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

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Lipids

Abstract

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.

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Abbreviations

BMI:

Body mass index

CHD:

Coronary heart disease

CI:

Confidence interval

CVD:

Cardiovascular disease

FA:

Fatty acid

HR:

Hazard ratio

IQR:

Interquartile range

LI:

Lipophilic index

MET:

Metabolic equivalent of task

MUFA:

Monounsaturated fatty acid

OR:

Odds ratio

PL:

Phospholipid

PUFA:

Polyunsaturated fatty acid

RR:

Risk ratio

SD:

Standard deviation

SFA:

Saturated fatty acid

TFA:

Trans fatty acid

WHI:

Women’s Health Initiative

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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA

    Qing Liu, Chanelle J. Howe, Simin Liu & Charles B. Eaton

  2. Jean Mayer USDA Human Nutrition Research Center ON Aging, Tufts University, Boston, MA, USA

    Alice H. Lichtenstein & Nirupa R. Matthan

  3. University of California, San Diego, La Jolla, CA, USA

    Matthew A. Allison

  4. VA San Diego Healthcare System, San Diego, CA, USA

    Matthew A. Allison

  5. MedStar Health Research Institute, Hyattsville, MD, USA

    Barbara V. Howard

  6. Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC, USA

    Barbara V. Howard

  7. Division of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Lisa W. Martin

  8. Medstar Washington Hospital Center and Georgetown University School of Medicine, Washington, DC, USA

    Carolina Valdiviezo

  9. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    JoAnn E. Manson

  10. Center for Primary Care and Prevention, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI, 02680, USA

    Charles B. Eaton

Authors
  1. Qing Liu
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Corresponding author

Correspondence to Charles B. Eaton.

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Appendices

Appendix 1. Causal diagrams hypothesized for the two study designs

See Fig. 2.

Fig. 2
figure 2

I Dietary LI in cohort study. II Plasma PL LI in matched case-control study. C1 includes age, region, race/ethnicity, education, income, BMI, physical activity, smoking, family history of myocardial infarction/diabetes/stroke, medication use, postmenopausal hormone use, self-reported baseline hypertension/diabetes/cancer/hypercholesterolemia/hysterectomy status, dietary alcohol, percent calories from protein and carbohydrates, and total energy intake. C2 includes age, region, race/ethnicity, education, income, self-reported baseline hypertension/diabetes/cancer/hypercholesterolemia, and hysterectomy status. C3 includes age, race/ethnicity, hysterectomy status, BMI, physical activity, smoking, family history of myocardial infarction/diabetes/stroke, medication use, postmenopausal hormone use, self-reported baseline hypertension/diabetes/cancer/hypercholesterolemia, dietary alcohol, percent calories from protein and carbohydrates, and total energy intake. A box around a node represents conditioning on that node

Full size image

Appendix 2

See Table 4.

Table 4 Melting points and median (IQR) levels for individual fatty acids and Spearman’s correlation coefficients (r) for correlation between individual fatty acids and the lipophilic index measured in diets from the cohort study (1994–2014) and in plasma PL from the case-control study (1994–2005) of the Women’s Health Initiative
Full size table

Appendix 3

See Table 5.

Table 5 Hazard ratios (95% confidence interval) for CHD according to quartiles of dietary lipophilic index/load among participants without missing covariates in the cohort study (1994–2014, N = 60,079) of the Women’s Health Initiative
Full size table

Appendix 4

See Table 6.

Table 6 Hazard ratios (95% confidence interval) for CHD according to quartiles of dietary lipids in the cohort study (1994–2014, N = 85,563) of the Women’s Health Initiative
Full size table

Appendix 5

See Table 7.

Table 7 Hazard ratios (95% confidence interval) for CHD according to quartiles of dietary lipophilic index and lipids among participants with blood lipids in the cohort study (1994–2014, N = 6,188) of the Women’s Health Initiative
Full size table

Appendix 6

See Table 8.

Table 8 Hazard ratios (95% confidence interval) for CHD according to quartiles of dietary lipophilic index/load calculated using different methods among participants in the cohort study (1994–2014, N = 85,563) of the Women’s Health Initiative
Full size table

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Liu, Q., Lichtenstein, A.H., Matthan, N.R. et al. Higher Lipophilic Index Indicates Higher Risk of Coronary Heart Disease in Postmenopausal Women. Lipids 52, 687–702 (2017). https://doi.org/10.1007/s11745-017-4276-8

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