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BACKGROUND: Elevated fibrinogen, activated factor XII (FXIIa), and factor VII coagulant activity (FVIIc) are associated with higher risk of fatal ischemic heart disease. This study tested the hypothesis that lowering the dietary ratio of n-6 to n-3 polyunsaturated fatty acids (n-6:n-3) would modify these risk factors in older men and women. OBJECTIVE: The objective of the study was to measure fasting hemostatic risk factors and postprandial changes in activated FVII (FVIIa) concentrations after a 6-mo alteration in dietary n-6:n-3. DESIGN: In a randomized, parallel design in 258 subjects aged 45-70 y, we compared 4 diets providing 6% of energy as polyunsaturated fatty acids at an n-6:n-3 between 5:1 and 3:1 with a control diet that had an n-6:n-3 of 10:1. The diets were enriched in alpha-linolenic acid, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid, or both. RESULTS: Fasting and 3-h plasma triacylglycerol concentrations were 11.1% and 7.2% lower with the diet that had an n-6:n-3 of approximately 3:1 and that was enriched with EPA and DHA than with the other diets. Fasting fibrinogen, FXIIa, FVIIc, FVIIa, and FVII antigen and postprandial FVIIa were not influenced by the diets. Avoiding foods high in fat the day before measurement decreased FVIIc and FVIIa by 8% and 19.2%, respectively. A test meal containing 50 g fat resulted in a mean 47% (95% CI: 42%, 52%) increase in FVIIa 6 h later, but the response did not differ by n-6:n-3. CONCLUSION: Decreasing the n-6:n-3 to approximately 3:1 by increasing the intake of EPA and DHA lowers fasting and postprandial plasma triacylglycerol concentrations in older persons but does not influence hemostatic risk factors. Copyright © 2006 American Society for Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: Soybeans contain estrogenic isoflavones that may influence plasma concentrations of transforming growth factor beta(1) (TGF-beta(1)) and plasma lipid and hemostatic risk factors for coronary heart disease. OBJECTIVE: We compared the effects of moderate intakes of soy protein containing intact phytoestrogens (high-isoflavone diet) and soy protein from which most of the phytoestrogens had been extracted (low-isoflavone diet) on active TGF-beta(1) concentrations and plasma lipid and hemostatic risk factors for coronary heart disease. DESIGN: A randomized crossover trial was conducted in 22 young, healthy, normolipidemic subjects (5 men and 17 women) who consumed diets providing 56 or 2 mg isoflavones/d for 17 d each with a 25-d washout period between treatments. Fasting blood samples were obtained on days 13 and 14 of each treatment to measure plasma isoflavone, lipid, fibrinogen, and active TGF-beta(1) concentrations and factor VII coagulant and plasminogen activator inhibitor type 1 activities. RESULTS: Plasma isoflavone concentrations were 100-999 times greater after the high-isoflavone diet than after the low-isoflavone diet (P < 0.05). Plasma HDL-cholesterol and apolipoprotein A-I concentrations were 4% (95% CI: 1%, 8%) and 6% (95% CI: 3%, 10%) higher, respectively, after the high-isoflavone diet than after the low-isoflavone diet (P < 0.01 for both). CONCLUSION: Compared with soy protein from which most of the phytoestrogens have been extracted, soy protein with intact phytoestrogens increases HDL-cholesterol and apolipoprotein A-I concentrations but does not influence LDL-cholesterol, TGF-beta(1), or fibrinogen concentrations; factor VII coagulant activity; or plasminogen activator inhibitor type 1 activity in normolipidemic, healthy subjects. Copyright © 2002 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: An elevated postprandial lipid concentration is believed to be atherogenic and to increase the risk of thrombosis. OBJECTIVE: The objective was to test whether the consumption of a stearic acid-rich structured triacylglycerol has adverse effects on postprandial fibrinolytic activity and lipemia, factor VII coagulant (FVII:c) activity, and activated FVII (FVIIa) concentrations. DESIGN: A randomized crossover design was used to compare the effects on middle-aged healthy men (n = 17) and women (n = 18) of meals enriched with cocoa butter, high-oleate sunflower oil (oleate), or a structured triacylglycerol containing stearic acid. RESULTS: The mean increases from fasting in plasma triacylglycerol 3 h after the oleate, cocoa butter, and structured triacylglycerol meals were 1.36 (95% CI: 1.17, 1.56), 1.39 (1.17,1.63), and 0.65 (0.50, 0.82) mmol/L, respectively. Tissue plasminogen activator activity increased and plasminogen activator type 1 activity decreased after all 3 meals. Plasma FVII:c increased after the oleate and cocoa butter meals but not after the structured triacylglycerol meal. The values 6 h after the oleate and cocoa butter meals were 11.3% (7.0%, 15.6%) and 9.9% (4.7%, 15.2%), respectively, and were significantly different (P < 0.0001 and P = 0.001, respectively) from the value after the triacylglycerol meal [2.1% (-1.1%, 5.3%)]. Plasma FVIIa increased after all 3 meals, more so after the oleate and cocoa butter meals than after the structured triacylglycerol meal. CONCLUSION: The consumption of stearic acid in the form of a structured triacylglycerol leads to less of an increase in plasma triacylglycerol and in FVII:c than does a meal enriched in cocoa butter or oleate. Copyright © 2001 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: Factor VII coagulant activity (FVII:c) is associated with an increased risk of fatal ischemic heart disease, is correlated with plasma triacylglycerol concentration, and increases after a meal rich in long-chain fatty acids. OBJECTIVE: We planned to compare effects of meals rich in oleate and butter fat with those of a low-fat meal on FVII:c and fibrinolytic activity. DESIGN: A crossover design was used to compare the postprandial effects on coagulant and fibrinolytic activities in 12 men of 3 high-fat (95 g) meals--high oleate, butter, and oleate + medium-chain triacylglycerols (oleate+MCT)--with an isoenergetic low-fat meal (18 g MCT). The oleate+MCT blend was used to mimic the ratio of long-chain to shorter-chain fatty acids in butter. RESULTS: Neither the amount nor type of fat consumed influenced plasminogen activator inhibitor 1 or t-plasminogen activator activities or D-dimer concentration. FVII:c increased by 12.5% (95% CI: 4.6%, 20.5%) after the high-fat meals at 3 h and by 6.7% (95% CI: 1.6%, 11.7%) at 7 h and changed 7 h after the low-fat meal by -14.3% (95% CI: -3.3%, -25.4%). The responses to the high-fat meals did not differ. Measurements of activated FVII (FVIIa), FVII zymogen, and activated FXII (FXIIa) concentrations made after the low-fat and high-oleate meals showed a significant increase in FVIIa only after the high-oleate meal. CONCLUSIONS: The results of this study confirm that FVII:c falls after a low-fat meal and suggests that postprandial activation of FVII occurs rapidly after a fat-rich meal without involving an increase in FXIIa. Copyright (c) 1998 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: Low plasma concentrations of HDLs are associated with an increased risk of coronary artery disease. Two uncontrolled studies suggested that plant monoterpenes may have substantial HDL-cholesterol-elevating activity in humans. Each study used a proprietary mixture of 6 monoterpenes in olive oil. OBJECTIVE: The present study was undertaken to test more rigorously the hypothesis that monoterpenes raise HDL concentrations in men with hypoalphalipoproteinemia. DESIGN: A double-blind, placebo-controlled crossover design was used. Twenty-four men aged 58-68 y (x: 62.3 y) with plasma HDL cholesterol <1.1 mmol/L, plasma triacylglycerols <3.5 mmol/L, and plasma total cholesterol <5.5 mmol/L at recruitment were randomly assigned to 6 capsules daily of a proprietary mixture of 6 monoterpenes in olive oil or 6 capsules daily of olive oil alone for 24 wk, followed by a washout period of 8 wk, and then the alternative capsules for 24 wk. RESULTS: Five men dropped out. In the others, compliance was excellent as judged by capsule counts and urinary menthol glucuronide concentrations. No significant effects were observed on plasma HDL-cholesterol or apolipoprotein A-I concentrations, nor on plasma triacylglycerol, LDL-cholesterol, or apolipoprotein B concentrations. CONCLUSIONS: Plant monoterpenes have no HDL-elevating activity of potential value for coronary artery disease prevention. Copyright (c) 1998 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Background: The process of randomization is used commercially to harden fats as an alternative to partial hydrogenation, but its effects on cardiovascular disease risk factors are uncertain., Objective: The objective was to compare the chronic and acute effects of randomization of a fat rich in 1,3-distearyl, 2-oleyl glycerol on fasting and postprandial lipids, glucose, insulin, and activated clotting factor VII (FVIIa) concentrations., Design: A crossover design study in 16 men compared fasting and postprandial lipid, glucose, insulin, and FVIIa concentrations at baseline and after a 3-wk diet providing 30 g unrandomized or randomized shea butter and sunflower oil blends (SSOBs), both of which contained approximately 50% stearic acid. Fecal fat excretion was measured during each dietary period. Postprandial changes were assessed after the consumption of meals providing 50 g test fat. A subsequent study compared postprandial changes after the consumption of an oleic acid-rich sunflower oil meal and an unrandomized SSOB meal., Results: Both SSOBs were well digested and absorbed. Randomization did not affect fasting or postprandial lipid, glucose, insulin, or FVIIa concentrations. Compared with the oleic acid-rich meal, the unrandomized SSOB resulted in 53% lower postprandial lipemia, 23% higher hepatic lipase activity, and a 25% lower postprandial increase in FVIIa concentration. The solid fat contents at 37 degrees C were 22%, 41%, and 0% with the unrandomized SSOB, randomized SSOB, and oleic acid-rich meals, respectively., Conclusions: Stearic acid-rich triacylglycerol in both unrandomized and randomized forms does not adversely affect lipid risk factors for cardiovascular disease. The high proportion of solid fat at 37 degrees C may explain the decreased postprandial lipemic response.

Background: Insulin resistance is associated with elevated plasma triacylglycerol, low HDL concentrations, elevated postprandial lipemia, and a predominance of small, dense LDLs (sdLDLs). It has been hypothesized that the dietary ratio of n-6 to n-3 (n-6:n-3) polyunsaturated fatty acids (PUFAs) may have favorable effects on these risk factors by increasing insulin sensitivity., Objective: The objective was to measure changes in insulin sensitivity, lipoprotein size, and postprandial lipemia after a 6-mo alteration in n-6:n-3., Design: In a randomized, parallel design in 258 subjects aged 45-70 y, we compared 4 diets providing 6% of energy as PUFAs with an n-6:n-3 between 5:1 and 3:1 with a control diet that had an n-6:n-3 of 10:1. The diets were enriched in alpha-linolenic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), or both. Insulin sensitivity was assessed with the homeostatic model assessment of insulin resistance and the revised quantitative insulin sensitivity test., Results: Dietary intervention did not influence insulin sensitivity or postprandial lipase activities. Fasting and postprandial triacylglycerol concentrations were lower, and the proportion of sdLDLs decreased (by 12.7%; 95% CI: -22.9%, 2.4%), with an n-6:n-3 of approximately 3:1, which was achieved by the addition of long-chain n-3 PUFAs (EPA and DHA)., Conclusions: Decreasing the n-6:n-3 does not influence insulin sensitivity or lipase activities in older subjects. The reduction in plasma triacylglycerol after an increased intake of n-3 long-chain PUFAs results in favorable changes in LDL size.

Background: Decreased fibrinolytic activity is associated with an increased risk of ischemic heart disease and elevated plasma triacylglycerol concentrations., Objective: The goal was to determine whether plasminogen activator inhibitor 1 (PAI-1) and fibrinolytic activities are influenced by 1) dietary fat intake from a test meal and 2) the PAI-1 4G allele., Design: A parallel randomized controlled trial was used to compare the effect on fibrinolytic activity, measured as dilute clot lysis time, of high-oleate or high-palmitate test meals (both containing 50 g fat; both n = 18) with that of a low-fat test meal (15 g fat; n = 15) in men aged > 52 y. In a second study, postprandial changes in PAI-1 activity were measured in 32 men in response to a high-oleate meal containing 50 g fat. The results from both studies were analyzed according to PAI-1 4G-675/5G genotype., Results: Fasting dilute clot lysis time was positively associated with body mass index (r = 0.326, P = 0.02) and was shortened postprandially (P < 0.00001) independent of the fat content of the meal. Fasting PAI-1 activity was higher in those carrying the 4G allele and was correlated with fasting plasma triacylglycerol concentrations (r = 0.48, P = 0.008) and factor VII coagulant activity (r = 0.46, P = 0.012) after adjustments for age, body mass index, and genotype. Plasma PAI-1 activity decreased significantly after a meal but was not associated with postprandial changes in plasma triacylglycerols after a high-fat meal. The postprandial increase in plasma triacylglycerols was higher in subjects carrying the 4G allele., Conclusion: Fibrinolytic activity is not lower after meals rich in palmitate or oleate than after a low-fat meal.

Background: Hypertriglyceridemia may represent a procoagulant state involving disturbances to the hemostatic system. Plasminogen activator inhibitor type 1 (PAI-1) is increased in the presence of hypertriglyceridemia. Free fatty acids (FFAs) in plasma may promote factor VII (FVII) activation., Objective: We tested the hypothesis that FVII activation would be less after consumption of saturated fatty acids than after other fatty acids., Design: The effects of 6 matching dietary test fats, rich in stearic (S), palmitic (P), palmitic + myristic (M), oleic (O), trans 18:1 (T), and linoleic (L) acid, respectively, on the postprandial lipid and hemostatic profile (after 2, 4, 6, and 8 h) were investigated in 16 young men. High-fat meals (1 g fat/kg body wt; 43% from the test fatty acid) were served in the morning on 6 separate days., Results: All fats increased FVII activation. The S fat resulted in a lower increase in activated FVII (FVIIa) than did the T fat and in a lower FVII coagulant activity (FVII:c) than did the O fat (P < 0.02, diet x time interaction). When the data were pooled, the saturated (S, P, and M) test fats resulted in a smaller postprandial increase in FVIIa (P = 0.036, diet effect), a smaller increase in FVII:c (P < 0.001, diet x time interaction), a greater rise in tissue plasminogen activator concentrations (P = 0.028, diet effect), and a tendency to a greater postprandial decline in PAI-1 (P = 0.06, diet effect) compared with the unsaturated test fats (O, T, and L). The increase in FVIIa was not significantly associated with the level of lipemia, plasma FFAs, or plasma lipoprotein lipase activity., Conclusion: Our results indicate a lesser increase in FVIIa after the consumption of saturated fats, especially the S fat, than after unsaturated test fats.

Background: The consumption of a synthetic, randomized, stearic acid-rich triacylglycerol results in decreased postprandial lipemia and activated factor VII (FVII:a) compared with cocoa butter (a nonrandomized, symmetrical, stearic acid-rich triacylglycerol). It was hypothesized that this difference is a consequence of the differences in structure between the 2 triacylglycerols., Objective: The objective was to test whether the consumption of randomized cocoa butter decreases postprandial lipemia and FVII:a., Design: A randomized crossover trial with 17 male subjects compared the effects of meals containing 50 g fat provided as a symmetrical (cocoa butter) or an asymmetrical (randomized cocoa butter) triacylglycerol on postprandial changes in lipids, chylomicron composition, and FVII:a., Results: After randomization, the postprandial area under the curve for plasma triacylglycerol decreased by 41% (P < 0.01). At 3 h the plasma concentrations of triacylglycerol, palmitic acid, stearic acid, and oleic acid were 26%, 18%, 34%, and 19% lower, respectively. The proportion of oleic acid in the sn-2 position of the chylomicron triacylglycerol was reduced from 67.4 mol% to 35.9 mol% and resulted in an increase in the proportion of stearic acid in the sn-2 position from 9.2 mol% to 25.4 mol%. FVII:a did not increase 6 h after consumption of the randomized cocoa butter (: 1.2; 95% CI: -2.7, 4.6 U/L) but increased significantly (: 7.7; 95% CI: 2.5,12.9 U/L) 6 h after consumption of the unrandomized cocoa butter., Conclusions: Symmetrical stearic acid-rich triacylglycerol with oleic acid in the sn-2 position appears to be absorbed more rapidly than is asymmetrical triacylglycerols with long-chain saturated fatty acids in the sn-2 position, which leads to activation of FVII.

Background: Soybeans contain estrogenic isoflavones that may influence plasma concentrations of transforming growth factor beta(1) (TGF-beta(1)) and plasma lipid and hemostatic risk factors for coronary heart disease., Objective: We compared the effects of moderate intakes of soy protein containing intact phytoestrogens (high-isoflavone diet) and soy protein from which most of the phytoestrogens had been extracted (low-isoflavone diet) on active TGF-beta(1) concentrations and plasma lipid and hemostatic risk factors for coronary heart disease., Design: A randomized crossover trial was conducted in 22 young, healthy, normolipidemic subjects (5 men and 17 women) who consumed diets providing 56 or 2 mg isoflavones/d for 17 d each with a 25-d washout period between treatments. Fasting blood samples were obtained on days 13 and 14 of each treatment to measure plasma isoflavone, lipid, fibrinogen, and active TGF-beta(1) concentrations and factor VII coagulant and plasminogen activator inhibitor type 1 activities., Results: Plasma isoflavone concentrations were 100-999 times greater after the high-isoflavone diet than after the low-isoflavone diet (P < 0.05). Plasma HDL-cholesterol and apolipoprotein A-I concentrations were 4% (95% CI: 1%, 8%) and 6% (95% CI: 3%, 10%) higher, respectively, after the high-isoflavone diet than after the low-isoflavone diet (P < 0.01 for both)., Conclusion: Compared with soy protein from which most of the phytoestrogens have been extracted, soy protein with intact phytoestrogens increases HDL-cholesterol and apolipoprotein A-I concentrations but does not influence LDL-cholesterol, TGF-beta(1), or fibrinogen concentrations; factor VII coagulant activity; or plasminogen activator inhibitor type 1 activity in normolipidemic, healthy subjects.

Background: The R353Q genotype is a major determinant of factor VII coagulant (FVIIc) activity, which is associated with an increased risk of ischemic heart disease (IHD) and elevated plasma triacylglycerol concentrations., Objective: The objectives were to 1) compare the effects of meals rich in palmitate or oleate with those of a meal low in fat on FVIIc in subjects with moderately elevated plasma nonfasting triacylglycerol concentrations and 2) determine whether the postprandial increase in FVIIc induced by dietary oleate differs in carriers of the Q allele., Design: Fifty-two men aged >52 y with nonfasting plasma triacylglycerol concentrations between 2 and 5.5 mmol/L were randomly assigned to receive isoenergetic (5.1 MJ) meals providing 50 g high-oleate or high-palmitate oils or a low-fat meal providing 15 g high-oleate oil. In a second study, 17 men aged >52 y who were heterozygous for factor VII R353Q polymorphism were age-matched with subjects homozygous for the R allele and their responses to a 50-g, high-oleate meal were measured., Results: FVIIc decreased by 11% after the low-fat meal. FVIIc increased by 9% and FVIIa (the activated form of FVII) increased by 55% after the high-oleate meal, whereas FVIIc did not change but FVIIa increased by 25% after the high-palmitate meal. Fasting FVIIc and FVIIa concentrations were 24% and 48% lower, respectively, in men with the RQ genotype than in men with the RR genotype but increased postprandially in both groups with no evidence of a genotype interaction., Conclusions: A high-fat meal rich in oleate increases FVIIa, whereas a low-fat meal does not, in men at high risk of IHD, independent of R353Q genotype.

Total dietary fat intake is an important determinant of factor VII coagulant activity, a hemostatic risk factor for fatal ischemic heart disease in middle-aged men. This association has a long-term effect by which a high-fat diet increases plasma factor VII antigen concentration, and an acute effect whereby a small proportion of factor VII is converted from its proenzyme to active serine protease for several hours postprandially. In adults whose usual diet is rich in long-chain saturated fatty acids, postprandial activation of factor VII occurs irrespective of the fatty acid composition. The underlying mechanism appears to require lipolysis and the presence of another coagulant protein, factor IX. There is limited evidence that factor VII activation after a meal rich in polyunsaturated fatty acid is blunted when the background diet also has a high content of polyunsaturated fatty acid. Meals rich in medium-chain triacylglycerols do not induce factor VII activation. The effects of dietary enrichment with n-3 fatty acids on factor VII are uncertain. All studies have been confined to the fasting state, and only one suggested changes consistent with factor VII activation. Fibrinogen concentration, another major hemostatic risk factor for ischemic heart disease, is uninfluenced by dietary fat content or composition, the one exception being inconsistent reports of a reduction after dietary enrichment with n-3 fatty acids. Overall, the evidence so far indicates that total dietary fat intake is more important than dietary fat composition for factor VII and by implication its attendant risk of fatal ischemic heart disease in high-risk populations.