The Type and Amount of Dietary Fat Affect Plasma Factor VIIc, Fibrinogen, and PAI-1 in Healthy Individuals and Individuals at High Cardiovascular Disease Risk: 2 Randomized Controlled Trials

Penny M Kris-Etherton, Paul W Stewart, Henry N Ginsberg, Russell P Tracy, Michael Lefevre, Patricia J Elmer, Lars Berglund, Abby G Ershow, Thomas A Pearson, Rajasekhar Ramakrishnan, Stephen F Holleran, Barbara H Dennis, Catherine M Champagne, Wahida Karmally, DELTA Investigators, Henry Ginsberg, Rajasekhar Ramakrishnan, Wahida Karmally, Lars Berglund, Maliha Siddiqui, Niem-Tzu Chen, Steve Holleran, Colleen Johnson, Roberta Holeman, Karen Chirgwin, Kellye Stennett, Lencey Ganga, Tajsudeen Towolawai, Minnie Myers, Colleen Ngai, Nelson Fontenez, Jeff Jones, Carmen Rodriguez, Norma Useche, Michael Lefevre, Paul S Roheim, Donna Ryan, Marlene Most, Catherine Champagne, Donald Williamson, Richard Tulley, Ricky Brock, Deonne Bodin, Betty Kennedy, Michelle Barkate, Elizabeth Foust, Deshoin York, Penny Kris-Etherton, Satya Jonnalagadda, Janice Derr, Abir Farhat-Wood, Vikkie Mustad, Kate Meaker, Edward Mills, Mary-Ann Tilley, Helen Smiciklas-Wright, Madeleine Sigman-Grant, Shaomei Yu, Jean-Xavier Guinard, Pamela Sechevich, C Channa Reddy, Andrea M Mastro, Allen D Cooper, Patricia Elmer, Aaron Folsom, Nancy Van Heel, Christine Wold, Kay Fritz, Joanne Slavin, David Jacobs, Barbara Dennis, Paul Stewart, C Davis, James Hosking, Nancy Anderson, Susan Blackwell, Lynn Martin, Hope Bryan, W Brian Stewart, Jeffrey Abolafia, Malachy Foley, Conroy Zien, Szu-Yun Leu, Marston Youngblood, Thomas Goodwin, Monica Miles, Jennifer Wehbie, Thomas Pearson, Roberta Reed, Russell Tracy, Elaine Cornell, Kent Stewart, Katherine Phillips, Bernestine McGee, Brenda Williams, Gary Beecher, Joanne Holden, Carol Davis, Abby Ershow, David Gordon, Michael Proschan, Basil Rifkind, Penny M Kris-Etherton, Paul W Stewart, Henry N Ginsberg, Russell P Tracy, Michael Lefevre, Patricia J Elmer, Lars Berglund, Abby G Ershow, Thomas A Pearson, Rajasekhar Ramakrishnan, Stephen F Holleran, Barbara H Dennis, Catherine M Champagne, Wahida Karmally, DELTA Investigators, Henry Ginsberg, Rajasekhar Ramakrishnan, Wahida Karmally, Lars Berglund, Maliha Siddiqui, Niem-Tzu Chen, Steve Holleran, Colleen Johnson, Roberta Holeman, Karen Chirgwin, Kellye Stennett, Lencey Ganga, Tajsudeen Towolawai, Minnie Myers, Colleen Ngai, Nelson Fontenez, Jeff Jones, Carmen Rodriguez, Norma Useche, Michael Lefevre, Paul S Roheim, Donna Ryan, Marlene Most, Catherine Champagne, Donald Williamson, Richard Tulley, Ricky Brock, Deonne Bodin, Betty Kennedy, Michelle Barkate, Elizabeth Foust, Deshoin York, Penny Kris-Etherton, Satya Jonnalagadda, Janice Derr, Abir Farhat-Wood, Vikkie Mustad, Kate Meaker, Edward Mills, Mary-Ann Tilley, Helen Smiciklas-Wright, Madeleine Sigman-Grant, Shaomei Yu, Jean-Xavier Guinard, Pamela Sechevich, C Channa Reddy, Andrea M Mastro, Allen D Cooper, Patricia Elmer, Aaron Folsom, Nancy Van Heel, Christine Wold, Kay Fritz, Joanne Slavin, David Jacobs, Barbara Dennis, Paul Stewart, C Davis, James Hosking, Nancy Anderson, Susan Blackwell, Lynn Martin, Hope Bryan, W Brian Stewart, Jeffrey Abolafia, Malachy Foley, Conroy Zien, Szu-Yun Leu, Marston Youngblood, Thomas Goodwin, Monica Miles, Jennifer Wehbie, Thomas Pearson, Roberta Reed, Russell Tracy, Elaine Cornell, Kent Stewart, Katherine Phillips, Bernestine McGee, Brenda Williams, Gary Beecher, Joanne Holden, Carol Davis, Abby Ershow, David Gordon, Michael Proschan, Basil Rifkind

Abstract

Background: Factor VIIc, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) are cardiovascular disease (CVD) risk factors and are modulated, in part, by fat type and amount.

Objective: We evaluated fat type and amount on the primary outcomes: factor VIIc, fibrinogen, and PAI-1.

Methods: In the Dietary Effects on Lipoproteins and Thrombogenic Activity (DELTA) Trial, 2 controlled crossover feeding studies evaluated substituting carbohydrate or MUFAs for SFAs. Study 1: healthy participants (n = 103) were provided with (8 wk) an average American diet [AAD; designed to provide 37% of energy (%E) as fat, 16% SFA], a Step 1 diet (30%E fat, 9% SFA), and a diet low in SFA (Low-Sat; 26%E fat, 5% SFA). Study 2: participants (n = 85) at risk for CVD and metabolic syndrome (MetSyn) were provided with (7 wk) an AAD, a step 1 diet, and a high-MUFA diet (designed to provide 37%E fat, 8% SFA, 22% MUFA).

Results: Study 1: compared with AAD, the Step 1 and Low-Sat diets decreased mean factor VIIc by 1.8% and 2.6% (overall P = 0.0001), increased mean fibrinogen by 1.2% and 2.8% (P = 0.0141), and increased mean square root PAI-1 by 0.0% and 6.0% (P = 0.0037), respectively. Study 2: compared with AAD, the Step 1 and high-MUFA diets decreased mean factor VIIc by 4.1% and 3.2% (overall P < 0.0001), increased mean fibrinogen by 3.9% and 1.5% (P = 0.0083), and increased mean square-root PAI-1 by 2.0% and 5.8% (P = 0.1319), respectively.

Conclusions: Replacing SFA with carbohydrate decreased factor VIIc and increased fibrinogen in healthy and metabolically unhealthy individuals and also increased PAI-1 in healthy subjects. Replacing SFA with MUFA decreased factor VIIc and increased fibrinogen but less than carbohydrate. Our results indicate an uncertain effect of replacing SFA with carbohydrate or MUFA on cardiometabolic risk because of small changes in hemostatic factors and directionally different responses to decreasing SFA. This trial was registered at https://ichgcp.net/clinical-trials-registry/NCT00000538?term=NCT00000538&rank=1 as NCT00000538.

Keywords: DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activity); PAI-1; dietary fat; factor VIIc; fibrinogen; plasminogen activator inhibitor.

Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.

Figures

FIGURE 1
FIGURE 1
CONSORT diagrams for DELTA study 1 and study 2. 1Methods, diets, and other information as described in Ginsberg et al. (31). 2Each participant was randomly assigned to a sequence of 3 protocol-specific experimental diets. 3Methods and diets as described in Berglund et al. (32); other information from unpublished data (Collaborative Studies Coordinating Center, School of Public Health, University of North Carolina, Chapel Hill, NC, 1995). CONSORT, Consolidated Standards of Reporting Trials; DELTA, Dietary Effects on Lipoproteins and Thrombogenic Activity.

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