Author + information
- Received April 21, 2019
- Revision received June 13, 2019
- Accepted June 24, 2019
- Published online September 16, 2019.
- Emily S. Lau, MDa,
- Samantha M. Paniagua, MPHa,b,
- James Sawalla Guseh, MDa,
- Vijeta Bhambhani, MS, MPHa,b,
- Markella V. Zanni, MDc,
- Paul Courchesne, MBAd,e,
- Asya Lyass, MA, PhDd,e,
- Martin G. Larson, ScDd,e,
- Daniel Levy, MDf and
- Jennifer E. Ho, MDa,b,∗ (, )@MassGeneralNews
- aCardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
- bCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts
- cNeuroendocrinology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
- dFramingham Heart Study, Framingham, Massachusetts
- eDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
- fPopulation Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
- ↵∗Address for correspondence:
Dr. Jennifer E. Ho, Cardiology Division, Department of Medicine, Massachusetts General Hospital, 185 Cambridge Street, CPZN #3192, Boston, Massachusetts 02114.
Background Differences in proteomic profiles between men and women may provide insights into the biological pathways that contribute to known sex differences in cardiovascular disease (CVD).
Objectives This study sought to investigate sex differences in circulating biomarkers representative of biological pathways implicated in the development of CVD among Framingham Heart Study participants.
Methods The authors measured 71 circulating CVD protein biomarkers in 7,184 participants (54% women, mean age 49 years). Multivariable models were used to evaluate the associations of sex, menopause, and hormone status with biomarkers. Cox models were used to examine whether sex modified the association of biomarkers with incident CVD.
Results Of 71 biomarkers examined, 61 (86%) differed significantly between men and women, of which 37 were higher in women (including adipokines and inflammatory markers such as leptin and C-reactive protein), and 24 were higher in men (including fibrosis and platelet markers such as MMP-8 (matrix metalloproteinase-8) and TIMP-1 (tissue inhibitor of metalloproteinases 1); false discovery rate q < 0.05 for all). Sex differences in biomarker profiles were most pronounced between pre-menopausal women versus men, with attenuated sex differences among post-menopausal women not taking hormone replacement therapy. Sex modified the association of specific biomarkers with incident CVD, including CD14 and apolipoprotein B (pinteraction <0.05 for all).
Conclusions In a predominantly Caucasian population, the authors identified widespread sex differences in circulating biomarkers that reflect distinct pathways implicated in CVD, including inflammation, adiposity, fibrosis, and platelet homeostasis. Menopause and hormone status accounted for some, but not all, of the observed sex differences. Further investigation into factors underlying sex-based differences may provide mechanistic insight into CVD development.
This work was supported by grants from the National Institutes of Health N01-HC25195 and HHSN268201500001I (Framingham Heart Study), NIH-5T32HL094301-07 (Dr. Lau), R01-HL134893 (Dr. Ho), R01-HL140224 (Dr. Ho), a Gilead Sciences Research Scholar Award (Dr. Ho), and a Hassenfeld Research Scholar award from Massachusetts General Hospital (Dr. Ho). The views expressed in this paper are those of the authors and do not necessarily represent the view of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Dr. Bhambhani is an employee of ICON plc. Dr. Zanni is principal investigator on an institutional research grant from Gilead. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received April 21, 2019.
- Revision received June 13, 2019.
- Accepted June 24, 2019.
- 2019 American College of Cardiology Foundation
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