Free fatty acids and heart failure in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Perturbation of energy metabolism exacerbates cardiac dysfunction, serving as a potential therapeutic target in congestive heart failure. Although circulating free fatty acids (FFAs) are linked to insulin resistance and risk of coronary heart disease, it still remains unclear whether circulating FFAs are associated with the prognosis of patients with acute heart failure (AHF).Methods: This single-center, observational cohort study enrolled 183 AHF patients (de novo heart failure or decompensated chronic heart failure) in the Second Affiliated Hospital, Zhejiang University School of Medicine. All-cause mortality and heart failure (HF) rehospitalization within 1 year after discharge were investigated. Serum FFAs were modeled as quartiles as well as a continuous variable (per SD of FFAs). The restricted cubic splines and cox proportional hazards models were applied to evaluate the association between the serum FFAs level and all-cause mortality or HF rehospitalization.Results: During a 1-year follow-up, a total of 71 (38.8%) patients had all-cause mortality or HF rehospitalization. The levels of serum FFAs positively contributed to the risk of death or HF rehospitalization, which was not associated with the status of insulin resistance. When modeled with restricted cubic splines, the serum FFAs increased linearly for the incidence of death or HF rehospitalization. In a multivariable analysis adjusting for sex, age, body-mass index, coronary artery disease, diabetes mellitus, hypertension, left ventricular ejection fraction and N-terminal pro-brain natriuretic peptid, each SD (303.07 μmol/L) higher FFAs were associated with 26% higher risk of death or HF rehospitalization (95% confidence interval, 2–55%). Each increasing quartile of FFAs was associated with differentially elevated hazard ratios for death or HF rehospitalization of 1 (reference), 1.71 (95% confidence interval, [0.81, 3.62]), 1.41 (95% confidence interval, [0.64, 3.09]), and 3.18 (95% confidence interval, [1.53, 6.63]), respectively.Conclusion: Serum FFA levels at admission among patients with AHF were associated with an increased risk of adverse outcomes. Additional studies are needed to determine the causal-effect relationship between FFAs and acute cardiac dysfunction and whether FFAs could be a potential target for AHF management.

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Abstract P436: The Role of Free Fatty Acids in Patients With Obesity and Heart Failure With Preserved Ejection Fraction: A Post-hoc Analysis of the UFA-preserved Pilot Study

Circulation ◽

10.1161/circ.141.suppl_1.p436 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Hayley Billingsley ◽

Justin M Canada ◽

ROSHANAK MARKLEY ◽

Brando Rotelli ◽

Dinesh Kadariya ◽

...

Keyword(s):

Heart Failure ◽

Fatty Acids ◽

Body Composition ◽

Pilot Study ◽

Ejection Fraction ◽

Cardiac Function ◽

Free Fatty Acids ◽

Dietary Intervention ◽

Rank Test ◽

Preserved Ejection Fraction

Background: Increased circulating free fatty acids (FFA) are associated with an increased risk for heart failure (HF). Interestingly, in the setting of established HF, the failing heart relies heavily on the use of FFA as energetic substrate, and therapeutics aimed at reducing FFA in HF have been found to worsen cardiac performance. A dietary intervention aimed at increasing unsaturated fatty acids (UFA) was associated with favorable changes in cardiorespiratory fitness (CRF) in patients with obesity and HF with preserved ejection fraction (HFpEF) in the UFA-Preserved Pilot Study, although the mechanism remains largely unknown. We hypothesized that dietary UFA supplementation is associated with an increase in circulating FFA and may improve determinants of CRF such as cardiac function and body composition. Methods: Eight subjects with obesity and HFpEF engaged in 12 weeks of UFA supplementation by increasing intake of foods rich in monounsaturated fatty acids (i.e., oleic acid) and polyunsaturated fatty acids (i.e., α-linolenic acid, linoleic acid) under instruction and monitoring of a research dietitian. Measures were performed at baseline and 12 weeks. Subjects underwent venipuncture to measure circulating FFA, plasma biomarkers of UFA consumption, and NT-proBNP.. Bioelectrical impedance analysis was used to estimate skeletal muscle mass (SMM). Maximal cardiopulmonary exercise testing was performed to measure CRF defined as peak oxygen consumption (VO 2 ). Data are presented as median and interquartile range. Within group changes were assessed using Wilcoxon rank test and correlations were performed using Spearman rank test. Results: Five subjects were female and median age was 53 [50-59] years. The dietary intervention resulted in a significant increase in FFA (from 0.29 [0.20-0.43] to 0.37 [0.32-0.73] μmol/L, p=0.012) and plasmatic UFA (from 1319 [1224-1477] to 1620 [1268-2110] μg/mL, p=0.05). Changes in FFA were positively associated with changes in plasmatic UFA (R=+0.74, p=0.035). Changes in FFA were associated with a trend toward improvement in peak VO 2 , although it did not reach statistical significance (R=+0.72, p=0.068). Changes in FFA were also positively and significantly associated with an increase in SMM expressed in kg (R=+0.99, p<0.001) and % of body weight (R=+0.90, p=0.006) and inversely associated with changes in NT-proBNP (R=-0.85, p=0.007). Conclusion: In patients with obesity and HFpEF, dietary UFA supplementation increases FFA, which are associated with favorable changes in cardiac function and body composition. This supports a novel mechanism through which UFA may positively affect CRF. Ongoing randomized controlled trials (NCT03966755) are underway investigating UFA supplementation as a therapeutic strategy to improve CRF in obesity and HFpEF.

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Free fatty acids, cardiovascular disease, and mortality in the Multi-Ethnic Study of Atherosclerosis

Journal of Clinical Lipidology ◽

10.1016/j.jacl.2020.06.005 ◽

2020 ◽

Vol 14 (4) ◽

pp. 531-541

Author(s):

Sarah O. Nomura ◽

Amy B. Karger ◽

Natalie L. Weir ◽

Daniel A. Duprez ◽

Michael Y. Tsai

Keyword(s):

Cardiovascular Disease ◽

Fatty Acids ◽

Free Fatty Acids ◽

Ethnic Study

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Inhibition of free fatty acids metabolism as a therapeutic target in patients with heart failure

International Journal of Clinical Practice ◽

10.1111/j.1742-1241.2006.01280.x ◽

2007 ◽

Vol 61 (4) ◽

pp. 603-610 ◽

Cited By ~ 16

Author(s):

G. Fragasso

Keyword(s):

Heart Failure ◽

Fatty Acids ◽

Free Fatty Acids ◽

Therapeutic Target ◽

Patients With Heart Failure ◽

Fatty Acids Metabolism

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Serum concentrations of free fatty acids are associated with 3-month mortality in acute heart failure patients

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-0037 ◽

2019 ◽

Vol 57 (11) ◽

pp. 1799-1804 ◽

Cited By ~ 1

Author(s):

Vesna Degoricija ◽

Matias Trbušić ◽

Ines Potočnjak ◽

Bojana Radulović ◽

Gudrun Pregartner ◽

...

Keyword(s):

Heart Failure ◽

Fatty Acids ◽

Free Fatty Acids ◽

Acute Heart Failure ◽

Positive Association ◽

Serum Levels ◽

Prognostic Indicator ◽

Serum Samples ◽

Significant Positive Association ◽

Univariate Analyses

Abstract Background Plasma free fatty acids (FFA) are higher in heart failure (HF) patients compared to healthy controls. Considering that the extent of FFA elevation in HF might mirror the severity of HF, we hypothesized that the serum levels of FFA may be a useful prognostic indicator for 3-month mortality in acute heart failure (AHF). Methods We analyzed the serum samples of AHF patients obtained at admission to the emergency department. Serum levels of FFA were analyzed using an enzymatic reagent on an automatic analyzer. Results Out of 152 included AHF patients that were originally included, serum samples of 132 patients were available for the quantification of FFA. Of these, 35 (26.5%) died within 3 months of onset of AHF. These patients had significantly higher serum levels of FFA compared to AHF patients who were alive 3 months after onset of AHF. Univariable logistic regression analyses showed a significant positive association of FFA levels with 3-month mortality (odds ratio [OR] 2.76 [95% confidence interval 1.32–6.27], p = 0.010). Importantly, this association remained significant after adjusting for age and sex, as well as for further clinical and laboratory parameters that showed a significant association with 3-month mortality in the univariate analyses. Conclusions We conclude that the admission serum levels of FFA are associated with 3-month mortality in AHF patients. Therefore, measurements of circulating FFA levels may help identifying high-risk AHF patients.

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