The association of non-alcoholic fatty liver disease and cardiac structure and function—Framingham Heart Study
Laura S. Chiu
Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
Search for more papers by this authorJoseph M. Massaro
National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA, USA
Department of Mathematics and Statistics, Boston University, Boston, MA, USA
Search for more papers by this authorEmelia J. Benjamin
National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA, USA
Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
Search for more papers by this authorGary F. Mitchell
Cardiovascular Engineering, Inc, Norwood, MA, USA
Search for more papers by this authorDavid D. McManus
Cardiology Division, Department of Medicine and the Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worchester, MA, USA
Search for more papers by this authorJayashri Aragam
Cardiovascular Division, VA Boston Healthcare System, Boston, MA, USA
Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA
Harvard Medical School, Boston, MA, USA
Search for more papers by this authorRamachandran S. Vasan
National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA, USA
Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston Medical Center, Boston, MA, USA
Search for more papers by this authorSusan Cheng
Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Search for more papers by this authorCorresponding Author
Michelle T. Long
Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
Correspondence
Michelle T. Long, Boston University School of Medicine, Section of Gastroenterology, 85 East Concord Street 7th Floor, Boston, MA 02118, USA.
Email: [email protected]
Search for more papers by this authorLaura S. Chiu
Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
Search for more papers by this authorJoseph M. Massaro
National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA, USA
Department of Mathematics and Statistics, Boston University, Boston, MA, USA
Search for more papers by this authorEmelia J. Benjamin
National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA, USA
Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
Search for more papers by this authorGary F. Mitchell
Cardiovascular Engineering, Inc, Norwood, MA, USA
Search for more papers by this authorDavid D. McManus
Cardiology Division, Department of Medicine and the Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worchester, MA, USA
Search for more papers by this authorJayashri Aragam
Cardiovascular Division, VA Boston Healthcare System, Boston, MA, USA
Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA
Harvard Medical School, Boston, MA, USA
Search for more papers by this authorRamachandran S. Vasan
National Heart, Lung, and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, MA, USA
Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston Medical Center, Boston, MA, USA
Search for more papers by this authorSusan Cheng
Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Search for more papers by this authorCorresponding Author
Michelle T. Long
Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
Correspondence
Michelle T. Long, Boston University School of Medicine, Section of Gastroenterology, 85 East Concord Street 7th Floor, Boston, MA 02118, USA.
Email: [email protected]
Search for more papers by this authorFunding information
This work was supported by: National Heart, Lung, and Blood Institute contracts N01-HC-25195 and HHSN268201500001l (Dr. Vasan) and grants R01HL126136 (Mitchell/Vasan), R01HL080124, R01HL077477, and 5R01AG047645 (Dr. Vasan), 1R01HL128914 and 2R01HL092577 (Dr. Benjamin), and the National Institute of Diabetes and Digestive and Kidney Diseases K23 DK113252 and the Boston University School of Medicine Department of Medicine (Long). Dr. Cheng was supported by R01HL131532, R01HL134168, R01HL143227 and R01HL142983 from the NIH. Dr. McManus was supported by KL2RR031981, 5R01HL126977-02, 1R15HL121761-01-A1 and IUH2TR000921-02 from the NIH. Career Investment Award to Dr. Long. Dr. Vasan is supported in part by the Evans Medical Foundation and the Jay and Louis Coffman Endowment from the Boston University School of Medicine.
Handling Editor: Luca Valenti
Abstract
Background & Aims
Non-alcoholic fatty liver disease confers increased risk for cardiovascular disease, including heart failure (HF), for reasons that remain unclear. Possible pathways could involve an association of liver fat with cardiac structural or functional abnormalities even after accounting for body size.
Methods
We analysed N = 2356 Framingham Heart Study participants (age 52 ± 12 years, 52% women) who underwent echocardiography and standardized computed tomography measures of liver fat.
Results
In cross-sectional multivariable regression models adjusted for age, gender, cohort and cardiovascular risk factors, liver fat was positively associated with left ventricular (LV) mass (β = 1.45; 95% confidence interval (CI): 0.01, 2.88), LV wall thickness (β = 0.01; 95% CI: 0.00, 0.02), mass volume ratio (β = 0.02; 95% CI 0.01, 0.03), mitral peak velocity (E) (β = 0.83; 95% CI 0.31, 1.36) and LV filling pressure (E/e′ ratio) (β = 0.16; 95% CI 0.09, 0.23); and inversely associated with global systolic longitudinal strain (β = 0.20, 95% CI 0.07, 0.33), diastolic annular velocity (e′) (β = −0.12; 95% CI − 0.22, −0.03), and E/A ratio (β = −0.01; 95% CI − 0.02, −0.00). After additional adjustment for body mass index (BMI), statistical significance was attenuated for all associations except for that of greater liver fat with increased LV filling pressure, a possible precursor to HF (β = 0.11; 95% CI 0.03, 0.18).
Conclusion
Increased liver fat was associated with multiple subclinical cardiac dysfunction measures, with most of associations mediated by obesity. Interestingly, the association of liver fat and LV filling pressure was only partially mediated by BMI, suggesting a possible direct effect of liver fat on LV filling pressure. Further confirmatory studies are needed.
CONFLICT OF INTEREST
The authors disclose the following potential conflicts of interest: Dr. Gary F. Mitchell is the owner of Cardiovascular Engineering, Inc., serves as a consultant to and receives honoraria from Novartis, Merck, Servier, and Philips Healthcare, and is funded by research grants from Novartis and the National Institutes of Health (NIH). Dr. Susan Cheng serves as a consultant to Zogenix. Dr. David D. McManus serves as a consultant to and receives honoraria from Bristol-Meyers Squibb, Pfizer, FlexCon, and Samsung Semiconductor and is an equity stakeholder in Mobile Sense Technologies, LLC. The remaining authors disclose no conflicts.
Supporting Information
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