP parameters, PWV or AIx at baseline between the two treatments (P > 0.05). There was a significant increase in brachial and aortic BP, mean arterial pressure (MAP), heart rate and PVW (time, P < 0.05) over the four hours after consumption of the fat-rich test-meal although the increase in PWV was no longer significant when adjusted for the increase in MAP. There was no difference in PWV between the two treatments (treatment*time, P > 0.05). There was a significant reduction in AIx (time, P < 0.05) over the four hour postprandial period although this was no longer significant when adjusted for the increase in heart rate and MAP (time, P > 0.05). There was no difference in AIx between the two treatments (treatment*time, P > 0.05). However, the reduction in heart rate corrected augmentation index (AIx75) was significant when corrected for the increase in MAP (time, P < 0.01) with no differential effect of the treatments (treatment*time, P > 0.05). This study has demonstrated a BP dependent increase in PWV and a decrease in arterial wave reflection in the four hour period in response to a high-fat meal. There was no evidence however that replacement of some of the SFA with MUFA had a differential effect on these parameters. The study highlights the need for further research to understand the effects of the substitution of SFA with MUFA on non-serum, new and emerging risk factors for CVD such as arterial stiffness.
... High-fat meals have been reported to reduce FMD [37][38][39], leading us to measure FMD in the postprandial period as well. When analyzing the entire study sample together, we also observed a decrease in FMD following administration of the high-fat meal. ...
Article
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The cardiovascular disease (CVD) risk of metabolically healthy obesity (MHO) remains controversial. We sought to further characterize the CVD risk profile in MHO by evaluating postprandial triglycerides, vascular function, and systemic inflammatory markers. Control individuals that were normal-weight and metabolically healthy (Con), MHO, and metabolic syndrome (MetS) were recruited (n = 10–11/group). Each participant underwent an abbreviated fat tolerance test, fasting and postprandial flow-mediated dilation (FMD), and had a panel of inflammatory cytokines measured. MHO displayed postprandial triglycerides similar to those in Con and both MHO and Con had lower values than those for MetS (p < 0.01). Fasting FMD was lower in MHO and MetS compared to that of Con (p < 0.01), but during the postprandial period the vasodilatory response of MHO was similar to that while fasting (p = 0.39), while FMD in Con and MetS decreased after the high-fat meal (p values < 0.01). MHO displayed a number of inflammatory cytokines greater than those of Con and MetS (all p values < 0.05), while MetS and MHO had higher TNF-α than did Con (p < 0.05). In conclusion, MHO was associated with lower fasting FMD and a greater inflammatory burden but did not suffer the same negative postprandial effects as did MetS.
... Moreover, the infusion of a triglyceride emulsion induces a loss of vascular reactivity [65]. Even in young healthy adults, postprandial triglyceride levels are closely associated with impaired brachial artery FMD after a high-fat meal [66]. ...
Article
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Postprandial plasma glucose and triglyceride concentrations are predictive of relative cardiovascular disease (CVD) risk, and the pathogenesis of both insulin resistance and atherosclerosis has been attributed to acute states of hyperglycemia and hypertriglyceridemia. Postprandial lipemia and hyperglycemia suppress vascular reactivity and induce endothelial dysfunction. Epidemiological studies suggest that chronically-high consumption of milk and milk products is associated with a reduced risk of type 2 diabetes, metabolic syndrome, and CVD. The addition of dairy products to meals high in carbohydrates and fat may lessen these risks through reductions in postprandial glucose and triglyceride responses. Purported mechanisms include dairy proteins and bioactive compounds, which may explain the inverse relationship between dairy consumption and cardiometabolic diseases. The current review evaluates the available literature describing the relationships between metabolic dysfunction, postprandial metabolism, and vascular dysfunction and discusses the potential role of milk and dairy products in attenuating these impairments.
... In this prior study, we detected significant group differences with n = 7-8 per group. With regard to vascular function, we selected a minimum necessary difference (between groups or in response to the meal) of 4% for FMD, with an estimated SD of 2%, based on previous studies (Marchesi et al., 2000;Pierce et al., 2011). This resulted in the minimum necessary sample size of seven per group. ...
Article
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The consumption of a high-fat meal can induce postprandial lipemia and endothelial dysfunction. The authors assessed the impact of age and physical activity on metabolic and vascular outcomes following meal consumption in healthy adults. The authors recruited four groups: younger active (age 22.1 ± 1.4 years; n = 9), younger inactive (age 22.6 ± 3.7 years; n = 8), older active (age 68.4 ± 7.7 years; n = 8), and older inactive (age 67.7 ± 7.2 years; n = 7). The metabolic outcomes were measured at the baseline and hourly for 6 hr post high-fat meal consumption (12 kcal/kg; 63% fat). Flow-mediated dilation was measured at the baseline, 2 hr, and 4 hr postmeal. The total area under the curve for triglycerides was significantly lower in the more active groups, but did not differ based on age (younger active = 6.5 ± 1.4 mmol/L × 6 hr, younger inactive = 11.7 ± 4.8, older active = 6.8 ± 2.7, older inactive = 12.1 ± 1.7; p = .0004). After adjusting for artery diameter, flow-mediated dilation differed between groups at the baseline (younger active = 4.8 ± 1.6%, younger inactive = 2.5 ± 0.5, older active = 3.4 ± 0.9, older inactive = 2.2 ± 0.4; p < .001) and decreased significantly across groups 4 hr postmeal (mean difference = 0.82; 95% CI [0.02, 1.6]; p = .04). These findings highlight the beneficial effect of regular physical activity on postprandial lipemia, independent of age
... improve postprandial FMD responses, were observed. In fact, other studies have reported a negative correlation between the magnitude of lipemia [28,29] or glycemia [30,31] with the change in FMD. However, like several other studies [32e34], these correlations did not reach statistical significance in our study. ...
Article
Background: Effects of weight loss on postprandial vascular function have not been studied so far. We therefore examined (i) effects of diet-induced weight loss on postprandial changes in various vascular function markers after consumption of a mixed meal and (ii) differences between normal-weight and abdominally obese men of comparable age at baseline and after weight loss. Methods: Fifty-four apparently healthy abdominally obese (waist circumference: 102-110 cm) and 25 normal-weight men (waist circumference: <94 cm) participated. The abdominally obese men were randomly allocated to a diet-induced weight-loss program or a no-weight loss control group. Men assigned to the weight-loss program followed a calorie-restricted diet for six weeks targeting a waist circumference of less than 102 cm, followed by a weight-maintenance period for two weeks. The control group maintained their habitual diet and physical activity levels. Measurements were performed before and two hours after consumption of the test meal consisting of two muffins (containing 56.6 g fat) and 300 mL low-fat milk. Results: The mean weight loss was 10.3 kg in the weight-loss compared with the control group. The postprandial change in flow-mediated vasodilation of the brachial artery (FMD) was significantly higher at baseline in normal-weight as compared with the postprandial change in abdominally obese men (1.89 ± 2.52 versus 0.48 ± 2.50 percentage points; P = 0.027). However, no differences in postprandial changes were observed in the abdominally obese men after weight loss compared with the control treatment. Also, weight reduction did not affect postprandial changes in carotid-to-femoral pulse wave velocity, retinal microvascular caliber properties, or plasma markers of microvascular endothelial function. Even though postprandial increases in triacylglycerol (P = 0.028), insulin (P = 0.029) and C-peptide concentrations (P < 0.001) were reduced in the abdominally obese men following weight loss, postprandial changes in FMD at the end of the weight-loss treatment were still more unfavorable as compared with those observed in normal-weight individuals. Conclusion: In this trial with abdominally obese men, we did not find effects of diet-induced weight loss on postprandial changes in vascular endothelial function, arterial stiffness and markers of microvascular function. This trial was registered on ClinicalTrials.gov under study number NCT01675401.
... An elevated postprandial lipaemia (as indicated by the size or duration of the increase in plasma TAG concentrations following a meal) is associated with an increased risk of cardiometabolic disease, which includes CHD (Eberly et al. 2003;Bansal et al. 2007). Other than the influence on lipoprotein re-modelling, postprandial lipaemia may also increase CHD risk through oxidative stress, inflammation, haemostatic perturbations and endothelial dysfunction (Marchesi et al. 2000;Bae et al. 2001). Thus, determining the postprandial response to different dietary fats may be a more important tool for predicting cardiometabolic risk than fasting lipid concentrations. ...
Article
Full-text available
Interesterification rearranges the position of fatty acids within triacylglycerols, the main component of dietary fat, altering physical properties such as the melting point and providing suitable functionality for use in a range of food applications. Interesterified (IE) fats are one of a number of alternatives which have been adopted to reformulate products to remove fats containing trans fatty acids generated during partial hydrogenation, which are known to be detrimental to cardiovascular health. The use of IE fats can also reduce the saturated fatty acid (SFA) content of the final product (e.g. up to 20% in spreads), while maintaining suitable physical properties (e.g. melt profile). A novel analysis was presented during the roundtable which combined data from the UK National Diet and Nutrition Survey (2012/2013–2013/2014) with expert industry knowledge of the IE fats typically used in food products, to provide the first known estimate of population intakes of IE fats among UK children and adults. IE fats were found to contribute approximately 1% of daily energy across all ages. The major contributors to overall IE fat intakes were fat spreads (~54%) and bakery products (~22%), as well as biscuits (~8%), dairy cream alternatives (~6%) and confectionery (~6%). Increasing use of IE fats could contribute towards reducing total SFA intakes in the population, but would depend on which food products were reformulated and their frequency of consumption among sub‐groups of the population. Studies comparing the effect of IE and non‐IE fats on markers of lipid metabolism have not shown any consistent differences, either in the fasted or in the postprandial state, suggesting a neutral effect of IE fats on cardiovascular disease risk. However, these studies did not use the type of IE fats present in the food supply. This issue has been addressed in two studies by King's College London, which measured the postprandial response to a commercially relevant palm stearin/palm kernel (80:20) IE ‘hard stock’, although again no consistent effects of the IE fat on markers of lipid metabolism were found. Another study is currently investigating the same IE hard stock, consumed as a fat spread (blended with vegetable oil), and will measure a broader range of postprandial cardiometabolic risk factors. However, further long‐term trials using commercially relevant IE fats are needed. Subsequent to the roundtable, a consumer survey of UK adults (n = 2062; aged 18+ years) suggested that there is confusion about the health effects of dietary fats/fatty acids, including trans fats and partially hydrogenated fats. This may indicate that providing evidence‐based information to the public on dietary fats and health could be helpful, including the reformulation efforts of food producers and retailers to improve the fatty acid profile of some commonly consumed foods.
... This indicates that FMD should be measured at 3 or 4 hours postprandially when lipidemia peaks. This timeframe is supported by Marchesi et al, 26 who showed that FMD is changed at 2 hours and 4 hours, but not 6 hours or 8 hours, after consumption of a high fat meal. 3) Exercise: studies have shown that high intensity aerobic exercise performed 16-18 hours before a high-fat meal could preserve endothelial function. ...
Article
Healthy and functional endothelial cells play important roles in maintaining vascular homeostasis, whereas endothelial dysfunction initiates and exacerbates vascular disease progression. Interventional studies with dietary fatty acids have shown that these molecules have varying effects on vascular function. It is hypothesized that the actions of dietary fatty acids on vascular function may be mediated in part through endothelial cells. This review summarizes the results of studies that have examined the acute and chronic effects of dietary fatty acids on endothelial function and vascular properties in humans, as well as the potential mechanisms by which n-3 polyunsaturated fatty acids regulate endothelial function. Altogether, this article provides an extensive review of how fatty acids contribute to vascular function through their ability to modulate endothelial cells and discusses relationships between dietary fatty acids and endothelial cells in the context of vascular dysfunction.
... It has been demonstrated that sustained high triglyceride levels can lead to vascular events, insulin resistance, impaired endothelial function, recruitment of pro-inflammatory cells and imbalance in lipoprotein profiles. [24][25][26][27][28] Considering that, on average, humans spend about 18 h of their day in the postprandial state (nonfasting), 21 postprandial triglyceridaemia is an important target in the prevention of chronic diseases. ...
Article
As the food matrix is a determinant of the rate of fat digestion and absorption, it is important in the modulation of postprandial triglyceridaemia. High postprandial triglyceride levels are associated with an increase in inflammation, oxidative stress, an imbalance in the lipoprotein profile and an increase in the risk of developing chronic diseases. This study was designed to assess the in vitro digestion patterns and the postprandial lipaemic responses to test foods with the same nutrient composition but differing in form and structure. A liquid, a semi-solid and a solid test food with the same nutrient and energy composition were designed. The digestion profiles of the three foods were assessed using a dynamic in vitro model. The foods were also consumed by healthy young adults who donated blood samples after an overnight fast and again 0.5, 1, 2, 3, 4 and 6 h after consuming each of the test foods and who were also assessed for appetite sensations. The solid food showed phase separation during gastric digestion and a lower release of fatty acids during intestinal digestion than the liquid and semi-solid foods. During the postprandial feeding experiments, the solid food caused a lower increase in serum triglycerides than the liquid food and produced higher fullness and satisfaction. In conclusion, food form and structure modulated fat release, postprandial triglyceridaemia and appetite sensations independent of nutrient and energy content. Thus, manipulation of food structure and form may be used in designing strategies for improving metabolic markers and satiety.
... The response to metabolic surplus can include various adverse outcomes, such as vascular events [14,15], insulin resistance [16] or inflammatory cell recruitment [17]. It has also been demonstrated that post-meal hypertriglyceridemia has adverse effects on endothelial function [17,18]. The exchange of core lipids between postprandial lipoproteins and low density lipoprotein and high density lipoprotein is increased during prolonged lipemia, resulting in the formation of highly atherogenic (small and dense) low density lipoprotein particles and reduced high density lipoprotein levels [19]. ...
Article
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One of the limitations for ranking foods and meals for healthiness on the basis of the glycaemic index (GI) is that the GI is subject to manipulation by addition of fat. Postprandial lipemia, defined as a rise in circulating triglyceride containing lipoproteins following consumption of a meal, has been recognised as a risk factor for the development of cardiovascular disease and other chronic diseases. Many non-modifiable factors (pathological conditions, genetic background, age, sex and menopausal status) and life-style factors (physical activity, smoking, alcohol and medication use, dietary choices) may modulate postprandial lipemia. The structure and the composition of a food or a meal consumed also plays an important role in the rate of postprandial appearance and clearance of triglycerides in the blood. However, a major difficulty in grading foods, meals and diets according to their potential to elevate postprandial triglyceride levels has been the lack of a standardised marker that takes into consideration both the general characteristics of the food and the food’s fat composition and quantity. The release rate of lipids from the food matrix during digestion also has an important role in determining the postprandial lipemic effects of a food product. This article reviews the factors that have been shown to influence postprandial lipemia with a view to develop a novel index for ranking foods according to their healthiness. This index should take into consideration not only the glycaemic but also lipemic responses.
... Numerous factors have been reported to be related to this dysfunction [9][10][11] . Among these, lipid abnormalities in the postprandial and fasting states are the important factors 12) . Increased level of serum TG associated with metabolic syndrome or insulin resistant state is particularly closely related to endothelial dysfunction 13) . ...
Article
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Aim: Elevated level of serum triglyceride (TG) is a characteristic of type 2 diabetes. We evaluated the clinical significance of intervention for the serum TG levels in the fasting and postprandial states in patients with type 2 diabetes. Methods: Fifty patients with type 2 diabetes, treated with statins, were selected and divided into two groups. One group was treated with a combination of fenofibrate and ezetimibe (F/E group) and the other group with statins (statin group) for 12 weeks. The lipoprotein profile of both groups was compared using high-performance liquid chromatography, and the vascular function was assessed using flow-mediated dilation (FMD) at the forearm. Results: The levels of very low-density lipoprotein (VLDL) cholesterol, malondialdehyde low-density lipoprotein (MDA-LDL), total TG, chylomicron-TG, VLDL-TG, and HDL-TG decreased in the F/E group, whereas those of HDL cholesterol increased. Furthermore, the peak particle size of LDL increased, but that of HDL decreased in the F/E group. The combination treatment significantly improved the FMD. The change in the cholesterol level in a very small fraction of HDL was a significant independent predictor for determining the improvement of FMD (p<0.01). Conclusions: Compared with the treatment with statins, the treatment with the combination of fenofibrate and ezetimibe effectively controlled the LDL cholesterol and TG levels, increased the HDL cholesterol level, especially in its small fraction, and improved vascular function of patients with type 2 diabetes.
... This resulting reduced NO bioavailability leads to endothelial dysfunction, which is indicated by a suppressed FMD response (26). Previous studies have shown that increases in postprandial TG-rich lipoproteins after a highfat meal temporarily impair endothelial function in young (23 6 2 y) participants (27,28). In the present study, the consumption of a high-fat control meal significantly decreased endothelial function, whereas it was maintained after the consumption of a macronutrient-matched meal with peanuts, and was accompanied by a blunted postprandial TG response. ...
Article
Background: Postprandial hyperlipidemia is associated with impaired endothelial function. Peanut consumption favorably affects the lipid and lipoprotein profile; however, the effects on endothelial function remain unclear. Objective: The purpose of the study was to evaluate the effects of acute peanut consumption as part of a high-fat meal on postprandial endothelial function. Methods: We conducted a randomized, controlled, crossover postprandial study to evaluate the effect of acute peanut consumption on postprandial lipids and endothelial function as assessed by flow-mediated dilatation (FMD) of the brachial artery in 15 healthy overweight or obese men [mean age: 26.7 y; mean body mass index (in kg/m²): 31.4]. Participants consumed, in a randomized order, a peanut meal containing 3 ounces (85 g) ground peanuts (1198 kcal; 40.0% carbohydrate, 47.7% fat, 19.4% saturated fat, 13.2% protein) and a control meal matched for energy and macronutrient content. Meals were in the form of a shake, scheduled ≥1 wk apart. Lipids, lipoproteins, glucose, and insulin were measured at baseline (0 min) and at 30, 60, 120, and 240 min after shake consumption. FMD was measured at baseline and at 240 min. Results: Acute peanut consumption blunted the serum triglyceride (TG) response 120 and 240 min after consumption compared with the control meal (means ± SEMs—120 min: 188.9 ± 19.4 compared with 197.5 ± 20.7 mg/dL; 240 min: 189.9 ± 24.3 compared with 197.3 ± 18.4 mg/dL; P < 0.05 for both). Total, LDL, and HDL cholesterol and glucose and insulin responses were similar between the test meals. Compared with baseline, only the control meal significantly decreased FMD at 240 min (control: −1.2% ± 0.5%; P = 0.029; peanut: −0.6% ± 0.5%; P = 0.3). Participants with higher baseline total (>150 mg/dL) and LDL (>100 mg/dL)-cholesterol concentrations showed a significant decrease in FMD after the control meal (−1.8%, P = 0.017; −2.0%, P = 0.038), whereas the peanut meal maintained endothelial function in all participants irrespective of total- and LDL-cholesterol concentrations. Conclusion: The inclusion of 85 g peanuts (3 ounces) as part of a high-fat meal improved the postprandial TG response and preserved endothelial function in healthy overweight or obese men. This trial was registered at clinicaltrials.gov as NCT01405300.
... Flow-mediated vasodilation was assessed in the brachial artery by ultrasonography as previously described 29 . The measurements were performed on the nondominant arm while the patient was in the supine position, after 10 to 20 minutes rest. ...
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Endothelial dysfunction, a marker of cardiovascular (CV) risk, is common in human immunodeficiency virus (HIV)-infected patients. Microalbuminuria is frequent in HIV-infected patients, and is a predictor of renal impairment and CV risk. We investigated the association between microalbuminuria and endothelial dysfunction among HIV-infected patients receiving highly-active antiretroviral therapy (HAART). Endothelial function, measured by brachial artery flow-mediated dilatation (bFMD), and urine albumin-to-creatinine ratio (UACR), were measured in 170 HAART-treated HIV-infected adults. The relationship between UACR and bFMD was evaluated. The prevalence of increased UACR, defined by two cut-off levels (20 mg/g and 30 mg/g), was 29% and 17%. UACR was significantly higher while bFMD was lower among patients with metabolic syndrome (MS). UACR was associated with bFMD (r = −0.31; p < 0.001). This association was stronger in MS-patients (r = −0.44; p = 0.003). UACR above 20 mg/g was associated with an increased risk (OR 2.37, 95% CI 1.15–4.89, p = 0.020) of severely impaired bFMD (bFMD ≤ 2.1%). Patients with MS and increased UACR had the lowest bFMD compared with those with none or one of the two conditions. Microalbuminuria and endothelial dysfunction are positively associated in HIV-infected patients regardless of known confounders. The coexistence of microalbuminuria and MS amplifies their deleterious influence on endothelial function.
... We have shown that children with type 1 diabetes have a less proatherogenic lipoprotein profile than controls despite increased arterial stiffness (1,11). In addition, small studies of young healthy adult males who received a high-fat meal did show transient impairment of brachial artery vasodilation (12,13). Thus, the lack of lipid studies obtained in the postmeal state is a limitation of our study. ...
Article
Objective: To determine the effects of omitting meal time insulin on arterial stiffness in children with type 1 diabetes. Research design and methods: In this prospective, randomized, crossover study, radial artery tonometry and augmentation index adjusted to heart rate 75 (AI75 ) were used to measure arterial stiffness. Children were randomized to receive or omit premeal insulin and completed the crossover portion of the study on a subsequent day. AI75 was determined when fasting, 1, and 2 h postmeal. Results: When comparing change in AI75 from baseline to 1 h and baseline to 2 h, when subjects received premeal insulin vs. no insulin, AI75 was 4.5 units lower at 1 h (p = 0.011, 95% CI:1.1 lower to 8 lower) and 4.3 units lower at 2 h (p = 0.062, 95% CI: 0.2 higher to 8.9 lower) (n = 40). Conclusions: Arterial stiffness is decreased by premeal insulin in children with type 1 diabetes.
... The majority of the experiments highlighted a significant impairment of postprandial endothelial function following a high fat meal [47][48][49][50]. Notably, Vogel et al. [49] and Plotnick et al. [50] showed a correlation between the magnitude of postprandial hypertriacylglycerolaemia and the degree of endothelial function impairment. ...
Article
Full-text available
Type 2 diabetes is characterized by a gradual decline in insulin secretion in response to nutrient loads; hence, it is primarily a disorder of postprandial glucose regulation. However, physicians continue to rely on fasting plasma glucose and glycated hemoglobin to guide management. There is a linear relationship between the risk of cardiovascular death and the 2-h oral glucose tolerance test, while a study confirms postprandial hyperglycemia as independent risk factor for cardiovascular disease in type 2 diabetes. At the same time, several studies show that postprandial hypertriglyceridemia may also be a cardiovascular risk factor. Interestingly, the simultaneous presence of postprandial hyperglycemia and postprandial hypertriglyceridemia has an additive effect in worsening endothelial function and inflammation. Evidence supports the hypothesis glucose postprandial hyperglycemia and hypertriglyceridemia may favor the appearance of the cardiovascular disease through the generation of an oxidative stress. Furthermore, clinical data suggest that postprandial hyperglycemia is a common phenomenon even in patients who may be considered in “good metabolic control”. Therefore, physicians should consider monitoring and targeting postprandial plasma glucose, as well as glycated hemoglobin and fasting plasma glucose, in patients with type 2 diabetes.
... Ainsi, en faisant abstraction de la nature des acides gras utilisés, il a été observé qu'une augmentation des concentrations en triglycérides plasmatiques de 60-130% induisait une diminution de la FMD de 40-100% par rapport aux données obtenues avant le test de provocation. Très souvent, une forte corrélation (Tableau 1) entre la diminution de FMD et l'hypertriglycéridémie induite a été rapportée Boquist et al. 1999;Marchesi et al. 2000;Raitakari et al. 2000;Bae et al. 2001;Gaenzer et al. 2001). Cependant, quand les tests de provocation utilisaient des doses très élevées en lipides ou des charges lipidiques pures, cette corrélation entre FMD et hypertriglycéridémie était moins forte. ...
Article
The alteration in vascular endothelial function is the key event in the pathophysiology of atherosclerosis. In healthy humans, a single high-saturated fat/high sucrose meal induces a series of transient vascular, inflammatory and oxidative disturbances that constitute a complex proatherogenic phenotype. However, little is known on early pathways that occur during the postprandial state. Furthermore, some amino acids have been suspected of having an impact on vascular homeostasis, but there is a paucity of information regarding the effect of dietary protein on the initiation of endothelial dysfunction. We aimed to characterize an animal model of postprandial endothelial dysfunction induced by a high-saturated fat meal (HFM), in healthy rats, in which to delineate the early inflammatory response in adipose tissue, and examine whether the nitric oxide (NO) pathway is impaired in the postprandial setting. Using this model, we have explored whether rapeseed protein, an emergent protein rich in arginine and cysteine may modulate postprandial endothelial dysfunction. We have clearly characterized a rat model of postprandial endothelial dysfunction, featuring oxidative stress, impairment of the NO pathway and low-grade inflammation. We have revealed that inflammatory pathways are activated very early in the visceral adipose tissue, and the HFM markedly impair basal systemic whole-body NO production. Interestingly, modulating the protein source of the HFM has a marked protective effect on postprandial endothelial function in healthy rats. Substituting rapeseed protein for milk protein in an HFM totally suppresses postprandial impairment of vascular reactivity and partially decreases postprandial oxidative stress. These results urge on further studies to examine the clinical relevance of specific protein source, in dietary strategies for the prevention of cardiovascular diseases.
... Only one previous study (22) reports quantitative data regarding OLE metabolites in plasma, suggesting peak plasma concentrations of 0·52 ng/ml oleuropein and 61 ng/ml HT after OLE consumption. Evidence suggests that lipaemia induced after consumption of high and moderate fat-containing meals causes acute vascular dysfunction (38) . In the present study, our intervention meal (containing 7·6 g fat and 48·5 g carbohydrate) caused an increased DVP-SI, peaking at 480 min. ...
Article
Full-text available
The leaves of the olive plant ( Olea europaea ) are rich in polyphenols, of which oleuropein and hydroxytyrosol (HT) are most characteristic. Such polyphenols have been demonstrated to favourably modify a variety of cardiovascular risk factors. The aim of the present intervention was to investigate the influence of olive leaf extract (OLE) on vascular function and inflammation in a postprandial setting and to link physiological outcomes with absorbed phenolics. A randomised, double-blind, placebo-controlled, cross-over, acute intervention trial was conducted with eighteen healthy volunteers (nine male, nine female), who consumed either OLE (51 mg oleuropein; 10 mg HT), or a matched control (separated by a 4-week wash out) on a single occasion. Vascular function was measured by digital volume pulse (DVP), while blood collected at baseline, 1, 3 and 6 h was cultured for 24 h in the presence of lipopolysaccharide in order to investigate effects on cytokine production. Urine was analysed for phenolic metabolites by HPLC. DVP-stiffness index and ex vivo IL-8 production were significantly reduced ( P < 0·05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8–24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production in vivo , adding to growing evidence that olive phenolics could be beneficial for health.
... Only one previous study (22) reports quantitative data regarding OLE metabolites in plasma, suggesting peak plasma concentrations of 0·52 ng/ml oleuropein and 61 ng/ml HT after OLE consumption. Evidence suggests that lipaemia induced after consumption of high and moderate fat-containing meals causes acute vascular dysfunction (38) . In the present study, our intervention meal (containing 7·6 g fat and 48·5 g carbohydrate) caused an increased DVP-SI, peaking at 480 min. ...
Article
Full-text available
The leaves of the olive plant (Olea europaea) are rich in polyphenols, of which oleuropein and hydroxytyrosol (HT) are most characteristic. Such polyphenols have been demonstrated to favourably modify a variety of cardiovascular risk factors. The aim of the present intervention was to investigate the influence of olive leaf extract (OLE) on vascular function and inflammation in a postprandial setting and to link physiological outcomes with absorbed phenolics. A randomised, double-blind, placebo-controlled, cross-over, acute intervention trial was conducted with eighteen healthy volunteers (nine male, nine female), who consumed either OLE (51 mg oleuropein; 10 mg HT), or a matched control (separated by a 4-week wash out) on a single occasion. Vascular function was measured by digital volume pulse (DVP), while blood collected at baseline, 1, 3 and 6 h was cultured for 24 h in the presence of lipopolysaccharide in order to investigate effects on cytokine production. Urine was analysed for phenolic metabolites by HPLC. DVP-stiffness index and ex vivo IL-8 production were significantly reduced (P,0·05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8 –24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production in vivo, adding to growing evidence that olive phenolics could be beneficial for health.
... Additionally, the accumulation of O 2 À and ONOO À leads to an inhibition of endothelial NO synthase (eNOS), the enzyme responsible for endogenous endothelial NO production [5]. Some studies have indeed reported a negative correlation between the magnitude of lipemia and the change in endothelial function [20,21]. However, like several other studies [22e24], we found no significant correlation. ...
Article
Through effects on nitric oxide (NO) bioavailability, endothelial function is improved after the intake of beetroot juice-which is rich in inorganic nitrate-, but decreased after the intake of a meal. The objective of this study was to examine if beetroot juice could counteract the impairment of endothelial function associated with the ingestion of a mixed meal. Twenty healthy overweight and slightly obese men with a BMI between 28 and 35 kg/m(2) received in random order a mixed meal providing 56.6 g of fat with beetroot juice or a control drink. The beetroot juice (140 mL) provided approximately 500 mg dietary nitrate. Flow-mediated dilation (FMD) of the brachial artery was measured before and 2 h after meal consumption. Blood was sampled at regular intervals. Postprandial changes in serum triacylglycerol (TAG) (P = 0.69), plasma glucose (P = 0.84) and insulin (P = 0.67) concentrations were comparable between the meals. After consumption of beetroot juice, the postprandial impairment in FMD following a standardized mixed meal was improved (P = 0.030) compared with the control drink (-0.37 ± 2.92% versus -1.56 ± 2.90%). Following beetroot juice consumption, plasma concentrations of the circulating NO pool were higher at T60, T120, and T240 (P < 0.001 at all time points). In healthy overweight and slightly obese men a single dose of beetroot juice attenuates the postprandial impairment of FMD following a mixed meal, possibly through increases in plasma NO concentrations.
... Está bem estabelecido que durante um estado prolongado e acentuado de lipemia pós-prandial ocorrem trocas de lípides neutros entre partículas ricas em triglicérides, LDL e HDL, levando à formação de partículas de LDL pequenas e densas e a uma menor concentração de HDL-C 34 . Mais recentemente, foi relatado que a função endotelial está alterada no estado pós-prandial, relacionando-se à elevação dos triglicérides pós-prandiais 35 . Outros estudos mostraram ainda que, em indivíduos saudáveis, as concentrações plasmáticas de citocinas infl amatórias e moléculas de adesão estavam elevadas após ingestão de dietas ricas em gorduras, mas não em carboidratos 36 , causando um estado pró-infl amatório transitório. ...
Article
Full-text available
OBJETIVO: Examinar os efeitos de uma sessão isolada de exercício físico isométrico na trigliceridemia pós-prandial em homens sedentários com valores de triglicérides em jejum < 150 mg/dl (NTG) ou > 150 mg/dl (TGALT). MÉTODOS: Foram avaliados 27 indivíduos (10 NTG e 17 TGALT), com idade entre trinta e 55 anos. Os triglicérides foram determinados no início, e após duas, quatro e seis horas da ingestão oral de uma solução com 50g/m2 de gordura em duas oportunidades, em repouso e após exercício isométrico em esteira. RESULTADOS: O exercício agudo não modificou os níveis pós-prandiais de triglicérides, ou a área sob a curva (AUC) de triglicérides. Entretanto, o padrão anormal da curva de lipemia pós-prandial associou-se a maior trigliceridemia basal com exercício (TG basais: 147 ± 90 versus 238 ± 89 mg/dl, p = 0,02) e sem exercício (TG basais: 168 ± 93 versus 265 ± 140 mg/dl, p = 0,04). A análise das curvas ROC (receive operating characteristics) mostrou valores de corte de triglicérides basais com atividade física de 166,5 mg/dl (sensibilidade: 0,78; especificidade: 0,72) e AUC de 0,772 [IC 95%: 0,588-0,955], e sem atividade física de 172 mg/dl (sensibilidade: 0,78; especificidade: 0,61) e AUC de 0,722 [IC 95%: 0,530-0,914]. CONCLUSÃO: A trigliceridemia pós-prandial em homens sedentários não foi modificada pelo exercício agudo, sendo os valores basais de triglicérides preditores de uma resposta anormal dos triglicérides pós-prandiais.
... Está bem estabelecido que durante um estado prolongado e acentuado de lipemia pós-prandial ocorrem trocas de lípides neutros entre partículas ricas em triglicérides, LDL e HDL, levando à formação de partículas de LDL pequenas e densas e a uma menor concentração de HDL-C 34 . Mais recentemente, foi relatado que a função endotelial está alterada no estado pós-prandial, relacionando-se à elevação dos triglicérides pós-prandiais 35 . Outros estudos mostraram ainda que, em indivíduos saudáveis, as concentrações plasmáticas de citocinas infl amatórias e moléculas de adesão estavam elevadas após ingestão de dietas ricas em gorduras, mas não em carboidratos 36 , causando um estado pró-infl amatório transitório. ...
... Furthermore, other studies demonstrated that postprandial hyperlipemia caused by oral fat intake impairs endothelial dysfunction as detected with flowmediated dilatation (FMD) of the brachial artery in healthy volunteers. This endothelial dysfunction is associated with postprandial TG-rich lipoproteins [6,7]. Therefore, identification of novel therapeutic approaches that would beneficially affect postprandial concentrations of lipids is of great interest. ...
Article
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Background Postprandial hyperlipidemia impairs endothelial function and participates in the development of atherosclerosis. We investigated the postprandial effects of a dipeptidyl peptidase IV inhibitor, alogliptin, on endothelial dysfunction and the lipid profile. Methods A randomized cross-over trial design in 10 healthy volunteers (8 males and 2 females, 35 ± 10 years) was performed. The postprandial effects before and after a 1-week treatment of 25 mg/day alogliptin on endothelial function were assessed with brachial artery flow-mediated dilation (FMD) and changing levels of lipids, apolipoprotein B48 (apoB-48), glucose, glucagon, insulin, and glucagon-like peptide-1 (GLP-1) during fasting and at 2, 4, 6, and 8 h after a standard meal loading test. Results Alogliptin treatment significantly suppressed the postprandial elevation in serum triglyceride (incremental area under the curve [AUC]; 279 ± 31 vs. 182 ± 32 mg h/dl, p = 0.01), apoB-48 (incremental AUC; 15.4 ± 1.7 vs. 11.7 ± 1.1 μg h/ml, p = 0.04), and remnant lipoprotein cholesterol (RLP-C) (incremental AUC: 29.3 ± 3.2 vs. 17.6 ± 3.3 mg h/dl, p = 0.01). GLP-1 secretion was significantly increased after alogliptin treatment. Postprandial endothelial dysfunction (maximum decrease in%FMD, from −4.2 ± 0.5% to −2.6 ± 0.4%, p = 0.03) was significantly associated with the maximum change in apoB-48 (r = −0.46, p = 0.03) and RLP-C (r = −0.45, p = 0.04). Conclusion Alogliptin significantly improved postprandial endothelial dysfunction and postprandial lipemia, suggesting that alogliptin may be a promising anti-atherogenic agent.
Article
Problem Normal-weight obesity (NWO) is associated with increased cardiovascular disease (CVD) risk. However, NWO’s clinical presentation is often unremarkable based on common risk factors. We examined whether CVD risk factors not routinely measured clinically including postprandial triglycerides, flow-mediated dilation (FMD), and inflammatory cytokines would be abnormal in NWO, consistent with their future risk. Methods Individuals were recruited into 3 groups (n = 10/ group): controls (Con), NWO, and metabolic syndrome (MetS). Con was defined as a normal body mass index (BMI), < 25% (M) or < 35% (F) body fat, and < 1 International Diabetes Federation (IDF) criteria. NWO were above this body fat cutoff while maintaining a normal BMI and MetS was defined per the IDF. Participants underwent an abbreviated fat tolerance test (i.e., difference in fasting and 4 h triglycerides following a high-fat meal [9 kcal/kg; 73% fat)] and fasting and postprandial lipid and glucose metrics, as well as FMD were measured. A T cell cytokine bioplex was also performed using fasting serum. Results NWO and MetS had similar body fat% and both were higher than Con (p < 0.0001). Despite having similar fasting triglycerides to Con, NWO had 4-hour triglycerides 66% greater than Con, but 46% lower than MetS (p < 0.01). FMD decreased in all groups after the high-fat meal (p < 0.0001). MetS displayed lower fasting FMD than Con, and NWO was similar to both groups (p < 0.05). No group differences were observed with postprandial FMD and the majority of fasting cytokines assessed. However, MetS exhibited higher fasting TNF-α than Con (p < 0.05), and NWO was similar to both groups. Conclusions Overall, NWO was associated with higher postprandial triglycerides than Con, but displayed little evidence of impaired vascular health or inflammation.
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Background Endothelial dysfunction is a predictive risk factor for the development of atherosclerosis and is assessed by flow-mediated dilation (FMD). Although it is known that nitric oxide-dependent endothelial dysfunction occurs after consuming a high-fat meal, the magnitude of the effect and the factors that affect the response are unquantified. Objectives To conduct a systematic review and meta-analysis exploring the quantitative effect of a single high-fat meal on endothelial function and determine the factors that modify the FMD response. Design Six databases were systematically searched for original research published up to January 2022. Eligible studies measured fasting and postprandial FMD following consumption of a high-fat meal. Meta-regression was used to analyze the effect of moderator variables. The protocol was pre-registered in the Prospero database (ID# CRD42020187244). Results There were 131 studies included of which 90 were suitable for quantitative meta-analysis. A high-fat meal challenge transiently caused endothelial dysfunction, decreasing postprandial FMD at 2-hours: -1.02 percentage points (pp) (95% CI: [-1.34, -0.70], P < 0.01, I2 = 93.3%), 3-hours: -1.04 pp ([-1.48, -0.59], P < 0.001, I2 = 84.5%), and 4-hours: -1.19 pp ([-1.53, -0.84], P < 0.01, I2 = 94.6%). Younger, healthy-weight participants exhibited a greater postprandial reduction in FMD% than older, heavier, at-risk groups after a high-fat meal (P < 0.05). Percent fat of the meals was inversely associated with the magnitude of postprandial change in FMD at 3-hours (P < 0.01). Conclusion A single high-fat meal adversely impacts endothelial function, with the magnitude of the impact on postprandial FMD moderated by fasting FMD, participant age, body mass index, and fat content of the meal. Recommendations are made to standardize the design of future postprandial FMD studies and optimize interpretation of results, as high-fat meals are commonly used in clinical studies as a challenge to assess endothelial function and therapeutics.
Article
Aims: Type 2 Diabetes Mellitus (T2DM) is associated with an increased risk for cardiovascular disease (CVD) linked to atherogenic dyslipidemia and postprandial hyperlipidemia. Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, improves CVD risk by reducing the concentration of low-density lipoprotein-cholesterol (LDL-C). However, effects of PCK9 inhibitors on other aspects of diabetic dyslipidemia, especially in the postprandial situation, are less clear. Material and methods: Twelve male patients with T2DM on intensive insulin regimen completed a six week randomized, double-blind, placebo-controlled, proof-of-concept study. Participants received 3 biweekly dosages of subcutaneous alirocumab (150 mg) or placebo. Before and after the intervention, fasting and postprandial triglyceride (TG) plasma levels, apolipoprotein (apo) B48, lipoprotein composition isolated by ultracentrifugation, vascular function and markers of inflammation were evaluated. Results: Alirocumab treatment reduced fasting plasma TG levels (between group median change (-24.7%; p=0.018) and fasting apo B48 serum levels (-35.9%; p=0.039) compared to placebo. Alirocumab reduced the plasma TG area under the curve (AUC) (-26.43%; p=0.006) and apo B48 AUC (-55.7%; p=0.046), as well as plasma TG incremental AUC (-21.4%; p=0.04) and apo B48 incremental AUC (-26.8%; p=0.02). In addition, alirocumab reduced fasting and postprandial TG levels in VLDL and LDL. Alirocumab improved fasting pulse wave velocity, but no changes in postprandial markers of inflammation were observed. Conclusions: In addition to the well-known LDL-C-reducing effects, 6-weeks alirocumab treatment lowered both fasting and postprandial plasma TG levels by reducing the TG levels in VLDL and LDL and the concentration of intestinal remnants. This article is protected by copyright. All rights reserved.
Article
Background: Left ventricular ejection fraction (LVEF) is a valuable measure to assess left ventricular systolic function. Lipid lowering therapy by statins has been shown to have an impact on LVEF already after a 6 months treatment. Higher doses of statins have been claimed to be more effective as compared to a conventional one and even a difference between lipophilic and hydrophilic compounds has been reported. The effect of regular lipoprotein-apheresis (LP-apheresis) on LVEF was previously poorly examined. Patients involved in a regular LP-apheresis program are supposed to undergo a number of follow-up investigations among them myocardial scintigraphy and LVEF, measured by radionuclide ventriculography. Methods: We examined 18 patients before initiation and after one year of ongoing LP-apheresis. 13 patients (11 males, 2 females, mean age 58.3 ± 5.3 years, groups A) were since more than a year on stable, unchanged statin treatment (atorvastatin 40 mg, simvastatin 40 mg, rosuvastatin 20 mg±ezetimibe), the other 5 patients (3 males, 2 females, mean age 57.1 ± 4.6 years, group B) were intolerant to statins being on micronized fenofibrate±resorption inhibitors (cholestyramine). All patients had a Lp(a) < 30 mg/dl. As part of the usual follow-up monitoring, LVEF was determined by means of radionuclide ventriculography after application of 550 MBq 99m Tc-pertechnetate. Results: The follow-up LVEF was checked at a mean of 48.7 weeks in group A and 51.2 weeks in group B. Except in 1 patient (LVEF 46.8% before vs. 45.2% after LP-apheresis initiation) in group A we noted a significant increase in LVEF in 12 patients of group A (92%) and in all patients of group B. Mean LVEF increased significantly in both groups (A: 42.7±8.1 → 46.5±7.5% (p < 0.001) and B: 41.9±8.4 → 46.5±6.3 %; p < 0.001). The relative rise was nearly identical (group A 9.6%, in group B 9.7%). Conclusions: Our findings indicate that regular long-term LP-apheresis treatment apparently increases LVEF, independently on current statin treatment. This implies a role of lowering of atherogenic lipoproteins as underlying mechanism. A prospective study should clarify the relative extent of LVEF improvement induced by LP-apheresis.
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Post-prandial hyperlipidaemia (PPH) acutely impairs systemic vascular endothelial function, potentially attributable to a free radical-mediated reduction in vascular nitric oxide (NO) bioavailability (oxidative-nitrosative stress). However, it remains to be determined whether this extends to the cerebrovasculature. To examine this, 38 (19 young (≤ 35 years) and 19 aged (≥ 60 years)) healthy males were recruited. Cerebrovascular function (middle cerebral artery velocity, MCAv) and cerebrovascular reactivity to hypercapnea (CVRCO2Hyper) and hypocapnea (CVRCO2Hypo) were determined via trans-cranial Doppler ultrasound and capnography. Venous blood samples were obtained for the assessment of triglycerides (photometry), glucose (photometry), insulin (radio-immunoassay), ascorbate free radical (A(•-), electron paramagnetic resonance spectroscopy) and nitrite (NO2(-), ozone-based chemiluminescence) in the fasted state prior to and 4 hours following consumption of a standardised high-fat meal (1,362 kcal; 130g of fat). Circulating triglycerides, glucose and insulin increased in both groups following the high-fat meal ( P < 0.05), with triglycerides increasing by 1.37 + 1.09 mmol/L in the young and 1.54 + 1.00 mmol/L in the aged ( P < 0.05). This resulted in an increased systemic formation of free radicals in the young ( P < 0.05) but not the aged ( P > 0.05) and corresponding reduction in NO2(-) in both groups ( P < 0.05). While the meal had no effect on MCAv in either age group, CVRCO2Hyper was selectively impaired in the aged ( P < 0.05). These findings indicate that PPH causes acute cerebrovascular dysfunction in the aged subsequent to systemic nitrosative stress.
Article
Background: Only a few studies have reported on postprandial lipid responses and endothelial function in prediabetic subjects. None of the study has compared role of familial predisposition in determining postprandial endothelial dysfunction and postprandial hypertriglyceridemia in subjects with prediabetes. Objective: The objective was to study the postprandial triglyceride (PPTG) responses and endothelial function in prediabetic first-degree relatives of patients with diabetes. Methods: Thirty-nine subjects were recruited on the basis of oral glucose tolerance test into 3 groups: group 1, prediabetic subjects who had a first-degree relative with diabetes; group 2, prediabetic subjects without family history of diabetes; and group 3, normal glucose tolerance subjects without family history of diabetes. Oral fat challenge test was performed in all study subjects and PPTG responses were measured up to 8 hours. Postprandial endothelial function after 4 hours of fat challenge was estimated by flow-mediated dilation. Results: Postprandial endothelial dysfunction was greatest in group 1 and significantly higher in group 1 compared with group 2 (P < .001) and group 2 compared with group 3 (P < .001). PPTG responses (TG-AUC, TG-peak, TG-6 hour, and TG-8 hour) were significantly higher in group 1 compared with groups 2 and 3. However, they were similar between groups 2 and 3. Endothelial function showed significant negative correlation with TG-6 hour and TG-8 hour. Conclusion: Prediabetic subjects respond to fat challenge with a greater degree of TG response and endothelial dysfunction compared with normal glucose tolerance subjects especially if they have a first-degree relative with diabetes. This may contribute to enhanced cardiovascular risk reported in prediabetic individuals.
Article
Background Lipoprotein(LP)-apheresis is the treatment of choice in patients suffering from severe familial hypercholesterolemia. A wide range of mechanisms has been claimed to be responsible for the known clinical benefit. Methods Patients suffering from heterozygous familial hypercholesterolemia undergoing LP-apheresis either with direct adsorption of lipoproteins (DALI) or dextran sulfate (DS) were examined. A total volume of 10 l blood was exchanged. Non-lipid effects, mainly concerning endothelial function (circulating endothelial cells, circulating endothelial progenitor cells, flow-mediated vasodilation, microalbuminuria) as well as left ventricular ejection fraction and homocysteine were assessed. Results A single LP-apheresis session improves paradox contractile response in statin intolerant patients, but not in those on regular statin therapy. In contrast, over a 6-months follow-up after treatment initiation, all the examined parameters (circulating endothelial cells, circulating endothelial progenitor cells, flow mediated vasodilatation, homocysteine, microalbuminuria and left ventricular ejection fraction) improved. When available, a comparison between DS vs. DALI was performed. In none of the subgroups a significant difference was noted. Discussion These findings indicate that beyond the well known lipid/lipoprotein lowering action the broad spectrum of functional tests examined reflecting mainly endothelial function is significantly improved by LP-apheresis treatment on the long-term and seems to be a key underlying reason for the clinical improvement seen in these patients.
Article
Postprandial hypertriglyceridemia and hyperglycemia may promote endothelial and hemorheological dysfunction. The present study investigated the effects of pravastatin on endothelial function and hemorheology in patients with stable angina pectoris (AP) before and after eating a test meal. We recruited 26 patients with stable AP who had impaired glucose tolerance and mild dyslipidemia and six healthy men as controls to assess endothelial function and hemorheological behavior. In each group, we measured forearm blood flow (FBF) during post-ischemic reactive hyperemia and obtained blood samples before and 2 h after the test meal. Pravastatin 20 mg/day was then commenced in the 26 AP patients. The above tests were repeated after 2 days and 6 months. Maximum FBF during hyperemia in the baseline fasting phase was significantly lower in the AP patients than in the controls (p < 0.05). Fasting and postprandial FBF during reactive hyperemia time-dependently improved after pravastatin treatment (p < 0.05 vs. baseline data for each phase). Pravastatin treatment for 6 months, but not for 2 days, inhibited leukocyte activation and improved hemorheological parameters. In conclusion, pravastatin treatment for 6 months improved fasting and postprandial endothelial and hemorheological dysfunction in AP patients.
Article
Endothelial dysfunction has been proposed as an early manifestation of atherosclerosis. The risk for atherosclerosis is increased in patients with. diabetes mellitus, but the mechanism of the increased risk in these patients remains to be elucidated. Emerging evidence suggests that postprandial hyperglycaemia and hyperlipidemia are important risk factors in the development of atherosclerosis in patients with diabetes. Using a high-resolution ultrasound technique, we evaluated the acute effects of oral glucose loading on endothelium-dependent flow-mediated dilation (EFMD) and endothelium-independent flow-mediated dilation (EIFMD) of the brachial artery in 11 men (mean age: 59+/-5 years) with type 2 diabetes without chronic complications of diabetes. During these examinations, changes in the level of superoxide anion formation in the neutrophils were also measured. In addition, to investigate the relationship between acute hypertriglyceridemia and EFMD, we assessed the effects of high- and low-fat meals on EFMD of the brachial artery in 12 healthy volunteers. EFMD was diminished after glucose loading (13.2%+/-6.4%, 7.3%+/-3.3%*, 12.8%+/-5.6%, in fasting and at 1 and 2 hours, respectively, *P<0.001 vs fasting). Superoxide anion formation by neutrophils, (expressed as 10(-7) nmoll 10(6) cells/30 min) was increased after glucose loading (4.7&PLUSMN;2.8 and 6.2&PLUSMN;2.2 in fasting and at one hour, respectively, P<0.05). EIFMD and triglyceride concentrations were not significantly affected by glucose loading. EFMD was also decreased by high-fat feeding (13.1%+/-4.3%, 7.7%+/-3.7%*, 7.3%+/-2.2%*, basal, 2 hours, and 4 hours, respectively; *P<0.01 vs basal). These decreases were reversed by vitamin E treatment These results show that acute hyperglycaemia induced by 75 gm oral glucose intake and acute hypertriglyceridemia induced by high-fat feeding are implicated in endothelial dysfunction. In addition, these results suggest that chronic and repeated hyperglycaemia and hypertriglyceridemia may play important roles in the development and progression of vascular complications in diabetes, probably through increased oxidative stress.
Article
Statin therapy targeting reduction of low-density lipoprotein cholesterol (LDL-C) decreases the risk of coronary heart disease (CHD) and all-cause mortality. However, a substantial number of cases of CHD are not prevented and residual risk factors remain unsettled. A high triglyceride (TG) level is considered to be an important and residual risk factor. Postprandial hyperlipidemia is a condition in which TG-rich chylomicron remnants are increased during the postprandial period and hypertriglycedemia is protracted. Postprandial hyperlipidemia evokes atherogenesis during the postprandial period. Several prospective studies have revealed that nonfasting serum TG levels predict the incidence of CHD. Values of TG, remnant lipoprotein cholesterol, and remnant lipoprotein TG after fat loading were significantly higher in diabetes patients with insulin resistance than in diabetes patients without insulin resistance. Endothelial dysfunction is an initial process of atherogenesis and it contributes to the pathogenesis of CHD. Postprandial hyperlipidemia (postprandial hypertriglyceridemia) is involved in the production of proinflammatory cytokines, recruitment of neutrophils, and generation of oxidative stress, resulting in endothelial dysfunction in healthy subjects, hypertriglyceridemic patients, or type 2 diabetic patients. Effective treatment has not been established till date. Ezetimibe or omega-3 fatty acids significantly decrease postprandial TG elevation and postprandial endothelial dysfunction. Ezetimibe or omega-3 fatty acids added to statin therapy reduce serum TG levels and result in good outcomes in patients with CHD. In conclusion, postprandial hyperlipidemia is an important and residual risk factor especially in patients with insulin resistance syndrome (metabolic syndrome) and diabetes mellitus. Further studies are needed to establish effective treatment.
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It is well known that endothelial dysfunction (ED) contributes to the pathogenesis of atherosclerosis. Several risk factors such as hypertension, smoking, diabetes mellitus (DM) and others including hyperlipidemia predispose to endothelial ED. Studies have shown that hyperlipidemia has an impact on endothelium-derived nitric oxide (NO), an endogenous anti-atherogenic molecule promoting the initiation and evolution of atherosclerosis. Several studies have evaluated the vascular effects of hyperlipidemia demonstrating that impaired endothelium-dependent dilation exists in asymptomatic individuals with hyperlipidemia. Thus, several agents have been examined in terms of their effects on the lipid profile of these patients. Interestingly, many of them exert beneficial vascular effects beyond their hypolipidemic effects and have been found to improve and restore endothelial function. Whether these agents could prevent or slow-down atherosclerosis via their effects on vascular endothelium is still under investigation.
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The relevance of homocysteine to brachial flow-mediated vasodilatation and carotid and femoral intima-media thickness was investigated in 192 patients with hypercholesterolemia. Low-density lipoprotein cholesterol and homocysteine levels predicted brachial flow-mediated vasodilatation, internal carotid mean intima-media thickness, and intima-media thickening at all femoral sites. Homocysteine levels seem to be an additional factor in the initial atherosclerotic damage of patients with hypercholesterolemia.
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Purpose: Plant-based nutrition achieved coronary artery disease (CAD) arrest and reversal in a small study. However, there was skepticism that this approach could succeed in a larger group of patients. The purpose of our follow-up study was to define the degree of adherence and outcomes of 198 consecutive patient volunteers who received counseling to convert from a usual diet to plant-based nutrition. Methods: We followed 198 consecutive patients counseled in plant-based nutrition. These patients with established cardiovascular disease (CVD) were interested in transitioning to plant-based nutrition as an adjunct to usual cardiovascular care. We considered participants adherent if they eliminated dairy, fish, and meat, and added oil. Results: Of the 198 patients with CVD, 177 (89%) were adherent. Major cardiac events judged to be recurrent disease totaled one stroke in the adherent cardiovascular participants—a recurrent event rate of .6%, significantly less than reported by other studies of plant-based nutrition therapy. Thirteen of 21 (62%) nonadherent participants experienced adverse events. Conclusion: Most of the volunteer patients with CVD responded to intensive counseling, and those who sustained plant-based nutrition for a mean of 3.7 years experienced a low rate of subsequent cardiac events. This dietary approach to treatment deserves a wider test to see if adherence can be sustained in broader populations. Plant-based nutrition has the potential for a large effect on the CVD epidemic.
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Prior studies have demonstrated impaired endothelium-dependent flow-mediated dilation (FMD) in healthy subjects following a high-fat meal. Compared to uninfected individuals, HIV-infected persons have been shown to have impaired FMD. We examined the effect of 2 different high-fat meals on endothelial function in HIV-infected and uninfected men. We performed a randomized, parallel group crossover study comparing 47 white men (18 HIV-uninfected, 9 HIV-infected and antiretroviral therapy (ART)-naïve, and 20 HIV-infected on ART). Fasting participants consumed 1 of 2 randomly-assigned high-fat meals of either saturated or polyunsaturated fat, followed at least 24 hours later by the other meal. Brachial artery ultrasound measurements to assess vascular reactivity were performed before and 3 hours after each dietary challenge. There was no significant difference in mean baseline or postprandial FMD between HIV-infected and uninfected participants (mean baseline FMD ± SD, 9.0% ± 5 vs. 9.2% ± 5, p=0.9; mean postprandial FMD ± SD, 9.0% ± 4.7 vs. 9.1% ± 4.7, p=0.96, respectively). No significant difference in baseline or postprandial change in FMD was found between meals or HIV treatment groups. Fasting lipids and glucose, CD4+ count, and viral load did not predict FMD in HIV-infected participants. In contrast to previous reports, this study did not demonstrate impaired endothelium-dependent vasodilation after high-fat meals in either HIV-infected or HIV-uninfected men. Moreover, HIV infection itself may not be the primary explanation for the abnormal endothelial function reported in HIV-infected individuals.
Article
Experienced separately, both acute mental stress and high fat meal consumption can transiently impair endothelial function and the purpose of the present study was to investigate their combined impact. On 4 separate days, 10 healthy males (23 yrs) underwent brachial artery flow-mediated dilation (FMD) tests, before and hourly for 4 hours post-consumption of a high-fat (HFM; 54g fat) or low-fat (LFM; 0g fat) meal (~1000 calories), with hourly mental stress (mental arithmetic, speech) or Control (counting) tasks; (conditions HFM+S, LFM+S, HFM, LFM). Data are means ± SD. Plasma triglycerides increased and remained elevated post-high-fat meal, but not low-fat meal (P=0.004) and were not affected by mental stress (P=0.329). Indices of stress reactivity increased during mental stress tasks (mean arterial pressure, heart rate, salivary cortisol, and plasma norepinephrine respectively: ~20 mmHg, ~22 bpm, ~2.37 nmol/L, ~0.17 ng/ml), and were not influenced by meal (P>0.05). There was no effect of meal on FMD (P=0.562), however FMD was 4.5 ± 0.5 % in the Control conditions and 5.8 ± 0.6% in the mental Stress conditions (P=0.087) and this difference was significant when normalized for the shear stress stimulus (FMD/AUC shear stress, P=0.045). Overall, these preliminary data suggest that postprandial FMD was augmented with mental stress irrespective of meal type. These results are contrary to previous reports of impaired endothelial function post-mental stress or fat consumption independently and highlight the need to further investigate mechanisms underlying the interactions between these factors.
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Postprandial hyperlipemia is commonly associated with endothelial dysfunction modulated by the oxidative power of postprandial lipoproteins. Rice oil contains linoleic and oleic fatty acids and a various amount of antioxidants. The aim of the study was to evaluate the effects of postprandial lipemia subsequent to the administration of a fat load containing rice oil on endothelial reactivity, expressed as brachial artery flow-mediated vasodilation (FMV), in seven young healthy men. FMV fell significantly 2 and 4 hours after the fat load with a further increase at 6 hours. Triglycerides increased significantly 2 and 4 hours postprandially, and decreased thereafter. These data indicated that the antioxidant power of rice oil does not prevent postprandial endothelial impairment after a single rice oil administration. Nevertheless, the present study does not exclude the possibility that a regular dietary assumption of rice oil may protect endothelial function and reduce cardiovascular risk resulting from postprandial lipemia.
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Where the egg debate was initially focused on quantitative-cholesterol aspects, assuming all eggs are the same, recent understanding of atherosclerotic processes has raised questions regarding additional qualitative-composition aspects. According to the “lipid hypothesis” of atherosclerosis, in which diets high in cholesterol and animal fat were assumed to be high-risk, egg consumption was rigidly restricted. However, accumulating research showing a relatively small effect of dietary cholesterol on blood plasma levels, and the accepted possibility of including eggs in some cholesterol-reducing diets, partially alleviated these restrictions. Recent understanding of contributions by endothelial dysfunction (ED) and inflammation to CVD processes has prompted reconsideration of eggs, with a focus on composition-related risks and/or benefits. Aside from high cholesterol levels, eggs are rich in unsaturated fatty acids (FA) (≥60% fat), which may reduce blood cholesterol response. Egg composition may further influence blood lipids and endothelial response when high in antioxidants and monounsaturated FA (MUFA), which may reduce the LDL-oxidative response (by ≥30–40% compared to regular high-poly unsaturated FA [PUFA] eggs), or rich in n-3 FA, which may reduce postprandial lipemia (PPL) and resulting ED and inflammation. “Paleolithic,” “wild,” and/or traditional “ethnic” eggs, which are higher in MUFA, n-3 FA, and antioxidants than industrially-produced eggs, could offer functional advantages within current egg recommendations, possibly even leading to new guidelines to benefit the general public and/or specific population segments. CVD etiology and risk factors as relate to modern vs. traditional egg composition are discussed in this chapter, and may warrant consideration in future egg recommendations and production.
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Adipose Tissue Dysfunction (ATD) has been proposed as the pathophysiological route by which obesity confers its associated increased risk for cardiovascular disease and is characterized by an increased secretion of pro-inflammatory cytokines and adipokines and reduced secretion of anti-inflammatory adipokines such as adiponectin from adipose tissue. A review of literature shows that a range of currently available (non-)pharmacological interventions such as weight loss and statins influence ATD. The recently proposed intervention of blood letting, aimed at a reduction in free iron induced inflammation, is partly based on the relation between body iron stores and ATD while the etiologic relation remains poorly understood. This relation was absent in patients with manifest vascular disease probably due to the inflammation associated with vascular disease. In vitro studies did show a potential causal relation between body iron stores and ATD via free iron-induced inflammation in preadipocytes. ATD has mainly been researched in the fasting state while subjects in the western world spend most of the day in the postprandial phase. We showed that in the postprandial phase ATD plays a contraintuitive, but modest anti-inflammatory role probably with the aim of limiting the mostly pro-inflammatory postprandial phase. ATD is linked with thyroid function to influence energy expenditure and intake based on available energy stores in the form of adipose tissue. In patients with manifest vascular disease this relation is shown by the association between thyroid stimulating hormone (TSH) within the normal range (0.5-5.0 mU/L) and visceral adipose tissue thickness. Small changes in TSH in the normal range are associated with an increased risk for myocardial infarction in patients with manifest vascular disease per point increase in TSH (HR 1.33; 95%CI 1.03-1.73). The most important intervention available for improving cardiovascular risk in high-risk patients such as those with ATD is LDL-cholesterol lowering. To compare different LDL-cholesterol-lowering strategies (high-dose statin versus low-dose statin in combination with ezetimibe) we performed a multicenter cross-over trial comparing both lipid-lowering strategies on fasting and postprandial lipids and endothelial function as measured by Flow Mediated Dilatation (FMD) and EndoPAT in patients with metabolic syndrome. Strict attention was given to endothelial function test methodology as we also showed, using a meta-regression-based approach on available FMD-studies, that small alterations in methodology influence endothelial function test results. Both lipid-lowering strategies were associated with similar fasting LDL-cholesterol levels (1.79 mmol/L versus 1.81 mmol/L) and were associated with similar postprandial lipids, fasting and postprandial changes in endothelial function (change in FMD -0.34±0.21 vs. -0.43±0.20, p=0.766). ATD has complicated relations with other regulatory systems and organ systems such as iron-metabolism and thyroid function in patients with manifest vascular disease and metabolic syndrome. ATD has a modest contraintuitive anti-inflammatory role in the postprandial phase in which we place ourselves almost daylong. Interventions aimed at influencing ATD are already available while different lipid-lowering strategies designed for reducing the adipose tissue dysfunction associated cardiovascular risk are probably equally effective as witnessed by their similar effects on fasting and post fat-load endothelial function.
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We examined the effects of angiotensin II AT(1)-receptor blockade with olmesartan on high fat (HF) diet-induced vascular oxidative stress and endothelial dysfunction in normal salt (NS) diet-fed Dahl salt-sensitive (DSS) rats. Treatment with NS + HF diet (32% crude fat, 0.3% NaCl) for 20 weeks significantly increased blood pressure in DSS rats. NS + HF diet-fed DSS rats also showed higher plasma levels of thiobarbituric acid-reactive substances, aortic superoxide production, and mRNA levels of p22(phox) and gp91(phox) in aortic tissues than NS diet-fed DSS rats. Furthermore, acetylcholine-induced vasorelaxation of aorta from NS + HF diet-fed DSS rats was significantly reduced. In NS + HF diet-fed DSS rats, treatment with olmesartan medoxomil (10 mg/kg per day, p.o.) and hydralazine (25 mg/kg per day, p.o.) similarly decreased blood pressure. However, in these animals, only olmesartan normalized plasma levels of thiobarbituric acid-reactive substances, vascular superoxide in aortic tissues, and acetylcholine-induced vasorelaxation. These data indicate that HF diet-induced hypertension is associated with vascular oxidative stress and endothelial dysfunction in NS diet-treated DSS rats. Inhibition of angiotensin II AT(1) receptors may elicit beneficial effects on HF-induced hypertension and vascular injury in subjects that have genetically enhanced sodium-sensitive blood pressure.
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Endothelial dysfunction is a turning point in the initiation and development of atherosclerosis and its complications and is predictive of future cardiovascular events. Ingestion of high-carbohydrate or high-fat meals often results in postprandial hyperglycaemia and/or hypertriacylglycerolaemia that may lead to a transient impairment in endothelial function. The present review will discuss human studies evaluating the impact of high-carbohydrate and high-fat challenges on postprandial endothelial function as well as the potential role of oxidative stress in such postprandial metabolic alterations. Moreover, the present review will differentiate the postprandial endothelial and oxidative impact of meals rich in varying fatty acid types.
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Atheroma is the main cause of mortality and morbidity in patients with non-insulin dependent diabetes mellitus. Endothelial dysfunction underlies atheroma formation. Flow mediated vasodilatation is a measure of endothelial function as well as a determinant of arterial distensibility,1 measurements of which have not previously been reported in patients with non-insulin dependent diabetes. Subjects, methods, and results We studied 12 symptom free, non-smoking, healthy patients (six men) with well controlled non-insulin dependent diabetes diabnosed 1-7 (mean 3.8) years previously (mean age 50 (SD 9) years, body mass index 26.9 (4.8) kg/m2, serum cholesterol concentration 5.8 (0.5) mmol/l). Patients with known causes of endothelial dysfunction were excluded. All patients had insulin resistance with basal hyperinsulinaemia,2 no biochemical evidence of renal impairment, and no microalbuminuria. A group of 12 normal non-smoking subjects was matched for sex, age, body mass index, blood pressure, and serum cholesterol concentration and served as a control group. Artery diameter (D) and distensibility were measured by high resolution ultrasonic vessel wall tracking1; blood pressure (P) by finger photo-plethysmography; blood flow by ultrasound as the product of mean velocity corrected for Doppler angle and internal brachial artery diameter. Distensibility (δD/D.δ}P) was derived from systolic distension (systolic minus diastolic intravascular diameter, δD) and simultaneous pulse pressure ({δ}P). Fasting subjects were studied in a temperature controlled room (21-23°C) after 15 minutes of supine rest. Measurements were made at baseline, during reactive hyperaemia 60 seconds after deflation of a wrist cuff inflated to suprasystolic pressure for five minutes (flow related, endothelium dependent vasodilatation) three minutes after 10 µg (submaximal dose) sublingual glyceryl trinitrate and three minutes after 400 µg (supramaximal dose) sublingual glyceryl trinitrate (endothelium independent vasodilatation). Haemodynamic variables returned to baseline 15 minutes after each intervention. Groups were compared with unpaired t tests, apart from the glyceryl trinitrate distensibility data, which failed a test for normality and were analysed with the Mann-Whitney test. Paired t tests were used within groups to assess changes from baseline. P < 0.05 was regarded as significant. Baseline characteristics and resting brachial artery measurements were similar between diabetic and normal subjects (heart rate 61 (SD 4) v 56 (8) per minute; blood pressure 127 (12)/69 (13) v 124 (15)/63 (9) mm Hg; blood flow 45 (28) v 49 (41) ml/min; diastolic diameter 4.82 (0.60) v 4.47 (1.05) mm; distensibility 4.8 (1.4) v 5.9 (1.6) per kPa). During reactive hyperaemia, heart rate, blood pressure, and the increase in brachial artery blood flow (554.8% (99.5%) v 590% (106.6%)) were similar in diabetic and normal subjects (figure 1) but the increases in brachial artery diastolic diameter (1.2% (2.7%) v 9.1% (4.4%); difference 6.9% (95% confidence interval 4.9% to 11%)) and distensibility (-15.3% (10.4%) v 31% (31.7%); difference 46.3% (25.5% to 67.1%)) were significantly less in diabetic subjects (both P<0.001). After 10 µg glyceryl trinitrate or 400 µg glyceryl trinitrate the increase in flow, diameter, and distensibility was similar in diabetic and normal subjects (figure 1). View larger version:In a new windowDownload as PowerPoint SlideFig 1 Mean changes in blood flow, diastolic diameter, and distensibility of brachial artery in 12 diabetic subjects and 12 controls during reactive hyperaemia, 10 µg glyceryl trinitrate, and 400 µg glyceryl trinitrate. Bars show 95% confidence intervals Comment Endothelium dependent, flow related dilatation and increase in distensibility of the brachial artery are greatly impaired in patients with non-insulin dependent diabetes, but endothelium independent responses induced by glyceryl trinitrate are similar to those in normal subjects. Loss of flow related increase in arterial distensibility will augment systolic pressure, myocardial wall stress, and heart work relative to stroke output, potentially promoting left ventricular hypertrophy and lowering ischaemic threshold. Late systolic pressure will be further augmented by early wave reflection from the periphery3 because pulse wave velocity is increased when distensibility is reduced. Loss of flow mediated vasodilatation reflects endothelial dysfunction and may thus also provide a marker of atherogenetic susceptibility. Our data provide evidence of vascular dysfunction in non-insulin dependent diabetes before the appearance of microalbuminuria, previously regarded as its earliest marker.4 We thank Dr J R Peters for allowing us to study patients under his care and Wendy Simons and Julie-Ann Davies for their secretarial assistance. Footnotes Funding British Heart Foundation. Conflict of interest None.References1.↵Ramsey MW, Goodfellow J, Jones CJH, Luddington LA, Lewis MJ, Henderson AH.Endothelial maintenance of arterial distensibility is impaired in chronic heart failure.Circulation1995; 92:3212–9.OpenUrlFREE Full Text2.↵Coates PA, Ollerton RL, Luzio SD, Ismail IS, Owens DR.Reduced sampling protocols in estimation of insulin sensitivity and glucose effectiveness using the minimal model in NIDDM.Diabetes1993; 42:1635–41.OpenUrlCrossRefMedlineWeb of Science3.↵O'Rourke MF.Systolic blood pressure: arterial compliance and early wave reflection, and their modification by anti-hypertensive therapy.J Hum Hyperten1989; 10:47–52.4.↵Stehouwer CD, Nauta JJ, Zeldenrust GC, Hackeng WH, Donker AJ, den Ottolander GJ.Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin dependent diabetes.Lancet1992; 340:319–23.OpenUrlCrossRefMedlineWeb of Science
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Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.
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Hyperhomocyst(e)inemia is a risk factor for atherosclerosis and is prevalent in the elderly. The objective of this study was to determine whether hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans. High-resolution vascular ultrasonography was used to study endothelium-dependent and -independent vasodilation in a nonatherosclerotic peripheral conduit artery of 26 elderly hyperhomocyst(e)inemic subjects and 15 age- and sex-matched subjects with normal homocysteine levels. Flow-mediated, endothelium-dependent (nitric oxide-mediated) vasodilation was assessed by measuring the percent change in brachial artery diameter during reactive hyperemia. Endothelium-independent vasodilation was assessed after the administration of 0.4 mg sublingual nitroglycerin. Endothelium-dependent vasodilation was significantly impaired in the hyperhomocyst(e)inemic subjects compared with control subjects (3.7 +/- 0.6% versus 8.1 +/- 1.2%; P = .004), whereas endothelium-independent vasodilation was not different between the two groups (10.1 +/- 1.6% versus 9.3 +/- 1.5%; P = NS). In a linear regression analysis with serum homocysteine concentration, folic acid, age, sex, cholesterol (serum total, LDL, or HDL cholesterol), mean arterial blood pressure, use of antihypertensive medication, and baseline brachial artery diameter included as covariates, serum homocysteine concentration emerged as the only significant predictor of flow-mediated vasodilation. These data indicate that hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans and suggest that the bioavailability of nitric oxide is decreased in hyperhomocyst(e)inemic humans.
Article
Although LDL cholesterol (LDL-C) is generally accepted to be a major risk factor for progression of atherosclerosis, the traditional measurement of LDL-C includes measurement of IDL. Little is known about the relationship between IDL and progression of atherosclerosis. Therefore, we investigated the association of plasma lipoprotein subclasses with progression of preintrusive carotid artery atherosclerosis in the Monitored Atherosclerosis Regression Study (MARS). MARS was a randomized, double-blind, placebo-controlled serial arterial imaging trial conducted in subjects 37 to 67 years old with angiographically defined coronary artery disease. Analytical ultracentrifugation was used to determine lipoprotein subclasses, including LDL (Sf 0 to 12), IDL (Sf 12 to 20), VLDL (Sf 20 to 400), and HDL (F1.20 0 to 9) in 188 subjects. Subjects were randomized to a cholesterol-lowering diet plus placebo or lovastatin 80 mg/d. The outcome measure, the annual progression rate of the distal common carotid artery far wall intima-media thickness determined by high resolution B-mode ultrasonography, was determined at baseline and every 6 months on trial. When the major apolipoprotein B-containing lipoproteins were measured independently, IDL (r=.21, P<.005) but not VLDL (r=-.09, P=.24) or LDL (r=.09, P=.26) was associated with the progression of carotid artery intimamedia thickness. These data provide further evidence for the role of triglyceride-rich lipoproteins in the progression of atherosclerosis and support the evidence that indicates that the risk of atherosclerosis attributable to LDL-C may in part be the result of lipoproteins in the IDL fraction (Sf 12 to 20) that is included within the traditional measurements of LDL-C.
Article
Much has been written about the potential role of antioxidants in the prevention of atherosclerosis. To assess the short-term effect of a single high-fat meal with and without pretreatment with antioxidant vitamins on endothelial function in healthy, normocholesterolemic subjects. Observer-blinded randomized trial. University hospital. Twenty healthy, normocholesterolemic (total and low-density lipoprotein cholesterol <5.2 mmol/L and <3.4 mmol/L [<200 mg/dL and <130 mg/ dL], respectively), male (7) and female (13) hospital employee volunteers, aged 24 to 54 years. Three randomly administered breakfasts: (1) a high-fat meal (3766 J [900 calories], 50 g of fat); (2) a low-fat meal (3766 J [900 calories], 0 g of fat); and (3) a high-fat meal and pretreatment with oral administration of vitamins C (1 g) and E (800 IU) (high-fat meal with vitamins). A subgroup of 10 subjects also ate the low-fat meal with the same vitamin pretreatment (low-fat meal with vitamins). High-resolution ultrasound assessed flow-mediated (endothelium-dependent) brachial artery vasodilation measured as percent diameter change before and hourly for 6 hours following each meal. Flow-mediated vasodilation fell from a mean+/-SD of 20%+/-8% before to 12%+/-6%, 10%+/-6%, and 8%+/-9% at 2, 3, and 4 hours, respectively, after the high-fat meal (P<.001). No significant changes in flow-mediated vasodilation occurred after the low-fat meal, high-fat meal with vitamins, or low-fat meal with vitamins. The change in flow-mediated vasodilation after the low-fat and high-fat meals correlated inversely with the 2-hour postprandial change in triglyceride levels (r=-0.54; P<.001). A single high-fat meal transiently reduces endothelial function for up to 4 hours in healthy, normocholesterolemic subjects, probably through the accumulation of triglyceride-rich lipoproteins. This decrease is blocked by pretreatment with antioxidant vitamins C and E, suggesting an oxidative mechanism.
Article
Hypertriglyceridemia is now accepted as a risk factor for coronary heart disease, although the mechanism behind the increased risk is not well understood. The present study was undertaken to investigate the effects of triglyceridemia on endothelial function, because impaired endothelial function is considered a marker of atherogenesis. Flow- and nitroglycerin-induced dilatation of the brachial artery was investigated noninvasively by high-resolution ultrasound technique in seven young, healthy men without risk factors for coronary heart disease. Transient triglyceridemia was induced by infusion of a triglyceride emulsion, Intralipid, which raised free fatty acid concentrations twofold and triglyceride levels fourfold. Flow-induced vasodilatation decreased from 7.1+/-3.0% to 1.6+/-2.6% (P<.0002), whereas nitroglycerin-induced vasodilatation decreased from 20.5+/-5.8% to 11.5+/-3.2% (P<.002) before and after 1 hour of infusion of Intralipid, respectively. Transient triglyceridemia decreases vascular reactivity, presumably by both endothelium-dependent and endothelium-independent mechanisms.
Article
Plaque cholesterol is thought to be derived exclusively from low-density lipoproteins that have become trapped and modified in the subendothelial space of arterial vessels. However, in this study we provide the first visual evidence that demonstrates that (a) remnants of post-prandial lipoproteins rapidly penetrate arterial tissue; (b) efflux is not complete; and (c) focal accumulation of chylomicron remnants occurs within the subendothelial space. The arterial retention of chylomicron remnants is consistent with atherogenesis being in part a post-prandial phenomenon.