, Volume 52, Issue 8, pp 687–702 | Cite as

Higher Lipophilic Index Indicates Higher Risk of Coronary Heart Disease in Postmenopausal Women

  • Qing Liu
  • Alice H. Lichtenstein
  • Nirupa R. Matthan
  • Chanelle J. Howe
  • Matthew A. Allison
  • Barbara V. Howard
  • Lisa W. Martin
  • Carolina Valdiviezo
  • JoAnn E. Manson
  • Simin Liu
  • Charles B. Eaton
Original Article


Fatty acids (FAs) are essential components of cell membranes and play an integral role in membrane fluidity. The lipophilic index [LI, defined as the sum of the products between FA levels and melting points (°C), divided by the total amount of FA: \({\text{LI}} = \frac{{\mathop \sum \nolimits_{k} [{\text{fatty acid}} \times {\text{melting point}}]}}{{\mathop \sum \nolimits_{k} {\text{fatty acid}} }}\)] is thought to reflect membrane and lipoprotein fluidity and may be associated with the risk of coronary heart disease (CHD). Therefore, we examined the associations of dietary and plasma phospholipid (PL) LI with CHD risk among postmenopausal women. We determined dietary LI for the cohort with completed baseline food frequency questionnaires and free of prevalent cardiovascular diseases in the Women’s Health Initiative (WHI) observational study (N = 85,563). We additionally determined plasma PL LI in a matched case-control study (N = 2428) nested within the WHI observational cohort study. Cox proportional hazard regression and multivariable conditional logistic regression were used to calculate HRs/ORs for CHD risk between quartiles of LI after adjusting for potential sources of confounding and selection bias. Higher dietary LI in the cohort study and plasma PL LI in the case-control study were significantly associated with increased risk of CHD: HR = 1.18 (95% CI 1.07–1.31, P for trend <0.01) and OR = 1.76 (95% CI 1.33–2.33, P for trend <0.01) comparing extreme quartiles and adjusting for potential confounders. These associations still persisted after adjusting for the polyunsaturated to saturated fat ratio. Our study indicated that higher LI based on either dietary or plasma measurements, representing higher FA lipophilicity, was associated with elevated risk of CHD among postmenopausal women.


Lipophilic index Coronary heart disease Diet Plasma Postmenopausal women 



Body mass index


Coronary heart disease


Confidence interval


Cardiovascular disease


Fatty acid


Hazard ratio


Interquartile range


Lipophilic index


Metabolic equivalent of task


Monounsaturated fatty acid


Odds ratio




Polyunsaturated fatty acid


Risk ratio


Standard deviation


Saturated fatty acid


Trans fatty acid


Women’s Health Initiative



WHI investigators Program Office: (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Elizabeth Nabel, Jacques Rossouw, Shari Ludlam, Joan McGowan, Leslie Ford, and Nancy Geller. Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA). Ross Prentice, Garnet Anderson, Andrea LaCroix, Charles L. Kooperberg, Ruth E. Patterson, Anne McTiernan; (Medical Research Labs, Highland Heights, KY) Evan Stein; (University of California at San Francisco, San Francisco, CA) Steven Cummings. Clinical Centers: (Albert Einstein College of Medicine, Bronx, NY) Sylvia Wassertheil-Smoller; (Baylor College of Medicine, Houston, TX) Aleksandar Rajkovic; (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (Brown University, Providence, RI) Charles B. Eaton; (Emory University, Atlanta, GA) Lawrence Phillips; (Fred Hutchinson Cancer Research Center, Seattle, WA) Shirley Beresford; (George Washington University Medical Center, Washington, DC) Lisa Martin; (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA) Rowan Chlebowski; (Kaiser Permanente Center for Health Research, Portland, OR) Yvonne Michael; (Kaiser Permanente Division of Research, Oakland, CA) Bette Caan; (Medical College of Wisconsin, Milwaukee, WI) Jane Morley Kotchen; (MedStar Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Northwestern University, Chicago/Evanston, IL) Linda Van Horn; (Rush Medical Center, Chicago, IL) Henry Black; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (State University of New York at Stony Brook, Stony Brook, NY) Dorothy Lane; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Alabama at Birmingham, Birmingham, AL) Cora E. Lewis; (University of Arizona, Tucson/Phoenix, AZ) Cynthia A Thomson; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of California at Davis, Sacramento, CA) John Robbins; (University of California at Irvine, CA) F. Allan Hubbell; (University of California at Los Angeles, Los Angeles, CA) Lauren Nathan; (University of California at San Diego, LaJolla/Chula Vista, CA) Robert D. Langer; (University of Cincinnati, Cincinnati, OH) Margery Gass; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Hawaii, Honolulu, HI) J. David Curb; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Massachusetts/Fallon Clinic, Worcester, MA) Judith Ockene; (University of Medicine and Dentistry of New Jersey, Newark, NJ) Norman Lasser; (University of Miami, Miami, FL) Mary Jo O’Sullivan; (University of Minnesota, Minneapolis, MN) Karen Margolis; (University of Nevada, Reno, NV) Robert Brunner; (University of North Carolina, Chapel Hill, NC) Gerardo Heiss; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (University of Tennessee Health Science Center, Memphis, TN) Karen C. Johnson; (University of Texas Health Science Center, San Antonio, TX) Robert Brzyski; (University of Wisconsin, Madison, WI) Gloria E. Sarto; (Wake Forest University School of Medicine, Winston-Salem, NC) Mara Vitolins; (Wayne State University School of Medicine/Hutzel Hospital, Detroit, MI) Michael Simon. Women’s Health Initiative Memory Study: (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker.

Compliance with Ethical Standards

Conflict of interest

There is no potential conflict of interest.


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Copyright information

© AOCS 2017

Authors and Affiliations

  • Qing Liu
    • 1
  • Alice H. Lichtenstein
    • 2
  • Nirupa R. Matthan
    • 2
  • Chanelle J. Howe
    • 1
  • Matthew A. Allison
    • 3
    • 4
  • Barbara V. Howard
    • 5
    • 6
  • Lisa W. Martin
    • 7
  • Carolina Valdiviezo
    • 8
  • JoAnn E. Manson
    • 9
  • Simin Liu
    • 1
  • Charles B. Eaton
    • 1
    • 10
  1. 1.Department of Epidemiology, School of Public HealthBrown UniversityProvidenceUSA
  2. 2.Jean Mayer USDA Human Nutrition Research Center ON AgingTufts UniversityBostonUSA
  3. 3.University of California, San DiegoLa JollaUSA
  4. 4.VA San Diego Healthcare SystemSan DiegoUSA
  5. 5.MedStar Health Research InstituteHyattsvilleUSA
  6. 6.Georgetown-Howard Universities Center for Clinical and Translational ScienceWashington, DCUSA
  7. 7.Division of CardiologyGeorge Washington University School of Medicine and Health SciencesWashington, DCUSA
  8. 8.Medstar Washington Hospital Center and Georgetown University School of MedicineWashington, DCUSA
  9. 9.Brigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  10. 10.Center for Primary Care and PreventionMemorial Hospital of Rhode IslandPawtucketUSA

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