Donate Help Contact The AHA Sign In Home
American Heart Association
Arteriosclerosis, Thrombosis, and Vascular Biology
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1233-1237
doi: 10.1161/hq0701.092161
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by de Roos, N. M.
Right arrow Articles by Katan, M. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by de Roos, N. M.
Right arrow Articles by Katan, M. B.
Related Collections
Right arrow Nutrition
Right arrow Epidemiology
Right arrow Lipid and lipoprotein metabolism
Right arrow Endothelium/vascular type/nitric oxide
Right arrow Other imaging
(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1233.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Replacement of Dietary Saturated Fatty Acids by Trans Fatty Acids Lowers Serum HDL Cholesterol and Impairs Endothelial Function in Healthy Men and Women

Nicole M. de Roos; Michiel L. Bots; Martijn B. Katan

From the Division of Human Nutrition and Epidemiology (N.M.d.R., M.B.K.), Wageningen University, Wageningen, the Netherlands; Julius Center for Patient Oriented Research (M.L.B.), University Medical Center, Utrecht, the Netherlands; and The Wageningen Center for Food Sciences (M.B.K.), Wageningen, the Netherlands.

Correspondence to Dr Martijn B. Katan, Division of Human Nutrition and Epidemiology, Wageningen University, Bomenweg 2, 6703 HD Wageningen, Netherlands.


*    Abstract
up arrowTop
 *Abstract
down arrowIntroduction
 down arrowMethods
 down arrowResults
 down arrowDiscussion
 down arrowReferences
 
Abstract—We tested whether trans fatty acids and saturated fatty acids had different effects on flow-mediated vasodilation (FMD), a risk marker of coronary heart disease (CHD). Consumption of trans fatty acids is related to increased risk of CHD, probably through effects on lipoproteins. Trans fatty acids differ from most saturated fatty acids because they decrease serum high-density lipoprotein (HDL) cholesterol, and this may increase the risk of CHD. We fed 29 volunteers 2 controlled diets in a 2x4-week randomized crossover design. The "Trans-diet" contained 9.2 energy percent of trans fatty acids; these were replaced by saturated fatty acids in the "Sat-diet." Mean serum HDL cholesterol after the Trans-diet was 0.39 mmol/L (14.8 mg/dL), or 21% lower than after the Sat-diet (95% CI 0.28 to 0.50 mmol/L). Serum low density lipoprotein and triglyceride concentrations were stable. FMD+SD was 4.4±2.3% after the Trans-diet and 6.2±3.0% after the Sat-diet (difference -1.8%, 95% CI -3.2 to -0.4). Replacement of dietary saturated fatty acids by trans fatty acids impaired FMD of the brachial artery, which suggests increased risk of CHD. Further studies are needed to test whether the decrease in serum HDL cholesterol caused the impairment of FMD.


Key Words: lipoproteins • HDL • trans fatty acids • endothelium • arteriosclerosis


*    Introduction
up arrowTop
 up arrowAbstract
 *Introduction
down arrowMethods
 down arrowResults
 down arrowDiscussion
 down arrowReferences
 
When liquid oils are partially hydrogenated to form solid margarines and shortenings, trans isomers of fatty acids are formed. In countries such as the United States1 2 and the Netherlands,3 trans fatty acids (TFAs) constitute 4% to 7% of dietary fat intake. A high intake of TFAs is associated with an increased risk of coronary heart disease (CHD).4 5 6 One probable cause is the effect of TFAs on serum lipoproteins. Like saturated fatty acids, TFAs increase the concentration of serum LDL cholesterol.7 8 Moreover, and unlike saturated fatty acids, TFAs decrease serum HDL cholesterol (HDL-C).7 8 9 10 11 This might be harmful, inasmuch as there is increasing evidence that HDL-C is inversely related to CHD.12 13

We investigated whether the intake of trans fat would indeed increase the risk of CHD more than the intake of saturated fat by comparing the effects of these fats on endothelial function, a surrogate cardiovascular end point.14 15 16 We assessed endothelial function as flow-mediated vasodilation (FMD) of the brachial artery, because this is a noninvasive measurement that correlates well with known risk factors17 18 19 20 21 22 and other markers of CHD.23 24 25 Moreover, 2 longitudinal studies show an association between FMD in the past with future CHD events.26 27 The diets were given for a minimum of 3 weeks, a time period long enough to establish changes in serum lipids28 and FMD.21 We hypothesized that FMD would be lower after the diet rich in trans fat than after the diet rich in saturated fat because of the expected difference in serum HDL-C.


*    Methods
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 *Methods
down arrowResults
 down arrowDiscussion
 down arrowReferences
 
Subjects
The Medical Ethical Committee of Wageningen University approved the study aim and design. Each volunteer signed an informed consent form. We recruited 39 nonsmoking men and women and assessed their health by using a questionnaire; we eliminated 1 person because of use of medication, 2 because of missing information, and 1 because of poor veins for venipuncture. All subjects had normal concentrations of serum cholesterol and triglycerides and normal amounts of protein and glucose in their urine. We excluded 2 subjects because we could not obtain clear ultrasound images of their brachial arteries. One other subject withdrew before the start of the study; in the end, 32 subjects were enrolled. They all completed the study.

Study Design
We provided 2 controlled diets for 4 weeks, each in a randomized crossover design. The diets consisted of conventional food items supplemented with special margarines and were given in a 28-day menu cycle. On Mondays through Fridays, subjects came to our dining room and ate a hot meal under our supervision. All other foods (bread; margarine; meat and/or cheese; honey, jam, or sprinkles; fruit; milk and/or yogurt) were packed for consumption at home, as was food for the weekends.

Habitual energy intake of the subjects was estimated from a food-frequency questionnaire. We designed menus for 14 levels of energy intake, ranging from 7 to 20 MJ/d, and allocated the subjects to an intake level close to their habitual energy intake. We provided 90% of energy (en%); all this food was weighed out for each subject. We measured body weight twice a week; if body weight changed >1 kg, subjects were switched to a different energy intake level. The remaining 10 en% had to be chosen from a list of low-fat food items and recorded in a diary. Subjects received the diets for 21 to 32 days (mean 27.5 days).

Diets
The experimental diets differed in margarine only (Table 1Down). The composition of the diets was calculated by using food composition tables3 29 30 and checked by collecting duplicates of all meals (Table 2Down). The analyzed values were similar to the calculated composition.


View this table:
[in this window]
[in a new window]
  		Table 1. Fatty Acid Composition of Margarines Used in Diet Rich in TFAs and Diet Rich in Saturated Fatty Acids


View this table:
[in this window]
[in a new window]
  		Table 2. Analyzed Composition of the 2 Experimental Diets

The margarine in the diet rich in TFAs (Trans-diet) was a blend of 70 parts partially hydrogenated soy oil, containing 44% trans-C18:1 (Gouda’s Glorie, Van Dijk Foods), 14 parts vegetable oil containing 63% linoleic acid and 23% oleic acid (Becel, Unilever), and 16 parts water. The margarine in the diet rich in saturated fat (Sat-diet) was a blend of 60 parts palm kernel fat (Loders Croklaan) and 40 parts commercially available margarine made from a blend of vegetable oils and solid vegetable fats (Blue Band, Van den Bergh BV). Both margarines were produced at NIZO Food Research. The margarines were used as shortenings in bread and cookies, in sauce and gravy, and as a spread. They supplied 62% of fat in the diets; the remaining 38% was mainly derived from meat, cheese and other dairy products, eggs, and salad dressings.

Blood Lipids
We took blood samples after an overnight fast on 2 separate days after day 19 of each diet. All 4 blood samples of each subject were analyzed in duplicate within 1 run. Total cholesterol and triglycerides (Cholesterol Flex and Triglycerides Flex reagent cartridge, Dade Behring) and HDL-C (Liquid N-geneous HDL-C assay, Instruchemie BV) were measured, and LDL cholesterol was calculated with the Friedewald formula. The coefficient of variation of 64 duplicate measurements was 0.4% for total cholesterol, 1.5% for triglycerides, and 1.1% for HDL-C.

Brachial Artery Measurements
All subjects had an overnight fast of at least 12 hours before the measurements. We measured FMD of the brachial artery as described by Celermajer et al22 and Sorensen et al.31 We used the diameter of the artery at rest and at maximum vasodilation to calculate the percentage increase or FMD. All measurements were performed at end diastole by the use of the R wave of the ECG. The ultrasound images were made by 1 technician with a 7.5-MHz linear array transducer of an Ultramark 9 HDI duplex scanner. All images were stored on super-VHS videotapes for offline analysis.

Subjects were made to lie down in a temperature-controlled room (range 20°C to 23°C) with the right arm in 2 arm support cushions. An inflatable cuff was placed around the lower arm. The transducer was held in position at the site of the antecubital crease with a specially developed transducer arm holder (method developed by R. Meijer’s group, Vascular Imaging Center, The Julius Center for Patient Oriented Research UMC, Utrecht, the Netherlands).

We first obtained an optimal 2D B-mode ultrasound image of the brachial artery at rest and recorded 3 images to measure the diameter. We then inflated the cuff to 250 mm Hg and kept this pressure constant for 5 minutes to induce ischemia in the forearm and hand. After 5 minutes, the cuff was deflated. The image of the brachial artery was optimized, and changes in the diameter of the artery were recorded during the next 5 minutes. Every 15 seconds, a frozen image was stored on videotape. At the end of the second feeding period, we also measured endothelium-independent vasodilation after a sublingual dose of 400 µg of nitroglycerin.

One reader who was blinded to the treatment read all the images at the Vascular Imaging Center of the University Medical Center in Utrecht. The reader rated the quality of the images from class 1 (perfect) to class 4 (unfit for use). All 32 subjects were measured twice on both diets, so we had 4 measurements per subject. Of these 128 measurements, 24 were rated as perfect, 71 as fair, 26 as marginal, and 2 as unfit. Five measurements were missing. We used only measurements that were rated perfect or fair, which left us with 29 subjects for whom we had observations on both diets. At a mean FMD of 5.3% of the resting diameter, the SD within subjects was 2.6% points, so the corresponding coefficient of variation was 49%. The largest difference in a duplicate FMD measurement was 18.2% points (FMD 2.6% and 20.8% of the resting diameter); the smallest difference was 0.16% points (measurements were 7.2% and 7.4% of the resting diameter). The coefficient of variation of the resting and maximum diameter was 8%.

Statistical Analysis
We averaged the duplicate measurements in each dietary period and tested for order effects by ANOVA, with diet and order as main effects in the model.32 Because the order of the 2 diets did not significantly contribute to the model, we then calculated for each subject the difference between treatments. We tested whether these differences were significantly different from zero by the Student t test for paired samples. We give 2-sided 95% CIs for the differences.


*    Results
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 *Results
down arrowDiscussion
 down arrowReferences
 
We analyzed the data of 29 subjects (10 men and 19 women). Their mean (±SD) age was 30±16 years, their mean weight was 69±9 kg, and their mean body mass index was 22.5±2.4 kg/m2. Prestudy serum cholesterol concentrations were 5.1±1.1 mmol/L, and serum triglycerides were 1.2±0.7 mmol/L.

Body Weight
During the 4-week feeding periods, body weight remained basically stable, with mean decreases of 0.4 kg during the Trans-diet and 0.6 kg during the Sat-diet (P=0.43 for difference in change between diets).

Blood Lipids
Serum HDL-C decreased from 1.87±0.46 mmol/L (73.1±17.8 mg/dL) on the diet rich in saturated fats to 1.49±0.33 mmol/L (56.5±12.8 mg/dL) on the diet rich in trans fats (Table 3Down). The decrease was 0.39 mmol/L (95% CI -0.50 to -0.28), or 21%. Serum LDL cholesterol and triglycerides remained stable. The order of the 2 diets hardly affected the change in HDL-C: the mean change was 0.35±0.25 mmol/L in subjects who went from the Trans-diet to the Sat-diet and 0.43±0.32 mmol/L in the subjects who received the diets in the reverse order.


View this table:
[in this window]
[in a new window]
  		Table 3. Concentration of Serum Lipids After 4-wk Consumption of the 2 Diets

Brachial Artery Measurements
The diameter of the brachial artery at rest was 4.02±0.70 mm on the Sat-diet and 4.08±0.73 mm on the Trans-diet. The maximum diameter was 4.33±0.80 mm on the Sat-diet and 4.19±0.73 mm on the Trans-diet. FMD was 6.2±3.0% on the Sat-diet and 4.4±2.3% on the Trans-diet (P=0.015). Thus, FMD was 1.8% (95% CI -3.2 to -0.4), or 29% lower on the Trans-diet than on the Sat-diet (FigureDown). The order of the 2 diets hardly affected the results: 15 subjects went from an FMD of 4.8% after the Trans-diet to 6.4% after the Sat-diet, whereas 14 other subjects went from 5.9% after the Sat-diet to 4.2% after the Trans-diet.



View larger version (15K):
[in this window]
[in a new window]
  		Figure 1. FMD of the 29 subjects after the diet rich in TFAs (solid squares) and after the diet rich in saturated fatty acids (open squares). The subjects consumed both diets for 21 to 32 days in randomized order.

All subjects showed vasodilation after nitroglycerin (range 4.4% to 20.8%). Diet had no effect on nitroglycerin-mediated vasodilation, which was 14.3±3.4% on the Trans-diet and 13.4±5.3% on the Sat-diet (unpaired t test, P=0.64).

A decrease in HDL-C went together with a decrease in FMD in 18 of 29 subjects. The correlation between changes in HDL-C and FMD was positive (r=0.12, 95% CI -0.26 to 0.46) but not significant (P=0.55).


*    Discussion
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 *Discussion
down arrowReferences
 
Consumption of TFAs resulted in lower HDL-C and a smaller FMD than consumption of saturated fatty acids. This might explain the increased risk of cardiovascular disease at high intakes of TFAs. However, whether the impaired vasodilation was attributable to the decrease in HDL-C remains to be determined.

HDL-C, Other Dietary Factors, and Endothelial Function
There is some evidence that changes in HDL-C concentration could change endothelial function. First, higher serum HDL-C is associated with better endothelial function.24 33 34 This might be due to the proposed antioxidant capacity of HDL,35 which might prevent oxidation of LDL and therefore prevent adverse effects of oxidatively modified LDL on endothelial function. We know of no other interventions aimed at HDL, but other antioxidants, such as vitamin C,36 37 were shown to improve FMD. Second, there is ample evidence that reductions in other known risk factors, such as LDL cholesterol21 25 38 or homocysteine,39 improve FMD, suggesting that changes in HDL-C could have similar effects. The fact that we did not find a significant correlation between changes in HDL-C and FMD does not rule out a causal relation, because the data were too scarce to correct for possible confounding variables, such as sex and age. On the other hand, a significant correlation would be no proof of a causal relation.

Other factors in the diets might account for the effect on FMD. As shown in Table 2Up, there was a small difference in linoleic acid between the 2 diets, and studies with rats show that TFAs have stronger effects at low intakes of linoleic acid.40 Although this might apply to humans, those rat studies were performed at very high intakes of TFAs (20 en%), and the adverse effects could be counteracted with a linoleic acid intake as low as 2 en%. Thus, the 4.1 en% provided by linoleic acid in our 9.2 en% Trans-diet was not low compared with percentages in the rat studies. Also, we think that the difference in linoleic acid between the Sat-diet and Trans-diet was too small to fully explain the effects seen on FMD. Another factor is vitamin E; the different fat mixtures likely differed by 10 to 20 mg/100 g. However, studies that showed an effect of vitamin E on FMD41 used much higher doses, and even at these high doses, most studies did not show an effect.42 43 44 Last, FMD is impaired in diabetes,45 and if TFAs and saturated fatty acids have different effects on insulin metabolism, this could have biased the results. However, it is unlikely that fasting serum insulin was different between the 2 diets.46

We do not know of studies that compared long-term effects of different fats on FMD. Postprandial effects of saturated and cis-monounsaturated fats seem to be similar; they all appear to impair FMD compared with preprandial values or compared with low-fat control meals.36 47 48 However, some of these studies36 47 are flawed because the low-fat meals had a higher vitamin C content than the fat-enriched meals, which might have improved FMD.49 We know of no short-term effects of TFAs on FMD.

Study Limitations
We used a crossover design to eliminate variation due to differences between subjects. The order of the 2 diets was balanced and randomized per subject to eliminate bias due to a systematic drift of the outcome variables over time.32 Although we did not include a washout period, we did not find a significant order effect on any of the blood lipoproteins or for FMD.

We were interested only in differences between the 2 test diets but not in changes from the habitual diet; therefore, no baseline data were collected. We can only speculate on changes in blood lipoproteins and FMD from baseline. Both experimental diets differed in fat content from habitual diets: the amount of TFAs in the Trans-diet was {approx}23 g/d, which is 5-fold higher than the estimated 4.8 g/d for men and 3.8 g/d for women in the Netherlands.3 The amount of saturated fat in the Sat-diet was 58 g/d, which is also higher than the habitual intake of 42 g/d for men and 32 g/d for women in the Netherlands. Because of the low habitual intake of TFAs, replacing them all by saturated fatty acids would probably hardly improve endothelial function. Conversely, our findings imply that replacing all saturated fatty acids by TFAs could impair FMD and should therefore be discouraged.

The inclusion of women in the present study may have increased the variation in FMD response, because changes in serum estradiol concentrations affect FMD.50 However, we minimized this variation with 4-week study periods, the length of a menstrual cycle. Compared with the men, the women appeared to respond stronger to the diets, with a 2.3 percentage-unit (95% CI 0.4 to 4.2) smaller FMD on the Trans-diet than on the Sat-diet; in the men, the difference was 0.8 percentage units (95% CI -1.3 to 3.0). However, the number of men was small (n=10); therefore, the present study was not powered to test for sex differences. Further studies with larger numbers of men and women are needed to test for differences in response.

Repeatability of the FMD Measurement
We found a mean FMD of 5.3%. This is somewhat lower than values for healthy volunteers reported by others,16 36 50 but differences in methodology (eg, the position of the inflatable cuff)51 could account for this. The variability in FMD was high; we found a coefficient of variation of 49%. This is comparable with the variability found in some studies52 53 but higher than values reported by others.23 31 50 54 55 However, in most studies it is unclear how the values for variability have been calculated.

In conclusion, we showed that replacement of saturated fatty acids by TFAs in the diet lowered serum HDL-C and impaired FMD. This suggests that TFAs increase the risk of CHD more than the intake of saturated fats, with similar effects on LDL cholesterol. Further studies are needed to verify whether decreases in HDL-C indeed impair endothelial function and thereby explain the increased risk of CHD at high intakes of trans fats.


*    Acknowledgments
 
This study was financially supported by the Dutch Dairy Foundation on Nutrition and Health. We are indebted to the volunteers who took part in the study. We thank Loders Croklaan for the donation of palm kernel fat. We thank Peter Zock for his advice, Saskia Meyboom for calculating the diets, Els Siebelink for supervising the preparation of the diets, Jan Harryvan for the brachial artery measurements, Rudy Meijer (Radiology Department, University Medical Center Utrecht) for ultrasound training and support, Karin Duiser (Julius Center, University Medical Center Utrecht) for reading the images, Truus Kosmeyer for analysis of the duplicate diets, and all research students for their assistance during the study.

Received December 27, 2000; accepted March 30, 2001.


*    References
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 up arrowDiscussion
 *References
 

  1. Lemaitre RN, King IB, Patterson RE, Psaty BM, Kestin M, Heckbert SR. Assessment of trans-fatty acid intake with a food frequency questionnaire and validation with adipose tissue levels of trans-fatty acids. Am J Epidemiol. 1998;148:1085–1093.[Abstract/Free Full Text]
  2. Allison DB, Egan SK, Barraj LM, Caughman C, Infante M, Heimbach JT. Estimated intakes of trans fatty and other fatty acids in the US population. J Am Diet Assoc. 1999;99:166–174.[Medline] [Order article via Infotrieve]
  3. Hulshof KFAM, van Erp-Baart MA, Anntolainen M. Intake of fatty acids in Western-Europe with emphasis on trans fatty acids: the Transfair Study. Eur J Clin Nutr. 1999;53:143–157.[Medline] [Order article via Infotrieve]
  4. Willett WC, Stampfer MJ, Manson JE, Colditz GA, Speizer FE, Rosner BA, Sampson LA, Hennekens CH. Intake of trans fatty acids and risk of coronary heart disease among women. Lancet. 1993;341:581–585.[Medline] [Order article via Infotrieve]
  5. Ascherio A, Katan MB, Stampfer MJ, Willett WC. Trans fatty acids and coronary heart disease. N Engl J Med. 1999;340:1994–1998.[Free Full Text]
  6. Kromhout D, Menotti A, Bloemberg B, Aravanis C, Blackburn H, Buzina R, Dontas AS, Fidanza F, Giampaoli S, Jansen A, et al. Dietary saturated and trans fatty acids and cholesterol and 25-year mortality from coronary heart disease: the Seven Countries Study. Prev Med. 1995;24:308–315.[Medline] [Order article via Infotrieve]
  7. Mensink RP, Katan MB. Effect of dietary trans fatty acids on high-density and low-density lipoprotein cholesterol levels in healthy subjects. N Engl J Med. 1990;323:439–445.[Abstract]
  8. Judd JT, Clevidence BA, Muesing RA, Wittes J, Sunkin ME, Podczasy JJ. Dietary trans fatty acids: effects on plasma lipids and lipoproteins of healthy men and women. Am J Clin Nutr. 1994;59:861–868.[Abstract/Free Full Text]
  9. Zock PL, Katan MB, Mensink RP. Dietary trans fatty acids and lipoprotein cholesterol. Am J Clin Nutr. 1995;61:617.[Free Full Text]
  10. Sundram K, Ismail A, Hayes KC, Jeyamalar R, Pathmanathan R. Trans (elaidic) fatty acids adversely affect the lipoprotein profile relative to specific saturated fatty acids in humans. J Nutr. 1997;127:514S–520S.
  11. Aro A, Jauhiainen M, Partanen R, Salminen I, Mutanen M. Stearic acid, trans fatty acids, and dairy fat: effects on serum and lipoprotein lipids, apolipoproteins, lipoprotein(a), and lipid transfer proteins in healthy subjects. Am J Clin Nutr. 1997;65:1419–1426.[Abstract/Free Full Text]
  12. de Backer G, de Bacquer D, Kornitzer M. Epidemiological aspects of high density lipoprotein cholesterol. Atherosclerosis. 1998;137:S1–S6.
  13. Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, Jacobs DR Jr, Bangdiwala S, Tyroler HA. High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation. 1989;79:8–15.[Medline] [Order article via Infotrieve]
  14. Celermajer DS. Endothelial dysfunction: does it matter? Is it reversible? J Am Coll Cardiol. 1997;30:325–333.[Abstract]
  15. Schroeder S, Enderle MD, Ossen R, Meisner C, Baumbach A, Pfohl M, Herdeg C, Oberhoff M, Haering HU, Karsch KR. Noninvasive determination of endothelium-mediated vasodilation as a screening test for coronary artery disease: pilot study to assess the predictive value in comparison with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging. Am Heart J. 1999;138:731–739.[Medline] [Order article via Infotrieve]
  16. Neunteufl T, Katzenschlager R, Hassan A, Klaar U, Schwarzacher S, Glogar D, Bauer P, Weidinger F. Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. Atherosclerosis. 1997;129:111–118.[Medline] [Order article via Infotrieve]
  17. Sorensen KE, Celermajer DS, Georgakopoulos D, Hatcher G, Betteridge DJ, Deanfield JE. Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level. J Clin Invest. 1994;93:50–55.
  18. Mietus-Snyder M, Malloy MJ. Endothelial dysfunction occurs in children with two genetic hyperlipidemias: improvement with antioxidant vitamin therapy. J Pediatr. 1998;133:35–40.[Medline] [Order article via Infotrieve]
  19. Tawakol A, Omland T, Gerhard M, Wu JT, Creager MA. Hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans. Circulation. 1997;95:1119–1121.[Medline] [Order article via Infotrieve]
  20. Woo KS, Chook P, Lolin YI, Cheung AS, Chen LT, Sun YY, Sanderson JE, Metreweli C, Celermajer DS. Hyperhomocysteinemia is a risk factor for arterial endothelial dysfunction in humans. Circulation. 1997;96:2542–2544.[Medline] [Order article via Infotrieve]
  21. Vogel RA, Corretti MC, Plotnick GD. Changes in flow-mediated brachial artery vasoactivity with lowering of desirable cholesterol levels in healthy middle-aged men. Am J Cardiol. 1996;77:37–40.[Medline] [Order article via Infotrieve]
  22. Celermajer DS, Adams MR, Clarkson P, Robinson J, McCredie R, Donald A, Deanfield JE. Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults. N Engl J Med. 1996;334:150–154.[Abstract/Free Full Text]
  23. Enderle MD, Schroeder R, Ossen R, Meisner C, Baumbach A, Haering HU, Karsch KR, Pfohl M. Comparison of peripheral endothelial dysfunction and intimal media thickness in patients with suspected coronary artery disease. Heart. 1998;80:349–354.[Abstract/Free Full Text]
  24. Kuhn FE, Mohler ER, Satler LF, Reagan K, Lu DY, Rackley CE. Effects of high-density lipoprotein on acetylcholine-induced coronary vasoreactivity. Am J Cardiol. 1991;68:1425–1430.[Medline] [Order article via Infotrieve]
  25. Treasure CB, Klein JL, Weintraub WS, Talley JD, Stillabower ME, Kosinski AS, Zhang J, Boccuzzi SJ, Cedarholm JC, Alexander RW. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med. 1995;332:481–487.[Abstract/Free Full Text]
  26. Neunteufl T, Heher S, Katzenschlager R, Wslfl G, Maurer G, Weidinger F. Long-term prognostic value of low-mediated vasodilation in the brachial artery of patients with angina pectoris: results of a 5-year follow-up study. Circulation. 1999;100(suppl I):I-48. Abstract.
  27. Cohen JD, Drury JH, Ostdiek J, Finn J, Babu BR, Flaker G, Belew K, Donohue T, Labovitz A. Benefits of lipid lowering on vascular reactivity in patients with coronary artery disease and average cholesterol levels: a mechanism for reducing clinical events? Am Heart J. 2000;139:734–738.[Medline] [Order article via Infotrieve]
  28. Katan MB, Zock PL, Mensink RP. Effects of fats and fatty acids on blood lipids in humans: an overview. Am J Clin Nutr. 1994;60:1017S–1022S.[Abstract/Free Full Text]
  29. Anonymous. Nederlands Voedingsstoffenbestand 1996. The Hague, the Netherlands: Voorlichtingsbureau voor de Voeding; 1996.
  30. van Poppel G, van Erp-Baart MA, Leth T. Trans fatty acids in foods in Europe: the Transfair Study. J Food Comp Anal. 1998;11:112–136.
  31. Sorensen KE, Celermajer DS, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Thomas O, Deanfield JE. Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility. Br Heart J. 1995;74:247–253.[Abstract/Free Full Text]
  32. Snedecor GW, Cochran WG. Statistical Methods. Ames, Iowa: Iowa State University Press; 1989:503.
  33. Rubba P, Mancini M. Lipid-lowering treatment: effects on endothelial dysfunction. Curr Opin Lipidol. 1995;6:348–353.[Medline] [Order article via Infotrieve]
  34. Zeiher AM, Schachlinger V, Hohnloser SH, Saurbier B, Just H. Coronary atherosclerotic wall thickening and vascular reactivity in humans: elevated high-density lipoprotein levels ameliorate abnormal vasoconstriction in early atherosclerosis. Circulation. 1994;89:2525–2532.[Medline] [Order article via Infotrieve]
  35. Mackness MI, Durrington PN. HDL, its enzymes and its potential to influence lipid peroxidation. Atherosclerosis. 1995;115:243–253.[Medline] [Order article via Infotrieve]
  36. Plotnick GD, Corretti MC, Vogel RA. Effect of antioxidant vitamins on the transient impairment of endothelium-dependent brachial artery vasoactivity following a single high-fat meal. JAMA. 1997;278:1682–1686.[Abstract]
  37. Chambers JC, McGregor A, Jean-Marie J, Obeid OA, Kooner JS. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia, an effect reversible with vitamin C. Circulation. 1999;99:1156–1160.[Medline] [Order article via Infotrieve]
  38. Simons LA, Sullivan D, Simons J, Celermajer DS. Effects of atorvastatin monotherapy and simvastatin plus cholestyramine on arterial endothelial function in patients with severe primary hypercholesterolaemia. Atherosclerosis. 1998;137:197–203.[Medline] [Order article via Infotrieve]
  39. Title LM, Cummings PM, Giddens K, Genest JJ, Nassar BA. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol. 2000;36:758–765.[Abstract/Free Full Text]
  40. Zevenbergen JL, Houtsmuller UM, Gottenbos JJ. Linoleic acid requirement of rats fed trans fatty acids. Lipids. 1988;23:178–186.[Medline] [Order article via Infotrieve]
  41. Skyrme-Jones RA, O’Brien RC, Berry KL, Meredith IT. Vitamin E supplementation improves endothelial function in type I diabetes mellitus: a randomized, placebo-controlled study. J Am Coll Cardiol. 2000;36:94–102.[Abstract/Free Full Text]
  42. Neunteufl T, Priglinger U, Heher S, Zehetgruber M, Soregi G, Lehr S, Huber K, Maurer G, Weidinger F, Kostner K. Effects of vitamin E on chronic and acute endothelial dysfunction in smokers. J Am Coll Cardiol. 2000;35:277–283.[Abstract/Free Full Text]
  43. Simons LA, von Konigsmark M, Simons J, Stocker R, Celermajer DS. Vitamin E ingestion does not improve arterial endothelial dysfunction in older adults. Atherosclerosis. 1999;143:193–199.[Medline] [Order article via Infotrieve]
  44. Elliott TG, Barth JD, Mancini GB. Effects of vitamin E on endothelial function in men after myocardial infarction. Am J Cardiol. 1995;76:1188–1190.[Medline] [Order article via Infotrieve]
  45. Goodfellow J, Ramsey MW, Luddington LA, Jones CJ, Coates PA, Dunstan F, Lewis MJ, Owens DR, Henderson AH. Endothelium and inelastic arteries: an early marker of vascular dysfunction in non-insulin dependent diabetes. BMJ. 1996;312:744–745.[Free Full Text]
  46. Christiansen E, Schnider S, Palmvig B, Tauber-Lassen E, Pedersen O. Intake of a diet high in trans monounsaturated fatty acids or saturated fatty acids: effects on postprandial insulinemia and glycemia in obese patients with NIDDM. Diabetes Care. 1997;20:881–887.[Abstract]
  47. Vogel RA, Corretti MC, Plotnick GD. Effect of a single high-fat meal on endothelial function in healthy subjects. Am J Cardiol. 1997;79:350–354.[Medline] [Order article via Infotrieve]
  48. Ong PJ, Dean TS, Hayward CS, Della MP, Sanders TA, Collins P. Effect of fat and carbohydrate consumption on endothelial function. Lancet. 1999;354:2134.[Medline] [Order article via Infotrieve]
  49. Tomaino RM, Decker EA. High-fat meals and endothelial function. Nutr Rev. 1998;56:182–185.[Medline] [Order article via Infotrieve]
  50. Hashimoto M, Akishita M, Eto M, Ishikawa M, Kozaki K, Toba K, Sagara Y, Taketani Y, Orimo H, Ouchi Y. Modulation of endothelium-dependent flow-mediated dilatation of the brachial artery by sex and menstrual cycle. Circulation. 1995;92:3431–3435.[Medline] [Order article via Infotrieve]
  51. Berry KL, Skyrme-Jones RA, Meredith IT. Occlusion cuff position is an important determinant of the time course and magnitude of human brachial artery flow-mediated dilation. Clin Sci (Colch). 2000;99:261–267.[Medline] [Order article via Infotrieve]
  52. Andrews TC, Whitney EJ, Green G, Kalenian R, Personius BE. Effect of gemfibrozil +/- niacin +/- cholestyramine on endothelial function in patients with serum low-density lipoprotein cholesterol levels <160 mg/dl and high-density lipoprotein cholesterol levels <40 mg/dl. Am J Cardiol. 1997;80:831–835.[Medline] [Order article via Infotrieve]
  53. Hardie KL, Kinlay S, Hardy DB, Wlodarczyk J, Silberberg JS, Fletcher PJ. Reproducibility of brachial ultrasonography and flow-mediated dilatation (FMD) for assessing endothelial function. Aust N Z J Med. 1997;27:649–652.[Medline] [Order article via Infotrieve]
  54. Lambert J, Aarsen M, Donker AJM, Stehouwer CDA. Endothelium-dependent and -independent vasodilation of large arteries in normoalbuminuric insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol. 1996;16:705–711.[Abstract/Free Full Text]
  55. Celermajer DS, Sorensen KE, Georgakopoulos D, Bull C, Thomas O, Robinson J, Deanfield JE. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation. 1993;88:2149–2155.[Medline] [Order article via Infotrieve]



This article has been cited by other articles:


Home page
 AMERICAN JOURNAL OF LIFESTYLE MEDICINEHome page
S. S. Bassuk and J. E. Manson
Lifestyle and Risk of Cardiovascular Disease and Type 2 Diabetes in Women: A Review of the Epidemiologic Evidence
American Journal of Lifestyle Medicine, June 1, 2008; 2(3): 191 - 213.
[Abstract] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
M.D KONTOGIANNI, A ZAMPELAS, and C TSIGOS
Nutrition and Inflammatory Load
Ann. N.Y. Acad. Sci., November 1, 2006; 1083(1): 214 - 238.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
J. A Nettleton, L. M Steffen, E. J Mayer-Davis, N. S Jenny, R. Jiang, D. M Herrington, and D. R Jacobs Jr
Dietary patterns are associated with biochemical markers of inflammation and endothelial activation in the Multi-Ethnic Study of Atherosclerosis (MESA)
Am. J. Clinical Nutrition, June 1, 2006; 83(6): 1369 - 1379.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
D. Mozaffarian, M. B. Katan, A. Ascherio, M. J. Stampfer, and W. C. Willett
Trans Fatty Acids and Cardiovascular Disease
N. Engl. J. Med., April 13, 2006; 354(15): 1601 - 1613.
[Full Text] [PDF]

Home page
 Endocr. Rev.Home page
A. D. Mooradian, M. J. Haas, and N. C. W. Wong
The Effect of Select Nutrients on Serum High-Density Lipoprotein Cholesterol and Apolipoprotein A-I Levels
Endocr. Rev., February 1, 2006; 27(1): 2 - 16.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
J. B. Keogh, J. A. Grieger, M. Noakes, and P. M. Clifton
Flow-Mediated Dilatation Is Impaired by a High-Saturated Fat Diet but Not by a High-Carbohydrate Diet
Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1274 - 1279.
[Abstract] [Full Text] [PDF]

Home page
 Am J EpidemiolHome page
K. Oh, F. B. Hu, J. E. Manson, M. J. Stampfer, and W. C. Willett
Dietary Fat Intake and Risk of Coronary Heart Disease in Women: 20 Years of Follow-up of the Nurses' Health Study
Am. J. Epidemiol., April 1, 2005; 161(7): 672 - 679.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
E. Lopez-Garcia, M. B. Schulze, J. B. Meigs, J. E. Manson, N. Rifai, M. J. Stampfer, W. C. Willett, and F. B. Hu
Consumption of Trans Fatty Acids Is Related to Plasma Biomarkers of Inflammation and Endothelial Dysfunction
J. Nutr., March 1, 2005; 135(3): 562 - 566.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
M. L. Bots, J. Westerink, T. J. Rabelink, and E. J.P. de Koning
Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response
Eur. Heart J., February 2, 2005; 26(4): 363 - 368.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
S. Kreijkamp-Kaspers, L. Kok, M. L Bots, D. E Grobbee, J. W Lampe, and Y. T van der Schouw
Randomized controlled trial of the effects of soy protein containing isoflavones on vascular function in postmenopausal women
Am. J. Clinical Nutrition, January 1, 2005; 81(1): 189 - 195.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
W. M. R. Broekmans, I. A. A. Klopping-Ketelaars, J. A. Weststrate, L. B. M. Tijburg, G. van Poppel, A. A. Vink, T. T.J.M Berendschot, M. L. Bots, W. A. M. Castenmiller, and A. F. M. Kardinaal
Decreased Carotenoid Concentrations Due to Dietary Sucrose Polyesters Do Not Affect Possible Markers of Disease Risk in Humans
J. Nutr., March 1, 2003; 133(3): 720 - 726.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
C. A Francois, S. L Connor, L. C Bolewicz, and W. E Connor
Supplementing lactating women with flaxseed oil does not increase docosahexaenoic acid in their milk
Am. J. Clinical Nutrition, January 1, 2003; 77(1): 226 - 233.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
N. Dashti, Q. Feng, M. R. Freeman, M. Gandhi, and F. A. Franklin
Trans Polyunsaturated Fatty Acids Have More Adverse Effects than Saturated Fatty Acids on the Concentration and Composition of Lipoproteins Secreted by Human Hepatoma HepG2 Cells
J. Nutr., September 1, 2002; 132(9): 2651 - 2659.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by de Roos, N. M.
Right arrow Articles by Katan, M. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by de Roos, N. M.
Right arrow Articles by Katan, M. B.
Related Collections
Right arrow Nutrition
Right arrow Epidemiology
Right arrow Lipid and lipoprotein metabolism
Right arrow Endothelium/vascular type/nitric oxide
Right arrow Other imaging

ATVB Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 2001 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.